Mismatched related hematopoietic stem cell transplantation in primary immunodeficiency.

PubMed

Wahadneh, Adel M; Bin Dahman, Haifa A; Abu Shukear, Mohammed E; Habahbeh, Zeyad M; Ajarmeh, Mohammad A; Zyood, Raed M; Habashneh, Mueen S

2013-11-01

Hematopoietic stem cell transplantation (HSCT) is the definitive therapy for a variety of primary immunodeficiency syndromes (PIDs). However, no more than 30% of the patients will have a human leukocyte antigen (HLA)-identical sibling. We retrospectively analyzed our results of ten patients with PID; severe combined immunodeficiency (SCID) (n = 7), hyper IgM (HIgM) (n = 1) and combined immunodeficiency (CID) (n = 2), who lacked a fully matched donor and underwent mismatched related HSCT during the period from 2008 to 2010. The median age at the time of transplantation ranged between 3 and 84 months (median 6.5 months). Peripheral blood stem cells (PBSC) were used in all HSCTs. The mean value of the peripheral CD34+ cells infused was 9.19 × 10 (6) /kg recipient weight. Patients received different conditioning protocols. All patients received anti graft versus host disease (GVHD) prophylaxis and all were engrafted. Mixed chimerism (5-55%) was noticed. GVHD was observed in 50% of the patients. Post-transplant follow-up ranged from 3 weeks to 36 months (median 15 months). Five patients are still alive while one patient developed engraftment syndrome followed by graft slippage for which a second transplant with CD34+ stem cells 5.8 × 10 (6) /kg recipient's weight was infused. The others died from sepsis and transplant-related complications. Immune reconstitution was noticed in four patients. In conclusion, HLA-haploidentical stem cell transplantation may be feasible, with appropriate GVHD prophylaxis, for patients with PID who lack a fully matched donor.

Stem cell tourism and public education: the missing elements.

PubMed

Master, Zubin; Robertson, Kelsey; Frederick, Daniel; Rachul, Christen; Caulfield, Timothy

2014-09-04

Stem cell tourism describes the Internet-based industry where in patients receive unproven stem cell interventions. To better inform the public, several organizations provide educational material on stem cell therapies and tourism; however, an assessment of the currently available resources reveals a lack of comprehensive information, suggesting that further efforts are needed. Copyright © 2014 Elsevier Inc. All rights reserved.

Stem cell therapy for reconstruction of alveolar cleft and trauma defects in adults: A randomized controlled, clinical trial.

PubMed

Bajestan, Mona N; Rajan, Archana; Edwards, Sean P; Aronovich, Sharon; Cevidanes, Lucia H S; Polymeri, Angeliki; Travan, Suncica; Kaigler, Darnell

2017-10-01

Stem cell therapy with bone marrow-derived mesenchymal stem cells is a promising tissue engineering strategy to promote regeneration of craniofacial bone. To determine whether cell therapy with ex vivo expanded stem cell populations would be safe and efficacious in the regeneration of large alveolar defects in patients with a history of cleft palate or craniofacial trauma. Eighteen patients (10 patients with traumatic injury and 8 patients with cleft palate) presenting with missing teeth associated with horizontal alveolar bone deficiencies were included in this randomized controlled clinical trial. Patients were randomized to receive either conventional autogenous block grafts or stem cell therapy. After a healing period of 4 months the treated sites were re-entered and the bone width re-assessed prior to implant placement. Implant stability was evaluated through torque testing of the implant upon insertion and at 6 months postloading. The mean gain in bone width was 1.5 ± 1.5 mm in the stem cell therapy group and 3.3 ± 1.4 mm in the control group. Overall, bone gain was higher in trauma patients as compared to patients with cleft palate, for both the control and the stem cell therapy groups. Most postoperative complications were wound dehiscences and incision line openings. Implants were placed successfully in 5 out of 10 patients in the stem cell therapy group and in all 8 patients in the control group. One implant from the control/cleft palate group failed before loading, while the rest of the implants were loaded successfully and remained stable at 6 months. The patients who did not receive implants were re-treated with autogenous block bone graft. The ability of stem cells to treat large alveolar defects is safe, yet, their ability to completely reconstitute large alveolar defects is limited. This approach requires further optimization to meet the outcomes seen using current methods to treat large defects, particularly those resultant of cleft palate. © 2017 Wiley Periodicals, Inc.

Impact of conditioning with TBI in adult patients with T-cell ALL who receive a myeloablative allogeneic stem cell transplantation: a report from the acute leukemia working party of EBMT.

PubMed

Cahu, X; Labopin, M; Giebel, S; Aljurf, M; Kyrcz-Krzemien, S; Socié, G; Eder, M; Bonifazi, F; Bunjes, D; Vigouroux, S; Michallet, M; Stelljes, M; Zuckerman, T; Finke, J; Passweg, J; Yakoub-Agha, I; Niederwieser, D; Sucak, G; Sengeløv, H; Polge, E; Nagler, A; Esteve, J; Mohty, M

2016-03-01

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for adult patients with T-cell ALL (T-ALL). Meanwhile, few allo-SCT data specific to adult T-ALL have been described thus far. Specifically, the optimal myeloablative conditioning regimen is unknown. In this retrospective study, 601 patients were included. Patients received allo-SCT in CR1, CR2, CR >2 or in advanced disease in 69%, 15%, 2% and 14% of cases, respectively. With an overall follow-up of 58 months, 523 patients received a TBI-based regimen, whereas 78 patients received a chemotherapy-based regimen including IV busulfan-cyclophosphamide (IV Bu-Cy) (n=46). Unlike patients aged ⩾35 years, patients aged <35 years who received a TBI-based regimen displayed an improved outcome compared with patients who received a chemotherapy-based regimen (5-year leukemia-free survival (LFS) of 50% for TBI versus 18% for chemo-only regimen or IV Bu-Cy regimens, P=10(-5) and 10(-4), respectively). In multivariate analysis, use of TBI was associated with an improved LFS (hazard ratio (HR)=0.55 (0.34-0.86), P=0.01) and overall survival (HR=0.54 (0.34-0.87), P=0.01) in patients aged <35 years. In conclusion, younger adult patients with T-ALL entitled to receive a myeloablative allo-SCT may benefit from TBI-based regimens.

Neurotoxicity Associated With Dimethyl Sulfoxide Used in Allogeneic Stem Cell Transplantation.

PubMed

Ataseven, Eda; Tüfekçi, Özlem; Yilmaz, Şebnem; Güleryüz, Handan; Ören, Hale

2017-07-01

Dimethyl sulfoxide (DMSO) is a cryoprotective agent used in storage of frozen stem cells in stem cell transplantation. Central nervous system side effects of DMSO such as epileptic seizures, stroke, transient global amnesia, and temporary leucoencephalopathy are rarely seen. Here, we report a pediatric patient who developed seizures after DMSO-cryopreserved stem cell infusion and whose magnetic resonance imaging of the brain demonstrated parietal and occipital focal cortical T2-signal intensity increase. DMSO toxicity should be kept in mind in patients who received cryopreserved stem cell infusion and magnetic resonance imaging may be helpful in differential diagnosis of central nervous system involvement.

Stem cell tourism--a web-based analysis of clinical services available to international travellers.

PubMed

Connolly, Ruairi; O'Brien, Timothy; Flaherty, Gerard

2014-01-01

Stem cell therapies are advertised through online resources which describe a range of treatments with diverse clinical indications. Stem cell tourists may not be aware of the information they should seek when consulting these clinics, or of the potential risks involved. The aim of this study was to characterise the therapies offered by online stem cell clinics. A web based search utilising five search terms was employed. The first twenty pages of each search result were screened against 340 variables. 224 out of 1091 websites advertised stem cell clinics. 68 eligible sites covering 21 countries were evaluated. The top five clinical indications for stem cell therapy were multiple sclerosis, anti-ageing, Parkinson's disease, stroke and spinal cord injury. Adult, autologous stem cells were the most commonly utilised stem cell, and these were frequently sourced from bone marrow and adipose tissue and administered intravenously. Thirty-four per cent of sites mentioned the number of patients treated while one quarter of clinics provided outcome data. Twenty-nine per cent of clinics had an internationally recognised accreditation. Fifteen per cent of clinics stated that their therapies posed no risk. Eighty-eight per cent of clinics claimed treatment effectiveness, with 16% describing their curative potential. Over 40% of sites did not specify the number or duration of treatments. Fifty-three per cent of clinics requested access to patients' medical records, and 12% recommended patients discuss the proposed therapy with their doctor. No clinic recommended that travellers consult a travel medicine specialist or receive vaccinations prior to their intended travel. One quarter of sites discussed contraindications to treatment, with 41% of sites detailing follow up patient care. There is potential for stem cell tourists to receive misleading or deficient information from online stem cell clinics. Both the stem cell tourist and travel medicine practitioner should be educated on the potential risks associated with stem cell clinical services advertised online.

The emerging role of PET in Hodgkin lymphoma patients receiving autologous stem cell transplant.

PubMed

von Tresckow, Bastian; Engert, Andreas

2012-10-01

High-dose chemotherapy followed by autologous stem cell transplant (ASCT) is the standard therapy for patients with relapsed or refractory Hodgkin lymphoma. Several analyses have reported risk factors for a poor outcome after ASCT to allow for an individualized treatment, but there is no consensus on how the outcome in high-risk patients might be improved. A recent study by Cocorocchio et al. analyzes risk factors in 97 patients who received ASCT. Besides the established risk factor remission status after induction, result of positron emission tomography before and after transplant was the most important prognostic factor for progression-free survival and overall survival. This result is in line with other retrospective analyses and might allow for the selection of high-risk patients who should receive alternative treatment approaches, such as second-line salvage therapy, tandem ASCT, new drugs or maintenance therapy. Randomized trials characterizing the best therapeutic option for high-risk patients are highly warranted.

Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT.

PubMed

Neuenhahn, M; Albrecht, J; Odendahl, M; Schlott, F; Dössinger, G; Schiemann, M; Lakshmipathi, S; Martin, K; Bunjes, D; Harsdorf, S; Weissinger, E M; Menzel, H; Verbeek, M; Uharek, L; Kröger, N; Wagner, E; Kobbe, G; Schroeder, T; Schmitt, M; Held, G; Herr, W; Germeroth, L; Bonig, H; Tonn, T; Einsele, H; Busch, D H; Grigoleit, G U

2017-10-01

Cytomegalovirus (CMV) infection is a common, potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed prospectively the safety and efficacy of stem cell-donor- or third-party-donor-derived CMV-specific T cells for the treatment of persistent CMV infections after allo-HSCT in a phase I/IIa trial. Allo-HSCT patients with drug-refractory CMV infection and lacking virus-specific T cells were treated with a single dose of ex vivo major histocompatibility complex-Streptamer-isolated CMV epitope-specific donor T cells. Forty-four allo-HSCT patients receiving a T-cell-replete (D + repl; n=28) or T-cell-depleted (D + depl; n=16) graft from a CMV-seropositive donor were screened for CMV-specific T-cell immunity. Eight D + depl recipients received adoptive T-cell therapy from their stem cell donor. CMV epitope-specific T cells were well supported and became detectable in all treated patients. Complete and partial virological response rates were 62.5% and 25%, respectively. Owing to longsome third-party donor (TPD) identification, only 8 of the 57 CMV patients transplanted from CMV-seronegative donors (D - ) received antigen-specific T cells from partially human leukocyte antigen (HLA)-matched TPDs. In all but one, TPD-derived CMV-specific T cells remained undetectable. In summary, adoptive transfer correlated with functional virus-specific T-cell reconstitution in D + depl patients. Suboptimal HLA match may counteract expansion of TPD-derived virus-specific T cells in D - patients.

Prevention of dimethylsulfoxide-related nausea and vomiting by prophylactic administration of ondansetron for patients receiving autologous cryopreserved peripheral blood stem cells.

PubMed

Eisenberg, Seth; Wickline, Mihkaila; Linenberger, Michael; Gooley, Ted; Holmberg, Leona

2013-05-01

To evaluate the effectiveness of ondansetron for the prevention of nausea and vomiting from dimethylsulfoxide (DMSO) during autologous stem cell transplantation (ASCT) infusion. Nonrandomized cohort using historical control. Comprehensive cancer center outpatient infusion department. 50 patients receiving ASCT in the outpatient setting. Patients were assessed for nausea and vomiting on their infusion day using the Multinational Association of Supportive Care in Cancer Antiemesis Tool (MAT) at arrival, pre-ASCT infusion, pre-ondansetron administration, prior to the first bag, and after each bag of stem cells. A standard script was used to ensure consistency. Ondansetron, 16 mg IV, was administered 30-90 minutes prior to each ASCT infusion. Number and volume of stem cells bags, as well as infusion rate and emesis episodes, were recorded. Nausea scores and vomiting episodes were compared to historical data. Subjectivity of nausea, potential Hawthorne Effect. Forty-five percent of patients had an MAT score greater than 2 on arrival, decreasing to 18% after receiving ondansetron before the first bag. Twenty-four percent had MAT increases of more than two points by infusion end compared to 58% in the historic control group. Eighteen percent of patients vomited compared to 28% of historic controls. The administration of 16 mg of IV ondansetron significantly reduced DMSO-related nausea and episodes of vomiting in patients receiving ASCT. Prophylactic administration of ondansetron had a positive effect on reducing nausea symptoms and episodes of vomiting during ASCT infusions. These results prompted a change in clinical practice. More research is required to determine whether the inclusion of other antiemetic agents would provide even greater benefit. To date, no other published studies have explored the benefits of premedicating patients with ondansetron prior to ASCT infusions. This study is the first to establish efficacy of ondansetron for an unlabeled indication. These results may pave the way for future research in decreasing nausea and vomiting in this setting.

[Analysis of thyroid lesions in childhood recipients after hematopoietic stem cell transplantation].

PubMed

Maeda, Naoko; Hamajima, Takashi; Yambe, Yuko; Sekimizu, Masahiro; Horibe, Keizo

2013-03-01

We performed a physical examination and ultrasonography of the thyroid gland in 24 patients who had received hematopoietic stem cell transplantation with a total-body irradiation (TBI)-containing regimen during childhood. When ultrasonography revealed thyroid nodules larger than 1 cm in diameter, fine-needle aspiration biopsies were performed. Of 5 patients with palpable masses and thyroid nodules larger than 1 cm, adenomatous goiter was diagnosed in 4 cases and thyroid cancer in 1. Of the remaining 19 patients in whom no palpable mass was detected in the physical examination, 5 had thyroid nodules (including 1 adenomatous goiter), 6 had cystic lesions, and 8 exhibited no abnormalities on ultrasonography. No significant differences in sex, age at transplantation, interval between transplantation and evaluation, primary disease, preconditioning regimen, status at transplantation, stem cell source, chronic graft-versus-host disease, hypogonadism, or hypothyroidism were observed between patients with and without nodules. Individuals who received hematopoietic stem cell transplantation with a TBI-containing regimen are at risk of secondary thyroid cancer due to radiotherapy and require regular clinical evaluations of the thyroid gland by palpation, and ultrasonography should be incorporated into these checkups.

Ambivalent journeys of hope: embryonic stem cell therapy in a clinic in India.

PubMed

Prasad, Amit

2015-03-01

Stem cell therapy in non-Western countries such as India has received a lot of attention. Apart from media reports, there are a number of social science analyses of stem cell policy, therapy, and research, their ethical implications, and impact of advertising on patients. Nevertheless, in the media reports as well as in academic studies, experiences of patients, who undertake overseas journeys for stem cell therapy, have largely been either ignored or presented reductively, often as a "false hope." In this article, I analyze the experiences of patients and their "journeys of hope" to NuTech Mediworld, an embryonic stem cell therapy clinic in New Delhi, India. My analysis, which draws on my observations in the clinic and patients' experiences, instead of seeking to adjudicate whether embryonic stem cell therapy in clinics such as NuTech is right or wrong, true or false, focuses on how patients navigate and contest these concerns. I utilize Gilles Deleuze and Felix Guattari's "concepts," lines of flight and deterritorialization, to highlight how embryonic stem cell therapy's "political economy of hope" embodies deterritorialization of several "regimes of truth" and how these deterritorializations impact patients' experiences. © The Author(s) 2014.

Immunomodulatory effects of the Agaricus blazei Murrill-based mushroom extract AndoSan in patients with multiple myeloma undergoing high dose chemotherapy and autologous stem cell transplantation: a randomized, double blinded clinical study.

PubMed

Tangen, Jon-Magnus; Tierens, Anne; Caers, Jo; Binsfeld, Marilene; Olstad, Ole Kristoffer; Trøseid, Anne-Marie Siebke; Wang, Junbai; Tjønnfjord, Geir Erland; Hetland, Geir

2015-01-01

Forty patients with multiple myeloma scheduled to undergo high dose chemotherapy with autologous stem cell support were randomized in a double blinded fashion to receive adjuvant treatment with the mushroom extract AndoSan, containing 82% of Agaricus blazei Murrill (19 patients) or placebo (21 patients). Intake of the study product started on the day of stem cell mobilizing chemotherapy and continued until the end of aplasia after high dose chemotherapy, a period of about seven weeks. Thirty-three patients were evaluable for all study endpoints, while all 40 included patients were evaluable for survival endpoints. In the leukapheresis product harvested after stem cell mobilisation, increased percentages of Treg cells and plasmacytoid dendritic cells were found in patients receiving AndoSan. Also, in this group, a significant increase of serum levels of IL-1ra, IL-5, and IL-7 at the end of treatment was found. Whole genome microarray showed increased expression of immunoglobulin genes, Killer Immunoglobulin Receptor (KIR) genes, and HLA genes in the Agaricus group. Furthermore, AndoSan displayed a concentration dependent antiproliferative effect on mouse myeloma cells in vitro. There were no statistically significant differences in treatment response, overall survival, and time to new treatment. The study was registered with Clinicaltrials.gov NCT00970021.

Immunomodulatory Effects of the Agaricus blazei Murrill-Based Mushroom Extract AndoSan in Patients with Multiple Myeloma Undergoing High Dose Chemotherapy and Autologous Stem Cell Transplantation: A Randomized, Double Blinded Clinical Study

PubMed Central

Tierens, Anne; Caers, Jo; Binsfeld, Marilene; Olstad, Ole Kristoffer; Trøseid, Anne-Marie Siebke; Wang, Junbai; Tjønnfjord, Geir Erland; Hetland, Geir

2015-01-01

Forty patients with multiple myeloma scheduled to undergo high dose chemotherapy with autologous stem cell support were randomized in a double blinded fashion to receive adjuvant treatment with the mushroom extract AndoSan, containing 82% of Agaricus blazei Murrill (19 patients) or placebo (21 patients). Intake of the study product started on the day of stem cell mobilizing chemotherapy and continued until the end of aplasia after high dose chemotherapy, a period of about seven weeks. Thirty-three patients were evaluable for all study endpoints, while all 40 included patients were evaluable for survival endpoints. In the leukapheresis product harvested after stem cell mobilisation, increased percentages of Treg cells and plasmacytoid dendritic cells were found in patients receiving AndoSan. Also, in this group, a significant increase of serum levels of IL-1ra, IL-5, and IL-7 at the end of treatment was found. Whole genome microarray showed increased expression of immunoglobulin genes, Killer Immunoglobulin Receptor (KIR) genes, and HLA genes in the Agaricus group. Furthermore, AndoSan displayed a concentration dependent antiproliferative effect on mouse myeloma cells in vitro. There were no statistically significant differences in treatment response, overall survival, and time to new treatment. The study was registered with Clinicaltrials.gov NCT00970021. PMID:25664323

Comparison of Patient-Reported Outcome from Neck-Preserving, Short-Stem Arthroplasty and Resurfacing Arthroplasty in Younger Osteoarthritis Patients

PubMed Central

Dettmer, Marius; Pourmoghaddam, Amir; Kreuzer, Stefan W.

2015-01-01

Hip resurfacing has been considered a good treatment option for younger, active osteoarthritis patients. However, there are several identified issues concerning risk for neck fractures and issues related to current metal-on-metal implant designs. Neck-preserving short-stem implants have been discussed as a potential alternative, but it is yet unclear which method is better suited for younger adults. We compared hip disability and osteoarthritis outcome scores (HOOS) from a young group of patients (n = 52, age 48.9 ± 6.1 years) who had received hip resurfacing (HR) with a cohort of patients (n = 73, age 48.2 ± 6.6 years) who had received neck-preserving, short-stem implant total hip arthroplasty (THA). Additionally, durations for both types of surgery were compared. HOOS improved significantly preoperatively to last followup (>1 year) in both groups (p < 0.0001, η 2 = 0.69); there were no group effects or interactions. Surgery duration was significantly longer for resurfacing (104.4 min ± 17.8) than MiniHip surgery (62.5 min ± 14.8), U = 85.0, p < 0.0001, η 2 = 0.56. The neck-preserving short-stem approach may be preferable to resurfacing due to the less challenging surgery, similar outcome, and controversy regarding resurfacing implant designs. PMID:26101669

Unproven stem cell-based interventions and achieving a compromise policy among the multiple stakeholders.

PubMed

Matthews, Kirstin R W; Iltis, Ana S

2015-11-04

In 2004, patient advocate groups were major players in helping pass and implement significant public policy and funding initiatives in stem cells and regenerative medicine. In the following years, advocates were also actively engaged in Washington DC, encouraging policy makers to broaden embryonic stem cell research funding, which was ultimately passed after President Barack Obama came into office. Many advocates did this because they were told stem cell research would lead to cures. After waiting more than 10 years, many of these same patients are now approaching clinics around the world offering experimental stem cell-based interventions instead of waiting for scientists in the US to complete clinical trials. How did the same groups who were once (and often still are) the strongest supporters of stem cell research become stem cell tourists? And how can scientists, clinicians, and regulators work to bring stem cell patients back home to the US and into the clinical trial process? In this paper, we argue that the continued marketing and use of experimental stem cell-based interventions is problematic and unsustainable. Central problems include the lack of patient protection, US liability standards, regulation of clinical sites, and clinician licensing. These interventions have insufficient evidence of safety and efficacy; patients may be wasting money and time, and they may be forgoing other opportunities for an intervention that has not been shown to be safe and effective. Current practices do not contribute to scientific progress because the data from the procedures are unsuitable for follow-up research to measure outcomes. In addition, there is no assurance for patients that they are receiving the interventions promised or of what dosage they are receiving. Furthermore, there is inconsistent or non-existent follow-up care. Public policy should be developed to correct the current situation. The current landscape of stem cell tourism should prompt a re-evaluation of current approaches to study cell-based interventions with respect to the design, initiation, and conduct of US clinical trials. Stakeholders, including scientists, clinicians, regulators and patient advocates, need to work together to find a compromise to keep patients in the US and within the clinical trial process. Using HIV/AIDS and breast cancer advocate cases as examples, we identify key priorities and goals for this policy effort.

Thiotepa 10 mg/kg Treatment Regimen Is Superior to Thiotepa 5 mg/kg in TBF Conditioning in Patients Undergoing Allogeneic Stem-Cell Transplantation.

PubMed

El-Cheikh, Jean; Massoud, Radwan; Moukalled, Nour; Haffar, Basel; Assi, Hazem; Zahreddine, Ammar; Mahfouz, Rami; Bazarbachi, Ali

2018-05-01

The optimal intensity of myeloablation with a reduced-toxicity conditioning regimen to decrease relapse rate after allogeneic stem-cell transplantation without increasing transplant-related mortality (TRM) has not been well established. We compared outcomes between 5 mg/kg (T5) and 10 mg/kg (T10) thiotepa-based conditioning regimens in 29 adults who underwent allogeneic stem-cell transplantation for hematologic malignancies. After a median follow-up of 11 months, TRM was 0% and 14% at 100 days and 1 year, respectively, with TRM observed only in the T5 group (P = .016). The relapse incidence at 1 year was 20%. No patient had disease in first complete remission at the time of transplantation. At 1 year, progression-free and overall survival were 30% versus 87% (P = .012) and 46% versus 87% (P = .008) in the T5 and T10 groups, respectively. In univariate and multivariate analysis, only age at transplantation and total dose of thiotepa had a significant impact on TRM, overall, and progression-free survival. Patients deemed fit to receive T10-based conditioning for allogeneic stem-cell transplantation to treat high-risk hematologic malignancies had better overall and progression-free survival than those who received T5 with no additional toxicities. Patients should be stratified before conditioning, and those judged fit should receive T10, while the others should consider alternative reduced-intensity conditioning regimens. Copyright © 2018 Elsevier Inc. All rights reserved.

Allogeneic peripheral blood stem cell transplantation in patients with haematological malignancies.

PubMed

Shamsi, T S; Irfan, M; Ansari, S H; Farzana, T; Khalid, M Z; Panjwani, V K; Baig, M I; Shakoor, N

2004-09-01

To report the initial data on allogeneic peripheral blood stem cell transplantation for haematological malignancies in Pakistan. A single centre descriptive study. Bismillah Taqee Institute of Health Sciences and Blood Diseases Centre from September 1999 to June 2004. Patients with haematological malignancies were included who had received allogeneic PBSC transplantation of Filgrastim (rhG-CSF) mobilized peripheral blood stem cells from HLA-identical siblings (except one 5/6 antigen sibling) with Busulphan and Cyclophosphamide standard conditioning therapy in all patients. No patient received antibiotics for gut decontamination. Empirical antibiotics included Ceftriaxone and Amikacin for febrile neutropenia, oral Itraconazole for antifungal prophylaxis while oral acyclovir was used for antiviral prophylaxis. All donors and recipients were CMV IgG positive Cyclosporin A / Methotrexate were given for graft versus host disease (GvHD) prophylaxis. Stem cells were harvested using Haemonetics MCS+ cell separator. All patients received G-CSF starting from day +4 until their neutrophil count rose to normal. There were 21 patients with age range of 8-38 years and male to female ratio of 2:1. Engraftment was achieved in all patients; median time to absolute neutrophil count of > 0.5 x 10(9)/l was 10 days (range 8 - 12 days) and platelet count of > 20 x 10(9)/l was 14 days (12-17 days). Acute graft versus host disease ( aGvHD) was seen in 7 patients; one patient had grade IV skin and hepatic GvHD; another patient had grade III gut GvHD, grade II GvHD was seen in 3 patients while grade I skin aGvHD was seen in 2 patients. Median hospital stay was 34 days. Treatment related mortality was seen in 3 patients (18%). Chronic GvHD was seen in 5 patients. Four more patients died during the follow-up period. Malaria was seen in 2 while tuberculosis developed in one case. Relapse was seen in 2 patients. The estimated probability of survival at one hundred day, at one year and five years was 82, 47 and 40 percent respectively. Haematopoietic stem cell transplant programme can be developed in a developed country setting. Post transplant complications are similar to what have been reported in the developed countries. In endemic areas malaria could prove to be fatal if not recognised and treated early.

Impact of the use of autologous stem cell transplantation at first relapse both in naïve and previously rituximab exposed follicular lymphoma patients treated in the GELA/GOELAMS FL2000 study

PubMed Central

Le Gouill, Steven; De Guibert, Sophie; Planche, Lucie; Brice, Pauline; Dupuis, Jehan; Cartron, Guillaume; Van Hoof, Achiel; Casasnovas, Olivier; Gyan, Emmanuel; Tilly, Hervé; Fruchart, Christophe; Deconinck, Eric; Fitoussi, Olivier; Gastaud, Lauris; Delwail, Vincent; Gabarre, Jean; Gressin, Rémy; Blanc, Michel; Foussard, Charles; Salles, Gilles

2011-01-01

Background We analyzed detailed characteristics and salvage treatment in 175 follicular lymphoma patients from the FL2000 study who were in progression after first-line therapy with or without addition of rituximab to chemotherapy and interferon. Design and Methods The impact of using autologous stem cell transplantation and/or rituximab administration at first progression was investigated, taking into account initial therapy. With a median follow up of 31 months, 3-year event free and overall survival rates after progression were 50% (95%CI 42–58%) and 72% (95%CI 64–78%), respectively. Results The 3-year event free rate of rituximab re-treated patients (n=112) was 52% (95%CI 41–62%) versus 40% (95%CI 24–55%) for those not receiving rituximab second line (n=53) (P=0.075). There was a significant difference in 3-year overall survival between patients receiving autologous stem cell transplantation and those not: 92% (95%CI 78–97%) versus 63% (95%CI 51–72%) (P=0.0003), respectively. In multivariate analysis, both autologous stem cell transplantation and period of progression/relapse affected event free and overall survival. Conclusions Regardless of front-line rituximab exposure, this study supports incorporating autologous stem cell transplantation in the therapeutic approach at first relapse for follicular lymphoma patients. PMID:21486862

Targeting insulin resistance in type 2 diabetes via immune modulation of cord blood-derived multipotent stem cells (CB-SCs) in stem cell educator therapy: phase I/II clinical trial.

PubMed

Zhao, Yong; Jiang, Zhaoshun; Zhao, Tingbao; Ye, Mingliang; Hu, Chengjin; Zhou, Huimin; Yin, Zhaohui; Chen, Yana; Zhang, Ye; Wang, Shanfeng; Shen, Jie; Thaker, Hatim; Jain, Summit; Li, Yunxiang; Diao, Yalin; Chen, Yingjian; Sun, Xiaoming; Fisk, Mary Beth; Li, Heng

2013-07-09

The prevalence of type 2 diabetes (T2D) is increasing worldwide and creating a significant burden on health systems, highlighting the need for the development of innovative therapeutic approaches to overcome immune dysfunction, which is likely a key factor in the development of insulin resistance in T2D. It suggests that immune modulation may be a useful tool in treating the disease. In an open-label, phase 1/phase 2 study, patients (N=36) with long-standing T2D were divided into three groups (Group A, oral medications, n=18; Group B, oral medications+insulin injections, n=11; Group C having impaired β-cell function with oral medications+insulin injections, n=7). All patients received one treatment with the Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, briefly co-cultures them with adherent cord blood-derived multipotent stem cells (CB-SCs), and returns the educated autologous cells to the patient's circulation. Clinical findings indicate that T2D patients achieve improved metabolic control and reduced inflammation markers after receiving Stem Cell Educator therapy. Median glycated hemoglobin (HbA1C) in Group A and B was significantly reduced from 8.61%±1.12 at baseline to 7.25%±0.58 at 12 weeks (P=2.62E-06), and 7.33%±1.02 at one year post-treatment (P=0.0002). Homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) demonstrated that insulin sensitivity was improved post-treatment. Notably, the islet beta-cell function in Group C subjects was markedly recovered, as demonstrated by the restoration of C-peptide levels. Mechanistic studies revealed that Stem Cell Educator therapy reverses immune dysfunctions through immune modulation on monocytes and balancing Th1/Th2/Th3 cytokine production. Clinical data from the current phase 1/phase 2 study demonstrate that Stem Cell Educator therapy is a safe approach that produces lasting improvement in metabolic control for individuals with moderate or severe T2D who receive a single treatment. In addition, this approach does not appear to have the safety and ethical concerns associated with conventional stem cell-based approaches. ClinicalTrials.gov number, NCT01415726.

Can Arthroplasty Stem INfluence Outcome? (CASINO): a randomized controlled equivalence trial of 125 mm versus 150 mm Exeter V40 stems in total hip arthroplasty.

PubMed

Hamilton, David F; Ohly, Nicholas E; Gaston, Paul

2018-04-16

The use of shorter length femoral stems during total hip arthroplasty has been suggested to accommodate wider patient femoral geometry and offer maximal bone preservation. However, cemented short-stem designs may increase the risk of varus stem malalignment and influence patient outcomes. CASINO is a multi-centre randomised equivalence trial that will recruit 220 patients undergoing total hip arthroplasty for osteoarthritis at two NHS hospitals in Scotland. Patients will be aged 45-80, undergoing unilateral primary hip arthroplasty, with no plan for contralateral procedure within the study timeframe, and able to comply with the protocol. Participants will be randomised to receive either a short (125 mm) or a standard (150 mm) Exeter V40 stem. The Contemporary acetabular component will be used in all cases. All implants will be cemented. Patient pain, function and satisfaction will be assessed using change from baseline measurement in Oxford Hip Score, Forgotten Joint Score, EQ-5D, pain numerical rating scores, and patient satisfaction questionnaire at baseline and at 1 and 2 years following surgery. Radiographic assessment will evaluate stem position and will be appraised by independent reviewers. Patients will be blind to implant allocation. Stem length may be associated with outcome; however, we can find no randomised trial in which researchers investigated the effect of stem length on patient outcome following cemented total hip arthroplasty. The aim of this trial is to determine if the use of short cemented stems offers equivalent patient outcomes to those achieved following surgery with standard length stems. International Standard Randomised Controlled Trial Number, ISRCTN13154542 , Registered on 30 June 2017.

Overcoming the response plateau in multiple myeloma: a novel bortezomib-based strategy for secondary induction and high-yield CD34+ stem cell mobilization.

PubMed

Niesvizky, Ruben; Mark, Tomer M; Ward, Maureen; Jayabalan, David S; Pearse, Roger N; Manco, Megan; Stern, Jessica; Christos, Paul J; Mathews, Lena; Shore, Tsiporah B; Zafar, Faiza; Pekle, Karen; Xiang, Zhaoying; Ely, Scott; Skerret, Donna; Chen-Kiang, Selina; Coleman, Morton; Lane, Maureen E

2013-03-15

This phase II study evaluated bortezomib-based secondary induction and stem cell mobilization in 38 transplant-eligible patients with myeloma who had an incomplete and stalled response to, or had relapsed after, previous immunomodulatory drug-based induction. Patients received up to six 21-day cycles of bortezomib plus dexamethasone, with added liposomal doxorubicin for patients not achieving partial response or better by cycle 2 or very good partial response or better (≥VGPR) by cycle 4 (DoVeD), followed by bortezomib, high-dose cyclophosphamide, and filgrastim mobilization. Gene expression/signaling pathway analyses were conducted in purified CD34+ cells after bortezomib-based mobilization and compared against patients who received only filgrastim ± cyclophosphamide. Plasma samples were similarly analyzed for quantification of associated protein markers. The response rate to DoVeD relative to the pre-DoVeD baseline was 61%, including 39% ≥ VGPR. Deeper responses were achieved in 10 of 27 patients who received bortezomib-based mobilization; postmobilization response rate was 96%, including 48% ≥ VGPR, relative to the pre-DoVeD baseline. Median CD34+ cell yield was 23.2 × 10(6) cells/kg (median of 1 apheresis session). After a median follow-up of 46.6 months, median progression-free survival was 47.1 months from DoVeD initiation; 5-year overall survival rate was 76.4%. Grade ≥ 3 adverse events included thrombocytopenia (13%), hand-foot syndrome (11%), peripheral neuropathy (8%), and neutropenia (5%). Bortezomib-based mobilization was associated with modulated expression of genes involved in stem cell migration. Bortezomib-based secondary induction and mobilization could represent an alternative strategy for elimination of tumor burden in immunomodulatory drug-resistant patients that does not impact stem cell yield.

G-CSF plus preemptive plerixafor vs hyperfractionated CY plus G-CSF for autologous stem cell mobilization in multiple myeloma: effectiveness, safety and cost analysis.

PubMed

Antar, A; Otrock, Z K; Kharfan-Dabaja, M A; Ghaddara, H A; Kreidieh, N; Mahfouz, R; Bazarbachi, A

2015-06-01

The optimal stem cell mobilization regimen for patients with multiple myeloma (MM) remains undefined. We retrospectively compared our experience in hematopoietic cell mobilization in 83 MM patients using fractionated high-dose CY and G-CSF with G-CSF plus preemptive plerixafor. All patients in the CY group (n=56) received fractionated high-dose CY (5 g/m(2) divided into five doses of 1 g/m(2) every 3 h) with G-CSF. All patients in the plerixafor group (n=27) received G-CSF and plerixafor preemptively based on an established algorithm. Compared with plerixafor, CY use was associated with higher total CD34+ cell yield (7.5 × 10(6) vs 15.5 × 10(6) cells/kg, P=0.005). All patients in both groups yielded ⩾4 × 10(6) CD34+ cells/kg. Conversely, CY use was associated with high frequency of febrile neutropenia, blood and platelet transfusions need and hospitalizations. The average total cost of mobilization in Lebanon was slightly higher in the plerixafor group ($7886 vs $7536; P=0.16). Our data indicate robust stem cell mobilization in MM patients with either fractionated high-dose CY and G-CSF or G-CSF alone with preemptive plerixafor. The chemo-mobilization approach was associated with twofold stem cell yield, slightly lower cost but significantly increased toxicity.

Incidentally Detected Transfusion-associated Iron Overload in 3 Children After Cancer Chemotherapy.

PubMed

Kuo, Dennis John; Bhagia, Pooja

2018-04-01

Iron overload is a potential long-term complication among cancer survivors who received transfusions during treatment. Although there are screening guidelines for iron overload in pediatric survivors of hematopoietic stem cell transplant, these do not call for screening of other pediatric oncology patients. In our practice we incidentally discovered 3 patients in a population of 168 cancer survivors over the span of 17 years who were treated for cancer without hematopoietic stem cell transplant who had iron overload. The 3 patients had elevated liver iron on magnetic resonance imaging T2* and 2 received therapeutic phlebotomy. These cases, and others like them, suggest that collaborative groups should consider revisiting the literature to establish screening and treatment guidelines for iron overload after cancer therapy.

Partial T-cell depletion improves the composite endpoint graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic stem cell transplantation.

PubMed

Simonetta, Federico; Masouridi-Levrat, Stavroula; Beauverd, Yan; Tsopra, Olga; Tirefort, Yordanka; Koutsi, Aikaterini; Stephan, Caroline; Polchlopek-Blasiak, Karolina; Pradier, Amandine; Dantin, Carole; Ansari, Marc; Roosnek, Eddy; Chalandon, Yves

2018-03-01

Graft-versus-host disease (GvHD)-free, relapse-free survival (GRFS) is a recently reported composite endpoint that allows to simultaneously estimate risk of death, relapse and GvHD after allogeneic hematopoietic stem cell transplantation (HSCT). In this retrospective study comprising 333 patients transplanted for hematologic malignancies, we compared GRFS in patients receiving partial T-cell-depleted (pTCD) grafts with patients receiving T-cell-replete grafts (No-TCD). pTCD was associated with a significantly improved GRFS. The beneficial effect of pTCD on GRFS remained highly significant in multivariable analysis taking into account clinical factors differing between patient groups. We observed no effect of pTCD on overall survival, progression-free survival, and relapse cumulative incidence, while non-relapse mortality cumulative incidence was significantly lower in patients receiving pTCD. The results of our retrospective analysis suggest that pTCD could improve GRFS in allogeneic HSCT recipients without significantly affecting OS and PFS, thus improving patients' quality of life without impairing the curative potential of allogeneic HSCT.

Donor cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European group for blood and marrow transplantation.

PubMed

Ljungman, Per; Brand, Ronald; Hoek, Jennifer; de la Camara, Rafael; Cordonnier, Catherine; Einsele, Hermann; Styczynski, Jan; Ward, Katherine N; Cesaro, Simone

2014-08-15

The use of a cytomegalovirus (CMV)-seronegative donor for a CMV-seronegative allogeneic hematopoietic stem cell transplant (HSCT) recipient is generally accepted. However, the importance of donor serostatus in CMV-seropositive patients is controversial. A total of 49 542 HSCT patients, 29 349 seropositive and 20 193 seronegative, were identified from the European Group for Blood and Marrow Transplantation database. Cox multivariate models were fitted to estimate the effect of donor CMV serological status on outcome. Seronegative patients receiving seropositive unrelated-donor grafts had decreased overall survival (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.06-1.21; P < .0001) compared with seronegative donors, whereas no difference was seen in patients receiving HLA-matched sibling grafts. Seropositive patients receiving grafts from seropositive unrelated donors had improved overall survival (HR, 0.92; 95% CI, .86-.98; P < .01) compared with seronegative donors, if they had received myeloablative conditioning. This effect was absent when they received reduced-intensity conditioning. No effect was seen in patients grafted from HLA-identical sibling donors. The same association was found if the study was limited to patients receiving transplants from the year 2000 onward. We confirm the negative impact on overall survival if a CMV-seropositive unrelated donor is selected for a CMV-seronegative patient. For a CMV-seropositive patient, our data support selecting a CMV-seropositive donor if the patient receives a myeloablative conditioning regimen. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Detection of Catheter-Related Bloodstream Infections by the Differential-Time-to-Positivity Method and Gram Stain-Acridine Orange Leukocyte Cytospin Test in Neutropenic Patients after Hematopoietic Stem Cell Transplantation

PubMed Central

Krause, R.; Auner, H. W.; Gorkiewicz, G.; Wölfler, A.; Daxboeck, F.; Linkesch, W.; Krejs, G. J.; Wenisch, C.; Reisinger, E. C.

2004-01-01

For febrile neutropenic patients who received hematopoietic stem cell transplantation, the Gram stain-acridine orange leukocyte cytospin (AOLC) test and the differential-time-to-positivity method (DTP) were performed. As a diagnostic tool for catheter-related bloodstream infections in these patients, the Gram stain-AOLC test has a lower sensitivity than does the DTP method but acceptable positive and negative predictive values. PMID:15472355

CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation

ClinicalTrials.gov

2017-07-13

Bone Marrow Failure Syndrome; Severe Aplastic Anemia; Severe Congenital Neutropenia; Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Schwachman Diamond Syndrome; Primary Immunodeficiency Syndromes; Acquired Immunodeficiency Syndromes; Histiocytic Syndrome; Familial Hemophagocytic Lymphocytosis; Lymphohistiocytosis; Macrophage Activation Syndrome; Langerhans Cell Histiocytosis (LCH); Hemoglobinopathies; Sickle Cell Disease; Sickle Cell-beta-thalassemia

High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone

PubMed Central

O'Sullivan, J M; McCready, V R; Flux, G; Norman, A R; Buffa, F M; Chittenden, S; Guy, M; Pomeroy, K; Cook, G; Gadd, J; Treleaven, J; Al-Deen, A; Horwich, A; Huddart, R A; Dearnaley, D P

2002-01-01

We tested the feasibility and toxicity of high activities Rhenium-186 hydroxyethylidene diphosphonate, with peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. Twenty-five patients received between 2500 and 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate followed 14 days later by the return of peripheral blood peripheral blood stem cells. Activity limiting toxicity was defined as grade III haematological toxicity, lasting at least 7 days, or grade IV haematological toxicity of any duration or any serious unexpected toxicity. Activity limiting toxicity occurred in two of six who received activities of 5000 MBq and maximum tolerated activity was defined at this activity level. Prostate specific antigen reductions of 50% or more lasting at least 4 weeks were seen in five of the 25 patients (20%) all of whom received more than 3500 MBq of Rhenium-186 hydroxyethylidene diphosphonate. The actuarial survival at 1 year is 54%. Administered activities of 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate are feasible using autologous peripheral blood peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. The main toxicity is thrombocytopaenia, which is short lasting. A statistically significant activity/prostate specific antigen response was seen. We have now commenced a Phase II trial to further evaluate response rates. British Journal of Cancer (2002) 86, 1715–1720. doi:10.1038/sj.bjc.6600348 www.bjcancer.com © 2002 Cancer Research UK PMID:12087455

Validation of a Pediatric Early Warning Score in Hospitalized Pediatric Oncology and Hematopoietic Stem Cell Transplant Patients.

PubMed

Agulnik, Asya; Forbes, Peter W; Stenquist, Nicole; Rodriguez-Galindo, Carlos; Kleinman, Monica

2016-04-01

To evaluate the correlation of a Pediatric Early Warning Score with unplanned transfer to the PICU in hospitalized oncology and hematopoietic stem cell transplant patients. We performed a retrospective matched case-control study, comparing the highest documented Pediatric Early Warning Score within 24 hours prior to unplanned PICU transfers in hospitalized pediatric oncology and hematopoietic stem cell transplant patients between September 2011 and December 2013. Controls were patients who remained on the inpatient unit and were matched 2:1 using age, condition (oncology vs hematopoietic stem cell transplant), and length of hospital stay. Pediatric Early Warning Scores were documented by nursing staff at least every 4 hours as part of routine care. Need for transfer was determined by a PICU physician called to evaluate the patient. A large tertiary/quaternary free-standing academic children's hospital. One hundred ten hospitalized pediatric oncology patients (42 oncology, 68 hematopoietic stem cell transplant) requiring unplanned PICU transfer and 220 matched controls. None. Using the highest score in the 24 hours prior to transfer for cases and a matched time period for controls, the Pediatric Early Warning Score was highly correlated with the need for PICU transfer overall (area under the receiver operating characteristic = 0.96), and in the oncology and hematopoietic stem cell transplant groups individually (area under the receiver operating characteristic = 0.95 and 0.96, respectively). The difference in Pediatric Early Warning Score results between the cases and controls was noted as early as 24 hours prior to PICU admission. Seventeen patients died (15.4%). Patients with higher Pediatric Early Warning Scores prior to transfer had increased PICU mortality (p = 0.028) and length of stay (p = 0.004). We demonstrate that our institution's Pediatric Early Warning Score is highly correlated with the need for unplanned PICU transfer in hospitalized oncology and hematopoietic stem cell transplant patients. Furthermore, we found an association between higher scores and PICU mortality. This is the first validation of a Pediatric Early Warning Score specific to the pediatric oncology and hematopoietic stem cell transplant populations, and supports the use of Pediatric Early Warning Scores as a method of early identification of clinical deterioration in this high-risk population.

Intensified chemo-immunotherapy with or without stem cell transplantation in newly diagnosed patients with peripheral T-cell lymphoma.

PubMed

Corradini, P; Vitolo, U; Rambaldi, A; Miceli, R; Patriarca, F; Gallamini, A; Olivieri, A; Benedetti, F; Todeschini, G; Rossi, G; Salvi, F; Bruno, B; Baldini, L; Ferreri, A; Patti, C; Tarella, C; Pileri, S; Dodero, A

2014-09-01

Peripheral T-cell lymphomas (PTCLs) receiving conventional treatment have a poor clinical outcome. We conducted a phase II study to evaluate the feasibility and efficacy of chemo-immunotherapy in young (⩽60 years old, Clin A study) and elderly (>60 and < or =75 years old, Clin B study) patients with newly diagnosed PTCL. Clin A patients (n=61) received two courses of CHOP (cyclophosphamide, adriamycin, vincristine, prednisone)-21 with alemtuzumab (AL, 30 mg) followed by two courses of high-dose chemotherapy. On the basis of donor availability, patients in response received allogeneic (allo) or autologous (auto) stem cell transplantation (SCT). Clin B patients (n=25) received six courses of CHOP-21 and AL (10 mg). Clin A responding patients were 38 of 61 (62%) and received alloSCT (n=23) or autoSCT (n=14); one complete remission (CR) patient was not transplanted. At a median follow-up of 40 months, the 4-year overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) rates were 49, 44 and 65%, respectively. In Clin B study, the response rate was 72%. At a median follow-up of 48 months, the 4-year OS, PFS and DFS rates were 31, 26 and 44%, respectively. In conclusion, front-line alloSCT or autoSCT is effective in prolonging DFS in young patients; AL in elderly improved response with no survival benefit.

Total Hip Intraoperative Femur Fracture: Do the Design Enhancements of a Second-Generation Tapered-Wedge Stem Reduce the Incidence?

PubMed

Colacchio, Nicholas D; Robbins, Claire E; Aghazadeh, Mehran S; Talmo, Carl T; Bono, James V

2017-10-01

Intraoperative femur fracture (IFF) is a well-known complication in primary uncemented total hip arthroplasty (THA). Variations in implant instrumentation design and operative technique may influence the risk of IFF. This study investigates IFF between a standard uncemented tapered-wedge femoral stem and its second-generation successor with the following design changes: size-specific medial curvature, proportional incremental stem growth, modest reduction in stem length, and distal lateral relief. A single experienced surgeon's patient database was retrospectively queried for IFF occurring during primary uncemented THA using a standard tapered-wedge femoral stem system or a second-generation stem. All procedures were performed using soft tissue preserving anatomic capsule repair and posterior approach. The primary outcome measure was IFF. A z-test of proportions was performed to determine significant difference between the 2 stems with respect to IFF. Patient demographics, Dorr classification, and implant characteristics were also examined. Forty-one of 1510 patients (2.72%) who received a standard tapered-wedge femoral stem sustained an IFF, whereas 5 of 800 patients (0.63%) using the second-generation stem incurred an IFF. No other significant associations were found. A standard tapered-wedge femoral stem instrumentation system resulted in greater than 4 times higher incidence of IFF than its second-generation successor used for primary uncemented THA. Identifying risk factors for IFF is necessary to facilitate implant system improvements and thus maximize patient outcomes. Copyright © 2017. Published by Elsevier Inc.

[Tandem transplantation with peripheral autologous hematopoietic blood stem cells in treatment of oncologic and hematologic malignancies. Initial results of the Donauspital, Vienna].

PubMed

Ruckser, R; Kier, P; Sebesta, C; Kittl, E; Kurz, M; Selleny, S; Höniger, S; Scherz, M; Habertheuer, K H; Zelenka, P

1995-01-01

10 patients were subjected to tandem transplantation for breast cancer (n = 3), ovarian cancer (n = 2) and multiple myeloma (n = 5), at the Second Department of Medicine, Donauspital, Vienna. The breast cancer patients were in stages 2 and 3, respectively, at diagnosis and entered complete remission thereafter. 2 of them developed lymph node metastasis and additional local recurrence, the 3rd patient presented with distant metastasis. The 2 patients with ovarian cancer were in stages Figo III and IV, respectively, at the time of diagnosis, and showed minimal residual disease at second-look-operation. 5 patients with multiple myeloma were in stage 3 pretransplant. Peripheral stem cells were obtained after either high-dose cyclophosphamide or FEC induction and application of cytokines. In 4 patients, tandem transplantation has been completed. 1 patient with multiple myeloma, who had received total body irradiation in combination with chemotherapy for the 2nd transplant, succumbed from idiopathic interstitial pneumonia. No severe clinical complications were observed in all other patients. All patients with solid tumors entered complete remission after the 1st transplantation. 3 of them completed tandem transplantation. Of these, 2 remain in continuous complete remission, the 3rd patient relapsed in lymph nodes day 485. In patients who received only 1 course of high dose chemotherapy with stem cell transplantation, relapses occurred on days 29 and 75, respectively. All patients with multiple myeloma entered only partial remission. We conclude that supralethal chemotherapy with peripheral blood stem cell support is a safe procedure that may at least induce prolonged remissions in solid tumors and hematologic malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective, randomized study of cryotherapy during administration of high-dose melphalan to decrease the severity and duration of oral mucositis in patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation.

PubMed

Lilleby, K; Garcia, P; Gooley, T; McDonnnell, P; Taber, R; Holmberg, L; Maloney, D G; Press, O W; Bensinger, W

2006-06-01

Forty patients with multiple myeloma scheduled to receive melphalan 200 mg/m(2) followed by autologous stem cell transplantation were randomly assigned to receive oral cryotherapy or room temperature normal saline rinses 30 min before and for 6 h after high-dose therapy. Patients were evaluated for the development of mucositis using the National Cancer Institute grading system as well as evaluation of secondary measures such as days of total parenteral nutrition (TPN), narcotic use, hospitalization, weight loss and resumption of oral caloric intake for 28 days after transplant. Patients self-scored their pain, swallowing, drinking, eating, sleeping and taste alterations for 28 days. The primary end point of this trial was the incidence of grades 3-4 mucositis. Compared to the normal saline group, patients using cryotherapy experienced less grade 3-4 mucositis, 14 vs 74%, P=0.0005. Patients receiving cryotherapy also had statistically lower uses of narcotics and TPN, although there were no differences in length of hospitalization or weight loss. Patient-reported pain was significantly lower and activities were significantly better in the cryotherapy group.

[G-CSF administration following autologous peripheral blood stem cell transplantation--the effect of G-CSF level on neutrophil recovery].

PubMed

Saigo, K; Sugimoto, T; Matsuo, M; Narita, H; Ryo, R; Kumagai, S

2000-03-01

We studied the usefulness of rhG-CSF (filgrastim) administration in patients who received autologous peripheral blood stem cell transplantation (PBSCT) combined with super-high dose chemotherapy. Twenty patients received 0-8.3 micrograms/kg/day filgrastim after PBSCT. There was a significant relationship between G-CSF dose and the neutrophil recovery rate, and the highest levels of serum G-CSF tended to correlate with neutrophil recovery rate. The highest G-CSF level after 75 micrograms injection in normal volunteers is reported to be 1,500 pg/ml. On the other hand, as one patient in our series exhibited extremely high endogenous G-CSF of 11,500 pg/ml, measurements of G-CSF might reduce the over-administration of rhG-CSF.

Immunomodulation Induced by Stem Cell Mobilization and Harvesting in Healthy Donors: Increased Systemic Osteopontin Levels after Treatment with Granulocyte Colony-Stimulating Factor

PubMed Central

Melve, Guro Kristin; Ersvaer, Elisabeth; Akkök, Çiğdem Akalın; Ahmed, Aymen Bushra; Kristoffersen, Einar K.; Hervig, Tor; Bruserud, Øystein

2016-01-01

Peripheral blood stem cells from healthy donors mobilized by granulocyte colony-stimulating factor (G-CSF) and harvested by leukapheresis are commonly used for allogeneic stem cell transplantation. The frequency of severe graft versus host disease is similar for patients receiving peripheral blood and bone marrow allografts, even though the blood grafts contain more T cells, indicating mobilization-related immunoregulatory effects. The regulatory phosphoprotein osteopontin was quantified in plasma samples from healthy donors before G-CSF treatment, after four days of treatment immediately before and after leukapheresis, and 18–24 h after apheresis. Myeloma patients received chemotherapy, combined with G-CSF, for stem cell mobilization and plasma samples were prepared immediately before, immediately after, and 18–24 h after leukapheresis. G-CSF treatment of healthy stem cell donors increased plasma osteopontin levels, and a further increase was seen immediately after leukapheresis. The pre-apheresis levels were also increased in myeloma patients compared to healthy individuals. Finally, in vivo G-CSF exposure did not alter T cell expression of osteopontin ligand CD44, and in vitro osteopontin exposure induced only small increases in anti-CD3- and anti-CD28-stimulated T cell proliferation. G-CSF treatment, followed by leukapheresis, can increase systemic osteopontin levels, and this effect may contribute to the immunomodulatory effects of G-CSF treatment. PMID:27447610

[Retrospective study of the implementation of the qualitative PCR technique in biological samples for monitoring toxoplasmosis in pediatric patients receiving hematopoietic stem cell transplantation].

PubMed

Nigro, Mónica G; Figueroa, Carlos; Ledesma, Bibiana A

2014-01-01

Toxoplasmosis is an opportunistic infection caused by the parasite Toxoplasma gondii. The infection is severe and difficult to diagnose in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Twelve patients receiving HSCT were monitored post-transplant, by qualitative PCR at the Children's Hospital S.A.M.I.C. "Prof. Dr. Juan P. Garrahan". The monitoring of these patients was defined by a history of positive serology for toxoplasmosis in the donor or recipient and because their hematologic condition did not allow the use of trimethoprim-sulfamethoxazole for prophylaxis. During the patients' monitoring, two of them with positive PCR results showed signs of illness by T. gondii and were treated with pyrimethamine-clindamycin. In two other patients, toxoplasmosis was the cause of death and an autopsy finding, showing negative PCR results. Four patients without clinical manifestations received treatment for toxoplasmosis because of positive PCR detection. In four patients there were no signs of toxoplasmosis disease and negative PCR results during follow-up. The qualitative PCR technique proved useful for the detection of toxoplasmosis reactivation in HSCT recipients, but has limitations in monitoring and making clinical decisions due to the persistence of positive PCR over time and manifestations of toxicity caused by the treatment. Copyright © 2014 Asociación Argentina de Microbiología. Publicado por Elsevier España. All rights reserved.

Clinical application of human adipose tissue-derived mesenchymal stem cells in progressive hemifacial atrophy (Parry-Romberg disease) with microfat grafting techniques using 3-dimensional computed tomography and 3-dimensional camera.

PubMed

Koh, Kyung Suk; Oh, Tae Suk; Kim, Hoon; Chung, In Wook; Lee, Kang Woo; Lee, Hyo Bo; Park, Eun Jung; Jung, Jae Seob; Shin, Il Seob; Ra, Jeong Chan; Choi, Jong Woo

2012-09-01

Parry-Romberg disease is a rare condition that results in progressive hemifacial atrophy, involving the skin, dermis, subcutaneous fat, muscle, and, finally, cartilage and bone. Patients have been treated with dermofat or fat grafts or by microvascular free flap transfer. We hypothesized that adipose-derived stem cells (ASCs) may improve the results of microfat grafting through enhancing angiogenesis. We evaluated the utility of ASC in microfat grafting of patients with Parry-Romberg disease by measuring the change in the hemifacial volumes after injection of ASCs with microfat grafts or microfat grafts alone. In April 2008, this investigation was approved by the Korean Food and Drug Administration and the institutional review board of the Asan Medical Center (Seoul, Korea) that monitor investigator-initiated trials. Between May 2008 and January 2009, 10 volunteers with Parry-Romberg disease (5 men and 5 women; mean age, 28 y) were recruited; 5 received ASC and microfat grafts and 5 received microfat grafts only. The mean follow-up period was 15 months. Adipose-derived stem cells were obtained from abdominal fat by liposuction and were cultured for 2 weeks. On day 14, patients were injected with fat grafts alone or plus (in the test group) 1 × 10 ASCs. Patients were evaluated postoperatively using a 3-dimensional camera and 3-dimensional CT scans, and grafted fat volumes were objectively calculated. Successful outcomes were evident in all 5 patients receiving microfat grafts and ASCs, and the survival of grafted fat was better than in patients receiving microfat grafts alone. Before surgery, the mean difference between ipsilateral and contralateral hemiface volume in patients receiving microfat grafts and ASCs was 21.71 mL decreasing to 4.47 mL after surgery. Overall resorption in this ASC group was 20.59%. The mean preoperative difference in hemiface volume in those receiving microfat grafts alone was 8.32 mL decreasing to 3.89 mL after surgery. Overall resorption in this group was 46.81%. The preoperative and postoperative volume differences between the groups was statistically significant (P = 0.002; random-effects model [SAS 9.1]). Adipose-derived stem cells enhance the survival of fat grafted into the face. A microfat graft with simultaneous ASC injection may be used to treat Parry-Romberg disease without the need for microvascular free flap transfer.

Hair regrowth in alopecia areata patients following Stem Cell Educator therapy.

PubMed

Li, Yanjia; Yan, Baoyong; Wang, Hepeng; Li, Heng; Li, Quanhai; Zhao, Dong; Chen, Yana; Zhang, Ye; Li, Wenxia; Zhang, Jun; Wang, Shanfeng; Shen, Jie; Li, Yunxiang; Guindi, Edward; Zhao, Yong

2015-04-20

Alopecia areata (AA) is one of the most common autoimmune diseases and targets the hair follicles, with high impact on the quality of life and self-esteem of patients due to hair loss. Clinical management and outcomes are challenged by current limited immunosuppressive and immunomodulating regimens. We have developed a Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, allows the cells to briefly interact with adherent human cord blood-derived multipotent stem cells (CB-SC), and returns the "educated" autologous cells to the patient's circulation. In an open-label, phase 1/phase 2 study, patients (N = 9) with severe AA received one treatment with the Stem Cell Educator therapy. The median age was 20 years (median alopecic duration, 5 years). Clinical data demonstrated that patients with severe AA achieved improved hair regrowth and quality of life after receiving Stem Cell Educator therapy. Flow cytometry revealed the up-regulation of Th2 cytokines and restoration of balancing Th1/Th2/Th3 cytokine production in the peripheral blood of AA subjects. Immunohistochemistry indicated the formation of a "ring of transforming growth factor beta 1 (TGF-β1)" around the hair follicles, leading to the restoration of immune privilege of hair follicles and the protection of newly generated hair follicles against autoimmune destruction. Mechanistic studies revealed that co-culture with CB-SC may up-regulate the expression of coinhibitory molecules B and T lymphocyte attenuator (BTLA) and programmed death-1 receptor (PD-1) on CD8β(+)NKG2D(+) effector T cells and suppress their proliferation via herpesvirus entry mediator (HVEM) ligands and programmed death-1 ligand (PD-L1) on CB-SCs. Current clinical data demonstrated the safety and efficacy of the Stem Cell Educator therapy for the treatment of AA. This innovative approach produced lasting improvement in hair regrowth in subjects with moderate or severe AA. ClinicalTrials.gov, NCT01673789, 21 August 2012.

[Treatment outcome and prognosis of autologous hematopoietic stem cell transplantation combined with high dose radiotherapy/chemotherapy in 22 patients with nasal NK/T cell lymphoma].

PubMed

Cui, Xiu-Zhen; Wang, Hua-Qing; Liu, Xian-Ming; Zhang, Hui-Lai; Li, Wei

2007-09-01

To analyze the outcome and prognosis of autologous hematopoietic stem cell transplantation (AHSCT) combined with high dose radiotherapy/chemotherapy in 22 patients with nasal NK/T cell lymphoma. From July 1992 to December 2005, 22 patients with nasal NK/T cell lymphoma were diagnosed pathologically. Immunophenotyping was performed in 13 cases. The patients were classified by Ann Arbor staging system and international prognosis index (IPI). The patients received cycles of chemotherapy every other two weeks or combined with radiotherapy for remission induction, followed high dose radiotherapy/chemotherapy, combined with autologous peripheral blood stem cell transplantation (APBSCT), or autologous bone-marrow transplantation (ABMT). Patients were given complementary radiotherapy after transplantation if they did not have it before. Twelve patients of IPI 3 -4 received consolidation chemotherapy, and one of them received the second transplantation. The median follow-up duration was 64 (12 - 168) months. The 5 and 8-year overall survivals (OS) were 79.3% and 64.1%, and disease free survivals (DFS) were 36.4% and 27.3%, respectively. The 5-year OS were as follows: for stage I - II and III - IV disease were 90.0% and 70.0% (P = 0. 041); for patients without and with B symptom were 100.0% and 70.7% (P = 0.045); and for IPI 1 - 2 and 3 - 4 were 100.0% and 60.0% (P = 0.035), respectively. Multivariate analysis by COX regression revealed that disease stage, B symptom and IPI were independent prognostic factors. AHSCT combined with high dose radiotherapy/chemotherapy is an effective treatment for patients with poor prognosis nasal NK/T cell lymphoma.

Real-world effectiveness of brentuximab vedotin versus physicians' choice chemotherapy in patients with relapsed/refractory Hodgkin lymphoma following autologous stem cell transplantation in the United Kingdom and Germany.

PubMed

Zagadailov, Erin A; Corman, Shelby; Chirikov, Viktor; Johnson, Courtney; Macahilig, Cynthia; Seal, Brian; Dalal, Mehul R; Bröckelmann, Paul J; Illidge, Tim

2018-06-01

This retrospective study compared effectiveness of (brentuximab vedotin) BV to other chemotherapies in patients with rrHL following an autologous stem cell transplant (ASCT). Data originated from a medical chart review of patients treated in real-world clinical settings at 50 sites in the United Kingdom and Germany. Inverse probability of treatment weights based on propensity scores were used to adjust for differences in baseline characteristics between treatment groups. Among 312 rrHL patients included, 196 received BV and 116 received physicians' choice chemotherapy. Median PFS was significantly longer (27.0 months vs. 13.4 months; p = .0144) and 12-month OS survival greater (78.1% vs. 65.9%; p = .0129) with BV compared to chemotherapy. Documented adverse events included leukopenia (12.8%) and peripheral neuropathy (8.7%) for BV and leukopenia (12.1%), anemia (5.2%) and diarrhea (5.2%) for chemotherapy. In this real-world study, rrHL patients treated for relapse after ASCT with BV had longer median PFS and 12-month OS than patients receiving chemotherapy.

Fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation.

PubMed

Mori, T; Nakamura, Y; Kato, J; Sugita, K; Murata, M; Kamei, K; Okamoto, S

2012-02-01

Rhodotorula species have been increasingly recognized as emerging pathogens, particularly in immunocompromised patients. We herein report on a patient with myelodysplastic syndrome who developed fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor. He developed severe acute graft-versus-host disease requiring high-dose steroids, and had serially been administered fluconazole and micafungin for the prophylaxis of fungal infection. Although several cases of Rhodotorula infection after HSCT have been reported, all of them were recipients of autologous HSCT, not allogeneic HSCT. A review of all the reported cases of Rhodotorula infection after HSCT revealed that all patients had received fluconazole or echinocandins before the onset of infection. The findings suggest that Rhodotorula species could be causative yeasts, particularly in patients receiving fluconazole or echinocandins, both of which are inactive against the species. © 2011 John Wiley & Sons A/S.

An algorithm for utilizing peripheral blood CD34 count as a predictor of the need for plerixafor in autologous stem cell mobilization--cost-effectiveness analysis.

PubMed

Abusin, Ghada A; Abu-Arja, Rolla F; Gingrich, Roger D; Silverman, Margarida D; Zamba, Gideon K D; Schlueter, Annette J

2013-08-01

Certain patients who receive granulocyte colony-stimulating factor (GCSF) for autologous hematopoietic stem cell (AHSC) collection fail to mobilize well enough to proceed with transplant. When plerixafor is used with GCSF, the likelihood of achieving the CD34⁺ stem cell target in fewer collections is higher; plerixafor use in all patients is unlikely to be cost-effective. This study retrospectively evaluated the effectiveness of utilizing a peripheral blood CD34⁺ stem cell count (PBCD34) ≤8/µL on day 4 of GCSF-based AHSC mobilization as a threshold for plerixafor administration, and compared the efficacy of collection and cost analysis using historical controls. All patients in the study cohort reached their CD34⁺ targets in ≤3 collections. Significantly more patients who received plerixafor + GCSF versus GCSF alone reached their CD34⁺ target in one collection (P = 0.045); however, there were no significant differences in the number of collections or in cumulative product yields. The historical cohort had 10.3% mobilization failures; the number of collections per patient needed to reach the target was significantly higher in the historical cohort versus study cohort (P = 0.001) as was the number of patients requiring more than one collection to reach their target (P = 0.023). However, the average cost per patient was also significantly higher in the study cohort (P = 0.025). Further refinement of the algorithm may reduce the difference in cost between the two mobilization strategies. Copyright © 2013 Wiley Periodicals, Inc.

Curved-stem Hip Resurfacing

PubMed Central

2008-01-01

Hip resurfacing is an attractive concept because it preserves rather than removes the femoral head and neck. Most early designs had high failure rates, but one unique design had a femoral stem. Because that particular device appeared to have better implant survival, this study assessed the clinical outcome and long-term survivorship of a hip resurfacing prosthesis. Four hundred forty-five patients (561 hips) were retrospectively reviewed after a minimum of 20 years’ followup or until death; 23 additional patients were lost to followup. Patients received a metal femoral prosthesis with a small curved stem. Three types of acetabular reconstructions were used: (1) cemented polyurethane; (2) metal-on-metal; and (3) polyethylene secured with cement or used as the liner of a two-piece porous-coated implant. Long-term results were favorable with the metal-on-metal combination only. The mean overall Harris hip score was 92 at 2 years of followup. None of the 121 patients (133 hips) who received metal-on-metal articulation experienced failure. The failure rate with polyurethane was 100%, and the failure rate with cemented polyethylene was 41%. Hip resurfacing with a curved-stem femoral component had a durable clinical outcome when a metal-on-metal articulation was used. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18338217

Bone Engineering of Maxillary Sinus Bone Deficiencies Using Enriched CD90+ Stem Cell Therapy: A Randomized Clinical Trial.

PubMed

Kaigler, Darnell; Avila-Ortiz, Gustavo; Travan, Suncica; Taut, Andrei D; Padial-Molina, Miguel; Rudek, Ivan; Wang, Feng; Lanis, Alejandro; Giannobile, William V

2015-07-01

Bone engineering of localized craniofacial osseous defects or deficiencies by stem cell therapy offers strong prospects to improve treatment predictability for patient care. The aim of this phase 1/2 randomized, controlled clinical trial was to evaluate reconstruction of bone deficiencies of the maxillary sinus with transplantation of autologous cells enriched with CD90+ stem cells and CD14+ monocytes. Thirty human participants requiring bone augmentation of the maxillary sinus were enrolled. Patients presenting with 50% to 80% bone deficiencies of the maxillary sinus were randomized to receive either stem cells delivered onto a β-tricalcium phosphate scaffold or scaffold alone. Four months after treatment, clinical, radiographic, and histologic analyses were performed to evaluate de novo engineered bone. At the time of alveolar bone core harvest, oral implants were installed in the engineered bone and later functionally restored with dental tooth prostheses. Radiographic analyses showed no difference in the total bone volume gained between treatment groups; however, density of the engineered bone was higher in patients receiving stem cells. Bone core biopsies showed that stem cell therapy provided the greatest benefit in the most severe deficiencies, yielding better bone quality than control patients, as evidenced by higher bone volume fraction (BVF; 0.5 versus 0.4; p = 0.04). Assessment of the relation between degree of CD90+ stem cell enrichment and BVF showed that the higher the CD90 composition of transplanted cells, the greater the BVF of regenerated bone (r = 0.56; p = 0.05). Oral implants were placed and restored with functionally loaded dental restorations in all patients and no treatment-related adverse events were reported at the 1-year follow-up. These results provide evidence that cell-based therapy using enriched CD90+ stem cell populations is safe for maxillary sinus floor reconstruction and offers potential to accelerate and enhance tissue engineered bone quality in other craniofacial bone defects and deficiencies (Clinicaltrials.gov NCT00980278). © 2015 American Society for Bone and Mineral Research.

Beneficial Effect of the Nutritional Support in Children Who Underwent Hematopoietic Stem Cell Transplant.

PubMed

Koç, Nevra; Gündüz, Mehmet; Tavil, Betül; Azik, M Fatih; Coşkun, Zeynep; Yardımcı, Hülya; Uçkan, Duygu; Tunç, Bahattin

2017-08-01

The aim of this study was to evaluate nutritional status in children who underwent hematopoietic stem cell transplant compared with a healthy control group. A secondary aim was to utilize mid-upper arm circumference as a measure of nutritional status in these groups of children. Our study group included 40 children (18 girls, 22 boys) with mean age of 9.2 ± 4.6 years (range, 2-17 y) who underwent hematopoietic stem cell transplant. Our control group consisted of 20 healthy children (9 girls, 11 boys). The children were evaluated at admission to the hospital and followed regularly 3, 6, 9, and 12 months after discharge from the hospital. In the study group, 27 of 40 patients (67.5%) received nutritional support during hematopoietic stem cell transplant, with 15 patients (56%) receiving enteral nutrition, 6 (22%) receiving total parenteral nutrition, and 6 (22%) receiving enteral and total parenteral nutrition. Chronic malnutrition rate in the study group was 47.5% on admission to the hospital, with the control group having a rate of 20%. One year after transplant, the rate decreased to 20% in the study group and 5% in the control group. The mid-upper arm circumference was lower in children in the study group versus the control group at the beginning of the study (P < .05). However, there were no significant differences in mid-upper arm circumference measurements between groups at follow-up examinations (P > .05). During follow-up, all anthropometric measurements increased significantly in both groups. Monitoring nutritional status and initiating appropriate nutritional support improved the success of hematopoietic stem cell transplant and provided a more comfortable process during the transplant period. Furthermore, mid-upper arm circumference is a more sensitive, useful, and safer parameter that can be used to measure nutritional status of children who undergo hematopoietic stem cell transplant.

Grammont humeral design versus onlay curved-stem reverse shoulder arthroplasty: comparison of clinical and radiographic outcomes with minimum 2-year follow-up.

PubMed

Merolla, Giovanni; Walch, Gilles; Ascione, Francesco; Paladini, Paolo; Fabbri, Elisabetta; Padolino, Antonio; Porcellini, Giuseppe

2018-04-01

There are few investigations comparing lateralized and medialized reverse total shoulder arthroplasty (RTSA) in patients with cuff tear arthropathy. This study assessed the outcomes of 2 RTSA designs. Sixty-eight consecutive cuff tear arthropathy patients (74 shoulders) with a follow-up of at least 24 months received a Grammont or an onlay curved short-stem humeral component, with or without glenoid lateralization; a cementless humeral stem was implanted in >90%. Clinical outcome measures included active range of motion (anterior and lateral elevation, external and internal rotation), pain, and the Constant-Murley score. Radiologic outcomes included radiolucency, condensation lines, cortical thinning, spot weld, loosening and subsidence, and tuberosity resorption for the humeral component and radiolucency, scapular notching, formation of scapular bone spurs, ossifications, and loosening for the glenoid component. Both prostheses provided significant differences between preoperative and postoperative scores and showed a similar complication rate. Scapular fractures were found only in the patients who received the curved short-stem implant. Glenoid bone grafting did not significantly affect clinical scores. Both implants provided similar postoperative shoulder mobility, even though the lateralized curved stem was associated with higher delta scores for external rotation (P = .002) and lower rates of scapular notching (P = .0003), glenoid radiolucency (P = .016), and humeral bone remodeling (P = .004 and P = .030 for cortical thinning and spot weld, respectively). Medialized and short-stem lateralized RTSA implants provided similar midterm clinical outcomes and range of motion. The curved short stem was associated with higher delta scores for external rotation and a lower rate of radiographic risk factors. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Ciprofloxacin decreased polyoma BK virus load in patients who underwent allogeneic hematopoietic stem cell transplantation.

PubMed

Leung, Anskar Y H; Chan, Maggie T L; Yuen, Kwok-Yung; Cheng, Vincent C C; Chan, Kwok-Hung; Wong, Chris L P; Liang, Raymond; Lie, Albert K W; Kwong, Yok-Lam

2005-02-15

Polyoma BK virus (BKV) is associated with hemorrhagic cystitis during hematopoietic stem cell transplantation (HSCT). The objective of this study was to test whether standard-dose ciprofloxacin might suppress reactivation of BKV infection during HSCT. Sixty-eight patients received ciprofloxacin or a cephalosporin as antibiotic prophylaxis after undergoing allogeneic HSCT. Urine samples were collected weekly from day 7 before HSCT to day 50 after HSCT. Laboratory investigations included quantification of BKV load and urinary ciprofloxacin levels and in vitro drug sensitivity of BKV. Twenty-two patients received ciprofloxacin, 21 received cephalosporins, 12 received concomitant corticosteroids and antibiotics (9 received ciprofloxacin, and 3 received cephalosporins), and 13 received interrupted ciprofloxacin therapy. Ciprofloxacin recipients developed a significantly lower peak BKV load, compared with cephalosporin recipients (median, 3x10(5) copies/mL vs. 2.6x10(9) copies/mL; P=.021), irrespective of concomitant receipt of corticosteroid therapy. Fewer ciprofloxacin recipients than cephalosporin recipients (P=.013) developed BKV viruria with a > or =3-log increase in BKV load during HSCT, which was associated with significantly more cases of hemorrhagic cystitis (8 of 29 patients with a peak increase of > or =3 log vs. 0 of 39 patients without a peak increase of this level; P<.001). Ciprofloxacin recipients excreted ciprofloxacin in urine at a mean 24-h rate of 71.7 microg/mL (range, 23.0-152.9 microg/mL), which was comparable with the in vitro inhibitory concentration of 125-250 microg/mL of ciprofloxacin found for 3 of 7 BKV isolates. Ciprofloxacin decreased urinary BKV reactivation after HSCT.

Effect of time to infusion of autologous stem cells (24 vs. 48 h) after high-dose melphalan in patients with multiple myeloma.

PubMed

Talamo, Giampaolo; Rakszawski, Kevin L; Rybka, Witold B; Dolloff, Nathan G; Malysz, Jozef; Berno, Tamara; Zangari, Maurizio

2012-08-01

High-dose melphalan (HD-Mel) is considered the current standard of care among the preparative regimens used in autologous peripheral blood stem cell transplantation (SCT) for multiple myeloma (MM), but optimal time and schedule of administration is not defined. We retrospectively analyzed outcomes and toxicities of HD-Mel administered on day -2 vs. day -1 before autologous stem cells infusion. A total of 138 consecutive MM patients treated at Penn State Hershey Cancer Institute between 2007 and 2010 were included in this study. No difference in time to hematopoietic recovery, common SCT-related toxicities, and clinical outcomes was seen between patients who received HD-Mel on day -2 (group A, n = 47), and those who received it on day -1 (group B, n = 91). Prompt and full hematopoietic recovery occurred even when stem cells were infused between 8 and 24 h after completion of chemotherapy. In the absence of prospective and randomized data, we conclude that a single I.V. infusion of HD-Mel on day -1 is a safe and effective practice, and the so-called 'day of rest' before the transplant appears not to be necessary. © 2012 John Wiley & Sons A/S.

Application of Induced Pluripotent Stem Cells in Liver Diseases

PubMed Central

Yu, Yue; Wang, Xuehao; Nyberg, Scott L.

2014-01-01

Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from therapy involving hepatocyte transplantation. Liver transplantation is presently the only proven treatment for many medically refractory liver diseases including end-stage liver failure and inherited metabolic liver disease. However, the shortage in transplantable livers prevents over 40% of listed patients per year from receiving a liver transplant; many of these patients die before receiving an organ offer or become too sick to transplant. Therefore, new therapies are needed to supplement whole-organ liver transplantation and reduce mortality on waiting lists worldwide. Furthermore, the remarkable regenerative capacity of hepatocytes in vivo is exemplified by the increasing number of innovative cell-based therapies and animal models of human liver disorders. Induced pluripotent stem cells (iPSCs) have similar properties to those of embryonic stem cells (ESCs) but bypass the ethical concerns of embryo destruction. Therefore, generation of hepatocyte-like cells (HLCs) using iPSC technology may be beneficial for the treatment of severe liver diseases, screening of drug toxicities, basic research of several hepatocytic disorders, and liver transplantation. Here we briefly summarize the growing number of potential applications of iPSCs for treatment of liver disease. PMID:26858888

Evidence of a cellular immune response against sialyl-Tn in breast and ovarian cancer patients after high-dose chemotherapy, stem cell rescue, and immunization with Theratope STn-KLH cancer vaccine.

PubMed

Sandmaier, B M; Oparin, D V; Holmberg, L A; Reddish, M A; MacLean, G D; Longenecker, B M

1999-01-01

Seven ovarian and 33 breast high-risk stage II/III and stage IV cancer patients received high-dose chemotherapy followed by stem cell rescue. Thirty to 151 days after stem cell transplantation, the patients received their first immunotherapy treatment with Theratope STn-KLH cancer vaccine. Most patients developed increasing IgG anti-STn titers to a sustained peak after the fourth or fifth immunizations. Only one patient had elevated CA27.29 (MUC1 mucin) serum levels at trial entry. Five of the seven patients with preimmunotherapy elevated serum CA125 levels demonstrated decreasing CA125 levels during immunotherapy, consistent with an antitumor response. Evidence of STn antigen-specific T-cell proliferation was obtained from 17 of the 27 evaluable patients who received at least three immunotherapy treatments. Eleven of the 26 patients tested had evidence of an anti-STn TH1 antigen-specific T-cell response as determined by interferon-gamma, but not interleukin (IL)-4, production. After immunization, lytic activity of peripheral blood lymphocytes (PBLs) tested against a lymphokine activated killer (LAK)-sensitive cell line, a natural killer (NK)-sensitive cell line, and an STn-expressing cancer cell line (OVCAR) increased significantly. In vitro IL-2 treatment of the PBLs after vaccination greatly enhanced killing of the STn+ cancer cell line. Evidence of the development of OVCAR specific killing activity, over and above that seen due to LAK or NK killing, is presented. These studies provide the strongest evidence in humans of the development of an antitumor T-cell response after immunization with a cancer-associated carbohydrate antigen.

Representations of stem cell clinics on Twitter.

PubMed

Kamenova, Kalina; Reshef, Amir; Caulfield, Timothy

2014-12-01

The practice of travelling abroad to receive unproven and unregulated stem cell treatments has become an increasingly problematic global phenomenon known as 'stem cell tourism'. In this paper, we examine representations of nine major clinics and providers of such treatments on the microblogging network Twitter. We collected and conducted a content analysis of Twitter posts (n = 363) by these establishments and by other users mentioning them, focusing specifically on marketing claims about treatment procedures and outcomes, discussions of safety and efficacy of stem cell transplants, and specific representations of patients' experiences. Our analysis has shown that there were explicit claims or suggestions of benefits associated with unproven stem cell treatments in approximately one third of the tweets and that patients' experiences, whenever referenced, were presented as invariably positive and as testimonials about the efficacy of stem cell transplants. Furthermore, the results indicated that the tone of most tweets (60.2 %) was overwhelmingly positive and there were rarely critical discussions about significant health risks associated with unproven stem cell therapies. When placed in the context of past research on the problems associated with the marketing of unproven stem cell therapies, this analysis of representations on Twitter suggests that discussions in social media have also remained largely uncritical of the stem cell tourism phenomenon, with inaccurate representations of risks and benefits for patients.

Overcoming the response plateau in multiple myeloma: A novel bortezomib-based strategy for secondary induction and high-yield CD34+ stem cell mobilization

PubMed Central

Niesvizky, Ruben; Mark, Tomer M.; Ward, Maureen; Jayabalan, David S.; Pearse, Roger N.; Manco, Megan; Stern, Jessica; Christos, Paul J.; Mathews, Lena; Shore, Tsiporah B.; Zafar, Faiza; Pekle, Karen; Xiang, Zhaoying; Ely, Scott; Skerret, Donna; Chen-Kiang, Selina; Coleman, Morton; Lane, Maureen E.

2014-01-01

Purpose This phase 2 study evaluated bortezomib-based secondary induction and stem cell mobilization in 38 transplant-eligible myeloma patients who had an incomplete and stalled response to, or had relapsed after, previous immunomodulatory drug-based induction. Experimental design Patients received up to six 21-day cycles of bortezomib plus dexamethasone, with added liposomal doxorubicin for patients not achieving partial response or better by cycle 2 or very good partial response or better (≥VGPR) by cycle 4 (DoVeD), followed by bortezomib, high-dose cyclophosphamide, and filgrastim mobilization. Gene expression/signaling pathway analyses were conducted in purified CD34+ cells post-bortezomib-based mobilization and compared against patients who received only filgrastim ± cyclophosphamide. Plasma samples were similarly analyzed for quantification of associated protein markers. Results The response rate to DoVeD relative to the pre-DoVeD baseline was 61%, including 39% ≥VGPR. Deeper responses were achieved in 10 of 27 patients who received bortezomib-based mobilization; post-mobilization response rate was 96%, including 48% ≥VGPR, relative to the pre-DoVeD baseline. Median CD34+ cell yield was 23.2 × 106 cells/kg (median of 1 apheresis session). After a median follow-up of 46.6 months, median progression-free survival was 47.1 months from DoVeD initiation;5-year overall survival rate was 76.4%. Grade ≥3 adverse events included thrombocytopenia (13%), hand-foot syndrome (11%), peripheral neuropathy (8%), and neutropenia (5%). Bortezomib-based mobilization was associated with modulated expression of genes involved in stem cell migration. Conclusion Bortezomib-based secondary induction and mobilization could represent an alternative strategy for elimination of tumor burden in immunomodulatory drug-resistant patients that does not impact stem cell yield. PMID:23357980

Effect of autologous adipose-derived mesenchymal stem cell therapy in the treatment of a post-traumatic chondral defect of the knee

PubMed Central

Freitag, Julien; Li, Douglas; Wickham, James; Shah, Kiran; Tenen, Abi

2017-01-01

Isolated chondral defects have a limited capacity to heal and predispose to the development of osteoarthritis. Current surgical management can be unpredictable in outcome. Improved understanding of the action of mesenchymal stem cells (MSCs) has seen renewed interest in their role in cartilage repair. A 26-year-old athlete presented with a post-traumatic, isolated patella chondral defect. The patient underwent an arthroscopy with removal of a chondral loose body. After failure to symptomatically improve 12 months following surgery, the patient received intra-articular autologous adipose-derived mesenchymal stem cell (ADMSC) therapy. PMID:29038190

Posaconazole plasma exposure correlated to intestinal mucositis in allogeneic stem cell transplant patients.

PubMed

Vanstraelen, Kim; Prattes, Juergen; Maertens, Johan; Lagrou, Katrien; Schoemans, Hélène; Peersman, Nele; Vermeersch, Pieter; Theunissen, Koen; Mols, Raf; Augustijns, Patrick; Annaert, Pieter; Hoenigl, Martin; Spriet, Isabel

2016-08-01

Low posaconazole plasma concentrations (PPCs) are frequently encountered in allogeneic hematopoietic stem cell transplant (HSCT) patients, due to variable gastrointestinal absorption. In this study, the impact of intestinal mucositis on posaconazole exposure is investigated. A prospective pharmacokinetic study was performed including allogeneic HSCT patients receiving posaconazole prophylaxis with the oral suspension or tablets. Steady state PPCs were determined using high-performance liquid chromatography-fluorescence detection at the day of transplantation (=day 0), day +7, and +14. Citrulline was measured using liquid chromatography-tandem mass spectrometry to evaluate severity of mucositis, at baseline (day -7 or -6), and at day 0, +7 and +14. Additionally, citrulline plasma concentrations and steady state trough PPCs were determined in hematological patients without HSCT or mucositis. Thirty-four HSCT patients received posaconazole oral suspension together with 25 cL of Coca Cola, 6 HSCT patients received posaconazole tablets and 33 hematological patients not receiving HSCT received posaconazole oral suspension. The median (interquartile range) average PPC was 0.26 mg/L (0.17-0.43), 0.67 mg/L (0.27-1.38), and 1.08 mg/L (0.96-1.38), with suspension in HSCT patients, suspension in hematological patients and tablets in HSCT patients, respectively. A higher trough PPC was encountered with the oral suspension when citrulline plasma concentrations were above 10 μmol/L compared to values below 10 μmol/L (p < 0.001), whereas for tablets, average PPCs remained high with citrulline plasma concentrations below or above 10 μmol/L (p = 0.64). Posaconazole tablets should be preferred to suspension in HSCT patients immediately after transplantation to prevent insufficient plasma exposure due to intestinal mucositis.

Difference in Postoperative Periprosthetic Bone Mineral Density Changes Between 3 Major Designs of Uncemented Stems: A 3-Year Follow-Up Study.

PubMed

Inaba, Yutaka; Kobayashi, Naomi; Oba, Masatoshi; Ike, Hiroyuki; Kubota, So; Saito, Tomoyuki

2016-08-01

Although few studies have examined the direct effect of stress shielding on clinical outcomes, periprosthetic bone loss due to stress shielding is still an issue of concern, especially when physicians perform uncemented total hip arthroplasty (THA) in younger patients. Differences in femoral stem design may affect the degree of postoperative stress shielding. Therefore, the characteristics of the behavior for stress shielding of each type of femoral stem should be determined. This study compares differences in bone mineral density (BMD) change in the femur after primary THA between 3 major types of uncemented stems. Among a total of 89 hips, 26 hips received THA with a fit-and-fill type stem (VerSys Fiber Metal MidCoat; Zimmer, Inc, Warsaw, IN), 32 hips received a tapered rectangular Zweymüller-type stem (SL-Plus; Smith & Nephew Inc, Memphis, TN), and 31 received a tapered wedge-type stem (Accolade TMZF; Stryker Orthopaedics, Mahwah, NJ). BMD measurements were performed with a HOLOGIC Discovery device (Hologic Inc, Waltham, MA). BMD in the medial-proximal femur was maintained for 3 years after THA in the group with the tapered wedge-type stem. BMD in the lateral-proximal femur was maintained for 3 years after THA in the group with the Zweymüller-type stem. There were no significant differences in the Harris Hip Score among the 3 stem groups preoperatively and 1, 2, and 3 years after surgery. There are clear differences in postoperative BMD loss of the proximal femur among these 3 commonly used uncemented stems. Copyright © 2016 Elsevier Inc. All rights reserved.

Septicemia from Lactobacillus rhamnosus GG, from a Probiotic Enriched Yogurt, in a Patient with Autologous Stem Cell Transplantation.

PubMed

Koyama, Satoshi; Fujita, Hiroyuki; Shimosato, Takeshi; Kamijo, Aki; Ishiyama, Yasufumi; Yamamoto, Eri; Ishii, Yoshimi; Hattori, Yukako; Hagihara, Maki; Yamazaki, Etsuko; Tomita, Naoto; Nakajima, Hideaki

2018-02-17

Probiotic-rich foods are consumed without much restriction. We report here, a case of septic shock caused by yogurt derived Lactobacillus species in a 54-year-old male patient with acute promyelocytic leukemia, in second complete remission, and who was an autologous stem cell transplantation recipient. He received high dose chemotherapy and autologous peripheral blood stem cell transplantation. He ingested commercially available probiotic-enriched yogurt because of severe diarrhea. One week later, he developed septic shock, and the pathogen was determined by strain-specific PCR analysis as Lactobacillus rhamnosus GG (ATCC 53103), which was found to be identical with the strain in the yogurt he consumed. Thus, because even low virulent Lactobacilli in the probiotic products can be pathogenic in the compromised hosts, ingestion of such products should be considered with caution in neutropenic patients with severe diarrhea, such as stem cell transplantation recipients.

Successful treatment of lymphoproliferative disease complicating primary immunodeficiency/immunodysregulatory disorders with reduced-intensity allogeneic stem-cell transplantation.

PubMed

Cohen, Jonathan M; Sebire, Neil J; Harvey, Julia; Gaspar, H Bobby; Cathy, Cale; Jones, Alison; Rao, Kanchan; Cubitt, David; Amrolia, Persis J; Davies, E Graham; Veys, Paul

2007-09-15

Lymphoproliferative disease (LPD) is a recognized complication of primary immunodeficiency (PID) and immunodysregulatory syndromes. Historically, it has a very poor outcome. For patients surviving LPD, myeloablative hematopoietic stem cell transplantation (SCT) was the only cure for the underlying PID, with a high risk of developing posttransplantation complications, including recurrent lymphoproliferative disease. We describe 8 patients with a range of PID and immunodysregulatory syndromes complicated by LPD. After initial treatment of the LPD (including the use of anti-CD20 monoclonal antibody, rituximab, in 6 of the patients), all patients underwent reduced-intensity conditioning (RIC) SCT with prospective monitoring for Epstein-Barr virus (EBV) viremia. After transplantation, 3 patients received rituximab, and 3 patients received prophylactic EBV-specific cytotoxic T-lymphocytes. Only 1 patient developed recurrent LPD posttransplantation, which responded to rituximab. All patients who underwent transplantation survive free of LPD and are cured of their PID at a median follow-up of 4 years (range, 1-7 years). With careful monitoring and pre-emptive therapy, we advocate this RIC SCT approach to patients with PID who have pre-existing EBV-LPD.

Two- to 4-Year Followup of a Short Stem THA Construct: Excellent Fixation, Thigh Pain a Concern.

PubMed

Amendola, Richard L; Goetz, Devon D; Liu, Steve S; Callaghan, John J

2017-02-01

Short stem cementless femoral components were developed to aid insertion through smaller incisions, preserve metaphyseal bone, and potentially decrease or limit the incidence of thigh pain. Despite some clinical success, the senior author (DDG) believed a higher percentage of his patients who had received a cementless short stem design were experiencing thigh pain, which, coupled with concerns about bone ingrowth fixation, motivated the review of this case series. (1) What is the proportion of patients treated with a short stem cementless THA femoral component that develop thigh pain and what are the hip scores of this population? (2) What are the radiographic results, specifically with respect to bone ingrowth fixation and stress shielding, of this design? (3) Are there particular patient or procedural factors that are associated with thigh pain with this short stem design? Two hundred sixty-one primary THAs were performed in 238 patients by one surgeon between November 2010 and August 2012. During this time period, all patients undergoing primary THA by this surgeon received the same cementless short titanium taper stem. Seven patients (eight hips) died and five patients (five hips) were lost to followup, leaving 226 patients (248 hips) with a mean followup of 3 years (range, 2-5 years). Patients rated their thigh pain during activity or rest at final followup on a 10-point visual analog scale. Harris hip scores (HHS) were obtained at every clinic appointment. Thigh pain was evaluated at the final followup or by contacting the patient by phone. Radiographs were evaluated for bone-implant fixation, bone remodeling, and osteolysis. An attempt was made to correlate thigh pain with patient demographics, implant specifications, or radiographic findings. Seventy-six percent of hips (180 of 238) had no thigh pain, 16% of hips (37 of 238) had mild thigh pain, and 9% (21 of 238) had moderate or severe thigh pain. Preoperatively, mean HHS was 47 (SD, 16) and at last followup, mean HHS was 88 (SD, 13). There were two femoral revisions, one for severe thigh pain and the other for infection. All but two components demonstrated bone ingrowth fixation (99%). Femoral stress shielding was mild in 64% of hips (135 of 212), moderate in 0.5% (one of 212), and severe in no hips. There is an inverse linear relationship between age and severity of thigh pain (r = -0.196; p < 0.0024). Although reliable fixation was achieved and good HHS were attained, the frequency and severity of thigh pain with this short cementless stem were concerning. The surgeon has subsequently abandoned this short stem design and returned to a conventional length stem. Future study direction might investigate the biomechanical grounds for the thigh pain associated with this stem design. Level IV, therapeutic study.

High rate of long-term survival for high-risk lymphoma patients treated with hematopoietic stem cell transplantation as consolidation or salvage therapy.

PubMed

Espigado, I; Ríos, E; Marín-Niebla, A; Carmona, M; Parody, R; Pérez-Hurtado, J M; Márquez, F J; Urbano-Ispizua, A

2008-11-01

Patients with high-relapse-risk lymphomas or those relapsing after initial therapy have a limited probability of cure with conventional treatment. There is recent inconclusive evidence that, in such cases, intensification or salvage treatment with high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT) increases the response rate and may improve survival. Nevertheless, published data on long-term follow-up of high-risk lymphoma patients treated with HSCT are scarce. We analyzed 101 consecutive patients receiving high-dose chemotherapy followed by HSCT after induction with standard chemotherapy. The median age was 38 years (range, 12-63 years). The diagnoses were Hodgkin's disease (n = 32), follicular lymphoma (n = 33), diffuse large B-cell lymphoma (n = 12), mantle cell lymphoma (n = 7), T-cell lymphoma (n = 14), and others (n = 3). Patients received either an autologous graft (n = 72) in first complete remission (1CR; n = 23) or in advanced stages (AS; n = 49), or an allogeneic graft (n = 29) in 1CR (n = 7) or in AS (n = 22). We concluded that transplant-related mortality was 2.7% for patients receiving an autologous HSCT and 27% for patients receiving an allogeneic HSCT. The main etiologies were graft-versus-host disease and infection in the allogeneic setting, and infection in the autologous setting. The probability of long-term (12-year) overall survival was 71%, higher than that described for high-relapse-risk lymphoma patients treated without HSCT and significantly better (P < .05) for patients who received the transplant in 1CR (89%) than in AS (65%). Finally, the probability of long-term survival was significantly better for patients treated with HSCT during the period from 2000-2007 (85%) compared with the period from 1989-1999 (72%).

Should the standard dimethyl sulfoxide concentration be reduced? Results of a European Group for Blood and Marrow Transplantation prospective noninterventional study on usage and side effects of dimethyl sulfoxide.

PubMed

Morris, Curly; de Wreede, Liesbeth; Scholten, Marijke; Brand, Ronald; van Biezen, Anja; Sureda, Anna; Dickmeiss, Ebbe; Trneny, Marek; Apperley, Jane; Chiusolo, Patrizia; van Imhoff, Gustaaf W; Lenhoff, Stig; Martinelli, Giovanni; Hentrich, Marcus; Pabst, Thomas; Onida, Francesco; Quinn, Michael; Kroger, Nicolaus; de Witte, Theo; Ruutu, Tapani

2014-10-01

Dimethyl sulfoxide (DMSO) is essential for the preservation of liquid nitrogen-frozen stem cells, but is associated with toxicity in the transplant recipient. In this prospective noninterventional study, we describe the use of DMSO in 64 European Blood and Marrow Transplant Group centers undertaking autologous transplantation on patients with myeloma and lymphoma and analyze side effects after return of DMSO-preserved stem cells. While the majority of centers continue to use 10% DMSO, a significant proportion either use lower concentrations, mostly 5 or 7.5%, or wash cells before infusion (some for selected patients only). In contrast, the median dose of DMSO given (20 mL) was much less than the upper limit set by the same institutions (70 mL). In an accompanying statistical analysis of side effects noted after return of DMSO-preserved stem cells, we show that patients in the highest quartile receiving DMSO (mL and mL/kg body weight) had significantly more side effects attributed to DMSO, although this effect was not observed if DMSO was calculated as mL/min. Dividing the myeloma and lymphoma patients each into two equal groups by age we were able to confirm this result in all but young myeloma patients in whom an inversion of the odds ratio was seen, possibly related to the higher dose of melphalan received by young myeloma patients. We suggest better standardization of preservation method with reduced DMSO concentration and attention to the dose of DMSO received by patients could help reduce the toxicity and morbidity of the transplant procedure. © 2014 AABB.

Outcomes in Patients With Relapsed or Refractory Acute Promyelocytic Leukemia Treated With or Without Autologous or Allogeneic Hematopoietic Stem Cell Transplantation

PubMed Central

Pemmaraju, Naveen; Tanaka, Maria Florencia; Ravandi, Farhad; Lin, Heather; Baladandayuthapani, Veerabhadran; Rondon, Gabriela; Giralt, Sergio A.; Chen, Julianne; Pierce, Sherry; Cortes, Jorge; Kantarjian, Hagop; Champlin, Richard E.; De Lima, Marcos; Qazilbash, Muzaffar H.

2014-01-01

Outcomes in patients with acute promyelocytic leukemia have improved; however, a subset of patients relapse despite receiving all-trans-retinoic acid and/or arsenic-based therapies. Among 40 patients with acute promyelocytic leukemia who were treated at our institution (1980–2010), 24 received hematopoietic stem cell transplantation (HCT) (autologous HCT, 7; allogeneic HCT, 14; both, 3); 16 received chemotherapy only. All 3 strategies (autologous HCT, allogeneic HCT, chemotherapy) were feasible in patients with relapsed acute promyelocytic leukemia and result in long-term disease control in selected patients. Background Outcomes in patients with acute promyelocytic leukemia (APL) have improved; however, a significant number of patients still relapse despite receiving all-trans-retinoic acid (ATRA) and arsenic-based therapies. Patients and Methods Outcomes of patients with relapsed APL who were treated at our institution (1980–2010) and who received HCT were compared with those who received chemotherapy (CT) only. Results Among 40 patients, 24 received HCT (autologous [auto] HCT, 7; allogeneic [allo] HCT, 14; both, 3); 16 received CT only. The median age at diagnosis was 36 years (range, 13–50 years), 31 years (range, 16–58 years), and 44 years (range, 24–79 years) for the auto-HCT, allo-HCT, and CT groups, respectively. Ten (100%) patients who received auto-HCT and 12 (71%) who received allo-HCT were in complete remission at the time of the HCT. The median follow-ups in the auto-HCT, allo-HCT, and CT groups were 74 months (range, 26–135 months), 118 months (range, 28–284 months), and 122 months (range, 32–216 months), respectively. Transplantation-related mortality (1 year) after auto-HCT and allo-HCT were 10% and 29%, respectively. The 7-year event-free survival after auto-HCT and allo-HCT was 68.6% and 40.6%, respectively (P = .45). The 7-year overall survival was 85.7%, 49.4%, and 40% in the auto-HCT, allo-HCT, and CT groups, respectively (P = .48). Conclusion Both auto-HCT and allo-HCT are associated with durable remission and prolonged survival. All 3 strategies (auto-HCT, allo-HCT, CT) were found to be feasible in the relapsed APL setting and result in long-term disease control in selected patients. In this retrospective analysis, overall survival for patients who received HCT was not significantly better than patients who received CT only, but a trend toward better outcomes was seen in patients who underwent auto-HCT, although not statistically significant. PMID:23769669

Are the Polyomaviruses BK and JC Associated with Opportunistic Infections, Graft-versus-Host Disease, or Worse Outcomes in Adult Patients Receiving Their First Allogeneic Stem Cell Transplantation with Low-Dose Alemtuzumab?

PubMed

Schneidewind, Laila; Neumann, Thomas; Knoll, Florian; Zimmermann, Kathrin; Smola, Sigrun; Schmidt, Christian Andreas; Krüger, William

2017-01-01

The association of polyomaviruses BK and JC with other opportunistic infections and graft-versus-host disease (GvHD) in allogeneic stem cell transplantation is controversially discussed. We conducted a retrospective study of 64 adult patients who received their first allogeneic stem cell transplantation between March 2010 and December 2014; the follow-up time was 2 years. Acute leukemia was the most frequent underlying disease (45.3%), and conditioning included myeloablative (67.2%) and nonmyeloablative protocols (32.8%). All patients received 10 mg of alemtuzumab on day -2 (20 mg in case of mismatch) as GvHD prophylaxis. Twenty-seven patients (41.5%) developed cytomegalovirus (CMV) reactivation. BKPyV-associated hemorrhagic cystitis was diagnosed in 10 patients (15.6%). Other opportunistic infections caused by viruses or protozoa occurred rarely (<10%). There was no association of BKPyV or JCPyV with CMV reactivation, Epstein-Barr virus reactivation, human herpes virus 6, or parvovirus B19 infection requiring treatment. There was a significant correlation of BKPyV-associated hemorrhagic cystitis with toxoplasmosis (p = 0.013). Additionally, there was a significant link of simultaneous BKPyV and JCPyV viruria with toxoplasmosis (p = 0.047). BKPyV and JCPyV were not associated with GvHD, relapse, or death. We found no association of BKPyV or JCPyV with viral infections or GvHD. Only the correlation of both polyomaviruses with toxoplasmosis was significant. This is a novel and interesting finding. © 2017 S. Karger AG, Basel.

The Use of Intravenous Antibiotics at the Onset of Neutropenia in Patients Receiving Outpatient-Based Hematopoietic Stem Cell Transplants

PubMed Central

Hamadah, Aziz; Schreiber, Yoko; Toye, Baldwin; McDiarmid, Sheryl; Huebsch, Lothar; Bredeson, Christopher; Tay, Jason

2012-01-01

Empirical antibiotics at the onset of febrile neutropenia are one of several strategies for management of bacterial infections in patients undergoing Hematopoietic Stem Cell Transplant (HSCT) (empiric strategy). Our HSCT program aims to perform HSCT in an outpatient setting, where an empiric antibiotic strategy was employed. HSCT recipients began receiving intravenous antibiotics at the onset of neutropenia in the absence of fever as part of our institutional policy from 01 Jan 2009; intravenous Prophylactic strategy. A prospective study was conducted to compare two consecutive cohorts [Year 2008 (Empiric strategy) vs. Year 2009 (Prophylactic strategy)] of patients receiving HSCT. There were 238 HSCTs performed between 01 Jan 2008 and 31 Dec 2009 with 127 and 111 in the earlier and later cohorts respectively. Infection-related mortality pre- engraftment was similar with a prophylactic compared to an empiric strategy (3.6% vs. 7.1%; p = 0.24), but reduced among recipients of autologous HSCT (0% vs. 6.8%; p = 0.03). Microbiologically documented, blood stream infections and clinically documented infections pre-engraftment were reduced in those receiving a prophylactic compared to an empiric strategy, (11.7% vs. 28.3%; p = 0.001), (9.9% vs. 24.4%; p = 0.003) and (18.2% vs. 33.9% p = 0.007) respectively. The prophylactic use of intravenous once-daily ceftriaxone in patients receiving outpatient based HSCT is safe and may be particularly effective in patients receiving autologous HSCT. Further studies are warranted to study the impact of this Prophylactic strategy in an outpatient based HSCT program. PMID:23029441

Current role of radiation therapy for multiple myeloma.

PubMed

Talamo, Giampaolo; Dimaio, Christopher; Abbi, Kamal K S; Pandey, Manoj K; Malysz, Jozef; Creer, Michael H; Zhu, Junjia; Mir, Muhammad A; Varlotto, John M

2015-01-01

Radiation therapy (RT) is a treatment modality traditionally used in patients with multiple myeloma (MM), but little is known regarding the role and effectiveness of RT in the era of novel agents, i.e., immunomodulatory drugs and proteasome inhibitors. We retrospectively reviewed data from 449 consecutive MM patients seen at our institute in 2010-2012 to assess indications for RT as well as its effectiveness. Pain response was scored similarly to RTOG 0631 and used the Numerical Rating Pain Scale. Among 442 evaluable patients, 149 (34%) patients and 262 sites received RT. The most common indication for RT was palliation of bone pain (n = 109, 42%), followed by prevention/treatment of pathological fractures (n = 73, 28%), spinal cord compression (n = 26, 10%), and involvement of vital organs/extramedullary disease (n = 25, 10%). Of the 55 patients evaluable for pain relief, complete and partial responses were obtained in 76.4 and 7.2%, respectively. Prior RT did not significantly decrease the median number of peripheral blood stem cells collected for autologous transplant, even when prior RT was given to both the spine and pelvis. Inadequacy of stem cell collection for autologous stem cell transplant (ASCT) was not significantly different and it occurred in 9 and 15% of patients receiving no RT and spine/pelvic RT, respectively. None of the three cases of therapy-induced acute myelogenous leukemia/MDS occurred in the RT group. Despite the introduction of novel effective agents in the treatment of MM, RT remains a major therapeutic component for the management in 34% of patients, and it effectively provides pain relief while not interfering with successful peripheral blood stem cell collection for ASCT.

Current Role of Radiation Therapy for Multiple Myeloma

PubMed Central

Talamo, Giampaolo; Dimaio, Christopher; Abbi, Kamal K. S.; Pandey, Manoj K.; Malysz, Jozef; Creer, Michael H.; Zhu, Junjia; Mir, Muhammad A.; Varlotto, John M.

2015-01-01

Background: Radiation therapy (RT) is a treatment modality traditionally used in patients with multiple myeloma (MM), but little is known regarding the role and effectiveness of RT in the era of novel agents, i.e., immunomodulatory drugs and proteasome inhibitors. Methods: We retrospectively reviewed data from 449 consecutive MM patients seen at our institute in 2010–2012 to assess indications for RT as well as its effectiveness. Pain response was scored similarly to RTOG 0631 and used the Numerical Rating Pain Scale. Results: Among 442 evaluable patients, 149 (34%) patients and 262 sites received RT. The most common indication for RT was palliation of bone pain (n = 109, 42%), followed by prevention/treatment of pathological fractures (n = 73, 28%), spinal cord compression (n = 26, 10%), and involvement of vital organs/extramedullary disease (n = 25, 10%). Of the 55 patients evaluable for pain relief, complete and partial responses were obtained in 76.4 and 7.2%, respectively. Prior RT did not significantly decrease the median number of peripheral blood stem cells collected for autologous transplant, even when prior RT was given to both the spine and pelvis. Inadequacy of stem cell collection for autologous stem cell transplant (ASCT) was not significantly different and it occurred in 9 and 15% of patients receiving no RT and spine/pelvic RT, respectively. None of the three cases of therapy-induced acute myelogenous leukemia/MDS occurred in the RT group. Conclusion: Despite the introduction of novel effective agents in the treatment of MM, RT remains a major therapeutic component for the management in 34% of patients, and it effectively provides pain relief while not interfering with successful peripheral blood stem cell collection for ASCT. PMID:25741475

Blood use in patients receiving intensive chemotherapy for acute leukemia or hematopoietic stem cell transplantation: the impact of a health system-wide patient blood management program.

PubMed

Leahy, Michael F; Trentino, Kevin M; May, Colleen; Swain, Stuart G; Chuah, Hun; Farmer, Shannon L

2017-09-01

Little is published on patient blood management (PBM) programs in hematology. In 2008 Western Australia announced a health system-wide PBM program with PBM staff appointments commencing in November 2009. Our aim was to assess the impact this program had on blood utilization and patient outcomes in intensive chemotherapy for acute leukemia or hematopoietic stem cell transplantation. A retrospective study of 695 admissions at two tertiary hospitals receiving intensive chemotherapy for acute leukemia or undergoing hematopoietic stem cell transplantation between July 2010 and December 2014 was conducted. Main outcomes included pre-red blood cell (RBC) transfusion hemoglobin (Hb) levels, single-unit RBC transfusions, number of RBC and platelet (PLT) units transfused per admission, subsequent day case transfusions, length of stay, serious bleeding, and in-hospital mortality. Over the study period, the mean RBC units transfused per admission decreased 39% from 6.1 to 3.7 (p < 0.001), and the mean PLT units transfused decreased 35% from 6.3 to 4.1 (p < 0.001), with mean RBC and PLT units transfused for follow-up day cases decreasing from 0.6 to 0.4 units (p < 0.001). Mean pre-RBC transfusion Hb level decreased from 8.0 to 6.8 g/dL (p < 0.001), and single-unit RBC transfusions increased 39% to 67% (p < 0.001). This reduction represents blood product cost savings of AU$694,886 (US$654,007). There were no significant changes in unadjusted or adjusted length of stay, serious bleeding events, or in-hospital mortality over the study. The health system-wide PBM program had a significant impact, reducing blood product use and costs without increased morbidity or mortality in patients receiving intensive chemotherapy for acute leukemia or hematopoietic stem cell transplantation. © 2017 AABB.

Stem cell transplantation and mesenchymal cells to treat autoimmune diseases.

PubMed

Tyndall, Alan; van Laar, Jacob M

2016-06-01

Since the start of the international stem cell transplantation project in 1997, over 2000 patients have received a haematopoietic stem cell transplant (HSCT), mostly autologous, as treatment for a severe autoimmune disease, the majority being multiple sclerosis (MS), systemic sclerosis (SSc) and Crohn's disease. There was an overall 85% 5-year survival and 43% progression-free survival. Around 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many cases, e.g. systemic sclerosis, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented, beyond any predicted known effects of intense immunosuppression alone. It is hoped that the results of the three running large prospective randomized controlled trials will allow modification of the protocols to reduce the high transplant-related mortality which relates to regimen intensity, age of patient, and comorbidity. Mesenchymal stromal cells (MSC), often incorrectly called stem cells, have been the intense focus of in vitro studies and animal models of rheumatic and other diseases over more than a decade. Despite multiple plausible mechanisms of action and a plethora of positive in vivo animal studies, few randomised controlled clinical trials have demonstrated meaningful clinical benefit in any condition so far. This could be due to confusion in cell product terminology, complexity of clinical study design and execution or agreement on meaningful outcome measures. Within the rheumatic diseases, SLE and rheumatoid arthritis (RA) have received most attention. Uncontrolled multiple trial data from over 300 SLE patients have been published from one centre suggesting a positive outcome; one single centre comparative study in 172 RA was positive. In addition, small numbers of patients with Crohn's disease, multiple sclerosis, primary Sjögren's disease, polymyositis/dermatomyositis and type II diabetes mellitus have received MSC therapeutically. The possible reasons for this apparent mismatch between expectation and clinical reality will be discussed. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Phase I Trial: Cirmtuzumab Inhibits ROR1 Signaling and Stemness Signatures in Patients with Chronic Lymphocytic Leukemia.

PubMed

Choi, Michael Y; Widhopf, George F; Ghia, Emanuela M; Kidwell, Reilly L; Hasan, Md Kamrul; Yu, Jian; Rassenti, Laura Z; Chen, Liguang; Chen, Yun; Pittman, Emily; Pu, Minya; Messer, Karen; Prussak, Charles E; Castro, Januario E; Jamieson, Catriona; Kipps, Thomas J

2018-06-01

Cirmtuzumab is a humanized monoclonal antibody (mAb) that targets ROR1, an oncoembryonic orphan receptor for Wnt5a found on cancer stem cells (CSCs). Aberrant expression of ROR1 is seen in many malignancies and has been linked to Rho-GTPase activation and cancer stem cell self-renewal. For patients with chronic lymphocytic leukemia (CLL), self-renewing, neoplastic B cells express ROR1 in 95% of cases. High-level leukemia cell expression of ROR1 is associated with an unfavorable prognosis. We conducted a phase 1 study involving 26 patients with progressive, relapsed, or refractory CLL. Patients received four biweekly infusions, with doses ranging from 0.015 to 20 mg/kg. Cirmtuzumab had a long plasma half-life and did not have dose-limiting toxicity. Inhibition of ROR1 signaling was observed, including decreased activation of RhoA and HS1. Transcriptome analyses showed that therapy inhibited CLL stemness gene expression signatures in vivo. Cirmtuzumab is safe and effective at inhibiting tumor cell ROR1 signaling in patients with CLL. Copyright © 2018. Published by Elsevier Inc.

Corail uncemented hemiarthroplasty with a Cathcart head for intracapsular hip fractures.

PubMed

Kendrick, B J L; Wilson, H A; Lippett, J E; McAndrew, A R; Andrade, A J M D

2013-11-01

The National Institute for Health and Clinical Excellence (NICE) guidelines from 2011 recommend the use of cemented hemi-arthroplasty for appropriate patients with an intracapsular hip fracture. In our institution all patients who were admitted with an intracapsular hip fracture and were suitable for a hemi-arthroplasty between April 2010 and July 2012 received an uncemented prosthesis according to our established departmental routine practice. A retrospective analysis of outcome was performed to establish whether the continued use of an uncemented stem was justified. Patient, surgical and outcome data were collected on the National Hip Fracture database. A total of 306 patients received a Cathcart modular head on a Corail uncemented stem as a hemi-arthroplasty. The mean age of the patients was 83.3 years (SD 7.56; 46.6 to 94) and 216 (70.6%) were women. The mortality rate at 30 days was 5.8%. A total of 46.5% of patients returned to their own home by 30 days, which increased to 73.2% by 120 days. The implant used as a hemi-arthroplasty for intracapsular hip fracture provided satisfactory results, with a good rate of return to pre-injury place of residence and an acceptable mortality rate. Surgery should be performed by those who are familiar with the design of the stem and understand what is required for successful implantation.

SU-E-T-493: Analysis of the Impact of Range and Setup Uncertainties On the Dose to Brain Stem and Whole Brain in the Passively Scattered Proton Therapy Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sahoo, N; Zhu, X; Zhang, X

Purpose: To quantify the impact of range and setup uncertainties on various dosimetric indices that are used to assess normal tissue toxicities of patients receiving passive scattering proton beam therapy (PSPBT). Methods: Robust analysis of sample treatment plans of six brain cancer patients treated with PSPBT at our facility for whom the maximum brain stem dose exceeded 5800 CcGE were performed. The DVH of each plan was calculated in an Eclipse treatment planning system (TPS) version 11 applying ±3.5% range uncertainty and ±3 mm shift of the isocenter in x, y and z directions to account for setup uncertainties. Worst-casemore » dose indices for brain stem and whole brain were compared to their values in the nominal plan to determine the average change in their values. For the brain stem, maximum dose to 1 cc of volume, dose to 10%, 50%, 90% of volume (D10, D50, D90) and volume receiving 6000, 5400, 5000, 4500, 4000 CcGE (V60, V54, V50, V45, V40) were evaluated. For the whole brain, maximum dose to 1 cc of volume, and volume receiving 5400, 5000, 4500, 4000, 3000 CcGE (V54, V50, V45, V40 and V30) were assessed. Results: The average change in the values of these indices in the worst scenario cases from the nominal plan were as follows. Brain stem; Maximum dose to 1 cc of volume: 1.1%, D10: 1.4%, D50: 8.0%, D90:73.3%, V60:116.9%, V54:27.7%, V50: 21.2%, V45:16.2%, V40:13.6%,Whole brain; Maximum dose to 1 cc of volume: 0.3%, V54:11.4%, V50: 13.0%, V45:13.6%, V40:14.1%, V30:13.5%. Conclusion: Large to modest changes in the dosiemtric indices for brain stem and whole brain compared to nominal plan due to range and set up uncertainties were observed. Such potential changes should be taken into account while using any dosimetric parameters for outcome evaluation of patients receiving proton therapy.« less

2-year follow-up report on micromotion of a short tibia stem. A prospective, randomized RSA study of 59 patients.

PubMed

Molt, Mats; Toksvig-Larsen, Sören

2015-01-01

A shortened tibial stem could influence the early prosthetic fixation. We therefore compared the short stem to the standard-length stem using radiostereometric analysis (RSA) as primary outcome measure. 60 patients were randomized to receive a cemented Triathlon total knee arthroplasty (TKA) with a tibial tray of either standard or short stem length. The patients were blinded regarding treatment allocation. The micromotion of the tibial component was measured by RSA postoperatively, at 3 months, and after 1 and 2 years; clinical outcome was measured with the American Knee Society score (AKSS) and the knee osteoarthritis and injury outcome score (KOOS). The maximum total point motion (MTPM) for the standard stem was 0.36 (SD 0.16) mm at 3 months, 0.51 (SD 0.27) mm at 1 year, and 0.54 (SD 0.28) mm at 2 years. For the short stem, it was 0.42 (0.24) mm, 0.59 (0.43) mm, and 0.61 (0.39) mm. 4 short-stemmed components and 2 standard-stemmed components had more than 0.2 mm of migration between the first- and second-year follow-up, and were classified as continuously migrating. The short-stemmed cemented tibial prosthesis showed an early prosthetic migratory pattern similar to that of the standard-stemmed cemented Triathlon knee prosthesis. The number of continuously migrating tibial plates in each group is predictive of a lower revision rate than 5% at 10 years.

Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type

PubMed Central

de Padua Silva, Leandro; Patah, Poliana A.; Saliba, Rima M.; Szewczyk, Nicholas A.; Gilman, Lisa; Neumann, Joyce; Han, Xiang-Yang; Tarrand, Jeffrey; Ribeiro, Rachel; Gulbis, Alison; Shpall, Elizabeth J.; Jones, Roy; Popat, Uday; Walker, Julia A.; Petropoulos, Demetrios; Chiattone, Alexandre; Stewart, John; El-Zimaity, Maha; Anderlini, Paolo; Giralt, Sergio; Champlin, Richard E; de Lima, Marcos

2010-01-01

Background Hemorrhagic cystitis is a common cause of morbidity after allogeneic stem cell transplantation, frequently associated with BK virus infection. We hypothesized that patients with positive BK viruria before unrelated or mismatched related donor allogeneic hematopoietic stem cell transplantation have a higher incidence of hemorrhagic cystitis. Design and Methods To test this hypothesis, we prospectively studied 209 patients (median age 49 years, range 19–71) with hematologic malignancies who received bone marrow (n=78), peripheral blood (n=108) or umbilical cord blood (n=23) allogeneic hematopoietic stem cell transplantation after myeloablative (n=110) or reduced intensity conditioning (n=99). Donors were unrelated (n=201) or haploidentical related (n=8). Results Twenty-five patients developed hemorrhagic cystitis. Pre-transplant BK viruria detected by quantitative PCR was positive in 96 patients. The one-year cumulative incidence of hemorrhagic cystitis was 16% in the PCR-positive group versus 9% in the PCR-negative group (P=0.1). The use of umbilical cord blood or a haploidentical donor was the only significant predictor of the incidence of hemorrhagic cystitis on univariate analysis. There was also a trend for a higher incidence after myeloablative conditioning. Multivariate analysis showed that patients who had a positive PCR pre-transplant and received haploidentical or cord blood grafts with myeloablative conditioning had a significantly higher risk of developing hemorrhagic cystitis (58%) than all other recipients (7%, P<0.001). Conclusions Hemorrhagic cystitis is the result of a complex interaction of donor type, preparative regimen intensity, and BK viruria. PMID:20410183

Icing oral mucositis: Oral cryotherapy in multiple myeloma patients undergoing autologous hematopoietic stem cell transplant.

PubMed

Chen, Joey; Seabrook, Jamie; Fulford, Adrienne; Rajakumar, Irina

2017-03-01

Background Up to 70% of patients receiving hematopoietic stem cell transplant develop oral mucositis as a side effect of high-dose melphalan conditioning chemotherapy. Oral cryotherapy has been documented to be potentially effective in reducing oral mucositis. The aim of this study was to examine the effectiveness of the cryotherapy protocol implemented within the hematopoietic stem cell transplant program. Methods A retrospective chart review was conducted of adult multiple myeloma patients who received high-dose melphalan conditioning therapy for autologous hematopoietic stem cell transplant. Primary endpoints were incidence and severity of oral mucositis. Secondary endpoints included duration of oral mucositis, duration of hospital stay, parenteral narcotics use and total parenteral nutrition use. Results One hundred and forty patients were included in the study, 70 patients in both no cryotherapy and cryotherapy groups. Both oral mucositis incidence and severity were found to be significantly lower in the cryotherapy group. Fifty (71.4%) experienced mucositis post cryotherapy compared to 67 (95.7%) in the no cryotherapy group (p < 0.001). The median oral mucositis severity, assessed using the WHO oral toxicity scale from grade 0-4, experienced in the no group was 2.5 vs. 2 in the cryotherapy group (p = 0.03). Oral mucositis duration and use of parenteral narcotics were also significantly reduced. Duration of hospital stay and use of parenteral nutrition were similar between the two groups. Conclusion The cryotherapy protocol resulted in a significantly lower incidence and severity of oral mucositis. These results provide evidence for the continued use of oral cryotherapy, an inexpensive and generally well-tolerated practice.

A Pilot Study of Mesenchymal Stem Cell Therapy for Acute Liver Allograft Rejection

PubMed Central

Liu, Zhenwen; Wang, Ying; Xu, Rounan; Sun, Yanling; Zhang, Min; Yu, Xi; Wang, Hongbo; Meng, Lingzhan; Su, Haibin; Jin, Lei

2017-01-01

Abstract Acute allograft rejection remains common after liver transplantation despite modern immunosuppressive agents. In addition, the long‐term side effects of these regimens, including opportunistic infections, are challenging. This study evaluated the safety and clinical feasibility of umbilical cord‐derived mesenchymal stem cell (UC‐MSC) therapy in liver transplant patients with acute graft rejection. Twenty‐seven liver allograft recipients with acute rejection were randomly assigned into the UC‐MSC infusion group or the control group. Thirteen patients received one infusion of UC‐MSCs (1 × 106/kg body weight); one patient received multiple UC‐MSC infusions; 13 patients were used as controls. All enrolled patients received conventional immunosuppressive agents with follow‐up for 12 weeks after UC‐MSC infusions. No side effects occurred in treated patients. Four weeks after UC‐MSC infusions, alanine aminotransferase levels had decreased markedly and remained lower throughout the 12‐week follow‐up period. Importantly, allograft histology was improved after administration of UC‐MSCs. The percentage of regulatory T cells (Tregs) and the Treg/T helper 17 (Th17) cell ratio were significantly increased 4 weeks after infusions; in contrast, the percentage of Th17 cells showed a decreasing trend. In controls, the percentages of Tregs and Th17 cells and the Treg/Th17 ratio were statistically unchanged from the baseline measurements. Transforming growth factor beta 1 and prostaglandin E2 were increased significantly after UC‐MSC infusions; by contrast, there were no significant changes in controls. Our data suggest that UC‐MSC infusion for acute graft rejection following liver transplantation is feasible and may mediate a therapeutic immunosuppressive effect. Stem Cells Translational Medicine 2017;6:2053–2061 PMID:29178564

Remission induction using alemtuzumab can permit chemotherapy-refractory chronic lymphocytic leukemia (CLL) patients to undergo allogeneic stem cell transplantation.

PubMed

Knauf, Wolfgang; Rieger, Kathrin; Blau, Wolfgang; Hegenbart, Ute; Von Gruenhagen, Ulrich; Niederwieser, Dietger; Thiel, Eckhard

2004-12-01

The outcome of allogeneic stem cell transplantation depends upon the disease status before transplantation. Patients with refractory disease are at high risk for relapse. To improve the curative potential of the transplant procedure, we treated 3 chemotherapy-refractory CLL patients with alemtuzumab before allogeneic stem cell transplantation. Prior to therapy, all patients suffered from B-symptoms, and had massive adenopathy, splenomegaly, thrombocytopenia, and anemia; two patients had hepatomegaly. Alemtuzumab greatly reduced tumor mass in blood and bone marrow, B-symptoms resolved, and organomegaly improved. Two patients became blood product independent. All patients proceeded to transplantation after conditioning with TBI 2 Gy (n=1) or Treosulfan (n=2) in combination with Fludarabine either from an HLA-matched sibling (n=2) or from an HLA-matched unrelated donor (n=1). All patients engrafted, and are alive and well. Two patients reached complete remission (CR); one patient attained stable partial remission (PR). These heavily pre-treated refractory patients gained substantial clinical benefit from alemtuzumab, and received successful allografts.

Preclinical Assessment of the Proliferation Capacity of Gingival and Periodontal Ligament Stem Cells from Diabetic Patients.

PubMed

Assem, Mostafa; Kamal, Samia; Sabry, Dina; Soliman, Nadia; Aly, Riham M

2018-02-15

Stem cells have recently received great interest as potential therapeutics alternative for a variety of diseases. The oral and maxillofacial region, in particular, encompasses a variety of distinctive mesenchymal (MSC) populations and is characterized by a potent multilineage differentiation capacity. In this report, we aimed to investigate the effect of diabetes on the proliferation potential of stem cells isolated from controlled diabetic patients (type 2) and healthy individuals. The proliferation rate of gingival and periodontal derived stem cells isolated from diabetic & healthy individuals were compared using MTT Assay. Expression levels of Survivin in isolated stem cells from all groups were measured by qRt - PCR. There was a significantly positive correlation between proliferation rate and expression of Survivin in all groups which sheds light on the importance of Survivin as a reliable indicator of proliferation. The expression of Survivin further confirmed the proliferation results from MTT Assay where the expression of stem cells from non - diabetic individuals was higher than diabetic patients. Taking together all the results, it could be concluded that PDLSC and GSC are promising candidates for autologous regenerative therapy due to their ease of accessibility in addition to their high proliferative rates.

Complete neurologic and cognitive recovery after plasmapheresis in a patient with chronic inflammatory demyelinating polyneuropathy after allogeneic hematopoietic stem cell transplantation.

PubMed

Vogl, Ursula; Leitner, Gerda; Dal-Bianco, Assunta; Bojic, Marija; Mitterbauer, Margit; Rabitsch, Werner; Kalhs, Peter; Schulenburg, Axel

2016-05-01

Neurologic complications after allogeneic hematopoietic stem cell transplantation (HSCT) are rare but poorly understood. We present a case report of a 57-year-old-male patient who was diagnosed in 2009 with acute myeloid leukemia (AML). He received two standard induction chemotherapies, as well as a following consolidation. Six months later, an allogeneic HSCT was performed. Shortly after HSCT the patient developed progressive polyneuropathy of the lower legs and hypoesthesia. Five months later a severe dementia followed. All images of the brain and spine showed no specific pathologies. High dose corticosteroids and immunoglobulins did not improve the neurologic symptoms. Due to severe worsening of the neuropsychiatric status and the clinical presentation, chronic inflammatory demyelinating polyneuropathy (CIDP) was suspected. Therefore, the patient received ten cycles of plasmapheresis. The patient showed a significant improvement of the neuropsychiatric symptoms and cognitive status. Immune mediated neuropathies after allogeneic HSCT, such as CIDP, have great variability in symptoms and presentation and are challenging to diagnose and treat. Plasmapheresis is a safe and efficient treatment for patients with unclear persisting autoimmune neuropathy after HSCT.

Marital adjustment, satisfaction and dissolution among hematopoietic stem cell transplant patients and spouses: a prospective, five-year longitudinal investigation.

PubMed

Langer, Shelby L; Yi, Jean C; Storer, Barry E; Syrjala, Karen L

2010-02-01

To examine the trajectory of marital adjustment, satisfaction and dissolution among 121 hematopoietic stem cell transplant (HSCT) couples-as a function of role (patient or spouse) and gender. Prospective, longitudinal design. Participants completed the Dyadic Adjustment Scale at six time points: pre-transplant (4-7 days after beginning medical workup prior to starting transplant), 6 months post-transplant, and 1, 2, 3 and 5 years post-transplant. They also reported on marital status over time. Participants ranged in age from 23-68 (52% female patients and 48% female spouses). Ninety-eight patients received an allogeneic transplant; 23 received an autologous transplant. Marital dissolution was uncommon (four divorces since the transplant among 55 participating 5-year survivors, 7%). Dyadic satisfaction was stable over time for both male and female patients and male spouses, but not for female spouses who reported reductions in satisfaction at all time points relative to baseline. Couples were by and large resilient. However, caregiver-specific gender differences indicate an increased risk for relationship maladjustment and dissatisfaction among female spouses and ultimately, female spouse/male patient couples.

Cidofovir for BK virus-associated hemorrhagic cystitis: a retrospective study.

PubMed

Cesaro, Simone; Hirsch, Hans H; Faraci, Maura; Owoc-Lempach, Joanna; Beltrame, Angela; Tendas, Andrea; Baltadakis, Ioannis; Dalle, Jean-Hughes; Koc, Yener; Toporski, Jacek; Styczynski, Jan; Yesilipek, M Akif; Heinz, Werner; Caniglia, Maurizio; Rascon, Jelena; Fauser, Axel A; Michallet, Mauricette; Lopez-Corral, Lucia; Neuburger, Stefan; Tridello, Gloria; Einsele, Herman

2009-07-15

BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation (HSCT), but antiviral treatment for this condition has not been evaluated. We conducted a retrospective survey on the safety and outcome of cidofovir treatment for patients with BKV-HC in centers affiliated with the European Group for Blood and Marrow Transplantation. From 1 April 2004 to 31 December 2007, 62 patients received a diagnosis of BKV-HC after a median interval of 35 days after HSCT (range, 3-577 days). Fifty-seven patients (92%) received intravenous cidofovir, whereas 5 patients received cidofovir intravesically. Complete response (CR) was recorded in 38 (67%) of 57 patients with HC treated with intravenous cidofovir, whereas partial response (PR) was documented in 7 patients (12%). CR was documented in 3 patients and PR in 1 patient with HC treated with intravesical cidofovir. A reduction of 1-3 logs in BKV load was documented in 8 of the 10 patients achieving CR. Mild-to-moderate toxic effects were recorded in 18 of 57 patients who received intravenous cidofovir administration. In a multivariate analysis, the factors significantly associated with response to cidofovir were the stem cell source (P = .01) and the use of total body irradiation (P = .03). After a median follow-up of 287 days, overall survival and total treatment-related mortality rates were 63% and 40% for patients achieving CR, compared with 14% and 72% for patients with PR or no response to cidofovir, respectively (P = .001 and P = .001, respectively). Cidofovir may be a potentially effective therapy for BKV-HC, but evidence supporting its use requires randomized controlled trials.

Potential use of mesenchymal stem cells in human meniscal repair: current insights

PubMed Central

Pak, Jaewoo; Lee, Jung Hun; Park, Kwang Seung; Jeon, Jeong Ho; Lee, Sang Hee

2017-01-01

The menisci of the human knee play an important role in maintaining normal functions to provide stability and nutrition to the articular cartilage, and to absorb shock. Once injured, these important structures have very limited natural healing potential. Unfortunately, the traditional arthroscopic meniscectomy performed on these damaged menisci may predispose the joint toward early development of osteoarthritis. Although a very limited number of studies are available, mesenchymal stem cells (MSCs) have been investigated as an alternative therapeutic modality to repair human knee meniscal tears. This review summarizes the results of published applications of MSCs in human patients, which showed that the patients who received MSCs (autologous adipose tissue-derived stem cells or culture-expanded bone marrow-derived stem cells) presented symptomatic improvements, along with magnetic resonance imaging evidences of the meniscal repair. PMID:28356779

Management of relapsed and refractory classical Hodgkin lymphoma in children and adolescents.

PubMed

Daw, Stephen; Wynn, Rob; Wallace, Hamish

2011-02-01

There are a number of options for salvage treatment in children and adolescents with relapsed and refractory classical Hodgkin Lymphoma. These include salvage with standard dose chemotherapy, high dose chemotherapy with autologous stem cell transplant, allogeneic stem cell transplant or other novel approach. Radiotherapy has an important role in the salvage of some patients as part of a combined modality approach. This review outlines these salvage approaches and discusses whether the evidence from paediatric studies justifies a risk-adapted approach to salvage for individual patients or whether all patients should receive consolidation with high dose chemotherapy and autologous stem cell transplantation, which is often described as standard salvage management in adults. The important prognostic factors and how these may be used to allocate patients to standard versus high dose chemotherapy regimens are discussed. The role of allogeneic transplantation, novel agents and late effects will also be discussed. © 2010 Blackwell Publishing Ltd.

Hematopoietic Stem Cell Transplantation in Thalassemia and Sickle Cell Anemia

PubMed Central

Lucarelli, Guido; Isgrò, Antonella; Sodani, Pietro; Gaziev, Javid

2012-01-01

The globally widespread single-gene disorders β-thalassemia and sickle cell anemia (SCA) can only be cured by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT treatment of thalassemia has substantially improved over the last two decades, with advancements in preventive strategies, control of transplant-related complications, and preparative regimens. A risk class–based transplantation approach results in disease-free survival probabilities of 90%, 84%, and 78% for class 1, 2, and 3 thalassemia patients, respectively. Because of disease advancement, adult thalassemia patients have a higher risk for transplant-related toxicity and a 65% cure rate. Patients without matched donors could benefit from haploidentical mother-to-child transplantation. There is a high cure rate for children with SCA who receive HSCT following myeloablative conditioning protocols. Novel non-myeloablative transplantation protocols could make HSCT available to adult SCA patients who were previously excluded from allogeneic stem cell transplantation. PMID:22553502

Stem cell implantation for osteonecrosis of the femoral head.

PubMed

Lim, Young Wook; Kim, Yong Sik; Lee, Jong Wook; Kwon, Soon Yong

2013-11-15

What is the most effective treatment for the early stages of osteonecrosis of the femoral head? We assessed multiple drilling and stem cell implantation to treat the early stages of osteonecrosis of the femoral head. We report the clinical and radiological results of stem cell implantation and core decompression. In total, 128 patients (190 hips) who had undergone surgery were divided into two groups based on which treatment they had received: (1) multiple drilling and stem cell implantation or (2) core decompression, curettage and a bone graft. The clinical and radiographic results of the two groups were compared. At 5-year follow-up, in the stem cell implantation group, 64.3% (27/42) of the patients with Stage IIa disease, 56.7% (21/37) of the patients with Stage IIb disease and 42.9% (21/49) of the patients with Stage III disease had undergone no additional surgery. In the conventional core decompression group, 64.3% (9/14) of the patients with Stage IIa disease, 55.6% (5/9) of the patients with Stage IIb disease and 37.5% (3/8) of the patients with Stage III disease had undergone no additional surgery. Success rates were higher in patients with Ficat Stage I or II lesions than in those with Stage III lesions. There were no statistically significant differences between the groups in terms of success rate or in the clinical and radiographic results of the two methods. Essentially the same results were found with stem cell implantation as with the conventional method of core decompression.

HLA-mismatched stem-cell microtransplantation as postremission therapy for acute myeloid leukemia: long-term follow-up.

PubMed

Guo, Mei; Hu, Kai-Xun; Liu, Guang-Xian; Yu, Chang-Lin; Qiao, Jian-Hui; Sun, Qi-Yun; Qiao, Jun-Xiao; Dong, Zheng; Sun, Wan-Jun; Sun, Xue-Dong; Zuo, Hong-Li; Man, Qiu-Hong; Liu, Zhi-Qing; Liu, Tie-Qiang; Zhao, Hong-Xia; Huang, Ya-Jing; Wei, Li; Liu, Bing; Wang, Juan; Shen, Xu-Liang; Ai, Hui-Sheng

2012-11-20

Despite best current therapies, approximately half of patients with acute myeloid leukemia in first complete remission (AML-CR1) with no HLA-identical donors experience relapse. Whether HLA-mismatched stem-cell microtransplantation as a novel postremission therapy in these patients will improve survival and avoid graft-versus-host disease (GVHD) is still unknown. One hundred one patients with AML-CR1 (9 to 65 years old) from four treatment centers received programmed infusions of G-CSF-mobilized HLA-mismatched donor peripheral-blood stem cells after each of three cycles of high-dose cytarabine conditioning without GVHD prophylaxis. Donor chimerism and microchimerism and WT1+CD8+ T cells were analyzed. The 6-year leukemia-free survival (LFS) and overall survival (OS) rates were 84.4% and 89.5%, respectively, in the low-risk group, which were similar to the rates in the intermediate-risk group (59.2% and 65.2%, respectively; P=.272 and P=.308). The 6-year LFS and OS were 76.4% and 82.1%, respectively, in patients who received a high dose of donor CD3+ T cells (≥1.1×10(8)/kg) in each infusion, which were significantly higher than the LFS and OS in patients who received a lower dose (<1.1×10(8)/kg) of donor CD3+ T cells (49.5% and 55.3%, respectively; P=.091 and P=.041). No GVHD was observed in any of the patients. Donor microchimerism (2 to 1,020 days) was detected in 20 of the 23 female patients who were available for Y chromosome analysis. A significant increase in WT1+CD8+ T cells (from 0.2% to 4.56%) was observed in 33 of 39 patients with positive HLA-A*02:01 antigen by a pentamer analysis. Microtransplantation as a postremission therapy may improve outcomes and avoid GVHD in patients with AML-CR1.

The changing scene of allogeneic stem cell transplantation for chronic myeloid leukemia--a report from the German Registry covering the period from 1998 to 2004.

PubMed

Bacher, Ulrike; Klyuchnikov, Evgeny; Zabelina, Tatjana; Ottinger, Hellmut; Beelen, Dietrich W; Schrezenmeier, Hubert; Ehninger, Gerhard; Müller, Carlheinz; Berger, Jürgen; Suttorp, Meinolf; Kolb, Hans-Jochem; Kröger, Nicolaus; Zander, Axel R

2009-12-01

Due to the recent changes in the indication to allogeneic stem cell transplantation (SCT) in chronic myeloid leukemia (CML), we retrospectively analyzed 1,716 patients with different CML stages who received an allograft from related (n = 767) or unrelated donors (n = 938) within the German Registry of Stem Cell Transplantation (DRST) from 1998 to 2004. Myeloablative conditioning was performed in 724/871 cases (83%), dose-reduced conditioning in 147/871 (17%). Annual transplantations were decreasing from 357 to 98 (28%) in the period of study, but the proportion of advanced cases was increasing from 32% (112/346) to 53% (50/94) of all SCTs. Stage of disease, intervals from diagnosis, and patients' age were independent prognostic parameters, while peripheral stem cells and unrelated transplantation seemed equal to bone marrow/related transplantation. This study demonstrates that allo-SCT still has an important role in advanced CML, which emphasizes the need for optimized transplantation strategies for these high-risk patients.

Safety and efficacy of high-dose chemotherapy with autologous stem cell transplantation for patients with malignant astrocytomas.

PubMed

Chen, Benjamin; Ahmed, Tauseef; Mannancheril, Anney; Gruber, Michael; Benzil, Deborah L

2004-05-15

Malignant astrocytomas are among the most resistant tumors to curative treatments. Mean survival without treatment is measured in weeks, and even with maximal surgery and radiation, the mean reported survival is < 1 year. The advent of supportive treatments and newer agents has resulted in benefits for many patients with cancer. The authors investigated the safety and effect on survival of a high-dose thiotepa and carboplatin regimen with autologous stem cell transplantation (ASCT) in patients with malignant astrocytomas who were enrolled in a prospective trial approved by an institutional review board (IRB). Twenty-one patients were enrolled in an IRB-approved, prospective trial. After baseline testing was completed, patients underwent peripheral stem cell mobilization with cyclophosphamide (4 g/m2) and etoposide (450 mg/m2) followed by granulocyte-colony-stimulating factor (10 microg/kg). Peripheral stem cells were harvested when leukocyte counts recovered. Patients received 2 cycles of thiotepa (750 mg/m2) and carboplatin (1600 mg/m2) followed by infusion of the preserved stem cells. The cycles were administered 6-10 weeks apart. Primary outcome measures were patient survival (Kaplan-Meier analysis) and treatment toxicity (using National Cancer Institute common toxicity criteria). Autologous stem cells were harvested effectively and transfused in all patients. Kaplan-Meier survival analysis demonstrated a survival time of 34.3 +/- 5.5 months (range, 9-94 months). Despite significant myelosuppression, only three patients experienced Grade 4 complications and eight experienced Grade 3 complications. High-dose chemotherapy with thiotepa and carboplatin with concomitant ASCT was used safely to treat patients with malignant astrocytomas and may provide a survival advantage. Copyright 2004 American Cancer Society.

Recommendations for screening, monitoring, prevention, prophylaxis and therapy of hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation-a position paper.

PubMed

Sarmati, L; Andreoni, M; Antonelli, G; Arcese, W; Bruno, R; Coppola, N; Gaeta, G B; Galli, M; Girmenia, C; Mikulska, M; Pane, F; Perno, C F; Picardi, M; Puoti, M; Rambaldi, A; Svicher, V; Taliani, G; Gentile, G

2017-12-01

Hepatitis B virus (HBV) infection reactivation is associated with high morbidity and mortality in patients with haematologic malignancy and/or haematopoietic stem cell transplantation (HSCT). However, information on this issue is limited. The scope of this position paper is to provide recommendations on HBV screening, monitoring, prophylaxis, treatment and vaccination in the patients described above. These recommendations were developed from one meeting of experts attended by different Italian scientific societies as well as from a systematic literature review (of articles published through December 31, 2016) on HBV infection in haematologic patients and in patients who underwent haematopoietic stem cell transplantation published in the same issue of the journal. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess each recommendation's quality. These recommendations provide the answers to the following questions: (a) HBV screening and monitoring: Who should be screened before chemotherapy? Which screening tests should be used? Should HBV-DNA detection be used to monitor HBV reactivation before starting antivirals? What is the best timeline to monitor HBV reactivation? (b) Prophylaxis in HBsAg-positive patients: Which antiviral drugs should be used to treat HBsAg-positive patients? How long should antiviral prophylaxis be provided to HBsAg-positive patients? (c) Prophylaxis in patients with resolved HBV infection: Which patients with resolved HBV infection should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (d) HBV infection management strategy in autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT): Which HSCT recipients should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (e) Choice of antiviral drugs in the treatment of HBV reactivation: Should third-generation anti-HBV drugs be preferred to first- or second-generation antiviral drugs in the treatment of HBV reactivation with or without hepatitis flare in haematologic patients? (f) Immunization against HBV in patients with haematologic malignancies and/or patients who underwent HSCT: Should these patients be vaccinated? Which HBV vaccination schedule should be adopted? Haematologic patients should be screened for hepatitis B surface antigen (HBsAg) plus anti-hepatitis B core protein (HBc), and HBV DNA before chemotherapy. HBV DNA levels should be monitored monthly in all HBV-positive patients who do not receive prophylaxis. HBsAg-positive haematologic patients and those undergoing HSCT should receive third-generation antiviral therapy as prophylaxis. Anti-HBc-positive lymphoma patients and those receiving HSCT should receive antiviral prophylaxis. All HBV-negative haematologic patients should be vaccinated for HBV. The acquisition of data from well-designed studies is desirable in the near future. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Five-year follow-up of survival and relapse in patients who received cryotherapy during high-dose chemotherapy for stem cell transplantation shows no safety concerns.

PubMed

Svanberg, A; Ohrn, K; Birgegård, G

2012-11-01

We have previously published a randomised controlled study of the efficacy of cryotherapy in preventing acute oral mucositis after high-dose chemotherapy for stem cell transplantation. The present study is a 5-year follow-up safety study of survival in these patients. In the previously published study oral cryotherapy (cooling of the oral cavity) during high-dose chemotherapy significantly reduced mucositis grade and opiate use in the treated group. All patients were followed up for at least 5 years with regard to relapse and death rates. Baseline data, transplant complications and mucositis data were compared. Significantly more patients (25/39) who received oral cryotherapy were alive after 5 years compared to 15/39 in the control group (P= 0.025). Relapse rates were similar. The only baseline difference was a lower proportion of patients in complete remission at transplantation in the control group (6 vs. 13, P= 0.047). This 5-year follow-up study gave no support for safety concerns with cryotherapy. © 2012 Blackwell Publishing Ltd.

Selective T-Cell Depletion to Reduce GVHD (Patients) Receiving Stem Cell Tx to Treat Leukemia, Lymphoma or MDS

ClinicalTrials.gov

2016-09-21

Graft vs Host Disease; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myelomonocytic, Chronic; Leukemia, Lymphocytic; Lymphoma; Lymphoma, Mantle-cell; Lymphoma, Non-Hodgkin; Hodgkin Disease

Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children's Cancer Study Group.

PubMed Central

Estlin, E. J.; Lashford, L.; Ablett, S.; Price, L.; Gowing, R.; Gholkar, A.; Kohler, J.; Lewis, I. J.; Morland, B.; Pinkerton, C. R.; Stevens, M. C.; Mott, M.; Stevens, R.; Newell, D. R.; Walker, D.; Dicks-Mireaux, C.; McDowell, H.; Reidenberg, P.; Statkevich, P.; Marco, A.; Batra, V.; Dugan, M.; Pearson, A. D.

1998-01-01

A phase I study of temozolomide administered orally once a day, on 5 consecutive days, between 500 and 1200 mg m(-2) per 28-day cycle was performed. Children were stratified according to prior craniospinal irradiation or nitrosourea therapy. Sixteen of 20 patients who had not received prior craniospinal irradiation or nitrosourea therapy were evaluable. Myelosuppression was dose limiting, with Common Toxicity Criteria (CTC) grade 4 thrombocytopenia occurring in one of six patients receiving 1000 mg m(-2) per cycle, and two of four patients treated at 1200 mg m(-2) per cycle. Therefore, the maximum-tolerated dose (MTD) was 1000 mg m(-2) per cycle. The MTD was not defined for children with prior craniospinal irradiation because of poor recruitment. Plasma pharmacokinetic analyses showed temozolomide to be rapidly absorbed and eliminated, with linear increases in peak plasma concentrations and systemic exposure with increasing dose. Responses (CR and PR) were seen in two out of five patients with high-grade astrocytomas, and one patient had stable disease. One of ten patients with diffuse intrinsic brain stem glioma achieved a long-term partial response, and a further two patients had stable disease. Therefore, the dose recommended for phase II studies in patients who have not received prior craniospinal irradiation or nitrosoureas is 1000 mg m(-2) per cycle. Further evaluation in diffuse intrinsic brain stem gliomas and other high-grade astrocytomas is warranted. Images Figure 5 p658-b Figure 6 p659-b PMID:9744506

Tandem Autologous Stem Cell Transplantation for Multiple Myeloma Patients Based on Response to Their First Transplant—A Prospective Phase II Study

PubMed Central

Byrne, Michael; Salmasinia, Donya; Leather, Helen; Cogle, Christopher R; Davis, Amy; Hsu, Jack W; Wiggins, Laura; Chang, Myron N; An, Qi; Wingard, John R; Moreb, Jan S

2014-01-01

In this prospective phase II clinical trial, multiple myeloma (MM) patients were randomized to receive a second (tandem) autologous stem cell transplantation (ASCT) based on whether they achieved a partial response or worse (≤PR) following initial ASCT (ASCT1). Patients who achieved a very good partial response or better (≥VGPR) had salvage ASCT at relapse. Seventy-five patients received conditioning therapy and ASCT1. A total of 44 patients (59%) achieved ≥VGPR, whereas 31 patients entered ≤PR and were offered tandem ASCT. In all, 20 patients agreed to tandem ASCT. Demographic and clinical characteristics were similar between the two cohorts except for median lactate dehydrogenase (LDH) (P = 0.0141) and percentage of marrow plasma cells before ASCT1 (P = 0.0047), both lower in the ≥VGPR group. Intent to treat analysis showed that patients who achieved ≥VGPR to ASCT1 had a trend toward improved progression-free survival (PFS) (37 vs. 26 months, P = 0.078) and superior overall survival (OS) (not reached vs. 50 months, P = 0.0073). Patients with ≤PR who declined tandem transplantation had shortened PFS (20 vs. 28 months, P = 0.05) but similar OS (53 vs. 57.5 months, P = 0.29) compared to those who received it. Thus, a favorable clinical response to ASCT1 identifies a low-risk group with superior long-term prognosis despite similar PFS. PMID:25232286

Treatment of Tularemia in Patient with Chronic Graft-versus-Host Disease

PubMed Central

Seibold, Erik; Knabbe, Cornelius; Kaufmann, Martin; Splettstoesser, Wolf

2013-01-01

We describe a case of human tularemia caused by Francisella tularensis subsp. holarctica in a stem cell transplant recipient with chronic graft-versus-host disease who was receiving levofloxacin prophylaxis. The infection was characterized by pneumonia with septic complications. The patient was successfully treated with doxycycline. PMID:23647853

Typhilitis in the pediatric patient.

PubMed

Haut, Cathy

2008-01-01

Cancer statistics in children are promising as mortality rates consistently decrease, reflecting newer chemotherapeutic agents and the evolution of hematopoietic stem cell transplant. Typhilitis or neutropenic enterocolitis is a potentially life-threatening complication of cancer treatment often found in immunocompromised children receiving vigorous chemotherapeutic regimens and noted in children post-stem-cell transplant. Recent literature suggests a relationship between typhilitis and other types of cancers and immunocompromised illness occurring in both children and adults. The pathogenesis of typhilitis is poorly understood, with limited evidence regarding incidence. Nursing care and assessment of children receiving oncologic treatment requires vigilance and immediate response to prevent and manage complications, especially gastrointestinally related typhilitis.

Rationale and design of the German-Speaking Myeloma Multicenter Group (GMMG) trial ReLApsE: a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma.

PubMed

Baertsch, Marc-Andrea; Schlenzka, Jana; Mai, Elias K; Merz, Maximilian; Hillengaß, Jens; Raab, Marc S; Hose, Dirk; Wuchter, Patrick; Ho, Anthony D; Jauch, Anna; Hielscher, Thomas; Kunz, Christina; Luntz, Steffen; Klein, Stefan; Schmidt-Wolf, Ingo G H; Goerner, Martin; Schmidt-Hieber, Martin; Reimer, Peter; Graeven, Ullrich; Fenk, Roland; Salwender, Hans; Scheid, Christof; Nogai, Axel; Haenel, Mathias; Lindemann, Hans W; Martin, Hans; Noppeney, Richard; Weisel, Katja; Goldschmidt, Hartmut

2016-04-25

Despite novel therapeutic agents, most multiple myeloma (MM) patients eventually relapse. Two large phase III trials have shown significantly improved response rates (RR) of lenalidomide/dexamethasone compared with placebo/dexamethasone in relapsed MM (RMM) patients. These results have led to the approval of lenalidomide for RMM patients and lenalidomide/dexamethasone has since become a widely accepted second-line treatment. Furthermore, in RMM patients consolidation with high-dose chemotherapy plus autologous stem cell transplantation has been shown to significantly increase progression free survival (PFS) as compared to cyclophosphamide in a phase III trial. The randomized prospective ReLApsE trial is designed to evaluate PFS after lenalidomide/dexamethasone induction, high-dose chemotherapy consolidation plus autologous stem cell transplantation and lenalidomide maintenance compared with the well-established lenalidomide/dexamethasone regimen in RMM patients. ReLApsE is a randomized, open, multicenter phase III trial in a planned study population of 282 RMM patients. All patients receive three lenalidomide/dexamethasone cycles and--in absence of available stem cells from earlier harvesting--undergo peripheral blood stem cell mobilization and harvesting. Subsequently, patients in arm A continue on consecutive lenalidomide/dexamethasone cycles, patients in arm B undergo high dose chemotherapy plus autologous stem cell transplantation followed by lenalidomide maintenance until discontinuation criteria are met. Therapeutic response is evaluated after the 3(rd) (arm A + B) and the 5(th) lenalidomide/dexamethasone cycle (arm A) or 2 months after autologous stem cell transplantation (arm B) and every 3 months thereafter (arm A + B). After finishing the study treatment, patients are followed up for survival and subsequent myeloma therapies. The expected trial duration is 6.25 years from first patient in to last patient out. The primary endpoint is PFS, secondary endpoints include overall survival (OS), RR, time to best response and the influence of early versus late salvage high dose chemotherapy plus autologous stem cell transplantation on OS. This phase III trial is designed to evaluate whether high dose chemotherapy plus autologous stem cell transplantation and lenalidomide maintenance after lenalidomide/dexamethasone induction improves PFS compared with the well-established continued lenalidomide/dexamethasone regimen in RMM patients. ISRCTN16345835 (date of registration 2010-08-24).

Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants.

PubMed

Marr, Kieren A; Crippa, Fulvio; Leisenring, Wendy; Hoyle, Maggie; Boeckh, Michael; Balajee, S Arunmozhi; Nichols, W Garrett; Musher, Benjamin; Corey, Lawrence

2004-02-15

Prophylactic fluconazole prevents candidiasis; however, this drug has no activity against molds. We performed a randomized trial to determine whether prophylactic itraconazole prevents invasive mold infections (IMIs). A total of 304 patients receiving allogeneic stem cell transplants (SCT) were randomized to receive fluconazole (400 mg/d) or itraconazole (oral solution 2.5 mg/kg 3 times daily, or intravenous 200 mg daily) for 180 days after SC transplantation, or until 4 weeks after discontinuation of graft-versus-host disease (GVHD) therapy. Proven or probable invasive fungal infections (IFI) were evaluated by intent-to-treat and "on-treatment" analyses. More patients in the itraconazole arm developed hepatotoxicities, and more patients were discontinued from itraconazole because of toxicities or gastrointestinal (GI) intolerance (36% versus 16%, P <.001). Intent-to-treat analysis demonstrated no difference in the incidence of IFI during the intended study period (fluconazole 16% versus itraconazole 13%, P =.46); however, fewer patients in the itraconazole arm developed IFI on treatment (fluconazole 15% versus itraconazole 7%, P =.03). Itraconazole provided better protection against IMI (fluconazole 12% versus itraconazole 5%, P =.03), but similar protection against candidiasis (3% versus 2%, P =.69). There was no difference in overall or fungal-free survival. Itraconazole appears to prevent IMI in the subset of patients who tolerate the drug; however, toxicities and poor tolerability limit its success as prophylactic therapy.

Fever after peripheral blood stem cell infusion in haploidentical transplantation with post-transplant cyclophosphamide.

PubMed

Arango, Marcos; Combariza, Juan F

2017-06-01

Noninfection-related fever can occur after peripheral blood stem cell infusion in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide. The objective of this study was to analyze the incidence of fever and characterize some clinical features of affected patients. A retrospective case-series study with 40 patients who received haploidentical hematopoietic stem cell transplantation was carried out. Thirty-three patients (82.5%) developed fever; no baseline characteristic was associated with its development. Median time to fever onset was 25.5h (range, 9.5-100h) and median peak temperature was 39.0°C (range, 38.1-40.5°C). Not a single patient developed hemodynamic or respiratory compromise that required admission to the intensive care unit. Fever was not explained by infection in any case. Ninety-one percent of the febrile episodes resolved within 96h of cyclophosphamide administration. No significant difference in overall survival, event-free survival, or graft versus host disease-free/relapse-free survival was found in the group of febrile individuals after peripheral blood stem cell infusion. Fever after peripheral blood stem cell infusion in this clinical setting was common; it usually subsides with cyclophosphamide administration. The development of fever was not associated with an adverse prognosis. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

The Ethics of Stem Cell-Based Aesthetic Surgery: Attitudes and Perceptions of the Plastic Surgery Community.

PubMed

Nayar, Harry S; Caplan, Arthur L; Eaves, Felmont F; Rubin, J Peter

2014-08-01

The emerging field of stem cell-based aesthetics has raised ethical concerns related to advertising campaigns and standards for safety and efficacy. The authors sought to characterize the attitudes of plastic surgeons regarding the ethics of stem cell-based aesthetics. A cross-sectional electronic survey was distributed to 4592 members of the American Society for Aesthetic Plastic Surgery and the American Society of Plastic Surgeons. Statements addressed ethical concerns about informed consent, conflicts of interest, advertising, regulation, and stem cell tourism. An agreement score (AS) from 0 to 100 was calculated for each statement. Majority agreement was designated as ≥60 and majority disagreement as ≤40. A total of 770 questionnaires were received (16.7%). The majority of respondents indicated that knowledge regarding the risks and benefits of stem cell procedures is insufficient to obtain valid informed consent (AS, 29) and that direct-to-consumer advertising for these technologies is inappropriate and unethical (AS, 23). Most respondents reported that patients should be actively warned against traveling abroad to receive aesthetic cell therapies (AS, 86) and that registries and evaluations of these clinics should be made publicly available (AS, 71). Even more respondents noted that financial conflicts of interest should be disclosed to patients (AS, 96) and that professional societies should participate in establishing regulatory standards (AS, 93). The plastic surgeons surveyed in this study support a well-regulated, evidence-based approach to aesthetic procedures involving stem cells. © 2014 The American Society for Aesthetic Plastic Surgery, Inc.

Targeting insulin resistance in type 2 diabetes via immune modulation of cord blood-derived multipotent stem cells (CB-SCs) in stem cell educator therapy: phase I/II clinical trial

PubMed Central

2013-01-01

Background The prevalence of type 2 diabetes (T2D) is increasing worldwide and creating a significant burden on health systems, highlighting the need for the development of innovative therapeutic approaches to overcome immune dysfunction, which is likely a key factor in the development of insulin resistance in T2D. It suggests that immune modulation may be a useful tool in treating the disease. Methods In an open-label, phase 1/phase 2 study, patients (N = 36) with long-standing T2D were divided into three groups (Group A, oral medications, n = 18; Group B, oral medications + insulin injections, n = 11; Group C having impaired β-cell function with oral medications + insulin injections, n = 7). All patients received one treatment with the Stem Cell Educator therapy in which a patient’s blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, briefly co-cultures them with adherent cord blood-derived multipotent stem cells (CB-SCs), and returns the educated autologous cells to the patient’s circulation. Results Clinical findings indicate that T2D patients achieve improved metabolic control and reduced inflammation markers after receiving Stem Cell Educator therapy. Median glycated hemoglobin (HbA1C) in Group A and B was significantly reduced from 8.61% ± 1.12 at baseline to 7.25% ± 0.58 at 12 weeks (P = 2.62E-06), and 7.33% ± 1.02 at one year post-treatment (P = 0.0002). Homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) demonstrated that insulin sensitivity was improved post-treatment. Notably, the islet beta-cell function in Group C subjects was markedly recovered, as demonstrated by the restoration of C-peptide levels. Mechanistic studies revealed that Stem Cell Educator therapy reverses immune dysfunctions through immune modulation on monocytes and balancing Th1/Th2/Th3 cytokine production. Conclusions Clinical data from the current phase 1/phase 2 study demonstrate that Stem Cell Educator therapy is a safe approach that produces lasting improvement in metabolic control for individuals with moderate or severe T2D who receive a single treatment. In addition, this approach does not appear to have the safety and ethical concerns associated with conventional stem cell-based approaches. Trial registration ClinicalTrials.gov number, NCT01415726 PMID:23837842

A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders.

PubMed

Shenoy, S; Grossman, W J; DiPersio, J; Yu, L C; Wilson, D; Barnes, Y J; Mohanakumar, T; Rao, A; Hayashi, R J

2005-02-01

Bone marrow transplantation (BMT) benefits nonmalignant diseases but is limited by regimen-related toxicity, graft-versus-host disease (GVHD), donor availability, and graft rejection (GR). To overcome some of these barriers, we developed a new conditioning strategy for these patients. In total, 16 patients received Campath-1H (33/48 mg; days -21 to -19), fludarabine (150 mg/m(2); days -8 to -4), melphalan (140/70 mg/m(2); day -3), and transplant using related/unrelated stem cells. GVHD prophylaxis included cyclosporine/methylprednisolone for cord cells. Other recipients also received methotrexate. Risk factors for GR included multiple transfusions (6), low stem cell numbers (1), and immunologic/metabolic disorders (3). Donor engraftment was present in 14/16 recipients. Neutrophils (ANC>0.5 x 10(9)/l) and platelets (>50 x 10(9)/l) engrafted at a median of 13 and 24 days. Two patients died of Pseudomonas sepsis prior to engraftment, one of CMV disease, and another of intracranial hemorrhage. With median follow-up of 281 days (78-907), 12/16 are stable/improved, or cured. Acute GVHD was absent (n=10) or mild and transient (grade1-2 skin) (n=4). There was no chronic GVHD. Toxicities were predominantly early infections within 100 days, and correlated with lymphopenia (CD4+ T and B cells). Stable engraftment and low incidence of significant GVHD, irrespective of age or stem cell source, make this reduced-intensity regimen attractive for nonmalignant disorders.

[Outcome of patients with relapsed/refractory adult T-cell leukemia-lymphoma after salvage therapy].

PubMed

Taniguchi, Hiroaki; Imaizumi, Yoshitaka; Makiyama, Junya; Itonaga, Hidehiro; Ando, Koji; Sawayama, Yasushi; Imanishi, Daisuke; Taguchi, Jun; Tsushima, Hideki; Hata, Tomoko; Hasegawa, Hiroo; Hayashi, Tomayoshi; Niino, Daisuke; Ohshima, Koichi; Tsukasaki, Kunihiro; Miyazaki, Yasushi

2013-12-01

We retrospectively analyzed 81 relapsed or refractory adult T-cell leukemia-lymphoma (ATL) patients who received salvage therapy in our institution between 2000 and 2010. These patients had received chemotherapy, radiation, or hematopoietic stem cell transplantation (HSCT) as an initial treatment, and were then given chemotherapy, radiation, HSCT, or donor lymphocyte infusion (DLI) as salvage therapy. Median survival time was 3.9 months. Of 5 long-term survivors, who survived more than 2 years after the first salvage therapy, 4 patients received HSCT or DLI, and the other was given mogamulizumab as the salvage therapy. For patients with relapsed or refractory ATL, HSCT/DLI is a promising treatment for achieving long-term survival. Mogamulizumab may be the good choice for those who are ineligible for HSCT.

Prophylactic antibiotics for the prevention of neutropenic fever in patients undergoing autologous stem-cell transplantation: results of a single institution, randomized phase 2 trial.

PubMed

Eleutherakis-Papaiakovou, Evangelos; Kostis, Evangelos; Migkou, Magda; Christoulas, Dimitrios; Terpos, Evangelos; Gavriatopoulou, Maria; Roussou, Maria; Bournakis, Evangelos; Kastritis, Efstathios; Efstathiou, Eleni; Dimopoulos, Meletios A; Papadimitriou, Christos A

2010-11-01

One hundred and fifty-seven patients undergoing high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) for hematopoietic malignancies and solid tumors were randomly assigned to receive (Group A) or not (Group B) prophylaxis with ciprofloxacin, orally, and vancomycin, intravenously. Prophylactic antibiotics were given from day 0 until resolution of neutropenia or the appearance of a febrile event. Furthermore, patients in both groups received once a day fluconazole, orally. The primary end-point of our study was the incidence of neutropenic febrile episodes attributed to infection. One hundred and twelve (71.3%) patients developed neutropenic fever, 50 (56.2%) in Group A and 62 (91.2%) in Group B (P < 0.001) with the majority (82%) of patients developing fever of unknown origin. Patients on prophylactic antibiotics had a significantly lower rate of bacteremias (5.6%) than did those randomized to no prophylaxis (29.4%) (P = 0.005) and, when developing neutropenic fever, they had a lower probability of response to first-line empirical antibiotics (P = 0.025). Prophylactic administration of ciprofloxacin and vancomycin reduced the incidence of neutropenic fever in patients receiving HDT with ASCT, however, without affecting the total interval of hospitalization, time to engraftment, or all-cause mortality. Therefore, our results do not support the use of antibiotic prophylaxis for patients undergoing HDT and ASCT. © 2010 Wiley-Liss, Inc.

FDA Approves First Immunotherapy for Lymphoma

Cancer.gov

The FDA has approved nivolumab (Opdivo®) for the treatment of patients with classical Hodgkin lymphoma whose disease has relapsed or worsened after receiving an autologous hematopoietic stem cell transplantation followed by brentuximab vedotin (Adcetris®)

Design modifications of the uncemented Furlong hip stem result in minor early subsidence but do not affect further stability: a randomized controlled RSA study with 5-year follow-up.

PubMed

Weber, Erik; Sundberg, Martin; Flivik, Gunnar

2014-12-01

Even small design modifications of uncemented hip stems may alter the postoperative 3-D migration pattern. The Furlong Active is an uncemented femoral stem which, in terms of design, is based on its precursor-the well-proven Furlong HAC-but has undergone several design changes. The collar has been removed on the Active stem along with the lateral fin; it is shorter and has more rounded edges in the proximal part. We compared the migration patterns of the uncemented Furlong HAC stem and the modified Furlong Active stem in a randomized, controlled trial over 5 years using radiostereometry (RSA). 50 patients with primary osteoarthritis were randomized to receive either the HAC stem or the Active stem. The patients underwent repeated RSA examinations (postoperatively, at 3 months, and after 1, 2, and 5 years) and conventional radiography, and they also filled out hip-specific questionnaires. During the first 3 months, the collarless Active stem subsided to a greater extent than the collar-fitted HAC stem (0.99 mm vs. 0.31 mm, p=0.05). There were, however, no other differences in movement measured by RSA or in clinical outcome between the 2 stems. After 3 months, both stem types had stabilized and almost no further migration was seen. The Active stem showed no signs of unfavorable migration. Our results suggest that the osseointegration is not compromised by the new design features.

Upfront allogeneic stem cell transplantation after reduced-intensity/nonmyeloablative conditioning for patients with myelodysplastic syndrome: a study by the Société Française de Greffe de Moelle et de Thérapie Cellulaire.

PubMed

Damaj, Gandhi; Mohty, Mohammad; Robin, Marie; Michallet, Mauricette; Chevallier, Patrice; Beguin, Yves; Nguyen, Stephanie; Bories, Pierre; Blaise, Didier; Maillard, Natacha; Rubio, Marie Therese; Fegueux, Nathalie; Cornillon, Jerome; Clavert, Aline; Huynh, Anne; Adès, Lionel; Thiébaut-Bertrand, Anne; Hermine, Olivier; Vigouroux, Stephane; Fenaux, Pierre; Duhamel, Alain; Yakoub-Agha, Ibrahim

2014-09-01

Cytoreduction before allogeneic stem cell transplantation (allo-SCT) for patients with myelodysplastic syndromes remains a debatable issue. After excluding patients who had received preconditioning induction chemotherapy, we analyzed 128 consecutive patients with myelodysplastic syndrome who received reduced-intensity or nonmyeloablative conditioning (RIC/NMA) allo-SCT. Among them, 40 received azacitidine (AZA) before transplant (AZA group) and 88 were transplanted up front (best supportive care [BSC] group). At diagnosis, 55 patients had intermediate 2 or high-risk scores per the International Prognostic Scoring System and 33 had a high cytogenetic risk score. Progression to a more advanced disease before allo-SCT was recorded in 22 patients. Source of stem cells were blood (n = 112) or marrow (n = 16) from sibling (n = 78) or HLA-matched unrelated (n = 50) donors. With a median follow-up of 60 months, 3-year overall survival, relapse-free survival, cumulative incidence of relapse, and nonrelapse mortality were, respectively, 53% versus 53% (P = .69), 37% versus 42% (P = .78), 35% versus 36% (P = .99), and 20% versus 23% (P = .74), for the AZA group and BSC group, respectively. Multivariate analysis confirmed the absence of statistical differences in outcome between the AZA and BSC groups, after adjusting for potential confounders using the propensity score approach. The absence of cytoreduction before RIC/NMA allo-SCT did not seem to alter the outcome. However, our results emphasize the need to perform prospective protocols to delineate the role of debulking strategy and to identify subsets of patients who may benefit from this approach. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Usefulness and safety of oral cryotherapy in the prevention of oral mucositis after conditioning regimens with high-dose melphalan for autologous stem cell transplantation for lymphoma and myeloma.

PubMed

Batlle, Montserrat; Morgades, Mireia; Vives, Susana; Ferrà, Christelle; Oriol, Albert; Sancho, Juan-Manuel; Xicoy, Blanca; Moreno, Miriam; Magallón, Laura; Ribera, Josep-Maria

2014-12-01

Oral mucositis (OM) is a common complication of conditioning regimens with high-dose melphalan (HDmel). This retrospective cohort study analyzes the impact of oral cryotherapy (OC) or room temperature saline rinses on the prevention of OM in patients with multiple myeloma (MM) or lymphoid neoplasias submitted to autologous stem cell transplantation (ASCT) in a single center. From August 2006 to July 2011, 134 consecutive patients were enrolled. Two consecutive groups were included: Non-OC (August 2006 to April 2009, 68 patients) and OC (May 2009 to July 2011, 66 cases). MM cases (78, 58%) received HDmel as the conditioning regimen and 56 patients (42%) with lymphoma received BEAM. The non-OC and OC groups were comparable for the main clinicobiologic features and type of neoplasia. OM was more frequent and severe in patients receiving BEAM as the conditioning therapy. The group of OC showed less frequent and less severe mucositis and fewer days on antibiotics. No differences were observed in the duration of OM, need for parenteral nutrition and narcotics, and the length of hospital stay on comparison with the OC and non-OC groups. By multivariate analyses, OC was an independent favorable prognostic factor for OM development. This study shows that OC is more effective than saline rinses in the prevention of OM in patients with lymphoma and myeloma receiving conditioning regimens with HDmel for ASCT. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A monoclonal expansion of Epstein-Barr virus-infected natural killer cells after allogeneic peripheral blood stem cell transplantation.

PubMed

Isobe, Yasushi; Hamano, Yasuharu; Ito, Yoshinori; Kimura, Hiroshi; Tsukada, Nobuhiro; Sugimoto, Koichi; Komatsu, Norio

2013-02-01

Here, we describe a Japanese woman showing a monoclonal expansion of EBV-infected natural killer (NK) cells after receiving allogeneic peripheral blood stem cell transplantation (PBSCT). The patient initially had T-cell-type chronic active EBV disease (CAEBV) and subsequently developed liver T-cell lymphoma. L-Asparaginase-containing chemotherapy led to a favorable lymphoma response. To eradicate CAEBV and the lymphoma, she further received allogeneic PBSCT from a human leukocyte antigen-matched sibling donor. After the PBSCT, the patient presented with transient lymphocytosis of NK cells, which were infected with a monoclonal EBV strain other than previously detected ones. These NK cells seemed to have been transmitted from the healthy donor to the recipient. The patient and donor remain well in spite of carrying these NK cells. This is the first report of an asymptomatic Japanese carrier harboring monoclonal EBV-infected NK cells. Copyright © 2012 Elsevier B.V. All rights reserved.

Outcomes of haploidentical stem cell transplantation for chronic lymphocytic leukemia: a retrospective study on behalf of the chronic malignancies working party of the EBMT.

PubMed

van Gorkom, Gwendolyn; van Gelder, Michel; Eikema, Dirk-Jan; Blok, Henric-Jan; van Lint, M T; Koc, Yener; Ciceri, Fabio; Beelen, Dietrich; Chevallier, Patrice; Selleslag, Dominik; Blaise, Didier; Foá, Roberto; Corradini, Paolo; Castagna, Luca; Moreno, Carol; Solano, Carlos; Müller, Lutz Peter; Tischer, Johanna; Hilgendorf, Inken; Hallek, Michael; Bittenbring, Jörg; Theobald, Matthias; Schetelig, Johannes; Kröger, Nicolaus

2018-03-01

Allogeneic hematopoietic stem cell transplantation (HCT) may result in long-term disease control in high-risk chronic lymphocytic leukemia (CLL). Recently, haploidentical HCT is gaining interest because of better outcomes with post-transplantation cyclophosphamide (PTCY). We analyzed patients with CLL who received an allogeneic HCT with a haploidentical donor and whose data were available in the EBMT registry. In total 117 patients (74% males) were included; 38% received PTCY as GVHD prophylaxis. For the whole study cohort OS at 2 and 5 yrs was 48 and 38%, respectively. PFS at 2 and 5 yrs was 38 and 31%, respectively. Cumulative incidence (CI) of NRM in the whole group at 2 and 5 years were 40 and 44%, respectively. CI of relapse at 2 and 5 yrs were 22 and 26%, respectively. All outcomes were not statistically different in patients who received PTCY compared to other types of GVHD prophylaxis. In conclusion, results of haploidentical HCT in CLL seem almost identical to those with HLA-matched donors. Thereby, haploidentical HCT is an appropriate alternative in high risk CLL patients with a transplant indication but no available HLA-matched donor. Despite the use of PTCY, the CI of relapse seems not higher than observed after HLA-matched HCT.

Prophylactic defibrotide in allogeneic stem cell transplantation: minimal morbidity and zero mortality from veno-occlusive disease.

PubMed

Dignan, F; Gujral, D; Ethell, M; Evans, S; Treleaven, J; Morgan, G; Potter, M

2007-07-01

Veno-occlusive disease (VOD) is a common and high-risk complication of allogeneic stem cell transplantation (SCT). Defibrotide has recently been used successfully to treat the disorder. We report on 58 patients who received defibrotide prophylaxis without concurrent heparin. No patients fulfilled the Baltimore criteria for VOD or died of the condition within 100 days of SCT. None of this group developed haemorrhagic complications secondary to defibrotide. These observations suggest that prophylaxis with defibrotide alone may reduce the incidence of VOD post-SCT although a randomised controlled trial is warranted to further evaluate its role.

Severe Hepatic Sinusoidal Obstruction Syndrome in a Child Receiving Vincristine, Actinomycin-D, and Cyclophosphamide for Rhabdomyosarcoma: Successful Treatment with Defibrotide.

PubMed

Choi, Aery; Kang, Young Kyung; Lim, Sewon; Kim, Dong Ho; Lim, Jung Sub; Lee, Jun Ah

2016-10-01

Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening syndrome that generally occurs as a complication after hematopoietic stem cell transplantation or, less commonly, after conventional chemotherapy. Regarding SOS in rhabdomyosarcoma patients who received conventional chemotherapy, the doses of chemotherapeutic agents are associated with the development of SOS. Several cases of SOS in rhabdomyosarcoma patients after receiving chemotherapy with escalated doses of cyclophosphamide have been reported. Here, we report on a 9-year-old female with rhabdomyosarcoma who developed severe SOS after receiving chemotherapy consisting of vincristine, actinomycin-D, and a moderate dose of cyclophosphamide. She was treated successfully with defibrotide without sequelae to the liver.

Insulin-secreting adipose-derived mesenchymal stromal cells with bone marrow-derived hematopoietic stem cells from autologous and allogenic sources for type 1 diabetes mellitus.

PubMed

Thakkar, Umang G; Trivedi, Hargovind L; Vanikar, Aruna V; Dave, Shruti D

2015-07-01

Stem cell therapy (SCT) is now the up-coming therapeutic modality for treatment of type 1 diabetes mellitus (T1DM). Our study was a prospective, open-labeled, two-armed trial for 10 T1DM patients in each arm of allogenic and autologous adipose-derived insulin-secreting mesenchymal stromal cells (IS-AD-MSC)+bone marrow-derived hematopoietic stem cell (BM-HSC) infusion. Group 1 received autologous SCT: nine male patients and one female patient; mean age, 20.2 years, disease duration 8.1 years; group 2 received allogenic SCT: six male patients and four female patients, mean age, 19.7 years and disease duration, 7.9 years. Glycosylated hemoglobin (HbA1c) was 10.99%; serum (S.) C-peptide, 0.22 ng/mL and insulin requirement, 63.9 IU/day in group 1; HbA1c was 11.93%, S.C-peptide, 0.028 ng/mL and insulin requirement, 57.55 IU/day in group 2. SCs were infused into the portal+thymic circulation and subcutaneous tissue under non-myelo-ablative conditioning. Patients were monitored for blood sugar, S.C-peptide, glutamic acid decarboxylase antibodies and HbA1c at 3-month intervals. Group 1 received mean SCs 103.14 mL with 2.65 ± 0.8 × 10(4) ISCs/kg body wt, CD34+ 0.81% and CD45-/90+/73+, 81.55%. Group 2 received mean SCs 95.33 mL with 2.07 ± 0.67 × 10(4) ISCs/kg body wt, CD34+ 0.32% and CD45-/90+/73+ 54.04%. No untoward effect was observed with sustained improvement in HbA1c and S.C-peptide in both groups with a decrease in glutamic acid decarboxylase antibodies and reduction in mean insulin requirement. SCT is a safe and viable treatment option for T1DM. Autologous IS-AD-MSC+ BM-HSC co-infusion offers better long-term control of hyperglycemia as compared with allogenic SCT. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Granulocyte Colony Stimulating Factor and Physiotherapy after Stroke: Results of a Feasibility Randomised Controlled Trial: Stem Cell Trial of Recovery EnhanceMent after Stroke-3 (STEMS-3 ISRCTN16714730)

PubMed Central

Sprigg, Nikola; O’Connor, Rebecca; Woodhouse, Lisa; Krishnan, Kailash; England, Timothy J.; Connell, Louise A.; Walker, Marion F.; Bath, Philip M.

2016-01-01

Background Granulocyte-colony stimulating factor (G-CSF) mobilises endogenous haematopoietic stem cells and enhances recovery in experimental stroke. Recovery may also be dependent on an enriched environment and physical activity. G-CSF may have the potential to enhance recovery when used in combination with physiotherapy, in patients with disability late after stroke. Methods A pilot 2 x 2 factorial randomised (1:1) placebo-controlled trial of G-CSF (double-blind), and/or a 6 week course of physiotherapy, in 60 participants with disability (mRS >1), at least 3 months after stroke. Primary outcome was feasibility, acceptability and tolerability. Secondary outcomes included death, dependency, motor function and quality of life measured 90 and 365 days after enrolment. Results Recruitment to the trial was feasible and acceptable; of 118 screened patients, 92 were eligible and 32 declined to participate. 60 patients were recruited between November 2011 and July 2013. All participants received some allocated treatment. Although 29 out of 30 participants received all 5 G-CSF/placebo injections, only 7 of 30 participants received all 18 therapy sessions. G-CSF was well tolerated but associated with a tendency to more adverse events than placebo (16 vs 10 patients, p = 0.12) and serious adverse events (SAE) (9 vs 3, p = 0.10). On average, patients received 14 (out of 18 planned) therapy sessions, interquartile range [12, 17]. Only a minority (23%) of participants completed all physiotherapy sessions, a large proportion of sessions (114 of 540, 21%) were cancelled due to patient (94, 17%) and therapist factors (20, 4%). No significant differences in functional outcomes were detected in either the G-CSF or physiotherapy group at day 90 or 365. Conclusions Delivery of G-CSF is feasible in chronic stroke. However, the study failed to demonstrate feasibility for delivering additional physiotherapy sessions late after stroke therefore a definitive study using this trial design is not supported. Future work should occur earlier after stroke, alongside on-going clinical rehabilitation. Trial Registration ISRCTN.com ISRCTN16714730 PMID:27610616

Critical care of the hematopoietic stem cell transplant recipient.

PubMed

Afessa, Bekele; Azoulay, Elie

2010-01-01

An estimated 50,000 to 60,000 patients undergo hematopoietic stem cell transplantation (HSCT) worldwide annually, of which 15.7% are admitted to the intensive care unit (ICU). The most common reason for ICU admission is respiratory failure and almost all develop single or multiorgan failure. Most HSCT recipients admitted to ICU receive invasive mechanical ventilation (MV). The overall short-term mortality rate of HSCT recipients admitted to ICU is 65%, and 86.4% for those receiving MV. Patient outcome has improved over time. Poor prognostic indicators include advanced age, poor functional status, active disease at transplant, allogeneic transplant, the severity of acute illness, and the development of multiorgan failure. ICU resource limitations often lead to triage decisions for admission. For HSCT recipients, the authors recommend (1) ICU admission for full support during their pre-engraftment period and when there is no evidence of disease recurrence; (2) no ICU admission for patients who refuse it and those who are bedridden with disease recurrence and without treatment options except palliation; (3) a trial ICU admission for patients with unknown status of disease recurrence with available treatment options.

Efficacy, safety and feasibility of antifungal prophylaxis with posaconazole tablet in paediatric patients after haematopoietic stem cell transplantation.

PubMed

Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Queudeville, Manon; Feucht, Judith; Blaeschke, Franziska; Schlegel, Patrick; Feuchtinger, Tobias; Lang, Peter; Müller, Ingo; Handgretinger, Rupert; Heinz, Werner J

2017-07-01

Paediatric recipients of haematopoietic stem cell transplantation (HSCT) have a high risk for invasive fungal infections. Posaconazole oral suspension has proven to be effective in antifungal prophylaxis in adult and paediatric patients. A new posaconazole tablet formulation with absorption independent of the gastric conditions was approved by the FDA in 2013. This is the first report on the use of posaconazole tablets in paediatric patients. This single-centre study included 63 paediatric patients with haemato-oncological malignancies who received posaconazole for antifungal prophylaxis after HSCT. They were analysed for efficacy, feasibility and the safety of posaconazole. Out of 63 patients, 31 received posaconazole oral suspension and 32 received posaconazole tablets up to 200 days after transplantation. Analyses of the posaconazole trough levels were determined. No possible, probable or proven invasive fungal infection was observed in either group. Posaconazole trough levels were significantly higher in the tablet group than in the suspension group at all analysed time points. Drug-related adverse events were similarly low in both groups. Posaconazole tablets are effective in preventing invasive fungal infections in paediatric patients. As early as day 3 after starting posaconazole tablets, over 50% of the posaconazole trough levels were >500 ng/mL, while this was observed on day 14 after start with posaconazole suspension. The administration of posaconazole tablets was safe, effective and feasible as antifungal prophylaxis in paediatric patients after HSCT.

[Allogenic hematopoietic stem cell transplantation with unrelated cord blood: report of three cases from the Chilean cord blood bank].

PubMed

Barriga, Francisco; Wietstruck, Angélica; Rojas, Nicolás; Bertin, Pablo; Pizarro, Isabel; Carmona, Amanda; Guilof, Alejandro; Rojas, Iván; Oyarzún, Enrique

2013-08-01

Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

Hematopoietic Stem-Cell Transplantation for Advanced Systemic Mastocytosis

PubMed Central

Ustun, Celalettin; Reiter, Andreas; Scott, Bart L.; Nakamura, Ryotaro; Damaj, Gandhi; Kreil, Sebastian; Shanley, Ryan; Hogan, William J.; Perales, Miguel-Angel; Shore, Tsiporah; Baurmann, Herrad; Stuart, Robert; Gruhn, Bernd; Doubek, Michael; Hsu, Jack W.; Tholouli, Eleni; Gromke, Tanja; Godley, Lucy A.; Pagano, Livio; Gilman, Andrew; Wagner, Eva Maria; Shwayder, Tor; Bornhäuser, Martin; Papadopoulos, Esperanza B.; Böhm, Alexandra; Vercellotti, Gregory; Van Lint, Maria Teresa; Schmid, Christoph; Rabitsch, Werner; Pullarkat, Vinod; Legrand, Faezeh; Yakoub-agha, Ibrahim; Saber, Wael; Barrett, John; Hermine, Olivier; Hagglund, Hans; Sperr, Wolfgang R.; Popat, Uday; Alyea, Edwin P.; Devine, Steven; Deeg, H. Joachim; Weisdorf, Daniel; Akin, Cem; Valent, Peter

2014-01-01

Purpose Advanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown. Patients and Methods In a global effort to define the value of HCT in SM, 57 patients with the following subtypes of SM were evaluated: SM associated with clonal hematologic non–mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia (MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of patients was 46 years (range, 11 to 67 years). Donors were HLA-identical (n = 34), unrelated (n = 17), umbilical cord blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3). Thirty-six patients received myeloablative conditioning (MAC), and 21 patients received reduced-intensity conditioning (RIC). Results Responses in SM were observed in 40 patients (70%), with complete remission in 16 patients (28%). Twelve patients (21%) had stable disease, and five patients (9%) had primary refractory disease. Overall survival (OS) at 3 years was 57% for all patients, 74% for patients with SM-AHNMD, 43% for those with ASM, and 17% for those with MCL. The strongest risk factor for poor OS was MCL. Survival was also lower in patients receiving RIC compared with MAC and in patients having progression compared with patients having stable disease or response. Conclusion AlloHCT was associated with long-term survival in patients with advanced SM. Although alloHCT may be considered as a viable and potentially curative therapeutic option for advanced SM in the meantime, given that this is a retrospective analysis with no control group, the definitive role of alloHCT will need to be determined by a prospective trial. PMID:25154823

Music Therapy for Symptom Management After Autologous Stem Cell Transplantation: Results From a Randomized Study.

PubMed

Bates, Debbie; Bolwell, Brian; Majhail, Navneet S; Rybicki, Lisa; Yurch, Melissa; Abounader, Donna; Kohuth, Joseph; Jarancik, Shannon; Koniarczyk, Heather; McLellan, Linda; Dabney, Jane; Lawrence, Christine; Gallagher, Lisa; Kalaycio, Matt; Sobecks, Ronald; Dean, Robert; Hill, Brian; Pohlman, Brad; Hamilton, Betty K; Gerds, Aaron T; Jagadeesh, Deepa; Liu, Hien D

2017-09-01

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is frequently performed in patients with hematologic malignancies. ASCT can result in significant nausea, pain, and discomfort. Supportive care has improved, and pharmacologic therapies are frequently used, but with limitations. Music has been demonstrated to improve nausea and pain in patients undergoing chemotherapy, but little data are available regarding the effects of music therapy in the transplantation setting. In a prospective study, patients with lymphoma or multiple myeloma undergoing ASCT were randomized to receive either interactive music therapy with a board-certified music therapist or no music therapy. The music therapy arm received 2 music therapy sessions on days +1 and +5. Primary outcomes were perception of pain and nausea measured on a visual analog scale. Secondary outcomes were narcotic pain medication use from day -1 to day +5 and impact of ASCT on patient mood as assessed by Profile of Mood States (POMS) on day +5. Eighty-two patients were enrolled, with 37 in the music therapy arm and 45 in the no music therapy arm. Patients who received MT had slightly increased nausea by day +7 compared with the no music therapy patients. The music therapy and no music therapy patients had similar pain scores; however, the patients who received music therapy used significantly less narcotic pain medication (median, 24 mg versus 73 mg; P = .038). Music therapy may be a viable nonpharmacologic method of pain management for patients undergoing ASCT; the music therapy patients required significantly fewer morphine equivalent doses compared with the no music therapy patients. Additional research is needed to better understand the effects of music therapy on patient-perceived symptoms, such as pain and nausea. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Treatment With Bortezomib-based Therapy, Followed by Autologous Stem Cell Transplantation, Improves Outcomes in Light Chain Amyloidosis: A Retrospective Study.

PubMed

Jain, Tania; Kosiorek, Heidi E; Kung, Shu T; Shah, Vishal S; Dueck, Amylou C; Gonzalez-Calle, Veronica; Luft, Susan; Reeder, Craig B; Adams, Roberta; Noel, Pierre; Larsen, Jeremy T; Mikhael, Joseph; Bergsagel, Leif; Stewart, A Keith; Fonseca, Rafael

2018-05-04

The hematologic response is critical in patients with light chain amyloidosis because a good response is known to improve organ response and overall survival. We present a retrospective analysis to compare the hematologic and organ response in patients who received bortezomib-based therapy before autologous stem cell transplantation (ASCT) versus those who received non-bortezomib-based therapy before ASCT and those who underwent ASCT at diagnosis. Of a total of 63 patients who underwent ASCT for light chain amyloidosis, 34 received bortezomib-based therapy before ASCT (Bor-ASCT) and 29 did not receive bortezomib therapy (non-Bor-ASCT). A greater number of patients had involvement of ≥ 3 organs and cardiac involvement in the Bor-ASCT group, suggesting a greater risk at baseline in the Bor-ASCT group. At 3, 6, and 12 months after ASCT, the hematologic response was better in the Bor-ASCT group, with a statistically significance difference at 6 months (partial response or better in 82% vs. 20%; P = .002) and 12 months (partial response or better in 76% vs. 33%; P = .02). Organ responses (66% vs. 21%; P < .001) and median overall survival (not reached vs. 53 months; P = .001) were also greater in the Bor-ASCT group. Our study has shown that bortezomib-based therapy before ASCT improves the hematologic response, organ response and overall survival, potentially by decreasing the light chain load before ASCT. Copyright © 2018 Elsevier Inc. All rights reserved.

Analysis of risk factors for post-operative complications and prognostic predictors of disease recurrence following definitive treatment of patients with esophageal cancer from two medical centers in Northwest China

PubMed Central

Wang, Jichang; Zhang, Boxiang; Meng, Jinying; Xiao, Guodong; Li, Xiang; Li, Gang; Qin, Sida; Du, Ning; Zhang, Jia; Zhang, Jing; Xu, Chongwen; Tang, Shou-Ching; Liang, Rui; Ren, Hong; Sun, Xin

2017-01-01

Evaluating the clinicopathological features of patients receiving definitive treatment for esophageal cancer may facilitate the identification of patterns and factors associated with post-operative complications, and enable the development of a surveillance strategy for surviving patients at a higher risk of disease recurrence. In the present study, clinical data from 579 patients with esophageal cancer that underwent radical resection of esophagus were collected. These patients were admitted to two medical centers in Northwest China, and information regarding the presence or absence of basic chronic diseases and post-operative results were retrospectively analyzed. The level of selected stem cell markers, including aldehyde dehydrogenase 1, CD133, integrin subunit α 6, integrin subunit β 4 and T-cell factor-4, were determined in esophageal cancer tissue samples in order to determine whether these markers may be useful predictors of disease prognosis and recurrence. Post-operative complications in patients receiving radical resection of the esophagus included respiratory system complications, cardiovascular abnormalities and esophageal anastomotic fistulae. Diabetes, basic respiratory disease and lower pre-surgical serum albumin levels were observed to be individual risk factors associated with post-operative complications, including respiratory system complications of acute respiratory failure and pulmonary infection, cardiovascular abnormalities of atrial fibrillation and arrhythmia, as well as the development of esophageal anastomotic fistulae. Diagnosis of esophageal cancer at later stage was significantly correlated with anastomotic fistula. Molecular detection of stem cell markers for prognosis prediction was achieved by immunohistochemical and immunofluorescence staining assays. The results demonstrated that the presence of stem-like cells in cancer tissues was associated with poor disease prognosis and a high recurrence ratio. In conclusion, the results of the current study suggested that post-operative complications were more likely to occur in patients with diabetes, basic respiratory disease or lower serum albumin levels prior to surgery. Therefore, sufficient intensive peri-operative care, rigorous operative risk assessments, and the selection of the patients with early or mid-stage esophageal cancer, may decrease the risk of post-surgical complications in patients receiving radical resection of the esophagus. In addition, a high ratio of esophageal cancer stem-like cells was associated with cancer recurrence. These results suggest that an intensive surveillance strategy should be implemented in order to facilitate early detection of disease recurrence and improve the clinical management of these patients post-surgery. PMID:28962198

Stem cell collection in unmanipulated HLA-haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised blood and bone marrow for patients with haematologic malignancies: the impact of donor characteristics and procedural settings.

PubMed

Zhang, C; Chen, X-H; Zhang, X; Gao, L; Gao, L; Kong, P-Y; Peng, X-G; Sun, A-H; Gong, Y; Zeng, D-F; Wang, Q-Y

2010-06-01

Unmanipulated haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised peripheral blood stem cells (G-PBSCs) and granulocyte-colony stimulating factor-mobilised bone marrow (G-BM) has been developed as an alternative transplantation strategy for patients with haematologic malignancies. However, little information is available about the factors predicting the outcome of peripheral blood stem cell (PBSC) collection and bone marrow (BM) harvest in this transplantation. The effects of donor characteristics and procedure factors on CD34(+) cell yield were investigated. A total of 104 related healthy donors received granulocyte-colony stimulating factor (G-CSF) followed by PBSC collection and BM harvest. Male donors had significantly higher yields compared with female donors. In multiple regression analysis for peripheral blood collection, age and flow rate were negatively correlated with cell yield, whereas body mass index, pre-aphaeresis white blood cell (WBC) and circulating immature cell (CIC) counts were positively correlated with cell yields. For BM harvest, age was negatively correlated with cell yields, whereas pre-BM collection CIC counts were positively correlated with cell yield. All donors achieved the final product of >or=6 x10(6) kg(-1) recipient body weight. This transplantation strategy has been shown to be a feasible approach with acceptable outcomes in stem cell collection for patients who received HLA-haploidentical/mismatched transplantation with combined G-PBSCs and G-BM. In donors with multiple high-risk characteristics for poor aphaeresis CD34(+) cell yield, BM was an alternative source.

Transplantation of spinal cord-derived neural stem cells for ALS: Analysis of phase 1 and 2 trials.

PubMed

Glass, Jonathan D; Hertzberg, Vicki S; Boulis, Nicholas M; Riley, Jonathan; Federici, Thais; Polak, Meraida; Bordeau, Jane; Fournier, Christina; Johe, Karl; Hazel, Tom; Cudkowicz, Merit; Atassi, Nazem; Borges, Lawrence F; Rutkove, Seward B; Duell, Jayna; Patil, Parag G; Goutman, Stephen A; Feldman, Eva L

2016-07-26

To test the safety of spinal cord transplantation of human stem cells in patients with amyotrophic lateral sclerosis (ALS) with escalating doses and expansion of the trial to multiple clinical centers. This open-label trial included 15 participants at 3 academic centers divided into 5 treatment groups receiving increasing doses of stem cells by increasing numbers of cells/injection and increasing numbers of injections. All participants received bilateral injections into the cervical spinal cord (C3-C5). The final group received injections into both the lumbar (L2-L4) and cervical cord through 2 separate surgical procedures. Participants were assessed for adverse events and progression of disease, as measured by the ALS Functional Rating Scale-Revised, forced vital capacity, and quantitative measures of strength. Statistical analysis focused on the slopes of decline of these phase 2 trial participants alone or in combination with the phase 1 participants (previously reported), comparing these groups to 3 separate historical control groups. Adverse events were mostly related to transient pain associated with surgery and to side effects of immunosuppressant medications. There was one incident of acute postoperative deterioration in neurologic function and another incident of a central pain syndrome. We could not discern differences in surgical outcomes between surgeons. Comparisons of the slopes of decline with the 3 separate historical control groups showed no differences in mean rates of progression. Intraspinal transplantation of human spinal cord-derived neural stem cells can be safely accomplished at high doses, including successive lumbar and cervical procedures. The procedure can be expanded safely to multiple surgical centers. This study provides Class IV evidence that for patients with ALS, spinal cord transplantation of human stem cells can be safely accomplished and does not accelerate the progression of the disease. This study lacks the precision to exclude important benefit or safety issues. © 2016 American Academy of Neurology.

Liver fibrosis alleviation after co-transplantation of hematopoietic stem cells with mesenchymal stem cells in patients with thalassemia major.

PubMed

Ghavamzadeh, Ardeshir; Sotoudeh, Masoud; Hashemi Taheri, Amir Pejman; Alimoghaddam, Kamran; Pashaiefar, Hossein; Jalili, Mahdi; Shahi, Farhad; Jahani, Mohammad; Yaghmaie, Marjan

2018-02-01

The aims of this study are to determine the replacement rate of damaged hepatocytes by donor-derived cells in sex-mismatched recipient patients with thalassemia major and to determine whether co-transplantation of mesenchymal stem cells and hematopoietic stem cells (HSCs) can alleviate liver fibrosis. Ten sex-mismatched donor-recipient pairs who received co-transplantation of HSCs with mesenchymal stem cells were included in our study. Liver biopsy was performed before transplantation. Two other liver biopsies were performed between 2 and 5 years after transplantation. The specimens were studied for the presence of donor-derived epithelial cells or hepatocytes using fluorescence in situ hybridization by X- and Y-centromeric probes and immunohistochemical staining for pancytokeratin, CD45, and a hepatocyte-specific antigen. All sex-mismatched tissue samples demonstrated donor-derived hepatocyte independent of donor gender. XY-positive epithelial cells or hepatocytes accounted for 11 to 25% of the cells in histologic sections of female recipients in the first follow-up. It rose to 47-95% in the second follow-up. Although not statistically significant, four out of ten patients showed signs of improvement in liver fibrosis. Our results showed that co-transplantation of HSC with mesenchymal stem cells increases the rate of replacement of recipient hepatocytes by donor-derived cells and may improve liver fibrosis.

Umbilical cord mesenchymal stem cell (UC-MSC) transplantations for cerebral palsy

PubMed Central

Dong, Huajiang; Li, Gang; Shang, Chongzhi; Yin, Huijuan; Luo, Yuechen; Meng, Huipeng; Li, Xiaohong; Wang, Yali; Lin, Ling; Zhao, Mingliang

2018-01-01

This study reports a case of a 4-year-old boy patient with abnormalities of muscle tone, movement and motor skills, as well as unstable gait leading to frequent falls. The results of the electroencephalogram (EEG) indicate moderately abnormal EEG, accompanied by irregular seizures. Based on these clinical characteristics, the patient was diagnosed with cerebral palsy (CP) in our hospital. In this study, the patient was treated with umbilical cord mesenchymal stem cell (UC-MSC) transplantation therapy. This patient received UC-MSC transplantation 3 times (5.3*107) in total. After three successive cell transplantations, the patient recovered well and showed obvious improvements in EEG and limb strength, motor function, and language expression. However, the improvement in intelligence quotient (IQ) was less obvious. These results indicate that UC-MSC transplantation is a promising treatment for cerebral palsy. PMID:29636880

Survival and Neurocognitive Outcomes After Cranial or Craniospinal Irradiation Plus Total-Body Irradiation Before Stem Cell Transplantation in Pediatric Leukemia Patients With Central Nervous System Involvement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hiniker, Susan M.; Agarwal, Rajni; Modlin, Leslie A.

Purpose: To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen. Methods and Materials: Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methodsmore » with outcomes. Results: All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college. Conclusion: The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy of further protocol investigation in children with CNS leukemia.« less

Severe Hepatic Sinusoidal Obstruction Syndrome in a Child Receiving Vincristine, Actinomycin-D, and Cyclophosphamide for Rhabdomyosarcoma: Successful Treatment with Defibrotide

PubMed Central

Choi, Aery; Kang, Young Kyung; Lim, Sewon; Kim, Dong Ho; Lim, Jung Sub; Lee, Jun Ah

2016-01-01

Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening syndrome that generally occurs as a complication after hematopoietic stem cell transplantation or, less commonly, after conventional chemotherapy. Regarding SOS in rhabdomyosarcoma patients who received conventional chemotherapy, the doses of chemotherapeutic agents are associated with the development of SOS. Several cases of SOS in rhabdomyosarcoma patients after receiving chemotherapy with escalated doses of cyclophosphamide have been reported. Here, we report on a 9-year-old female with rhabdomyosarcoma who developed severe SOS after receiving chemotherapy consisting of vincristine, actinomycin-D, and a moderate dose of cyclophosphamide. She was treated successfully with defibrotide without sequelae to the liver. PMID:27034141

Hodgkin Lymphoma: Diagnosis and Treatment.

PubMed

Ansell, Stephen M

2015-11-01

Hodgkin lymphoma is a rare B-cell malignant neoplasm affecting approximately 9000 new patients annually. This disease represents approximately 11% of all lymphomas seen in the United States and comprises 2 discrete disease entities--classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Within the subcategorization of classical Hodgkin lymphoma are defined subgroups: nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich Hodgkin lymphoma. Staging of this disease is essential for the choice of optimal therapy. Prognostic models to identify patients at high or low risk for recurrence have been developed, and these models, along with positron emission tomography, are used to provide optimal therapy. The initial treatment for patients with Hodgkin lymphoma is based on the histologic characteristics of the disease, the stage at presentation, and the presence or absence of prognostic factors associated with poor outcome. Patients with early-stage Hodgkin lymphoma commonly receive combined-modality therapies that include abbreviated courses of chemotherapy followed by involved-field radiation treatment. In contrast, patients with advanced-stage Hodgkin lymphoma commonly receive a more prolonged course of combination chemotherapy, with radiation therapy used only in selected cases. For patients with relapse or refractory disease, salvage chemotherapy followed by high-dose treatment and an autologous stem cell transplant is the standard of care. For patients who are ineligible for this therapy or those in whom high-dose therapy and autologous stem cell transplant have failed, treatment with brentuximab vedotin is a standard approach. Additional options include palliative chemotherapy, immune checkpoint inhibitors, nonmyeloablative allogeneic stem cell transplant, or participation in a clinical trial testing novel agents. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

The natural history and treatment outcome of blast phase BCR-ABL− myeloproliferative neoplasms

PubMed Central

Tam, Constantine S.; Nussenzveig, Roberto M.; Popat, Uday; Bueso-Ramos, Carlos E.; Thomas, Deborah A.; Cortes, Jorge A.; Champlin, Richard E.; Ciurea, Stefan E.; Manshouri, Taghi; Pierce, Sherry M.; Kantarjian, Hagop M.

2008-01-01

We analyzed the outcomes of 74 patients diagnosed with BCR-ABL− myeloproliferative neoplasms in blast phase receiving induction chemotherapy (55%), low-intensity therapy (16%), stem cell transplantation (SCT; 3%), or supportive care (26%). Median survival from the date of blastic transformation was 5 months. Patients receiving supportive therapy had a median survival of 6 weeks. Complete remission with or without blood recovery was achieved in 46% of patients receiving induction chemotherapy, but remissions were not durable with a median progression-free survival of only 5 months. Eight patients received SCT either as first therapy or after responding to antileukemia therapy. These patients had a markedly superior survival, with 73% alive at a median follow-up of 31 months. JAK2V617F kinetics were assessed in 16 patients: 0 of 4 negative patients became positive at transformation, and among 12 positive patients, 1 had an increase in JAK2V617F% at transformation, 7 had a substantial decrease, and 4 had stable levels. Myeloproliferative neoplasm blast phase is associated with a dismal prognosis. Responses to chemotherapy can be achieved but are not durable. Long-term survivors had all received SCT either as first therapy or in first remission. PMID:18566326

Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation.

PubMed

Kochenderfer, James N; Dudley, Mark E; Carpenter, Robert O; Kassim, Sadik H; Rose, Jeremy J; Telford, William G; Hakim, Frances T; Halverson, David C; Fowler, Daniel H; Hardy, Nancy M; Mato, Anthony R; Hickstein, Dennis D; Gea-Banacloche, Juan C; Pavletic, Steven Z; Sportes, Claude; Maric, Irina; Feldman, Steven A; Hansen, Brenna G; Wilder, Jennifer S; Blacklock-Schuver, Bazetta; Jena, Bipulendu; Bishop, Michael R; Gress, Ronald E; Rosenberg, Steven A

2013-12-12

New treatments are needed for B-cell malignancies persisting after allogeneic hematopoietic stem cell transplantation (alloHSCT). We conducted a clinical trial of allogeneic T cells genetically modified to express a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19. T cells for genetic modification were obtained from each patient's alloHSCT donor. All patients had malignancy that persisted after alloHSCT and standard donor lymphocyte infusions (DLIs). Patients did not receive chemotherapy prior to the CAR T-cell infusions and were not lymphocyte depleted at the time of the infusions. The 10 treated patients received a single infusion of allogeneic anti-CD19-CAR T cells. Three patients had regressions of their malignancies. One patient with chronic lymphocytic leukemia (CLL) obtained an ongoing complete remission after treatment with allogeneic anti-CD19-CAR T cells, another CLL patient had tumor lysis syndrome as his leukemia dramatically regressed, and a patient with mantle cell lymphoma obtained an ongoing partial remission. None of the 10 patients developed graft-versus-host disease (GVHD). Toxicities included transient hypotension and fever. We detected cells containing the anti-CD19-CAR gene in the blood of 8 of 10 patients. These results show for the first time that donor-derived allogeneic anti-CD19-CAR T cells can cause regression of B-cell malignancies resistant to standard DLIs without causing GVHD.

High Dose Cyclophosphamide without Stem Cell Rescue in 207 Patients with Aplastic anemia and other Autoimmune Diseases

PubMed Central

DeZern, Amy E.; Petri, Michelle; Drachman, Daniel B.; Kerr, Doug; Hammond, Edward R.; Kowalski, Jeanne; Tsai, Hua-Ling; Loeb, David M.; Anhalt, Grant; Wigley, Fredrick; Jones, Richard J.; Brodsky, Robert A.

2011-01-01

High-dose cyclophosphamide has long been used an anticancer agent, a conditioning regimen for hematopoietic stem cell transplantation and as potent immunosuppressive agent in autoimmune diseases including aplastic anemia. High-dose cyclophosphamide is highly toxic to lymphocytes but spares hematopoietic stem cells because of their abundant levels of aldehyde dehydrogenase, the major mechanism of cyclophosphamide inactivation. High dose cyclophosphamide therapy induces durable remissions in most patients with acquired aplastic anemia. Moreover, high-dose cyclophosphamide without hematopoietic stem cell rescue has shown activity in a variety of other severe autoimmune diseases. Here we review the history of cyclophosphamide as is applies to aplastic anemia (AA) and other autoimmune diseases. Included here are the historical data from early patients treated for AA as well as an observational retrospective study in a single tertiary care hospital. This latter component was designed to assess the safety and efficacy of high-dose cyclophosphamide therapy without stem cell rescue in patients with refractory autoimmune diseases. We analyzed fully the 140 patients with severe, progressive autoimmune diseases treated. All patients discussed here received cyclophosphamide, 50 mg/kg per day for 4 consecutive days. Response, relapse and overall survival were measured. Response was defined as a decrease in disease activity in conjunction with a decrease or elimination of immune modulating drugs. Relapse was defined as worsening disease activity and/or a requirement of an increase in dose of, or administration of new, immunosuppressive medications. Hematologic recovery occurred in all patients. The overall response rate of the was 95%, and 44% of those patients remain progression-free with a median follow up time of 36 (range 1–120) months for the 140 patients analyzed together. The overall actuarial and event free survival across all diseases at 60 months is 90.7% and 20.6%, respectively. High- dose cyclophosphamide without stem cell rescue is well-tolerated and induces a high rate of remissions in severe autoimmune diseases. PMID:21358440

Umbilical Cord Mesenchymal Stem Cell Treatment for Crohn’s Disease: A Randomized Controlled Clinical Trial

PubMed Central

Zhang, Jian; Lv, Samei; Liu, Xiaojing; Song, Bin; Shi, Liping

2018-01-01

Background/Aims Stem cell therapy has been applied to treat a variety of autoimmune diseases, including Crohn’s disease (CD), but few studies have examined the use of umbilical cord mesenchymal stem cells (UC-MSCs). This trial sought to investigate the efficacy and safety of UC-MSCs for the treatment of CD. Methods Eighty-two patients who had been diagnosed with CD and had received steroid maintenance therapy for more than 6 months were included in this study. Forty-one patients were randomly selected to receive a total of four peripheral intravenous infusions of 1×106 UC-MSCs/kg, with one infusion per week. Patients were followed up for 12 months. The Crohn’s disease activity index (CDAI), Harvey-Bradshaw index (HBI), and corticosteroid dosage were assessed. Results Twelve months after treatment, the CDAI, HBI, and corticosteroid dosage had decreased by 62.5±23.2, 3.4±1.2, and 4.2±0.84 mg/day, respectively, in the UC-MSC group and by 23.6±12.4, 1.2±0.58, and 1.2±0.35 mg/day, respectively, in the control group (p<0.01, p<0.05, and p<0.05 for UC-MSC vs control, respectively). Four patients developed a fever after cell infusion. No serious adverse events were observed. Conclusions UC-MSCs were effective in the treatment of CD and produced mild side effects. PMID:28873511

Intra-discal injection of autologous, hypoxic cultured bone marrow-derived mesenchymal stem cells in five patients with chronic lower back pain: a long-term safety and feasibility study.

PubMed

Elabd, Christian; Centeno, Christopher J; Schultz, John R; Lutz, Gregory; Ichim, Thomas; Silva, Francisco J

2016-09-01

Chronic low back pain due to disc degeneration represents a major social and economic burden worldwide. The current standard of care is limited to symptomatic relief and no current approved therapy promotes disc regeneration. Bone marrow-derived mesenchymal stem cells (MSCs) are easily accessible and well characterized. These MSCs are multipotent and exhibit great tissue regenerative potential including bone, cartilage, and fibrous tissue regeneration. The use of this cell-based biologic for treating protruding disc herniation and/or intervertebral disc degeneration is a promising therapeutic strategy, due to their known regenerative, immuno-modulatory and anti-inflammatory properties. Five patients diagnosed with degenerative disc disease received an intra-discal injection of autologous, hypoxic cultured, bone marrow-derived mesenchymal stem cells (15.1-51.6 million cells) as part of a previous study. These patients were re-consented to participate in this study in order to assess long-term safety and feasibility of intra-discal injection of autologous, hypoxic cultured, bone marrow-derived mesenchymal stem cells 4-6 years post mesenchymal stem cell infusion. The follow-up study consisted of a physical examination, a low back MRI, and a quality of life questionnaire. Patients' lower back MRI showed absence of neoplasms or abnormalities surrounding the treated region. Based on the physical examination and the quality of life questionnaire, no adverse events were reported due to the procedure or to the stem cell treatment 4-6 years post autologous, hypoxic cultured mesenchymal stem cell infusion. All patients self-reported overall improvement, as well as improvement in strength, post stem cell treatment, and four out of five patients reported improvement in mobility. This early human clinical data suggests the safety and feasibility of the clinical use of hypoxic cultured bone marrow-derived mesenchymal stem cells for the treatment of lower back pain due to degenerative disc disorders and support further studies utilizing hypoxic cultured bone marrow-derived stem cells. The overall improvements reported are encouraging, but a larger double-blind, controlled, randomized clinical study with significant number of patients and implementation of validated endpoint measurements are next steps in order to demonstrate efficacy of this cell-based biologic.

Diffusion-weighted imaging score of the brain stem: A predictor of outcome in acute basilar artery occlusion treated with the Solitaire FR device.

PubMed

Mourand, I; Machi, P; Nogué, E; Arquizan, C; Costalat, V; Picot, M-C; Bonafé, A; Milhaud, D

2014-06-01

The prognosis for ischemic stroke due to acute basilar artery occlusion is very poor: Early recanalization remains the main factor that can improve outcomes. The baseline extent of brain stem ischemic damage can also influence outcomes. We evaluated the validity of an easy-to-use DWI score to predict clinical outcome in patients with acute basilar artery occlusion treated by mechanical thrombectomy. We analyzed the baseline clinical and DWI parameters of 31 patients with acute basilar artery occlusion, treated within 24 hours of symptom onset by using a Solitaire FR device. The DWI score of the brain stem was assessed with a 12-point semiquantitative score that separately considered each side of the medulla, pons, and midbrain. Clinical outcome was assessed at 180 days by using the mRS. According to receiver operating characteristic analyses, the cutoff score determined the optimal positive predictive value for outcome. The Spearman rank correlation coefficient assessed the correlation between the DWI brain stem score and baseline characteristics. Successful recanalization (Thrombolysis in Cerebral Infarction 3-2b) was achieved in 23 patients (74%). A favorable outcome (mRS ≤ 2) was observed in 11 patients (35%). An optimal DWI brain stem score of <3 predicted a favorable outcome. The probability of a very poor outcome (mRS ≥ 5) if the DWI brain stem score was ≥5 reached 80% (positive predictive value) and 100% if this score was ≥6. Interobserver reliability of the DWI brain stem score was excellent, with an intraclass correlation coefficient of 0.97 (95% CI, 0.96-0.99). The DWI brain stem score was significantly associated with baseline tetraplegia (P = .001) and coma (P = .005). In patients with acute basilar artery occlusion treated by mechanical thrombectomy, the baseline DWI brain lesion score seems to predict clinical outcome. © 2014 by American Journal of Neuroradiology.

Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes.

PubMed

Naik, Swati; Nicholas, Sarah K; Martinez, Caridad A; Leen, Ann M; Hanley, Patrick J; Gottschalk, Steven M; Rooney, Cliona M; Hanson, I Celine; Krance, Robert A; Shpall, Elizabeth J; Cruz, Conrad R; Amrolia, Persis; Lucchini, Giovanna; Bunin, Nancy; Heimall, Jennifer; Klein, Orly R; Gennery, Andrew R; Slatter, Mary A; Vickers, Mark A; Orange, Jordan S; Heslop, Helen E; Bollard, Catherine M; Keller, Michael D

2016-05-01

Viral infections are a leading fatal complication for patients with primary immunodeficiencies (PIDs) who require hematopoietic stem cell transplantation (HSCT). Use of virus-specific T lymphocytes (VSTs) has been successful for the treatment and prevention of viral infections after HSCT for malignant and nonmalignant conditions. Here we describe the clinical use of VSTs in patients with PIDs at 4 centers. We sought to evaluate the safety and efficacy of VSTs for treatment of viral infections in patients with PIDs. Patients with PIDs who have received VST therapy on previous or current protocols were reviewed in aggregate. Clinical information, including transplantation details, viral infections, and use of antiviral and immunosuppressive pharmacotherapy, were evaluated. Data regarding VST production, infusions, and adverse reactions were compared. Thirty-six patients with 12 classes of PID diagnoses received 37 VST products before or after HSCT. Twenty-six (72%) patients had received a diagnosis of infection with cytomegalovirus, EBV, adenovirus, BK virus, and/or human herpesvirus 6. Two patients were treated before HSCT because of EBV-associated lymphoproliferative disease. Partial or complete responses against targeted viruses occurred in 81% of patients overall. Time to response varied from 2 weeks to 3 months (median, 28 days). Overall survival at 6 months after therapy was 80%. Four patients had graft-versus-host disease in the 45 days after VST infusion, which in most cases was therapy responsive. VSTs derived from either stem cell donors or third-party donors are likely safe and effective for the treatment of viral infections in patients with PIDs. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chinese newspaper coverage of (unproven) stem cell therapies and their providers.

PubMed

Ogbogu, Ubaka; Du, Li; Rachul, Christen; Bélanger, Lisa; Caulfield, Timothy

2013-04-01

China is a primary destination for stem cell tourism, the phenomenon whereby patients travel abroad to receive unproven stem cell-based treatments that have not been approved in their home countries. Yet, much remains unknown about the state of the stem cell treatment industry in China and about how the Chinese view treatments and providers. Given the media's crucial role in science/health communication and in framing public dialogue, this study sought to examine Chinese newspaper portrayal and perceptions of stem cell treatments and their providers. Based on a content analysis of over 300 newspaper articles, the study revealed that while Chinese newspaper reporting is generally neutral in tone, it is also inaccurate, overly positive, heavily influenced by "interested" treatment providers and focused on the therapeutic uses of stem cells to address the health needs of the local population. The study findings suggest a need to counterbalance providers' influence on media reporting through strategies that encourage media uptake of accurate information about stem cell research and treatments.

Daily chlorhexidine bathing does not increase skin toxicity after remission induction or stem cell transplantation.

PubMed

Deeren, Dries; Dewulf, Evelyne; Verfaillie, Lydie

2016-12-01

A recent multicenter study demonstrated that bathing with chlorhexidine reduces the transmission of resistant organisms and the risk of hospital-acquired bloodstream infections in ICUs. We wanted to confirm the feasibility of this strategy in a cohort of patients in a typical intensive haematology unit. Patients treated with remission induction chemotherapy, autologous or allogeneic stem cell transplantation received daily chlorhexidine bathing. To avoid deshydratation of skin, we used prophylactic application of hydrating lotion, replaced by corticosteroid cream in case of skin toxicity of chemotherapy or conditioning. We studied 15 consecutive admissions of 12 patients. Daily chlorhexidine bathing never needed to be interrupted, even though 53% of patients were treated with intravenous cytarabine. Patients were satisfied with the skin treatment and reported few unwanted effects. Daily chlorhexidine bathing was feasible in our intensive haematology unit in all patients and did not increase skin toxicity, even when treated with IV cytarabine.

Allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia who had central nervous system involvement: a study from the Adult ALL Working Group of the Japan Society for Hematopoietic Cell Transplantation.

PubMed

Shigematsu, Akio; Kako, Shinichi; Mitsuhashi, Kenjiro; Iwato, Koji; Uchida, Naoyuki; Kanda, Yoshinobu; Fukuda, Takahiro; Sawa, Masashi; Senoo, Yasushi; Ogawa, Hiroyasu; Miyamura, Koichi; Takada, Satoru; Nagamura-Inoue, Tokiko; Morishima, Yasuo; Ichinohe, Tatsuo; Atsuta, Yoshiko; Mizuta, Shuichi; Tanaka, Junji

2017-06-01

The prognosis for adult acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement (CNS+) who received allogeneic hematopoietic stem cell transplantation (allo-SCT) remains unclear. We retrospectively compared the outcomes of allo-SCT for patients with CNS involvement and for patients without CNS involvement (CNS-) using a database in Japan. The eligibility criteria for this study were as follows: diagnosis of ALL, aged more than 16 years, allo-SCT between 2005 and 2012, and first SCT. Data for 2582 patients including 136 CNS+ patients and 2446 CNS- patients were used for analyses. As compared with CNS- patients, CNS+ patients were younger, had worse disease status at SCT and had poorer performance status (PS) at SCT (P < 0.01). Incidence of relapse was higher in CNS+ patients (P = 0.02), and incidence of CNS relapse was also higher (P < 0.01). The probability of 3-year overall survival (OS) was better in CNS- patients (P < 0.01) by univariate analysis. However, in patients who received SCT in CR, there was no difference in the probability of OS between CNS+ and CNS- patients (P = 0.38) and CNS involvement did not have an unfavorable effect on OS by multivariate analysis. CNS+ patients who achieved CR showed OS comparable to that of CNS- patients.

The outcome of allogeneic hematopoietic cell transplantation for children with FMS-like tyrosine kinase 3 internal tandem duplication-positive acute myelogenous leukemia.

PubMed

Schechter, Tal; Gassas, Adam; Chen, Heidi; Pollard, Jessica; Meshinchi, Soheil; Zaidman, Irina; Hitzler, Johann; Abdelhaleem, Mohamed; Ho, Richard; Domm, Jennifer; Woolfrey, Ann; Frangoul, Haydar

2015-01-01

FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is a somatic mutation associated with poor outcome when treated with chemotherapy alone. In children, hematopoietic stem cell transplantation (HSCT) is recommended, but very limited data on outcome are reported. We determined the outcome of 29 children with FLT3/ITD-positive acute myelogenous leukemia (AML) who underwent allogeneic HSCT in 4 pediatric centers. Eleven patients (38%) received matched related donor hematopoietic stem cells and 18 (62%) received alternative donors. Eighteen patients (62%) received total body irradiation (TBI)-based regimens. No patients experienced transplantation-related mortality. Eleven patients (38%) experienced relapsed disease. The cumulative incidence of relapse at 2 years was 34.7% (95% confidence interval [CI], 20.4% to 54.9%). Two-year disease-free survival (DFS) and overall survival (OS) were 65.3% (95% CI, 45.1% to 79.6%) and 82.2% (95% CI, 58.5% to 91.3%), respectively. There was no difference in the DFS of patients who received transplants from related donors versus the DFS of those who received transplants from alternative donors (hazard ratio [HR], 2.64; 95% CI, .79 to 8.76; P = .10), using univariate analysis. Patients with higher FLT3/ITD ratio at diagnosis had significantly worse DFS (HR, 1.42; 95% CI, 1.04 to 1.93; P = .03). The use of TBI in the preparative regimen was associated with superior DFS (HR, .29; 95% CI, .08 to .99; P = .04) and OS (HR, .07; 95% CI, .01 to .62; P = .002). We conclude that allogeneic HSCT improves DFS and OS in children with FLT3/ITD-positive AML compared with what has been reported in those treated with chemotherapy alone. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Phase II Study of Concomitant Thalidomide During Radiotherapy for Hepatocellular Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ch'ang, Hui-Ju, E-mail: hjmc@nhri.org.tw; Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan, Taiwan; Hsu, Chiun

2012-02-01

Purpose: Thalidomide has been demonstrated to possess antitumor activity in patients with advanced hepatocellular carcinoma (HCC). The objective of the present study was to determine whether the combined treatment of thalidomide with radiotherapy (RT) is associated with acceptable toxicity and an improved clinical outcome in HCC patients. Methods and Materials: A total of 24 patients were enrolled to receive RT combined with thalidomide. A total dose of 50 Gy was delivered in 2-Gy fractions within 5 weeks. Thalidomide was administered 100 mg twice daily starting 3 days before RT until the development of unacceptable toxicity or disease progression. Blood samplesmore » were collected before, during, and after treatment to measure the levels of angiogenic factors and cytokines. The results of patients receiving the combined therapy were compared with those from 18 HCC patients receiving RT only. Results: No significant difference in the clinical parameters was noted between the two groups, except for the baseline interleukin-6 level, which was greater in the concomitant group (p = .05). The most common toxicities related to thalidomide use were skin rash (54.2%), somnolence (37.5%), and constipation (33.3%). No significant differences were seen in the response rate (55.6% vs. 58.3%, p = .48), median progression-free survival (182 {+-} 48.9 vs. 148 {+-} 6.2 days, p = .15), or median overall survival (258 {+-} 45.6 vs. 241 {+-} 38.6, p = .16) between those who received concomitant therapy and those who received RT alone. Thalidomide suppressed the serum basic fibroblast growth factor level significantly during RT (p = .03) and, to a lesser extent, the interleukin-6 and tumor necrosis factor-{alpha} levels. After adjusting for other potential prognostic factors in the multivariate analysis, only the baseline interleukin-6 level and stem cell-derived factor-1 during RT independently predicted the progression-free survival. A decreased serum stem cell-derived factor-1 level 1 month after RT completion was a significant predictor of the overall survival of HCC patients receiving RT. Conclusions: Despite the acceptable toxicity, thalidomide provided no additional benefit for HCC patients undergoing RT.« less

Related HLA-mismatched/haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion: observations of a single Chinese center.

PubMed

Huang, Xiaojun; Liu, Daihong

2011-01-01

The Institute of Hematology, Peking University, is the largest hematopoietic stem cell transplantation (HSCT) center in China. A total of 400 HSCTs performed in 2010 accounted for a quarter of all allogeneic HSCTs performed in China. The GIAC protocol, which uses HLA-mismatched/haploidentical blood or bone marrow transplantation without in vitro T-cell depletion, entails administration of granulocyte-colony stimulating factor (G-CSF) to all donors, intensified immunological suppression, and treatment with anti-human thymocyte immunoglobulin. The stem cell grafts are a combination of G-CSF-primed bone marrow cells and G-CSF-mobilized peripheral blood stem cells, which may be critical to the success of this protocol through the immune modulation of G-CSF. Using this protocol, more than 99% engraftment and complete donor chimerism were achieved in pediatric and adult patients with hematological malignancies. The incidence of graft-versus-host disease (GVHD) grades 3 and 4 was 13.4% and that of extensive chronic GVHD 22.6%. Comparable relapse rates were observed between patients who received unmanipulated haploidentical transplantation, and those who received HLA-identical or unrelated HSCT. Patients with confirmed minimal residual disease, (expression levels of Wilms' tumor suppressor gene 1 and flow cytometry) after HSCT received pre-emptive modified donor lymphocyte infusion to prevent relapse. Infection was the main cause of non-relapse death. Prospective studies are ongoing to investigate the mechanisms of immune reconstitution in order to refine the protocol. In 1964, a patient with severe aplastic anemia received a bone marrow infusion from her syngeneic, pregnant sister, and remained disease-free over a 40-year follow-up period. Following this success, there was a 20-year interruption in the transplantation program at our center. The hiatus ended in 1981 with the first allogeneic HSCT, which was used to treat a girl with acute lymphoblastic leukemia (ALL). In the mid-1990s, the facility performed allo-HSCTs from unrelated donors (URD) and umbilical cord blood (UCB). Then, in 2000, a patient with refractory acute leukemia received related haploidentical HSCT and achieved long-term survival without relapse over an 11-year followup period. Coincident with the rapid economic development experienced in China since 2000, the transplantation program at our Institute has been expanded to include broadened indications, multiple sources of stem cells and improved outcomes. The Institute is the largest HSCT center in China, now with 130 beds in four wards, 33 of which are laminar-flow rooms. Between 2007 and 2009, over 350 HSCTs were performed per year, rising to a total of 400 in 2010. Further, in 2010, 94% of these HSCTs were allogeneic transplants, accounting for a quarter of all allo-HSCTs performed in China. Of these, transplants from URD accounted for 6%-7%, those using UCB for less than 5%, those from identical siblings for 25%-30%, and those from the related haploidentical for 55%-65%. The most common indications for treatment with allo-HSCT are intermediate-to-high risk of acute leukemia or myelodysplastic syndrome, advanced chronic myeloid leukemia (CML), refractory lymphoma, or severe aplastic anemia.

Evaluation of Dutch guideline for just-in-time addition of plerixafor to stem cell mobilization in patients who fail with granulocyte-colony-stimulating factor.

PubMed

Bilgin, Yavuz M; Visser, Otto; Beckers, Erik A M; te Boome, Liane C J; Huisman, Cynthia; Ypma, Paula F; Croockewit, Alexandra J; Netelenbos, Tanja; Kramer, Ellen P A; de Greef, Georgine E

2015-05-01

Plerixafor in combination with granulocyte-colony-stimulating factor (G-CSF) is approved for the use of stem cell collection in patients who fail to mobilize on G-CSF. In 2009 the Stem Cell Working Party of the Dutch-Belgian Cooperative Trial group for Hematology Oncology (HOVON) composed a guideline for the use of plerixafor. According to this guideline it is recommended to add plerixafor to G-CSF in patients with circulating CD34+ cell counts of fewer than 20 × 10(6) /L on 2 consecutive days accompanied by increasing white blood cells. In this analysis we evaluated retrospectively the outcome of the use of this guideline in the Netherlands. In total 111 patients received plerixafor with a median one administration (range, one to four administrations). Of these patients 55.8% had non-Hodgkin lymphoma, 31.5% multiple myeloma, 8.1% Hodgkin lymphoma, and 4.5% nonhematologic malignancies. In 63.9% patients sufficient numbers of CD34+ cells were collected. In patients with multiple myeloma more successful mobilizations with plerixafor were observed compared to patients with non-Hodgkin lymphoma (71.4% vs. 61.3%). In patients with circulating CD34+ cell counts of at least 2.0 × 10(6) /L before administration of plerixafor a successful mobilization was achieved in 76.5%, and in the patients with very low (0-1 × 10(6) /L) circulating CD34+ cell counts the success rate was 44.2%. Application of the HOVON guideline on the just-in-time administration of plerixafor is effective for mobilization of hematopoietic stem cells in the majority of patients. Stem cell yield in patients with non-Hodgkin lymphoma was lower compared to patients with multiple myeloma. Also patients with very low circulating CD34+ cells before addition of plerixafor might benefit from this approach. © 2014 AABB.

Retrospective review of intravenous pentamidine for Pneumocystis pneumonia prophylaxis in allogeneic hematopoietic stem cell transplantation.

PubMed

Diri, R; Anwer, F; Yeager, A; Krishnadasan, R; McBride, A

2016-02-01

Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk of numerous opportunistic infections. Pneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that can develop in immunocompromised individuals. Current prophylaxis for PJP includes trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, atovaquone, or inhaled pentamidine (PEN), often with varying breakthrough rates. The use of intravenous (IV) PEN for PJP prophylaxis has been evaluated in pediatric patients. A single-institution retrospective review of electronic medical records was conducted for patients who underwent allo-HSCT between January 2001 and May 2013 and who had received at least 1 dose of IV PEN for PJP prophylaxis. Data collected included patient demographics, diagnosis, previous chemotherapy, pre-transplant conditioning regimen, other medications, microbiology test results, and clinical outcomes. A total of 113 patients were included in the study. The median number of PEN doses administered per patient was 3 (range 1-23). IV PEN was primary PJP prophylaxis in 74 of the patients (65%) and second-line prophylaxis in 39 (35%) post transplant, with the majority switching from oral TMP-SMX. Side effects of IV PEN administration were minimal. No patients who received IV PEN prophylaxis developed PJP infection. No case of PJP was seen in patients who received other agents for PJP prophylaxis. This retrospective study showed that IV PEN is very effective and well-tolerated prophylaxis for PJP; IV PEN can be considered a favorable alternative for PJP in situations where other agents might be contraindicated. Our findings provide strong support for prospective studies of IV PEN for PJP prophylaxis in adult HSCT recipients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of ABO incompatibility on patients' outcome after haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia - a report from the Acute Leukemia Working Party of the EBMT.

PubMed

Canaani, Jonathan; Savani, Bipin N; Labopin, Myriam; Huang, Xiao-Jun; Ciceri, Fabio; Arcese, William; Tischer, Johanna; Koc, Yener; Bruno, Benedetto; Gülbas, Zafer; Blaise, Didier; Maertens, Johan; Ehninger, Gerhard; Mohty, Mohamad; Nagler, Arnon

2017-06-01

A significant proportion of hematopoietic stem cell transplants are performed with ABO-mismatched donors. The impact of ABO mismatch on outcome following transplantation remains controversial and there are no published data regarding the impact of ABO mismatch in acute myeloid leukemia patients receiving haploidentical transplants. Using the European Blood and Marrow Transplant Acute Leukemia Working Group registry we identified 837 patients who underwent haploidentical transplantation. Comparative analysis was performed between patients who received ABO-matched versus ABO-mismatched haploidentical transplants for common clinical outcome variables. Our cohort consisted of 522 ABO-matched patients and 315 ABO-mismatched patients including 150 with minor, 127 with major, and 38 with bi-directional ABO mismatching. There were no significant differences between ABO matched and mismatched patients in terms of baseline disease and clinical characteristics. Major ABO mismatching was associated with inferior day 100 engraftment rate whereas multivariate analysis showed that bi-directional mismatching was associated with increased risk of grade II-IV acute graft- versus -host disease [hazard ratio (HR) 2.387; 95% confidence interval (CI): 1.22-4.66; P =0.01). Non-relapse mortality, relapse incidence, leukemia-free survival, overall survival, and chronic graft- versus -host disease rates were comparable between ABO-matched and -mismatched patients. Focused analysis on stem cell source showed that patients with minor mismatching transplanted with bone marrow grafts experienced increased grade II-IV acute graft- versus -host disease rates (HR 2.03; 95% CI: 1.00-4.10; P =0.04). Patients with major ABO mismatching and bone marrow grafts had decreased survival (HR=1.82; CI 95%: 1.048 - 3.18; P =0.033). In conclusion, ABO incompatibility has a marginal but significant clinical effect in acute myeloid leukemia patients undergoing haploidentical transplantation. Copyright© Ferrata Storti Foundation.

[Early aseptic loosening of the CF 30 femoral stem].

PubMed

Kovanda, M; Havlícek, V; Hudec, J

2007-02-01

The CF 30 stem in combination with a cementless acetabulum was used at the First Department of Orthopedic Surgery in Brno in the years 1994 to 1995. From the second year following implantation, aseptic stem loosening was recorded. In order to find explanation of this early loosening, the authors, in cooperation with the Institute of Solid Mechanics, Mechatronics and Biomechanics, carried out the stress-strain analysis in a model system. Eighty patients (31 men and 49 women) received a cemented CF30 femoral component in 1994. Of them, 16 patients underwent revision arthroplasty, three died of causes unrelated to the surgery, and four were lost to follow-up. The final clinical and radiographic check-up was carried out in 2001. The results of a comprehensive examination were available in 57 patients with a CF30 stem. The patients were evaluated on the basis of the Harris hip score and anteroposterior radiographs of the hip. X-ray films obtained immediately after surgery and those taken at regular intervals during follow-up were compared. The following characteristics were noted: translucent lines in individual zones along the stem at the cement-bone interface; osteolysis, i. e., non-linear translucent areas, at least 5 mm long, at the cement-bone interface; and subsidence of the femoral component, i. e., migration of the stem distal to the tip of the greater trochanter. The CF 30 stem survival curve showed that aseptic stem loosening occurred from post-implantation year 2, and increased during the following years. At 6 years and 6 months, a total of 16 patients underwent revision surgery, involving reimplantation in 14 and implant removal in 2 patients. Potential causes of aseptic loosening: Polyethylene wear.However, no acetabular loosening was found in this group, although acetabular components are reported to become loose more often than femoral components. By comparison of the stem survival curves for Poldi and CF 30 stems it appeared that, at 6 years and 6 months, the Poldi stem survival curve showed better results. Matt surface finish of the stem. However, the link between the CF 30 stem and cement was so strong that, in all 16 revised hips, the stem was removed together with nearly a complete cement mantle. The authors therefore dismiss this as a cause. Also, in the remaining cases of CF 30 aseptic loosening, which had not been revised, radiographic evidence suggested loosening between bone and cement. The authors did not find any movement of the CF stem in its cement mantle. The stem always fitted in with the cement mantle. Erroneous surgical technique or cementing was unlikely. The procedures were performed by experienced orthopedic surgeons who used the second-generation cementing technique. In patients with a Poldi stem, the first-generation cementing method was used and the proportion of aseptic loosening at 6 years of follow-up was only 4 %. In contrast, loosening in patients with the CF 30 stem was 20 % at 6 years and 6 months postoperatively. Shape of the CF 30 stem with the intention to find a relationship between stem shape and its early aseptic loosening, the authors started cooperation with the Institute of Solid Mechanics, Mechatronics and Biomechanics at the Faculty of Mechanical Engineering, Brno University of Technology. Using the method of finite elements, they carried out the stressstrain analysis in a model system. Stress at the cement-bone interface in the CF 30 stem was higher than in the Poldi stem, and this difference was statistically significant. The authors believe that the more frequent loosening found in patients with the CF 30 stem can be accounted for by its shape. The survival curve for the CF 30 femoral stem did not show good results, and therefore this stem is not recommended for implantation. The authors suggest that a more frequent early aseptic loosening of CF 30 stems may have been caused by its unsuitable shape.

Outcomes of peripheral blood stem cell transplantation patients from HLA-mismatched unrelated donor with antithymocyte globulin (ATG)-Thymoglobulin versus ATG-Fresenius: a single-center study.

PubMed

Huang, Wenrong; Zhao, Xiaoli; Tian, Yamin; Cao, Tingting; Li, Yanfen; Liu, Zhanxiang; Jing, Yu; Wang, Shuhong; Gao, Chunji; Yu, Li

2015-02-01

Although antithymocyte globulin (ATG) had been widely used in hematopoietic stem cell transplantation from unrelated donor due to its ability to prevent acute and chronic graft-versus-host disease (GVHD), the comparative efficacy and safety of ATG-Thymoglobulin (ATG-T) and ATG-Fresenius (ATG-F) in patients undergoing HLA-mismatched allogeneic peripheral blood stem cell transplantation from unrelated donors (UR-PBSCT) has not been evaluated. Retrospective analysis of patients who underwent HLA-mismatched UR-PBSCT between January 2003 and December 2013 and received pre-transplant ATG-T at a total dose of 10 mg/kg or ATG-F at a total dose of 20 mg/kg was performed. Patients who received ATG-T (n = 23) or ATG-F (n = 28) had similar baseline demographic, disease, and transplant characteristics. There were no significant between-groups differences in the probability of acute GVHD (P = 0.721) and chronic GVHD (P = 0.439). ATG-F was associated with nonsignificant trends toward higher disease-free survival at 3-year follow-up compared with ATG-T (45.7 ± 11.1 vs 61.3 ± 9.7 %, respectively, P = 0.07). A significantly greater proportion of ATG-T patients experienced high fever than ATG-F patients (P < 0.01) during ATG infusion. There was no difference in the rate of infection between the two treatment groups. There were less adverse effects comparing ATG-F with ATG-T. ATG-T at a total dose of 10 mg/kg and ATG-F at a total dose of 20 mg/kg had a similar clinical outcome in the setting of HLA-mismatched UR-PBSCT.

Impact of the International Prognostic Scoring System cytogenetic risk groups on the outcome of patients with primary myelodysplastic syndromes undergoing allogeneic stem cell transplantation from human leukocyte antigen-identical siblings: a retrospective analysis of the European Society for Blood and Marrow Transplantation-Chronic Malignancies Working Party.

PubMed

Onida, Francesco; Brand, Ronald; van Biezen, Anja; Schaap, Michel; von dem Borne, Peter A; Maertens, Johan; Beelen, Dietrich W; Carreras, Enric; Alessandrino, Emilio P; Volin, Liisa; Kuball, Jürgen H E; Figuera, Angela; Sierra, Jorge; Finke, Jürgen; Kröger, Nicolaus; de Witte, Theo

2014-10-01

Acquired chromosomal abnormalities are important prognostic factors in patients with myelodysplastic syndromes treated with supportive care and with disease-modifying therapeutic interventions, including allogeneic hematopoietic stem cell transplantation. To assess the prognostic impact of cytogenetic characteristics after hematopoietic stem cell transplantation accurately, we investigated a homogeneous group of 523 patients with primary myelodysplastic syndromes who have received stem cells from human leukocyte antigen-identical siblings. Overall survival at five years from transplantation in good, intermediate, and poor cytogenetic risk groups according to the International Prognostic Scoring System was 48%, 45% and 30%, respectively (P<0.01). Both the disease status (complete remission vs. not in complete remission) and the morphological classification at transplant in the untreated patients were significantly associated with probability of overall survival and relapse-free survival (P<0.01). The cytogenetic risk groups have no prognostic impact in untreated patients with refractory anemia ± ringed sideroblasts (P=0.90). However, combining the good and intermediate cytogenetic risk groups and comparing them to the poor-risk group showed within the other three disease-status-at-transplant groups a hazard ratio of 1.86 (95%CI: 1.41-2.45). In conclusion, this study shows that, in a large series of patients with primary myelodysplastic syndromes, poor-risk cytogenetics as defined by the standard International Prognostic Scoring System is associated with a relatively poor survival after allogeneic stem cell transplantation from human leukocyte antigen-identical siblings except in patients who are transplanted in refractory anemia/refractory anemia with ringed sideroblasts stage before progression to higher myelodysplastic syndrome stages. Copyright© Ferrata Storti Foundation.

Curbing stem cell tourism in South Africa.

PubMed

Meissner-Roloff, Madelein; Pepper, Michael S

2013-12-01

Stem cells have received much attention globally due in part to the immense therapeutic potential they harbor. Unfortunately, malpractice and exploitation (financial and emotional) of vulnerable patients have also drawn attention to this field as a result of the detrimental consequences experienced by some individuals that have undergone unproven stem cell therapies. South Africa has had limited exposure to stem cells and their applications and, while any exploitation is detrimental to the field of stem cells, South Africa is particularly vulnerable in this regard. The current absence of adequate legislation and the inability to enforce existing legislation, coupled to the sea of misinformation available on the Internet could lead to an increase in illegitimate stem cell practices in South Africa. Circumstances are already precarious because of a lack of understanding of concepts involved in stem cell applications. What is more, credible and easily accessible information is not available to the public. This in turn cultivates fears born out of existing superstitions, cultural beliefs, rituals and practices. Certain cultural or religious concerns could potentially hinder the effective application of stem cell therapies in South Africa and novel ways of addressing these concerns are necessary. Understanding how scientific progress and its implementation will affect each individual and, consequently, the community, will be of cardinal importance to the success of the fields of stem cell therapy and regenerative medicine in South Africa. A failure to understand the ethical, cultural or moral ramifications when new scientific concepts are introduced could hinder the efficacy and speed of bringing discoveries to the patient. Neglecting proper procedure for establishing the field would lead to long delays in gaining public support in South Africa. Understanding the dangers of stem cell tourism - where vulnerable patients are subjected to unproven stem cell therapies that have not undergone peer review or been registered with the relevant local authorities - becomes imperative so that strategies to overcome this threat can be implemented.

Outcomes and predictors of survival in blast phase myeloproliferative neoplasms.

PubMed

Lancman, Guido; Brunner, Andrew; Hoffman, Ronald; Mascarenhas, John; Hobbs, Gabriela

2018-05-21

We retrospectively reviewed treatment outcomes for 57 patients with myeloproliferative neoplasms in blast phase (MPN-BP). The median overall survival (OS) of the entire cohort was 5.8 months. For patients receiving induction therapy, 67% achieved a complete response (CR) and 75% received stem cell transplantation (SCT). Median OS for all transplanted patients (n = 19) was not reached after a median follow-up of 19.2 months compared with 3.8 months in non-transplanted patients (p < 0.0001); patients who did not receive SCT after induction chemotherapy survived a median of 4.9 months. OS was not improved in patients transplanted after CR (OS not reached after median follow-up of 26.7 months) compared with those transplanted upfront or after suboptimal response to initial therapy (9.0 months; p = .097). Those who were transfusion-dependent during their MPN course and received SCT had a median OS of 4.4 months, with all patients dying from SCT complications. Patients receiving hypomethylating agents (HMA) survived 6.7 months, while those receiving supportive care survived 1.1 months. Although outcomes for MPN-BP remain poor, long-term survival can be achieved in appropriately selected patients utilizing SCT, optimally after attaining a complete response with induction therapy. For patients ineligible for SCT, HMAs can offer similar survival to induction chemotherapy with less toxicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Anti-infective vaccination strategies in patients with hematologic malignancies or solid tumors-Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO).

PubMed

Rieger, C T; Liss, B; Mellinghoff, S; Buchheidt, D; Cornely, O A; Egerer, G; Heinz, W J; Hentrich, M; Maschmeyer, G; Mayer, K; Sandherr, M; Silling, G; Ullmann, A; Vehreschild, M J G T; von Lilienfeld-Toal, M; Wolf, H H; Lehners, N

2018-06-01

Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject of a separate guideline. The document was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) by reviewing currently available data and applying evidence-based medicine criteria.

Hypervitaminosis a in pediatric hematopoietic stem cell patients requiring renal replacement therapy.

PubMed

Lipkin, Ann Connell; Lenssen, Polly

Chronic renal failure patients have been known to develop vitamin A toxicity, but a descriptive study of hypervitaminosis A in patients with acute renal failure (ARF) has not yet been published. The authors observed hypervitaminosis A in pediatric hematopoietic stem cell transplant (HSCT) patients. All HSCT patients admitted between January 2001 and May 2006 who experienced ARF, received renal replacement therapy (RRT), and had a vitamin A level drawn were included in this retrospective, descriptive study. Molar ratios of vitamin A and retinol-binding protein (RBP) were calculated to more accurately assess vitamin A status. Nineteen patients met the criteria for this study. At initial testing (generally between days 6 and 10 after initiation of RRT), 17 of the 19 patients had abnormally elevated vitamin A levels for their age. Molar ratios of vitamin A to RBP were elevated in 6 patients at initial testing. Prescribed vitamin A intake information (parenteral and enteral) was available for most patients; all but 3 had an average daily intake greater than 2000 IU/kg over the 30 days prior to RRT initiation. Many patients had symptoms possibly related to vitamin A toxicity, although interpretation of hair, skin, and liver abnormalities are difficult to ascertain in HSCT patients. Seven patients had other findings that may have been associated with vitamin A toxicity. Children undergoing HSCT who receive nutrition support (predominantly parenteral nutrition), experience ARF, and require RRT are at risk for hypervitaminosis A and toxicity.

Stem Cell Therapy for Treatment of Ocular Disorders

PubMed Central

Sivan, Padma Priya; Syed, Sakinah; Mok, Pooi-Ling; Higuchi, Akon; Murugan, Kadarkarai; Alarfaj, Abdullah A.; Munusamy, Murugan A.; Awang Hamat, Rukman; Umezawa, Akihiro; Kumar, Suresh

2016-01-01

Sustenance of visual function is the ultimate focus of ophthalmologists. Failure of complete recovery of visual function and complications that follow conventional treatments have shifted search to a new form of therapy using stem cells. Stem cell progenitors play a major role in replenishing degenerated cells despite being present in low quantity and quiescence in our body. Unlike other tissues and cells, regeneration of new optic cells responsible for visual function is rarely observed. Understanding the transcription factors and genes responsible for optic cells development will assist scientists in formulating a strategy to activate and direct stem cells renewal and differentiation. We review the processes of human eye development and address the strategies that have been exploited in an effort to regain visual function in the preclinical and clinical state. The update of clinical findings of patients receiving stem cell treatment is also presented. PMID:27293447

Intra-Abdominal Candidiasis: The Importance of Early Source Control and Antifungal Treatment

PubMed Central

Vergidis, Pascalis; Clancy, Cornelius J.; Shields, Ryan K.; Park, Seo Young; Wildfeuer, Brett N.; Simmons, Richard L.; Nguyen, M. Hong

2016-01-01

Intra-abdominal candidiasis (IAC) is poorly understood compared to candidemia. We described the clinical characteristics, microbiology, treatment and outcomes of IAC, and identified risk factors for mortality. We performed a retrospective study of adults diagnosed with IAC at our center in 2012–2013. Risk factors for mortality were evaluated using multivariable logistic regression. We identified 163 patients with IAC, compared to 161 with candidemia. Types of IAC were intra-abdominal abscesses (55%), secondary peritonitis (33%), primary peritonitis (5%), infected pancreatic necrosis (5%), and cholecystitis/cholangitis (3%). Eighty-three percent and 66% of secondary peritonitis and abscesses, respectively, stemmed from gastrointestinal (GI) tract sources. C. albicans (56%) and C. glabrata (24%) were the most common species. Bacterial co-infections and candidemia occurred in 67% and 6% of patients, respectively. Seventy-two percent of patients underwent an early source control intervention (within 5 days) and 72% received early antifungal treatment. 100-day mortality was 28%, and highest with primary (88%) or secondary (40%) peritonitis. Younger age, abscesses and early source control were independent predictors of survival. Younger age, abscesses and early antifungal treatment were independently associated with survival for IAC stemming from GI tract sources. Infectious diseases (ID) consultations were obtained in only 48% of patients. Consulted patients were significantly more likely to receive antifungal treatment. IAC is a common disease associated with heterogeneous manifestations, which result in poor outcomes. All patients should undergo source control interventions and receive antifungal treatment promptly. It is important for the ID community to become more engaged in treating IAC. PMID:27123857

Impact of ABO incompatibility on patients’ outcome after haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia - a report from the Acute Leukemia Working Party of the EBMT

PubMed Central

Canaani, Jonathan; Savani, Bipin N; Labopin, Myriam; Huang, Xiao-jun; Ciceri, Fabio; Arcese, William; Tischer, Johanna; Koc, Yener; Bruno, Benedetto; Gülbas, Zafer; Blaise, Didier; Maertens, Johan; Ehninger, Gerhard; Mohty, Mohamad; Nagler, Arnon

2017-01-01

A significant proportion of hematopoietic stem cell transplants are performed with ABO-mismatched donors. The impact of ABO mismatch on outcome following transplantation remains controversial and there are no published data regarding the impact of ABO mismatch in acute myeloid leukemia patients receiving haploidentical transplants. Using the European Blood and Marrow Transplant Acute Leukemia Working Group registry we identified 837 patients who underwent haploidentical transplantation. Comparative analysis was performed between patients who received ABO-matched versus ABO-mismatched haploidentical transplants for common clinical outcome variables. Our cohort consisted of 522 ABO-matched patients and 315 ABO-mismatched patients including 150 with minor, 127 with major, and 38 with bi-directional ABO mismatching. There were no significant differences between ABO matched and mismatched patients in terms of baseline disease and clinical characteristics. Major ABO mismatching was associated with inferior day 100 engraftment rate whereas multivariate analysis showed that bi-directional mismatching was associated with increased risk of grade II–IV acute graft-versus-host disease [hazard ratio (HR) 2.387; 95% confidence interval (CI): 1.22–4.66; P=0.01). Non-relapse mortality, relapse incidence, leukemia-free survival, overall survival, and chronic graft-versus-host disease rates were comparable between ABO-matched and -mismatched patients. Focused analysis on stem cell source showed that patients with minor mismatching transplanted with bone marrow grafts experienced increased grade II–IV acute graft-versus-host disease rates (HR 2.03; 95% CI: 1.00–4.10; P=0.04). Patients with major ABO mismatching and bone marrow grafts had decreased survival (HR=1.82; CI 95%: 1.048 – 3.18; P=0.033). In conclusion, ABO incompatibility has a marginal but significant clinical effect in acute myeloid leukemia patients undergoing haploidentical transplantation. PMID:28255020

Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

ClinicalTrials.gov

2018-05-07

Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

Gut microbiota injury in allogeneic haematopoietic stem cell transplantation.

PubMed

Shono, Yusuke; van den Brink, Marcel R M

2018-05-01

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered to be the strongest curative immunotherapy for various malignancies (primarily, but not limited to, haematologic malignancies). However, application of allo-HSCT is limited owing to its life-threatening major complications, such as graft-versus-host disease (GVHD), relapse and infections. Recent advances in large-scale DNA sequencing technology have facilitated rapid identification of the microorganisms that make up the microbiota and evaluation of their interactions with host immunity in various diseases, including cancer. This has resulted in renewed interest regarding the role of the intestinal flora in patients with haematopoietic malignancies who have received an allo-HSCT and in whether the microbiota affects clinical outcomes, including GVHD, relapse, infections and transplant-related mortality. In this Review, we discuss the potential role of intestinal microbiota in these major complications after allo-HSCT, summarize clinical trials evaluating the microbiota in patients who have received allo-HSCT and discuss how further studies of the microbiota could inform the development of strategies that improve outcomes of allo-HSCT.

Evaluation of Hematopoietic Stem Cell Mobilization Rates with Early Plerixafor Administration for Adult Stem Cell Transplantation.

PubMed

Stover, Jessica T; Shaw, J Ryan; Kuchibhatla, Maragatha; Horwitz, Mitchell E; Engemann, Ashley M

2017-08-01

The addition of plerixafor to high-dose colony-stimulating growth factor has been shown to improve stem cell mobilization rates in autologous transplant patients with multiple myeloma and non-Hodgkin lymphoma. This study evaluates the change in administration time of plerixafor to determine if cell mobilization rates are similar between the US Food and Drug Administration-approved administration time of 11 hours before apheresis and an earlier administration time of 16 hours before apheresis. Medical records of patients age ≥ 18 years undergoing autologous stem cell transplantation requiring the use of plerixafor after at least 4 days of granulocyte colony-stimulating factor therapy to complete stem cell mobilization from January 1, 2010 through September 30, 2014 were retrospectively reviewed. The primary outcome was CD34 + cell mobilization success rates when plerixafor was administered 11 ± 2 hours (standard administration group) compared with 16 ± 2 hours before cell apheresis (early administration group), as defined as collection of  ≥2 × 10 6 CD34 + cells/kg. Secondary outcomes included the number of plerixafor therapy days required to collect a total of ≥2 × 10 6 CD34 + cells/kg, the number of apheresis cycles required to achieve ≥2 × 10 6 CD34 + cells/kg, the median CD34 + cells/kg collected in each apheresis session, and the rates of reported adverse events that occurred in the standard administration time group compared with the early administration time group. Of the 197 patients included, 114 patients received plerixafor 11 ± 2 hours before apheresis and 83 patients received plerixafor 16 hours ± 2 hours before apheresis. Ninety-four percent of patients in the early administration group achieved successful stem cell mobilization compared with 81.6% in the standard administration group (P = .0111). The median number of plerixafor days to reach the collection goal of  ≥2 × 10 6 CD34 + cells/kg was 1 day for each group (P = .323), and the median number of apheresis days to reach the collection goal was 2 days for the standard administration group compared with 1 day for the early administration group (P = .0156). Most adverse events were similar between the 2 groups except for fever, which occurred in 4.8% of the patients in the early administration group and none of the patients in the standard administration group. This study demonstrates plerixafor effectively mobilizes peripheral blood stem cells when given at an early administration time of 16 hours before apheresis compared with standard administration of 11 hours before apheresis. However, further prospective studies could strengthen these results. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction - MI3 Trial

PubMed Central

Nair, Velu; Madan, Hemant; Sofat, Sunil; Ganguli, Prosenjit; Jacob, M.J.; Datta, Rajat; Bharadwaj, Prashant; Sarkar, R.S.; Pandit, A.J.; Nityanand, Soniya; Goel, Pravin K.; Garg, Naveen; Gambhir, Sanjay; George, Paul V.; Chandy, Sunil; Mathews, Vikram; George, Oomen K.; Talwar, K.K.; Bahl, Ajay; Marwah, Neelam; Bhatacharya, Anish; Bhargava, Balram; Airan, Balram; Mohanty, Sujata; Patel, Chetan D.; Sharma, Alka; Bhatnagar, Shinjini; Mondal, A.; Jose, Jacob; Srivastava, A.

2015-01-01

Background & objectives: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 108 autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. Methods: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). Results: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 × 108(n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. Interpretation & conclusions: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials. PMID:26354213

Cementless Tapered Wedge Femoral Stems Decrease Subsidence in Obese Patients Compared to Traditional Fit-and-Fill Stems.

PubMed

Grant, Tanner W; Lovro, Luke R; Licini, David J; Warth, Lucian C; Ziemba-Davis, Mary; Meneghini, Robert M

2017-03-01

Femoral component stability and resistance to subsidence is critical for osseointegration and clinical success in cementless total hip arthroplasty. The purpose of this study was to radiographically evaluate the anatomic fit and subsidence of 2 different proximally tapered, porous-coated modern cementless femoral component designs. A retrospective cohort study of 126 consecutive cementless total hip arthroplasties was performed. Traditional fit-and-fill stems were implanted in the first 61 hips with the remaining 65 receiving morphometric tapered wedge stems. Preoperative bone morphology was radiographically assessed by the canal flare index. Canal fill in the coronal plane, subsidence, and the sagittal alignment of stems was measured digitally on immediate and 1-month postoperative radiographs. Demographics and canal flare indices were similar between groups. The percentage of femoral canal fill was greater in the tapered wedge compared to the fit-and-fill stem (P = .001). There was significantly less subsidence in the tapered wedge design (0.3 mm) compared to the fit-and-fill design (1.1 mm) (P = .001). Subsidence significantly increased as body mass index (BMI) increased in the fit-and-fill stems, a finding not observed in the tapered wedge design (P = .013). An anatomically designed morphometric tapered wedge femoral stem demonstrated greater axial stability and decreased subsidence with increasing BMI than a traditional fit-and-fill stem. The resistance to subsidence, irrespective of BMI, is likely due to the inherent axial stability of a tapered wedge design and may be the optimal stem design for obese patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Early Improvement in Marrow Fibrosis Following Haploidentical Stem Cell Transplantation for a Patient with Myelodysplastic Syndrome with Bone Marrow Fibrosis

PubMed Central

Takahashi, Shuichiro; Tsumanuma, Riko; Aizawa, Keiko; Osakabe, Mitsumasa; Maeda, Kunihiko; Omoto, Ejiro

2016-01-01

The prognosis for myelodysplastic syndrome with bone marrow fibrosis (MDS-F) is worse than the prognosis of MDS without fibrosis. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy; however, the indications and the procedures involved in HSCT remain unclear. We herein describe a 69-year-old Japanese man with MDS-F who received haploidentical HSCT and post-transplantation cyclophosphamide. Although the first HSCT resulted in secondary graft failure, the second HSCT using PTCy led to successful engraftment after early improvement in fibrosis. Since the incidence of graft failure is high in myelofibrosis patients, a secondary HSCT using PTCy may be successful if employed. PMID:27853082

Can chronic myeloid leukaemia in children and adolescents be successfully treated without haematopoietic stem cell transplant? A single centre experience.

PubMed

Giona, Fiorina; Moleti, Maria L; De Benedittis, Daniela; Santopietro, Michelina; Nanni, Mauro; Testi, Anna M; Orlando, Sonia; Iori, Anna P; Piciocchi, Alfonso; Gottardi, Enrico; Barberi, Walter; Diverio, Daniela; Saglio, Giuseppe; Foà, Robin

2016-06-01

We analysed the long-term outcome of 35 children and adolescents (<20 years at diagnosis) with chronic myeloid leukaemia (CML) in chronic phase: 20 patients had received interferon-alpha and/or tyrosine kinase inhibitors (TKIs), and 15 underwent a haematopoietic stem cell transplant. The 10-year survival probabilities were similar in transplanted and non-transplanted patients (73·3% vs. 72·1%, respectively), whereas the survival probability was significantly lower in patients diagnosed before 1999 compared to those diagnosed afterwards (62·1% vs. 100%, P = 0·0384). The availability of TKIs and the standardized molecular monitoring have significantly improved treatment, management and outcome in children and adolescents with CML. © 2016 John Wiley & Sons Ltd.

Microbial contamination of autologous peripheral blood stem cell products: incidence, clinical outcome, quality control and management strategies.

PubMed

Cheah, Poh Lin; Ong, Chong Wei; Crispin, Philip

2011-06-01

Microbial screening is part of quality control for autologous peripheral blood stem cell (PBSC) manipulation. The incidence of culture positive products varies widely. The clinical significance of infusing culture positive products is uncertain, with no consensus on the interventions required. Microbial cultures of 606 consecutive autologous PBSC products from 278 patients between 1995 and 2005 were retrospectively analysed to determine the incidence of culture positivity and classified according to likely clinical significance. Clinical outcomes of patients who received culture positive products were reviewed. Using the baseline probability of contamination, a quality control method to detect a systematic source of contamination during product manipulation was developed. Eleven (1.8%) of 606 products were culture positive in eight (2.9%) patients. Ten products yielded coagulase negative Staphylococcus species and one Corynebacterium accolens. One patient had catheter sepsis during collection. Five patients received culture positive products, with prophylactic antibiotics when there was known coagulase negative Staphylococcus species. None had clinical evidence of infection following product infusion. The incidence of culture positive products was comparable to published series. Only skin commensals were isolated. Infusion of skin commensal positive products appears safe with antibiotic prophylaxis. Using local and published experience, clinical and laboratory policies were developed for culture positive products.

Cytomegalovirus retinitis in a patient with secondary acute lymphosarcoma leukemia undergoing allogeneic hematopoietic stem-cell transplantation

PubMed Central

Zhao, Ning; Liu, Lei; Xu, Junjie

2017-01-01

Abstract Rationale: Cytomegalovirus (CMV) retinitis is a common opportunistic infection in immunocompromised patients, which may lead to blindness. CMV retinitis is not an uncommon infectious disease in patients with immune regulatory abnormalities, for example, human immunodeficiency virus (HIV) patients. However, CMV retinitis in a patient with acute lymphosarcoma leukemia (ALL) undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) phase is very rare. Patient concerns: A case of CMV retinitis in a patient receiving immunosuppressive therapy as a part of ALL allogeneic HSCT is described including the pathogenesis, clinical signs, and therapy. Diagnoses: CMV retinitis. Interventions: Ganciclovir intravitreal injection at weekly intervals for 4 weeks. Outcomes: Patient's vision had improved and the load of CMV deoxyribonucleic acid (DNA) in the aqueous humor declined. The CMV retinitis and perivascular of retina infiltration regressed. Lessons: We propose that the concentration of CMV DNA load in the aqueous humor could be useful in making the diagnosis and in selecting the optimal treatment in this kind of CMV retinitis. PMID:28489788

Granulocyte-colony stimulating factor (G-CSF)-primed, delayed marrow harvests as a source of hematopoietic stem and progenitor cells for allogeneic transplantation.

PubMed

Phillips, G L; Davey, D D; Hale, G A; Marshall, K W; Munn, R K; Nath, R; Reece, D E; Van Zant, G

1999-10-01

We evaluated the ability of G-CSF to increase the number of hematopoietic stem cells obtained by "delayed" BM harvest for allogeneic transplantation. Five normal donors received G-CSF @ 10 mcg/kg/day x 5 followed by repeat PB and BM assays at day 6 and 16, and BM harvest at day 16. Stem cells were not increased in the BM at day 16. Five patients underwent BMT and engrafted at +10 to +19 days. While the tested strategy offers no intrinsic advantages, its potential cannot be evaluated fully without alternative timing and/or additional, "early acting" growth factors.

Atovaquone for Prophylaxis of Toxoplasmosis after Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Mendorf, Alexander; Klyuchnikov, Evgeny; Langebrake, Claudia; Rohde, Holger; Ayuk, Francis; Regier, Marc; Christopeit, Maximilian; Zabelina, Tatjana; Bacher, Adelbert; Stübig, Thomas; Wolschke, Christine; Bacher, Ulrike; Kröger, Nicolaus

2015-01-01

Toxoplasmosis and infections by other opportunistic agents such as Pneumocystis jirovecii constitute life-threatening risks for patients after allogeneic hematopoietic stem cell transplantation. Trimethoprim/sulfamethoxazole (TMP-SMX) has been well established for post-transplant toxoplasmosis and pneumocystis prophylaxis, but treatment may be limited due to toxicity. We explored atovaquone as an alternative and compared it with TMP-SMX regarding toxicity and efficacy during the first 100 days after transplantation in 155 consecutive adult stem cell recipients. Eight patients with a prior history of TMP-SMX intolerance received atovaquone as first-line prophylaxis. TMP-SMX was used for 141 patients as first-line strategy, but 13 patients (9.2%) were later switched to atovaquone due to TMP-SMX toxicity or gastrointestinal symptoms. No active toxoplasmosis or active P. jirovecii infection developed under continued prophylaxis with either TMP-SMX or atovaquone. However, for reasons of TMP-SMX and/or atovaquone toxicity, 7 patients were unable to tolerate any efficacious toxoplasmosis prophylaxis and therefore obtained inhalative pentamidine as P. jirovecii prophylaxis but no toxoplasmosis prophylaxis. Importantly, 2 of these patients developed severe toxoplasmosis. In summary, atovaquone appears as a valid alternative for at least some post-transplant patients who cannot tolerate TMP-SMX. This should be further confirmed by multicenter trials. © 2015 S. Karger AG, Basel.

Very late nonfatal consequences of fractionated TBI in children undergoing bone marrow transplant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faraci, Maura; Barra, Salvina; Cohen, Amnon

Purpose: To describe long-term late consequences in children who received total body irradiation (TBI) for hematopoietic stem cell transplantation 10 years earlier. Methods and Materials: A cohort of 42 children treated with TBI between 1985 and 1993, still alive at least 10 years after fractionated TBI (FTBI), was evaluated. Twenty-five patients received FTBI at 330 cGy/day for 3 days (total dose 990 cGy), whereas 17 children were administered fractions of 200 cGy twice daily for 3 days (total dose 1200 cGy). Twenty-seven patients received autologous and 16 allogeneic hematopoietic stem cell transplantation. Median age at TBI was 6.3 years, andmore » 18.4 years at most recent follow-up. Results: Cataract was diagnosed in 78% of patients after a median of 5.7 years. Hypothyroidism was detected in 12%, whereas thyroid nodules were observed in 60% of our population after a median interval of 10.2 years. Patients treated with 990 cGy developed thyroid nodules more frequently than those treated with 1200 cGy (p = 0.0002). Thyroid carcinoma was diagnosed in 14% of the total population. Females who received FTBI after menarche more frequently developed temporary ovarian dysfunction than those treated before menarche, but cases of persistent ovarian dysfunction did not differ between the two groups. Indirect signs of germinal testicular dysfunction were detected in 87% of males. Restrictive pulmonary disease was observed in 74% of patients. Osteochondroma was found in 29% of patients after a median interval of 9.2 years. This latter complication appeared more frequently in patients irradiated before the age of 3 years (p < 0.001). Conclusions: This study shows that late effects that are likely permanent, although not fatal, are frequent in survivors 10 years after TBI. However, some of the side effects observed shortly after TBI either disappeared or remained unchanged without signs of evolution. Monitoring is recommended to pursue secondary prevention strategies and counseling on family planning.« less

Very late nonfatal consequences of fractionated TBI in children undergoing bone marrow transplant.

PubMed

Faraci, Maura; Barra, Salvina; Cohen, Amnon; Lanino, Edoardo; Grisolia, Francesca; Miano, Maurizio; Foppiano, Franca; Sacco, Oliviero; Cabria, Manlio; De Marco, Riccardo; Stella, Gilberto; Dallorso, Sandro; Bagnasco, Francesca; Vitale, Vito; Dini, Giorgio; Haupt, Riccardo

2005-12-01

To describe long-term late consequences in children who received total body irradiation (TBI) for hematopoietic stem cell transplantation 10 years earlier. A cohort of 42 children treated with TBI between 1985 and 1993, still alive at least 10 years after fractionated TBI (FTBI), was evaluated. Twenty-five patients received FTBI at 330 cGy/day for 3 days (total dose 990 cGy), whereas 17 children were administered fractions of 200 cGy twice daily for 3 days (total dose 1200 cGy). Twenty-seven patients received autologous and 16 allogeneic hematopoietic stem cell transplantation. Median age at TBI was 6.3 years, and 18.4 years at most recent follow-up. Cataract was diagnosed in 78% of patients after a median of 5.7 years. Hypothyroidism was detected in 12%, whereas thyroid nodules were observed in 60% of our population after a median interval of 10.2 years. Patients treated with 990 cGy developed thyroid nodules more frequently than those treated with 1200 cGy (p = 0.0002). Thyroid carcinoma was diagnosed in 14% of the total population. Females who received FTBI after menarche more frequently developed temporary ovarian dysfunction than those treated before menarche, but cases of persistent ovarian dysfunction did not differ between the two groups. Indirect signs of germinal testicular dysfunction were detected in 87% of males. Restrictive pulmonary disease was observed in 74% of patients. Osteochondroma was found in 29% of patients after a median interval of 9.2 years. This latter complication appeared more frequently in patients irradiated before the age of 3 years (p < 0.001). This study shows that late effects that are likely permanent, although not fatal, are frequent in survivors 10 years after TBI. However, some of the side effects observed shortly after TBI either disappeared or remained unchanged without signs of evolution. Monitoring is recommended to pursue secondary prevention strategies and counseling on family planning.

Disease-specific hematopoietic stem cell transplantation in children with inherited bone marrow failure syndromes.

PubMed

Li, Qian; Luo, Changying; Luo, Chengjuan; Wang, Jianmin; Li, Benshang; Ding, Lixia; Chen, Jing

2017-08-01

Hematopoietic stem cell transplantation (HSCT) using an optimized conditioning regimen is essential for the long-term survival of patients with inherited bone marrow failure syndromes (IBMFS). We report HSCT in 24 children with Fanconi anemia (FA, n = 12), Diamond-Blackfan anemia (DBA, n = 7), and dyskeratosis congenita (DC, n = 5) from a single HSCT center. The graft source was peripheral blood stem cells (n = 19) or cord blood stem cells (n = 5). FA and DC patients received reduced-intensity conditioning, while DBA patients had myeloablative conditioning. The median numbers of infused mononuclear cells and CD34+ cells were 14.20 × 10 8 /kg and 4.3 × 10 6 /kg, respectively. The median time for neutrophil and platelet recovery was 12 and 18 days, respectively. Complete donor engraftment was achieved in 23 of 24 patients. There was one primary graft failure. During a median follow-up of 27.5 months (range, 2-130 months), the overall survival in all patients was 95.8%. The incidence of grade II-III acute graft versus host disease (GvHD) and chronic GvHD was 29.2% and 16.7%, respectively. We conclude that HSCT can be a curative option for patients with IBMFS. Modification of the conditioning regimen based on the type of disease may lead to encouraging long-term outcomes.

Pre-transplantation risk factors to develop sclerotic chronic GvHD after allogeneic HSCT: a multicenter retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

PubMed

Detrait, M Y; Morisset, S; Peffault de Latour, R; Yakoub-Agha, I; Crocchiolo, R; Tabrizi, R; Bay, J-O; Chevalier, P; Barraco, F; Raus, N; Vigouroux, S; Magro, L; Mohty, M; Milpied, N; Blaise, D; Socié, G; Michallet, M

2015-02-01

Sclerotic chronic GvHD (cGvHD) is one of the most severe complications after allo-hematopoietic stem cell transplantation (HSCT). Risk factors associated with this complication remain not very well defined. With the aim to define a pre-transplantation risk profile, we have conducted a French retrospective analysis in 705 consecutive patients between 2005 and 2010. Analyses to determine pre-transplantation risk factors included as variables: patient and donor age, kind of donor, HLA matching, ABO matching, sex-matching, diagnosis, stem cell source, gender, GvHD prophylaxis and antithymocyte globulin (ATG) in the conditioning regimen. The cumulative incidence of sclerotic cGvHD was 18% (95% CI, 16.6-19.6) 3 years after onset of cGvHD. In univariate analysis, we found a significantly lower number of sclerotic cGvHD form in patients transplanted from cord blood cells (P=0.0021), in patients with a one mismatched donor (P=0.041) and in patients who had received ATG in the conditioning regimen (P=0.002). In multivariate analysis, factors associated with an increased risk of sclerotic cGvHD were young patient age, multiple myeloma and PBSC as the stem cell source. ATG in conditioning regimen and cord blood unit as the stem cell source were associated with a lower risk.

The Frank Stinchfield Award: the impact of socioeconomic factors on outcome after THA: a prospective, randomized study.

PubMed

Allen Butler, R; Rosenzweig, Seth; Myers, Leann; Barrack, Robert L

2011-02-01

Most studies of total hip arthroplasty (THA) focus on the effect of the type of implant on the clinical result. Relatively little data are available on the impact of the patient's preoperative status and socioeconomic factors on the clinical results following THA. We determined the relative importance of patient preoperative and socioeconomic status compared to implant and technique factors in predicting patient outcome as reflected by scores on commonly utilized rating scales (eg, Harris Hip Score, WOMAC, SF-12, degree of patient satisfaction, or presence or severity of thigh pain) following cementless THA. All patients during the study period were offered enrollment in a prospective, randomized study to receive either a titanium, tapered, proximally coated stem; or a Co-Cr, cylindrical, extensively coated stem; 102 patients were enrolled. We collected detailed patient data preoperatively including diagnosis, age, gender, insurance status, medical comorbidities, tobacco and alcohol use, household income, educational level, and history of treatment for lumbar spine pathology. Clinical evaluation included Harris Hip Score, SF-12, WOMAC, pain drawing, and UCLA activity rating and satisfaction questionnaire. Implant factors included stem type, stem size, fit in the canal, and stem-bone stiffness ratios. Minimum 2 year followup was obtained in 95% of the enrolled patients (102 patients). Patient demographics and preoperative status were more important than implant factors in predicting the presence of thigh pain, dissatisfaction, and a low hip score. The most predictive factors were ethnicity, educational level, poverty level, income, and a low preoperative WOMAC score or preoperative SF-12 mental component score. No implant parameter correlated with outcome or satisfaction. Socioeconomic factors and preoperative status have more impact on the clinical outcome of cementless THA than implant related factors. Level I, prospective, randomized clinical trial. See the guidelines online for a complete description of level of evidence.

A Phase I Study of Reduced-Intensity Conditioning and Allogeneic Stem Cell Transplantation Followed by Dose Escalation of Targeted Consolidation Immunotherapy with Gemtuzumab Ozogamicin in Children and Adolescents with CD33+ Acute Myeloid Leukemia.

PubMed

Zahler, Stacey; Bhatia, Monica; Ricci, Angela; Roy, Sumith; Morris, Erin; Harrison, Lauren; van de Ven, Carmella; Fabricatore, Sandra; Wolownik, Karen; Cooney-Qualter, Erin; Baxter-Lowe, Lee Ann; Luisi, Paul; Militano, Olga; Kletzel, Morris; Cairo, Mitchell S

2016-04-01

Myeloablative conditioning and allogeneic hematopoietic stem cell transplant (alloHSCT) in children with acute myeloid leukemia (AML) in first complete remission (CR1) may be associated with significant acute toxicity and late effects. Reduced-intensity conditioning (RIC) and alloHSCT in children is safe, feasible, and may be associated with less adverse effects. Gemtuzumab ozogamicin (GO) induces a response in 30% of patients with CD33+ relapsed/refractory AML. The dose of GO is significantly lower when combined with chemotherapy. We examined the feasibility and toxicity of RIC alloHSCT followed by GO targeted immunotherapy in children with CD33+ AML in CR1/CR2. Conditioning consisted of fludarabine 30 mg/m2 × 6 days, busulfan 3.2 to 4 mg/kg × 2 days ± rabbit antithymocyte globulin 2 mg/kg × 4 days followed by alloHSCT from matched related/unrelated donors. GO was administered ≥60 days after alloHSCT in 2 doses (8 weeks apart), following a dose-escalation design (4.5, 6, 7.5, and 9 mg/m2). Fourteen patients with average risk AML received RIC alloHSCT and post-GO consolidation: median age 13.5 years at transplant (range, 1 to 21), male-to-female 8:6, and disease status at alloHSCT 11 CR1 and 3 CR2. Eleven patients received alloHSCT from 5-6/6 HLA-matched family donors: 8 received peripheral blood stem cells, 2 received bone marrow, and 1 received related cord blood transplantation. Three patients received an unrelated allograft (two 4-5/6 and one 9/10) from unrelated cord blood unit and bone marrow, respectively. Neutrophil and platelet engraftment was observed in all assessable patients (100%), achieved at median 15.5 days (range, 7 to 31) and 21 days (range, 10 to 52), respectively. Three patients received GO at dose level 1 (4.5 mg/m2 per dose), 5 at dose level 2 (6 mg/m2 per dose), 3 at dose level 3 (7.5 mg/m2 per dose), and 3 at dose level 4 (9 mg/m2 per dose). Three of 14 patients received only 1 dose of GO after alloHSCT. One patient experienced grade III transaminitis, which resolved; no grade IV transaminitis, no grade III/IV hyperbilirubinemia, or sinusoidal obstructive syndrome were observed. The second dose of GO was given at median of 143 days (range, 120 to 209) after alloHSCT. Probability of grades II to IV acute and chronic graft-versus-host disease were 21% and 33.5%, respectively. Probability of overall survival after RIC alloHSCT and GO consolidation at 1 and 5 years was 78% and 61%, respectively. Probability of 5-year event-free survival after RIC alloHSCT and GO consolidation in patients in CR1 was 78%. No dose-limiting toxicities probably or directly related to GO were observed in this cohort. This preliminary data demonstrate that RIC followed by alloHSCT and consolidation with GO appears to be safe in children and adolescents with CD33+ AML in CR1/CR2. A phase II trial is currently underway investigating this approach with a GO dose of 9 mg/m2 per dose. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Acute cholecystitis is a common complication after allogeneic stem cell transplantation and is associated with the use of total parenteral nutrition.

PubMed

Bagley, Stephen J; Sehgal, Alison R; Gill, Saar; Frey, Noelle V; Hexner, Elizabeth O; Loren, Alison W; Mangan, James K; Porter, David L; Stadtmauer, Edward A; Reshef, Ran; Luger, Selina M

2015-04-01

The incidence and risk factors for acute cholecystitis after allogeneic hematopoietic stem cell transplantation (HSCT) are not well defined. Of 644 consecutive adult transplants performed at our institution between 2001 and 2011, acute cholecystitis occurred in the first year of transplant in 32 patients (5.0%). We conducted 2 retrospective case-control studies of this population to determine risk factors for cholecystitis after HSCT and to evaluate the performance of different methods of imaging to diagnosis cholecystitis in patients undergoing HSCT compared with non-HSCT patients. In the HSCT population, development of cholecystitis was associated with an increased 1-year overall mortality rate (62.5% versus 19.8%, P < .001). The risk of developing cholecystitis was higher in patients who received total parenteral nutrition (TPN) (adjusted odds ratio, 3.41; P = .009). There was a trend toward more equivocal abdominal ultrasound findings in HSCT recipients with acute cholecystitis compared with nontransplant patients (50.0% versus 30.6%, P = .06). However, hepatobiliary iminodiacetic acid (HIDA) scans were definitively positive for acute cholecystitis in most patients in both populations (80.0% of HSCT recipients versus 77.4% of control subjects, P = .82). In conclusion, acute cholecystitis is a common early complication of HSCT, the risk is increased in patients who receive TPN, and it is associated with high 1-year mortality. In HSCT recipients with findings suggestive of acute cholecystitis, especially those receiving TPN, early use of HIDA scan may be considered over ultrasound. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Cytomegalovirus retinitis in a patient with secondary acute lymphosarcoma leukemia undergoing allogeneic hematopoietic stem-cell transplantation: A rare case report: a care-compliant article.

PubMed

Zhao, Ning; Liu, Lei; Xu, Junjie

2017-05-01

Cytomegalovirus (CMV) retinitis is a common opportunistic infection in immunocompromised patients, which may lead to blindness. CMV retinitis is not an uncommon infectious disease in patients with immune regulatory abnormalities, for example, human immunodeficiency virus (HIV) patients. However, CMV retinitis in a patient with acute lymphosarcoma leukemia (ALL) undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) phase is very rare. A case of CMV retinitis in a patient receiving immunosuppressive therapy as a part of ALL allogeneic HSCT is described including the pathogenesis, clinical signs, and therapy. CMV retinitis. Ganciclovir intravitreal injection at weekly intervals for 4 weeks. Patient's vision had improved and the load of CMV deoxyribonucleic acid (DNA) in the aqueous humor declined. The CMV retinitis and perivascular of retina infiltration regressed. We propose that the concentration of CMV DNA load in the aqueous humor could be useful in making the diagnosis and in selecting the optimal treatment in this kind of CMV retinitis.

[High dosage therapy and autologous peripheral stem cell transplantation in breast carcinoma].

PubMed

Kier, P; Ruckser, R; Buxhofer, V; Habertheuer, K H; Zelenka, P; Tatzreiter, G; Hübl, G; Kittl, E; Hauser, A; Sebesta, C; Hinterberger, W

2000-01-01

42 breast cancer patients were treated by high-dose chemotherapy (HDC) and autologous peripheral stem-cell transplantation (ASTx) in the Donauspital between 1992 and 1999. 24 patients had stage II/III breast cancer with high risk for relapse. The other 18 patients underwent HDC and ASTx in chemosensitive stage IV. After previous conventional chemotherapy peripheral stem-cells were harvested by one cycle of mobilisation chemotherapy (epirubicin/taxol, FEC 120 or cyclophosphamide) followed by cytokine stimulation. 16 patients were treated by a tandem transplantation (conditioning protocol for 1st ASTx was melphalan 200 mg/m2 and for 2nd transplant it was CTC: cyclophosphamide 6 g/m2; thiotepa 500 mg/m2; carboplatin 800 mg/m2). The other 26 patients received one HDC with CTC as conditioning protocol. The HDC was well tolerated by all patients, there was no transplant-related mortality. The median survival and the progression-free survival (PFS) after HDC and ASTx in stage IV breast cancer patients were 28 and 11 months, respectively. The median survival and PFS were not yet reached in stage II/III patients after 55 months. The actuarial survival and PFS in that patient group were 70% after 55 months. Our data confirm the low risk and good efficacy of HDC and ASTx in breast cancer patients. Nevertheless randomised studies are necessary to evaluate the importance of HDC compared to intensified conventional protocols without ASTx.

International stem cell tourism and the need for effective regulation. Part II: Developing sound oversight measures and effective patient support.

PubMed

Cohen, Cynthia B; Cohen, Peter J

2010-09-01

Part I of this article, published in the March 2010 issue of the Kennedy Institute of Ethics Journal, traces and addresses the provision of unproven stem cell treatments in Russia and India, examines the concept of innovative treatment, and concludes that stronger regulations are needed to protect the health and informed choices of patients. The current paper, Part II, proposes that the regulatory frameworks for the development of safe and efficacious treatments in effect in the United States and the United Kingdom provide examples of strong oversight measures from which countries seeking to obtain international credibility for their biotechnological competence could draw when developing regulations for stem cell treatments. Major sources of information available to persons who consider receiving such unproven treatments are explored in order to understand and address their concerns. The paper concludes with proposed measures to inform those considering the pursuit of unproven stem cell treatments abroad more accurately about their efficacy and safety and provide them with improved medical and social support in their home countries.

Causes of mortality after haploidentical hematopoietic stem cell transplantation and the comparison with HLA-identical sibling hematopoietic stem cell transplantation.

PubMed

Yan, C H; Xu, L P; Wang, F R; Chen, H; Han, W; Wang, Yu; Wang, J Z; Liu, K Y; Huang, X J

2016-03-01

This study was performed to investigate incidence, causes and factors influencing mortality after haploidentical hematopoietic stem cell transplantation (HSCT) and to compare differences between haploidentical HSCT and HLA-identical sibling HSCT. From January 2000 to June 2011, 1411 patients with acute leukemia or myelodysplastic syndrome were included in this study. Of these patients, 571 received HLA-identical sibling HSCT and 840 received haploidentical HSCT. The cumulative incidence of overall mortality and transplant-related mortality (TRM) after haploidentical HSCT was higher than those after HLA-identical sibling HSCT (38.7% vs. 33.3%, P=0.012 and 27.5% vs. 19.9%, P=0.002), but the incidence of relapse-related mortality (RRM) did not differ between the two groups (15.6% vs. 16.7%, P=0.943). A multivariate analysis suggested that high-risk disease status and haploidentical HSCT correlated with a higher incidence of overall mortality (P<0.0001, hazard ratio=1.911 and P=0.019, hazard ratio=1.249); in addition, in haploidentical HSCT, only high-risk disease status correlated with a higher incidence of overall mortality (P<0.0001, hazard ratio=1.845). Our study suggested that haploidentical HSCT provided a higher incidence of overall mortality and TRM but the same incidence of RRM compared with HLA-identical sibling HSCT. Therefore, HLA-identical sibling HSCT remains the first choice, but haploidentical HSCT is available for patients without an HLA-identical sibling donor.

Cytokine-primed bone marrow stem cells vs. peripheral blood stem cells for autologous transplantation: a randomized comparison of GM-CSF vs. G-CSF.

PubMed

Weisdorf, D; Miller, J; Verfaillie, C; Burns, L; Wagner, J; Blazar, B; Davies, S; Miller, W; Hannan, P; Steinbuch, M; Ramsay, N; McGlave, P

1997-10-01

Autologous transplantation for non-Hodgkins lymphoma and Hodgkin's disease is widely used as standard therapy for those with high-risk or relapsed tumor. Peripheral blood stem cell (PBSC) collections have nearly completely replaced bone marrow stem cell (BMSC) harvests because of the perceived advantages of more rapid engraftment, less tumor contamination in the inoculum, and better survival after therapy. The advantage of PBSC, however, may derive from the hematopoietic stimulating cytokines used for PBSC mobilization. Therefore, we tested a randomized comparison of GM-CSF vs. G-CSF used to prime either BMSC or PBSC before collection for use in autologous transplantation. Sixty-two patients receiving transplants (31 PBSC; 31 BMSC) for non-Hodgkin's lymphoma (n = 51) or Hodgkin's disease (n = 11) were treated. All patients received 6 days of randomly assigned cytokine. Those with cellular marrow in morphologic remission underwent BMSC harvest, while those with hypocellular marrow or microscopic marrow tumor involvement had PBSC collected. Neutrophil recovery was similarly rapid in all groups (median 14 days; range 10-23 days), though two patients had delayed neutrophil recovery using GM-CSF primed PBSC (p = 0.01). Red cell and platelet recovery were significantly quicker after BMSC mobilized with GM-CSF or PBSC mobilized with G-CSF. This speedier hematologic recovery resulted in earlier hospital discharge as well. However, in multivariate analysis, neither the stem cell source nor randomly assigned G-CSF vs. GM-CSF was independently associated with earlier multilineage hematologic recovery or shorter hospital stay. Relapse-free survival was not independently affected by either the assigned stem cell source or the randomly assigned priming cytokine, though malignant relapse was more frequent in those assigned to PBSC (RR of relapse 3.15, p = 0.03). These data document that BMSC, when collected following cytokine priming, can yield a similarly rapid hematologic recovery and short hospital stay compared with cytokine-primed PBSC. Using primed BMSC, no difference in malignant relapse or relapse-free survival was observed. These findings suggest that despite widespread use of PBSC for transplantation, BMSC, when collected following hematopoietically stimulating cytokines, may remain a satisfactory source of stem cells for autologous transplantation. G-CSF and GM-CSF are both effective in priming autologous PBSC or BMSC for collection.

Response to anti-programmed cell death protein-1 antibodies in men treated for platinum refractory germ cell cancer relapsed after high-dose chemotherapy and stem cell transplantation.

PubMed

Zschäbitz, Stefanie; Lasitschka, Felix; Hadaschik, Boris; Hofheinz, Ralf-Dieter; Jentsch-Ullrich, Kathleen; Grüner, Marcus; Jäger, Dirk; Grüllich, Carsten

2017-05-01

Treatment options for patients with platinum refractory metastatic germ cell tumours (GCT) relapsing after high-dose chemotherapy and autologous stem cell transplantation are limited and survival is poor. Antibodies directed against programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) are currently assessed within clinical trials. We present updated data on our experience with checkpoint inhibitors as a compassionate use off-label treatment attempt for highly-pretreated patients with GCT and provide an overview of the current literature on PD-L1 expression in this rare tumour entity. We analysed all patients with platinum refractory GCT treated with checkpoint inhibitors at our institutions between 2015 and 2017. Data were retrieved retrospectively from the patient charts. Seven patients were treated with nivolumab or pembrolizumab. Four patients received single-dose treatment and died shortly afterwards due to tumour progression; the remaining three patients received treatment for at least 6 months. No significant treatment toxicity was observed. Long-term tumour response was achieved in two of the three patients, both of them highly positive for PD-L1 staining. We consider checkpoint inhibition to be efficient in carefully selected patients with platinum refractory GCT. However, predictive markers associated with tumour response are not yet known and larger prospective clinical trials are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Outcomes of allogeneic stem cell transplantation in patients with paroxysmal nocturnal hemoglobinuria with or without aplastic anemia.

PubMed

Lee, Sung-Eun; Park, Sung Soo; Jeon, Young-Woo; Yoon, Jae-Ho; Cho, Byung-Sik; Eom, Ki-Sung; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Kim, Hee-Je; Cho, Seok-Goo; Kim, Dong-Wook; Min, Woo-Sung; Lee, Jong Wook

2017-10-01

The aim of this study was to evaluate the long-term outcomes of allogeneic stem cell transplantation (SCT) in patients with paroxysmal nocturnal hemoglobinuria (PNH) with or without aplastic anemia (AA). A total of 33 patients with PNH clones who underwent allogeneic SCT were analyzed. After a median follow-up of 57 months (range, 6.0-151.3), the 5-year estimated overall survival rate was 87.9±5.7%. Four patients died of transplant-related mortality (TRM). With the exception of one patient with early TRM, 32 patients were engrafted. Two patients who had developed delayed GF received a second transplant and recovered. The cumulative incidences of acute graft-vs-host disease (GVHD) (≥grade II) and chronic GVHD (≥moderate) were 27.3±7.9% and 18.7±7.0%, respectively. Twenty-one patients receiving SCT with reduced-intensity conditioning (RIC) had available follow-up data for PNH cell population for the first 6 months post-transplant. Analysis of these data revealed that the PNH clones disappeared within approximately 2 months. RIC regimen was sufficient to eradicate PNH clones with sustained donor-type engraftment after allogeneic SCT. Therefore, application of allogeneic SCT with RIC should be considered in patients with PNH, in accordance with the severity of the underlying bone marrow failure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation

PubMed Central

Dudley, Mark E.; Carpenter, Robert O.; Kassim, Sadik H.; Rose, Jeremy J.; Telford, William G.; Hakim, Frances T.; Halverson, David C.; Fowler, Daniel H.; Hardy, Nancy M.; Mato, Anthony R.; Hickstein, Dennis D.; Gea-Banacloche, Juan C.; Pavletic, Steven Z.; Sportes, Claude; Maric, Irina; Feldman, Steven A.; Hansen, Brenna G.; Wilder, Jennifer S.; Blacklock-Schuver, Bazetta; Jena, Bipulendu; Bishop, Michael R.; Gress, Ronald E.; Rosenberg, Steven A.

2013-01-01

New treatments are needed for B-cell malignancies persisting after allogeneic hematopoietic stem cell transplantation (alloHSCT). We conducted a clinical trial of allogeneic T cells genetically modified to express a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19. T cells for genetic modification were obtained from each patient’s alloHSCT donor. All patients had malignancy that persisted after alloHSCT and standard donor lymphocyte infusions (DLIs). Patients did not receive chemotherapy prior to the CAR T-cell infusions and were not lymphocyte depleted at the time of the infusions. The 10 treated patients received a single infusion of allogeneic anti-CD19-CAR T cells. Three patients had regressions of their malignancies. One patient with chronic lymphocytic leukemia (CLL) obtained an ongoing complete remission after treatment with allogeneic anti-CD19-CAR T cells, another CLL patient had tumor lysis syndrome as his leukemia dramatically regressed, and a patient with mantle cell lymphoma obtained an ongoing partial remission. None of the 10 patients developed graft-versus-host disease (GVHD). Toxicities included transient hypotension and fever. We detected cells containing the anti-CD19-CAR gene in the blood of 8 of 10 patients. These results show for the first time that donor-derived allogeneic anti-CD19-CAR T cells can cause regression of B-cell malignancies resistant to standard DLIs without causing GVHD. This trial was registered at www.clinicaltrials.gov as #NCT01087294. PMID:24055823

Low, fixed dose defibrotide in management of hepatic veno-occlusive disease post stem cell transplantation.

PubMed

Bagal, Bhausaheb; Chandrasekharan, Arun; Chougle, Aliya; Khattry, Navin

2018-03-01

Hepatic veno-occlusive disease (VOD) is well recognized potentially serious regimen-related toxicity seen after stem cell transplantation. Severe VOD is associated with poor long-term outcomes with very high mortality. Besides supportive care, only defibrotide has been found to be effective in the management of VOD. The recommended dose of defibrotide is 25mg/kg/d but there has been no classical dose finding study done for this drug. A higher dose of defibrotide is associated with increased risk of bleeding and this drug is prohibitively expensive. We report our experience of using fixed low dose of defibrotide in patients with VOD. We retrospectively evaluated 511 patients who underwent stem cell transplant at our center from November 2007 and December 2015. All patients received ursodeoxycholic acid as VOD prophylaxis. Modified Seattle criterion was used for diagnosis and severity grading of VOD. Patients developing VOD were initially treated with furosemide and adequate analgesia. Defibrotide was started within 12 to 24 hours of diagnosis of VOD. All adult patients received defibrotide at a fixed dose of 200mg twice daily while two children were given dose of 100mg and 50mg twice daily. Nine (1.7%) of our patients developed VOD. Daily dose of defibrotide ranged from 5mg/kg/d to 20mg/kg/d till resolution of VOD. All patients had complete resolution of VOD. None of our patients required ventilator support or dialysis. No episodes of bleeding were observed. No dose response relationship was observed between defibrotide dose and time to resolution of VOD. Low fixed dose defibrotide initiated early seems to be effective and safe in treatment of VOD. This is relevant in a resource limited setting and warrants prospective evaluation. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Brief oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients.

PubMed

Mori, Takehiko; Yamazaki, Rie; Aisa, Yoshinobu; Nakazato, Tomonori; Kudo, Masumi; Yashima, Tomoko; Kondo, Sakiko; Ikeda, Yasuo; Okamoto, Shinichiro

2006-04-01

We previously reported the efficacy of oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis. The purpose of this study was to evaluate whether the further shortening of the duration of oral cryotherapy could minimize its side effects while sparing its efficacy. Seventeen consecutive recipients of allogeneic hematopoieic stem cell transplant conditioned with high-dose melphalan in combination with fludarabine alone or with fludarabine and additional radiation were enrolled in the study. The severity of stomatitis was graded according to the National Cancer Institute-Common Toxicity Criteria. Patients were kept on oral cryotherapy shortly before, during, and for additional 30 min after the completion of melphalan administration (60-min oral cryotherapy). Patients who were also enrolled in our previous study received the same type of oral cryotherapy but for additional 90 min after the completion of melphalan administration (120-min oral cryotherapy), and they served as controls. Only 2 (11.8%) of 17 patients receiving 60-min oral cryotherapy and 2 (11.1%) of 18 patients receiving 120-min oral cryotherapy developed grade 2 or 3 stomatitis, respectively. The difference between groups was not statistically significant (P = 0.677). The incidence of unpleasant symptoms such as chills and nausea during oral cryotherapy decreased significantly with 60-min oral cryotherapy, as compared with that associated with 120-min oral cryotherapy (P < 0.01). These results suggest that 60-min oral cryotherapy is as effective as 120-min oral cryotherapy at preventing high-dose melphalan-induced stomatitis, and shorter treatment might have contributed to relieve patient discomfort during oral cryotherapy.

No pain, no gain: lack of exercise obstructs neurogenesis.

PubMed

Watson, Nate; Ji, Xunming; Yasuhara, Takao; Date, Isao; Kaneko, Yuji; Tajiri, Naoki; Borlongan, Cesar V

2015-01-01

Bedridden patients develop atrophied muscles, their daily activities greatly reduced, and some display a depressive mood. Patients who are able to receive physical rehabilitation sometimes show surprising clinical improvements, including reduced depression and attenuation of other stress-related behaviors. Regenerative medicine has advanced two major stem cell-based therapies for CNS disorders, namely, transplantation of exogenous stem cells and amplification of endogenous neurogenesis. The latter strategy embraces a natural way of reinnervating the damaged brain and correcting the neurological impairments. In this study, we discussed how immobilization-induced disuse atrophy, using the hindlimb suspension model, affects neurogenesis in rats. The overarching hypothesis is that immobilization suppresses neurogenesis by reducing the circulating growth or trophic factors, such as vascular endothelial growth factor or brain-derived neurotrophic factor. That immobilization alters neurogenesis and stem cell differentiation in the CNS requires characterization of the stem cell microenvironment by examining the trophic and growth factors, as well as stress-related proteins that have been implicated in exercise-induced neurogenesis. Although accumulating evidence has revealed the contribution of "increased" exercise on neurogenesis, the reverse paradigm involving "lack of exercise," which mimics pathological states (e.g., stroke patients are often immobile), remains underexplored. This novel paradigm will enable us to examine the effects on neurogenesis by a nonpermissive stem cell microenvironment likely produced by lack of exercise. BrdU labeling of proliferative cells, biochemical assays of serum, cerebrospinal fluid and brain levels of trophic factors, growth factors, and stress-related proteins are proposed as indices of neurogenesis, while quantitative measurements of spontaneous movements will reveal psychomotor components of immobilization. Studies designed to reveal how in vivo stimulation, or lack thereof, alters the stem cell microenvironment are needed to begin to develop treatment strategies for enhancing neurogenesis in bedridden patients.

Myocardial regeneration potential of adipose tissue-derived stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bai, Xiaowen, E-mail: baixw01@yahoo.com; Alt, Eckhard, E-mail: ealt@mdanderson.org

Research highlights: {yields} Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. {yields} For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. {yields} This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derivedmore » stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the underlying mechanisms for beneficial effect on cardiac function, and safety issues.« less

Comparative pharmacokinetic study of high-dose etoposide and etoposide phosphate in patients with lymphoid malignancy receiving autologous stem cell transplantation.

PubMed

Dorr, R T; Briggs, A; Kintzel, P; Meyers, R; Chow, H-H S; List, A

2003-04-01

The pharmacokinetics of two etoposide (E) formulations were evaluated in patients with refractory hematologic malignancies receiving high-dose conditioning with autologous stem cell transplantation. Patients were randomized to either E at 800 mg/m(2) (containing polysorbate 80 and polyethylene glycol) or etoposide phosphate (EP) at 910 mg/m(2) on days -7 and -5, prior to melphalan, 80 mg/m(2) on day -5. On day -3, EP was repeated. Plasma E was analyzed after each formulation on days -7 and -5 to compare intrapatient pharmacokinetics. In total, 10 patients were treated: four each with multiple myeloma or Hodgkin's disease and two with non-Hodgkin's lymphoma. Mucositis was the major toxicity with seven patients. EP first produced grade 3 mucositis. There was no procedure-related mortality and eight patients remained alive 1 year post-transplant. Cumulative etoposide exposure (AUC) was slightly greater with EP (P=0.056). Conversely, the volume of distribution was slightly, 33%, larger (P=0.052) and clearance was increased with the E infusion (P=0.14). As none of the differences reached statistical significance, both E formulations appear to be pharmacokinetically equivalent in the high-dose transplant setting. The combination of high-dose EP with melphalan is an active preparative regimen prior to ABMT for hematologic malignancies.

Outcome after intensive reinduction therapy and allogeneic stem cell transplant in paediatric relapsed acute myeloid leukaemia.

PubMed

Karlsson, Lene; Forestier, Erik; Hasle, Henrik; Jahnukainen, Kirsi; Jónsson, Ólafur G; Lausen, Birgitte; Norén Nyström, Ulrika; Palle, Josefine; Tierens, Anne; Zeller, Bernward; Abrahamsson, Jonas

2017-08-01

Given that 30-40% of children with acute myeloid leukaemia (AML) relapse after primary therapy it is important to define prognostic factors and identify optimal therapy. From 1993 to 2012, 543 children from the Nordic countries were treated according to two consecutive protocols: 208 children relapsed. The influence of disease characteristics, first line treatment, relapse therapy and duration of first remission on outcome was analysed. Second complete remission (CR2) was achieved in 146 (70%) patients. Estimated 5-year overall survival (OS 5y ) was 39 ± 4% for the whole group and 43 ± 4% for the 190 patients given re-induction therapy, of whom 76% received regimens that included fludarabine, cytarabine (FLA) ± anthracyclines, 18% received Nordic Society for Paediatric Haematology and Oncology (NOPHO) upfront blocks and 5% received other regimens. Late relapse ≥1 year from diagnosis, no allogeneic stem cell transplantation (SCT) in first remission and core binding factor AML were independent favourable prognostic factors for survival. For the 128 children (124 in CR2) that received SCT as consolidation therapy after relapse, OS 5y was 61 ± 5%. Four of 19 children (21%) survived without receiving SCT as part of relapse therapy. Our data show that intensive re-induction followed by SCT can give cure rates of 40% in children with relapsed AML. © 2017 John Wiley & Sons Ltd.

Gemcitabine, Fludarabine, and Melphalan for Reduced-Intensity Conditioning and Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma.

PubMed

Anderlini, Paolo; Saliba, Rima M; Ledesma, Celina; Plair, Tamera; Alousi, Amin M; Hosing, Chitra M; Khouri, Issa F; Nieto, Yago; Popat, Uday R; Shpall, Elizabeth J; Fanale, Michelle A; Hagemeister, Frederick B; Oki, Yasuhiro; Neelapu, Saatva; Romaguera, Jorge E; Younes, Anas; Champlin, Richard E

2016-07-01

Forty patients (median age, 31 years; range, 20 to 63) with Hodgkin lymphoma underwent an allogeneic stem cell transplant with the gemcitabine-fludarabine-melphalan reduced-intensity conditioning regimen. Thirty-one patients (77%) had undergone a prior autologous stem cell transplant, with a median time to progression after transplant of 6 months (range, 1 to 68). Disease status at transplant was complete remission/complete remission, undetermined (n = 23; 57%), partial remission (n = 14; 35%), and other (n = 3; 8%). Twenty-six patients (65%) received brentuximab vedotin before allotransplant. The overall complete response rate before allotransplant was 65% in brentuximab-treated patients versus 42% in brentuximab-naive patients (P = .15). At the latest follow-up (October 2015) 31 patients were alive. The median follow-up was 41 months (range, 5 to 87). Transplant-related mortality rate at 3 years was 17%. Pulmonary, skin toxicities, and nausea were seen in 13 (33%), 11 (28%), and 37 (93%) patients, respectively. At 3 years, estimates for overall and progression-free survival were 75% (95% CI, 57% to 86%) and 54% (95% CI, 36% to 70%). Overall incidence for disease progression was 28% (95% CI, 16% to 50%). We believe the gemcitabine-fludarabine-melphalan regimen allows moderate dose intensification with acceptable morbidity and mortality. The inclusion of gemcitabine affected nausea, pulmonary, and likely skin toxicity. Exposure to brentuximab vedotin allowed more patients to reach allogeneic stem cell transplantation in complete remission. With over 50% of patients progression-free at 3 years, allogeneic stem cell transplantation with reduced-intensity conditioning remains an effective and relevant treatment option for Hodgkin lymphoma in the brentuximab vedotin era. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

[Combined therapy for children and adolescents with Ewing tumors (a 25-year experience)].

PubMed

Yukhta, T V; Punanov, Yu A; Kazantsev, I V; Malinin, A P; Safonova, S A; Gafton, G I; Gevorgyan, A G; Morozova, E V; Zubarovskaya, L S; Fanasiev, B V A

2015-01-01

A total of 115 children (median age 10.5 years, range 2-17) with Ewing sarcoma family tumors (ESFT) received therapy in N.N. Petrov Institute of Oncology pediatric department from April 1985 till August 2013. These patients were divided into two groups depending on treatment tactics used: patients treated according to modified T9 protocol (n = 64) and patients treated according to EICESS-92 or Euro-Ewing 99 regimens (n = 51). Twenty four patients from the second group with adverse prognostic factors received high-dose chemotherapy with autologous stem cell transplantation. All patients received surgical treatment and/or irradiation for primary tumor local control. Five-year overall and disease-free survival was 39% and 37,9% in the first group. In the second group these values were significantly higher; 55% and 39.5%, accordingly (p = 0.03 and 0.25). All patients from the first group with primary metastatic ESFT died of disease progression, while in the second group OS and DFS reached 45.8% and 28.9%, accordingly. There was a statistically significant correlation between local relapse rate and irradiation dose biological equivalent (in TDF units). The local relapse cumulative rate was minimal (12,6%) in patients receiving 80 TDF.

Risk-adapted, treosulfan-based therapy with auto- and allo-SCT for relapsed/refractory aggressive NHL: a prospective phase-II trial.

PubMed

Koenigsmann, M; Casper, J; Kahl, C; Basara, N; Sayer, H G; Behre, G; Theurich, S; Christopeit, M; Mohren, M; Reichle, A; Metzner, B; Ganser, A; Stadler, M; Uharek, L; Balleisen, L; Hinke, A; Hinke, R; Niederwieser, D

2014-03-01

Since the outcome of relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL) is highly variable, a risk-adapted treatment approach was evaluated. After two cycles of DHAP, patients received high-dose treosulfan/etoposide/carboplatinum (TEC) and autologous stem cell rescue. After TEC, low-risk patients with late relapse (>1 year after first CR who achieved CR after DHAP received no further treatment. Patients with late relapse who achieved CR or PR only after TEC underwent a second cycle of TEC. High-risk patients with early relapse/refractory disease received treosulfan/fludarabine followed by allogeneic transplantation. Rituximab was added in patients with B-cell lymphoma (86%). At entry, 36% of all 57 patients had refractory disease, 32% early and 32% late relapse. During DHAP treatment, progression occurred in 32% of patients. Of 33 patients who received TEC, 5 received second TEC and 15 allogeneic transplantation. Main toxicity after TEC was oral mucositis (CTC grades 3 and 4 in 50% and 13%, respectively). In total, 42% patients achieved CR. Median OS was 21.4 months for all patients and 32.6 for those who underwent allogeneic transplantation. International prognostic index (IPI) at study entry was highly discriminative at predicting OS (P<0.0001). Risk-adapted, treosulfan-based therapy with auto- and allo-SCT is feasible. Long-term survival is possible with allogeneic transplantation.

Five year follow-up after autologous peripheral blood hematopoietic stem cell transplantation for refractory, chronic, corticosteroid-dependent systemic lupus erythematosus: effect of conditioning regimen on outcome.

PubMed

Burt, Richard K; Han, Xiaoqiang; Gozdziak, Paula; Yaung, Kim; Morgan, Amy; Clendenan, Allison M; Henry, Jacquelyn; Calvario, Michelle A; Datta, Syamal K; Helenowski, Irene; Schroeder, James

2018-05-31

Some patients with systemic lupus erythematosus (SLE) are refractory to traditional therapies, dependent on chronic corticosteroids, have organ damage, and are at high risk of mortality. In this group of patients, we report outcome at a median of five years after autologous hematopoietic stem cell transplant (HSCT) using two different non-myeloablative regimens. Four patients received a conditioning regimen of cyclophosphamide (200 mg/kg) and alemtuzumab (60 mg), while 26 patients underwent conditioning with cyclophosphamide (200 mg/kg), rATG (Thymoglobulin) (5.5 mg/kg), and rituximab 1000 mg. Unselected peripheral blood stem cells were infused on day 0. There were no treatment related deaths. Of the four patients treated with cyclophosphamide and alemtuzumab, none entered remission. For the 26 patients treated with cyclophosphamide, rATG, and rituximab, disease remission defined as no immune suppressive drugs except hydroxychloroquine and/or 10 mg or less of prednisone a day was 92% at 6 months, 92% at one year, 81% at 2 years, 71% at 3 years, and 62% at 4 and 5 years post-HSCT. Autologous HSCT outcome is dependent on the conditioning regimen but prior organ damage may cause lingering symptoms.

Caregiver burden among primary caregivers of patients undergoing peripheral blood stem cell transplantation: a cross sectional study.

PubMed

Akgul, Nur; Ozdemir, Leyla

2014-08-01

This study aimed to identify caregiver burden and influencing factors on the burden in primary caregivers of peripheral blood stem cell transplantation patients within 2-12 months following transplant, indicating early recovery period after discharge. This descriptive cross sectional study was carried out at hematopoietic stem cell transplantation outpatient units of three university hospitals in Turkey. A total of 55 patient and caregiver dyads were recruited and interviewed. The data were collected using questionnaires developed by the researchers and caregiver burden was measured with the Zarit Burden Interview. The mean score of Zarit Burden Interview was 28.41 (SD = 13.90). Patients' symptoms including nausea and self depreciation feeling were related to greater caregiver burden. Self-depreciation was referred to feeling undervalued. The mean score of the tool was significantly higher in caregivers who have not been educated beyond primary school and also caregivers who had lower income. Caregivers who supported their patients to fulfill physical needs and who did not receive help for meeting patients' psychological needs had statistically more elevated levels of burden. Moreover, the extent of care giving activities undertaken was positively correlated with caregiver burden scores. While positive impact of the care giving process on family relations decreased caregiver burden; negative effect increased the burden. This study suggests that caregiver burden of primary caregivers caring for peripheral blood stem cell transplantation patients varies by education, income status, and the extent of care giving activities undertaken. Changes in family ties and relations due to care giving effected caregiver burden. Copyright © 2014 Elsevier Ltd. All rights reserved.

Spontaneous transient rise of CD34 cells in peripheral blood after 72 hours in patients suffering from advanced malignancy with anemia: effect and prognostic implications of treatment with placental umbilical cord whole blood transfusion.

PubMed

Bhattacharya, N

2006-01-01

Cord blood, because of its rich mix of fetal and adult hemoglobin, platelet and WBC counts, and a plasma filled with cytokine and growth factors, as well as its hypoantigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood during emergencies or any etiology of blood loss. In the present study transfusion-related CD34 levels of the peripheral blood from six randomly selected patients suffering from advanced clinical Stage IV malignancy were analyzed between 16 August 1999 and 16 May 2001. This study attempts to ascertain the fate of hematopoietic stem cells (CD34) after placental umbilical cord whole blood transfusion, as assessed from the peripheral blood CD34 level 72 hours after cord blood transfusion in sex- and HLA-randomized patients. Among the six cases, Case 2 (breast sarcoma) received the lowest amount of card blood (6 units), while Case 6 (breast cancer) received the largest amount (32 units). The youngest patient, suffering from non-Hodgkin's lymphoma (Case 3), was a 16-year-old boy who received eight units of cord blood to combat anemia. Other patients received amounts varying from 7-15 units: Case 4 received 15 units (metachronous lymph node metastatsis), Case 1 received 14 units (breast cancer), and Case 5 received seven units (lung cancer). There was no transfusion-related clinical immunological or nonimmunological reaction. Studies of CD34 levels showed an initial rise followed by a fall in two cases, two cases registered very little effect on the CD34 level, i.e., no change from the baseline, and one case demonstrated a very slow rise from the baseline. However, one case showed a frequent steep rise up to 99% and a sustained high CD34 level. This patient is alive with clinical remission of the disease. It appears from this preliminary study that freshly collected cord blood transfusion may cause a transient transplant impact of transfused cord blood CD34 stem cells on the host without provoking clinical graft vs host disease due to a of background immune suppression in advanced malignancy. The growth factor cytokine system of freshly collected cord blood may have a potentiating role on the immune system of the host.

Chemomobilization: Overview of an Educational Quality Improvement Project for Recipients of Autologous Stem Cell Transplantation
.

PubMed

Rivera, Zandra R; Nurse, Rachelle; Fellman, Bryan; Brunelle, Nicole; Brassil, Kelly J

2017-08-01

In preparation for an autologous stem cell transplantation, patients undergo chemomobilization; however, a dearth of standardized, evidence-based patient education on chemomobilization exists in the literature and in practice.
. The purpose of this quality improvement educational initiative is to identify an 
evidence-based approach to appraise the educational needs of patients and their caregivers and to enhance chemomobilization education. 
. A review of the literature related to chemomobilization was conducted, as well as an informal survey of educational practices at five 
National Cancer Institute-designated comprehensive cancer centers. A 14-item survey was administered to 50 patients who underwent chemomobilization to assess their educational needs, experiences, and preferences. 
. Patients prefer written information to review. Receiving verbal education from reliable healthcare providers in a structured format may enhance effective comprehension and retention. Patients identified timing, process, side effects, and expectations about chemomobilization as the most important topics to include in education.

The effect of long-term lithium treatment of bipolar disorder on stem cells circulating in peripheral blood.

PubMed

Ferensztajn-Rochowiak, Ewa; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy; Ratajczak, Mariusz Z; Michalak, Michal; Rybakowski, Janusz K

2017-02-01

To investigate the effect of long-term lithium treatment on very small embryonic-like stem cells (VSELs), haematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) circulating in peripheral blood (PB), in bipolar disorder (BD). The study included 15 BD patients (aged 55 ± 6 years) treated with lithium for 8-40 years (mean 16 years), 15 BD patients (aged 53 ± 7 years) with duration of illness >10 years, who had never received lithium, and 15 healthy controls (aged 50 ± 5 years). The VSELs, HSCs, MSCs and EPCs were measured by flow cytometric analysis. In BD subjects not taking lithium the number of CD34 +  VSELs was significantly higher, and MSCs and EPCs numerically higher, than in control subjects and the number of CD34 +  VSELs correlated with the duration of illness. In lithium-treated patients these values were similar to controls and the number of CD34 +  VSELs correlated negatively with the duration of lithium treatment and serum lithium concentration. Long-term treatment with lithium may suppress the activation of regenerative processes by reducing the number of VSELs circulating in PB. These cells, in BD patients not treated with lithium, may provide a new potential biological marker of the illness and its clinical progress.

Adjuvant high-dose chemotherapy with autologous hematopoietic stem cell support for high-risk primary breast cancer: results from the Italian national registry.

PubMed

Pedrazzoli, Paolo; Martinelli, Giovanni; Gianni, Alessandro Massimo; Da Prada, Gian Antonio; Ballestrero, Alberto; Rosti, Giovanni; Frassineti, Giovanni Luca; Aieta, Michele; Secondino, Simona; Cinieri, Saverio; Fedele, Roberta; Bengala, Carmelo; Bregni, Marco; Grasso, Donatella; De Giorgi, Ugo; Lanza, Francesco; Castagna, Luca; Bruno, Barbara; Martino, Massimo

2014-04-01

The efficacy of high-dose chemotherapy (HDC) and autologous hemopoietic progenitor cell transplantation (AHPCT) for breast cancer (BC) patients has been an area of intense controversy among the medical oncology community. The aim of this study was to assess toxicity and efficacy of this procedure in a large cohort of high-risk primary BC patients who underwent AHPCT in Italy. A total of 1183 patients receiving HDC for high-risk BC (HRBC) (>3 positive nodes) were identified in the Italian registry. The median age was 46 years, 62% of patients were premenopausal at treatment, 60.1% had endocrine-responsive tumors, and 20.7% had a human epidermal growth factor receptor 2 (HER2)-positive tumor. The median number of positive lymph nodes (LN) at surgery was 15, with 71.5% of patients having ≥ 10 positive nodes. Seventy-three percent received an alkylating agent-based HDC as a single procedure, whereas 27% received epirubicin or mitoxantrone-containing HDC, usually within a multitransplantation program. The source of stem cells was peripheral blood in the vast majority of patients. Transplantation-related mortality was .8%, whereas late cardiac and secondary tumor-related mortality were around 1%, overall. With a median follow-up of 79 months, median disease-free and overall survival (OS) in the entire population were 101 and 134 months, respectively. Subgroup analysis demonstrated that OS was significantly better in patients with endocrine-responsive tumors and in patients receiving multiple transplantation procedures. HER2 status did not affect survival probability. The size of the primary tumor and number of involved LN negatively affected OS. Adjuvant HDC with AHPCT has a low mortality rate and provides impressive long-term survival rates in patients with high-risk primary BC. Our results suggest that this treatment modality should be proposed in selected HRBC patients and further investigated in clinical trials. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

High-dose zinc oral supplementation after stem cell transplantation causes an increase of TRECs and CD4+ naïve lymphocytes and prevents TTV reactivation.

PubMed

Iovino, Lorenzo; Mazziotta, Francesco; Carulli, Giovanni; Guerrini, Francesca; Morganti, Riccardo; Mazzotti, Valentina; Maggi, Fabrizio; Macera, Lisa; Orciuolo, Enrico; Buda, Gabriele; Benedetti, Edoardo; Caracciolo, Francesco; Galimberti, Sara; Pistello, Mauro; Petrini, Mario

2018-05-02

Zinc plays an important role in thymic function and immune homeostasis. We performed a prospective clinical trial using a high-dose zinc oral supplementation to improve the immune reconstitution after hematopoietic stem cell transplant (HSCT). We enrolled 18 patients undergoing autologous HSCT for multiple myeloma. Nine patients were randomized to receive only a standard antimicrobial prophylaxis; whereas, nine patients received in addition 150 mg/day of zinc from day +5 to day +100 after transplant. CD4+ naïve lymphocytes and TRECs showed a significant increase from day +30 until day +100 only in the zinc-treated group. Moreover, the load of Torquetenovirus, a harmless virus that replicates in course of immunedepression, increased at day +100 only in the control group. No severe adverse events were reported during the zinc consumption. First data from the ZENITH trial suggest that high-dose zinc supplementation is safe and may enhance the thymic reconstitution after HSCT. Registered: http://Clinicaltrials.gov (NCT03159845); and EUDRACT: 2014-28 004499-47. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mesenchymal Stem Cells: Time to Change the Name!

PubMed

Caplan, Arnold I

2017-06-01

Mesenchymal stem cells (MSCs) were officially named more than 25 years ago to represent a class of cells from human and mammalian bone marrow and periosteum that could be isolated and expanded in culture while maintaining their in vitro capacity to be induced to form a variety of mesodermal phenotypes and tissues. The in vitro capacity to form bone, cartilage, fat, etc., became an assay for identifying this class of multipotent cells and around which several companies were formed in the 1990s to medically exploit the regenerative capabilities of MSCs. Today, there are hundreds of clinics and hundreds of clinical trials using human MSCs with very few, if any, focusing on the in vitro multipotential capacities of these cells. Unfortunately, the fact that MSCs are called "stem cells" is being used to infer that patients will receive direct medical benefit, because they imagine that these cells will differentiate into regenerating tissue-producing cells. Such a stem cell treatment will presumably cure the patient of their medically relevant difficulties ranging from osteoarthritic (bone-on-bone) knees to various neurological maladies including dementia. I now urge that we change the name of MSCs to Medicinal Signaling Cells to more accurately reflect the fact that these cells home in on sites of injury or disease and secrete bioactive factors that are immunomodulatory and trophic (regenerative) meaning that these cells make therapeutic drugs in situ that are medicinal. It is, indeed, the patient's own site-specific and tissue-specific resident stem cells that construct the new tissue as stimulated by the bioactive factors secreted by the exogenously supplied MSCs. Stem Cells Translational Medicine 2017;6:1445-1451. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Nutrition issues in hematopoietic stem cell transplantation: state of the art.

PubMed

Lipkin, Ann Connell; Lenssen, Polly; Dickson, Barbara J

2005-08-01

There have been many changes in hematopoietic stem cell transplantation (HSCT) that affect the patient's nutrition support. In the early 1970s, allogeneic transplants were the most common types of HSCTs; today, autologous transplants are the most common. Bone marrow, peripheral blood, and umbilical cord blood all now serve as sources of stem cells. Conditioning therapies include myeloablative, reduced-intensity myeloablative, and nonmyeloablative regimens. New medications are being developed and used to minimize the toxicities of the conditioning therapy and to minimize infectious complications. Supportive therapies for renal and liver complications have changed. In the past, HSCT patients received parenteral nutrition (PN) throughout their hospitalization and sometimes as home therapy. Because of medical complications and cost issues associated with PN, many centers are now working to use less PN and increase use of enteral nutrition. The immunosuppressed diet has changed from a sterile diet prepared under laminar-flow hoods to a more liberal diet that avoids high-risk foods and emphasizes safety in food handling practices. This article will review these changes in HSCT and the impact of these changes on the nutrition support of the patient.

Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury.

PubMed

Sureban, Sripathi M; May, Randal; Qu, Dongfeng; Chandrakesan, Parthasarathy; Weygant, Nathaniel; Ali, Naushad; Lightfoot, Stan A; Ding, Kai; Umar, Shahid; Schlosser, Michael J; Houchen, Courtney W

2015-01-01

Gastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis.

Mantle Cell Lymphoma International Prognostic Index but Not Pretransplantation Induction Regimen Predicts Survival for Patients With Mantle-Cell Lymphoma Receiving High-Dose Therapy and Autologous Stem-Cell Transplantation

PubMed Central

Budde, Lihua E.; Guthrie, Katherine A.; Till, Brian G.; Press, Oliver W.; Chauncey, Thomas R.; Pagel, John M.; Petersdorf, Steven H.; Bensinger, William I.; Holmberg, Leona A.; Shustov, Andrei R.; Green, Damian J.; Maloney, David G.; Gopal, Ajay K.

2011-01-01

Purpose High-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) are frequently used in an attempt to improve outcome in patients with mantle-cell lymphoma (MCL); however, the importance of intensive induction regimens before transplantation is unknown. Patients and Methods To address this question, we evaluated baseline characteristics, time to treatment, induction regimen, disease status at the time of transplantation, and MIPI score at diagnosis and their associations with survival in 118 consecutive patients with MCL who received HDT and ASCT at our centers. Results The MIPI was independently associated with survival after transplantation in all 118 patients (hazard ratio [HR], 3.5; P < .001) and in the 85 patients who underwent ASCT as initial consolidation (HR, 7.2; P < .001). Overall survival rates were 93%, 60%, and 32% at 2.5 years from ASCT for all patients with low-, intermediate-, and high-risk MIPI, respectively. Low-risk MIPI scores were more common in the intensive induction group than the standard induction group in all patients (64% v 46%, respectively; P = .03) and in the initial consolidation group (66% v 45%, respectively; P = .03). After adjustment for the MIPI, an intensive induction regimen was not associated with improved survival after transplantation in all patients (HR, 0.5; P = .10), the initial consolidation group (HR, 1.1; P = .86), or patients ≤ 60 years old (HR, 0.6; P = .50). Observation of more than 3 months before initiating therapy did not yield inferior survival (HR, 2.1; P = .12) after adjustment for the MIPI in patients receiving ASCT. Conclusion An intensive induction regimen before HDT and ASCT was not associated with improved survival after adjusting for differences in MIPI scores at diagnosis. PMID:21730271

Severe neuropathy after high dose carboplatin in three patients receiving multidrug chemotherapy

PubMed Central

Heinzlef, O.; Lotz, J.; Roullet, E.

1998-01-01

Three patients are described who developed a severe neuropathy after chemotherapy with high dose cis-diamine-(1,1-cyclobutane dicarboxylato) platinum (carboplatin). This toxic side effect, which is unusual at conventional doses, might become more frequent as increasing doses are administered to overcome drug resistance in cancer treatment, and might limit its use at very high doses before haematopoietic stem cell transplantation. 

 PMID:9598687

Fantasies About Stem Cell Therapy in Chronic Ischemic Stroke Patients

PubMed Central

Kim, Young Seo; Chung, Dan-il; Choi, Hojin; Baek, Wonki; Kim, Hyun Young; Heo, Sung Hyuk; Chang, Dae-Il; Na, Hae Ri; Kim, Seung Hyun

2013-01-01

Stem cell therapy (SCT) has been proposed for the treatment of neurological disorders. Although there is insufficient clinical evidence to support its efficacy, unproven SCTs are being performed worldwide. In this study, we investigated the perspectives and expectations of chronic ischemic stroke patients and physicians about SCTs. A total of 250 chronic ischemic stroke patients were interviewed at 4 hospitals. Structured open and closed questions about SCT for chronic stroke were asked by trained interviewers using the conventional in-person method. In addition, 250 stroke-related physicians were randomly interviewed via an e-mail questionnaire. Of the 250 patients (mean 63 years, 70% male), 121 (46%) responded that they wanted to receive SCT in spite of its unknown side effects. Around 60% of the patients anticipated physical, emotional, and psychological improvement after SCT, and 158 (63%) believed that SCT might prevent strokes. However, physicians had much lower expectations about the effectiveness of SCTs, which was not in line with patient expectations. Multivariate analysis revealed that the male gender [odds ratio (OR): 2.00, 95% confidence interval (CI): 1.10–3.64], longer disease duration (OR: 1.01, 95% CI: 1.00–1.02), higher modified Rankin Scale score (OR: 1.30, 95% CI: 1.06–1.60), and familiarity with stem cells (OR: 1.86, 95% CI: 1.10–3.15) were independently associated with wanting SCT. The major source of information about SCT was television (68%), and the most reliable source was physicians (49%). Patients have unfounded expectations that SCT will improve their functioning. Considering our finding that the major source of information on stem cells is media channels, but not the physician, to decrease patients' inappropriate exposure, doctors should make more effort to educate patients using mass media with accurate information. PMID:22784218

Reduced intensity versus full myeloablative stem cell transplant for advanced CLL.

PubMed

Peres, E; Braun, T; Krijanovski, O; Khaled, Y; Levine, J E; Yanik, G; Kato, K; Mineishi, S

2009-11-01

CLL remains incurable with the standard therapy. Allogeneic hematopoietic stem cell transplant may be curative. We examined 50 patients with advanced CLL who underwent allogeneic HCT at the University of Michigan between 1996 and 2006. Twenty-one patients received reduced-intensity conditioning (RIC) and twenty-nine patients received full-intensity conditioning (FIC) consisting of CY, etoposide and BCNU (n=20) or BU and CY (n=9). RIC recipients were older than FIC recipients (median age 54 vs 51, P=0.009). There were no statistically significant differences between groups in terms of the number of earlier therapies or patients with adverse cytogenetics. There were more unrelated donors in the RIC group 62% than in the FIC group 31% (P=0.030). Despite their older age and greater use of URD, the 5-year overall survival (OS) rate was 63% in the RIC group as compared with 18% in the FIC group (P=0.006). The primary cause of inferior survival in the FIC recipients was TRM, which was twice as high at day 100 for the FIC group 27% compared with the RIC group 14% (P=0.005). The relapse rate was 15% regardless with the majority of relapses occurring after day 100. These results suggest a favorable outcome for advanced CLL who undergo a RIC regimen compared with FIC.

Superior outcome using cyclosporin A alone versus cyclosporin A plus methotrexate for post-transplant immunosuppression in children with acute leukemia undergoing sibling hematopoietic stem cell transplantation.

PubMed

Weiss, Melissa; Steinbach, Daniel; Zintl, Felix; Beck, James; Gruhn, Bernd

2015-06-01

The outcome of cyclosporin A (CSA) alone (n = 19) as graft-versus-host disease (GVHD) prophylaxis was compared to that of CSA combined with methotrexate (MTX) (n = 43) in children with acute leukemia who underwent hematopoietic stem cell transplantation. All respective donors were HLA-identical siblings. All patients received CSA at a dose of 3 mg/kg/day starting on day -1. A CSA level of 80-130 ng/ml was aimed for. The 43 patients in the historical control were given an additional 10 mg/m(2) dosage of MTX on days 1, 3, 6, and 11. Patients who received CSA alone had a significantly reduced cumulative incidence of relapse (5 vs. 40 %; p = 0.002), a significantly increased 5-year event-free survival (84 vs. 35 %; p = 0.001), and a significantly increased 5-year overall survival (84 vs. 42 %; p = 0.004). The incidence of acute GVHD grade II-IV and chronic GVHD in patients in the CSA group was equivalent to the CSA+MTX group (26 vs. 19 %; p = 0.440, and 32 vs. 23 %; p = 0.428). In conclusion, post-transplant immunosuppression consisting of CSA alone is well tolerated and may contribute to a superior outcome.

Population pharmacokinetics of intravenous busulfan in patients undergoing hematopoietic stem cell transplantation.

PubMed

Takama, H; Tanaka, H; Nakashima, D; Ueda, R; Takaue, Y

2006-02-01

A population pharmacokinetic analysis was performed in 30 patients who received an intravenous busulfan and cyclophosphamide regimen before hematopoietic stem cell transplantation. Each patient received 0.8 mg/kg as a 2 h infusion every 6 h for 16 doses. A total of 690 concentration measurements were analyzed using the nonlinear mixed effect model (NONMEM) program. A one-compartment model with an additive error model as an intraindividual variability including an interoccasion variability (IOV) in clearance (CL) was sufficient to describe the concentration-time profile of busulfan. Actual body weight (ABW) was found to be the determinant for CL and the volume of distribution (V) according to NONMEM analysis. In this limited study, the age (range 7-53 years old; median, 30 years old) had no significant effect on busulfan pharmacokinetics. For a patient weighting 60 kg, the typical CL and V were estimated to be 8.87 l/h and 33.8 l, respectively. The interindividual variability of CL and V were 13.6 and 6.3%, respectively. The IOV (6.6%) in CL was estimated to be less than the intraindividual variability. These results indicate high interpatient and intrapatient consistency of busulfan pharmacokinetics after intravenous administration, which may eliminate the requirement for pharmacokinetic monitoring.

Long-term survival in patients with peripheral T-cell non-Hodgkin lymphomas after allogeneic hematopoietic stem cell transplant.

PubMed

Goldberg, Jenna D; Chou, Joanne F; Horwitz, Steven; Teruya-Feldstein, Julie; Barker, Juliet N; Boulad, Farid; Castro-Malaspina, Hugo; Giralt, Sergio; Jakubowski, Ann A; Koehne, Guenther; van den Brink, Marcel R M; Young, James W; Zhang, Zhigang; Papadopoulos, Esperanza B; Perales, Miguel-Angel

2012-06-01

Peripheral T-cell non-Hodgkin lymphomas (T-NHL) are rare diseases, with a worse prognosis compared to their B-cell counterparts. Allogeneic hematopoietic stem cell transplant may have a role in the treatment of relapsed/refractory disease or high-risk histologies in the upfront setting. However, there is limited information on the efficacy of allogeneic transplant for these diseases, as well as what factors may predict outcomes. We therefore performed a retrospective study of 34 patients who received an allogeneic transplant for the treatment of T-NHL at a single center between 1 January 1992 and 31 December 2009. The median follow-up for survivors was 45 months (range 9-160 months). The 2-year overall survival (OS) was 0.61 (95% confidence interval [CI]: 0.43-0.75) with a plateau at 28 months. Ki-67 expression ≤ 25% was predictive of improved OS (p < 0.01), and transplant in complete remission was predictive of a decreased cumulative incidence of events (p = 0.04). Three patients received a donor leukocyte infusion, and two patients demonstrated a response, supporting a graft-versus-lymphoma effect. These data demonstrate that allogeneic transplant is a viable option for the treatment of T-NHL and merits prospective evaluation.

Combined Haploidentical and Umbilical Cord Blood Allogeneic Stem Cell Transplantation for High-Risk Lymphoma and Chronic Lymphoblastic Leukemia.

PubMed

Hsu, Jingmei; Artz, Andrew; Mayer, Sebastian A; Guarner, Danielle; Bishop, Michael R; Reich-Slotky, Ronit; Smith, Sonali M; Greenberg, June; Kline, Justin; Ferrante, Rosanna; Phillips, Adrienne A; Gergis, Usama; Liu, Hongtao; Stock, Wendy; Cushing, Melissa; Shore, Tsiporah B; van Besien, Koen

2018-02-01

Limited studies have reported on outcomes for lymphoid malignancy patients receiving alternative donor allogeneic stem cell transplants. We have previously described combining CD34-selected haploidentical grafts with umbilical cord blood (haplo-cord) to accelerate neutrophil and platelet engraftment. Here, we examine the outcome of patients with lymphoid malignancies undergoing haplo-cord transplantation at the University of Chicago and Weill Cornell Medical College. We analyzed 42 lymphoma and chronic lymphoblastic leukemia (CLL) patients who underwent haplo-cord allogeneic stem cell transplantation. Patients underwent transplant for Hodgkin lymphoma (n = 9, 21%), CLL (n = 5, 12%) and non-Hodgkin lymphomas (n = 28, 67%), including 13 T cell lymphomas. Twenty-four patients (52%) had 3 or more lines of therapies. Six (14%) and 1 (2%) patients had prior autologous and allogeneic stem cell transplant, respectively. At the time of transplant 12 patients (29%) were in complete remission, 18 had chemotherapy-sensitive disease, and 12 patients had chemotherapy-resistant disease. Seven (17%), 11 (26%), and 24 (57%) patients had low, intermediate, and high disease risk index before transplant. Comorbidity index was evenly distributed among 3 groups, with 13 (31%), 14 (33%), and 15 (36%) patients scoring 0, 1 to 2, and ≥3. Median age for the cohort was 49 years (range, 23 to 71). All patients received fludarabine/melphalan/antithymocyte globulin conditioning regimen and post-transplant graft-versus-host disease (GVHD) prophylaxis with tacrolimus and mycophenolate mofetil. The median time to neutrophil engraftment was 11 days (range, 9 to 60) and to platelet engraftment 19.5 days (range, 11 to 88). Cumulative incidence of nonrelapse mortality was 11.6% at 100 days and 19 % at one year. Cumulative incidence of relapse was 9.3% at 100 days and 19% at one year. With a median follow-up of survivors of 42 months, the 3-year rates of GVHD relapse free survival, progression-free survival, and overall survival were 53%, 62%, and 65%, respectively, for these patients. Only 8% of the survivors had chronic GVHD. In conclusion, haplo-cord transplantation offers a transplant alternative for patients with recurrent or refractory lymphoid malignancies who lack matching donors. Both neutrophil and platelet count recovery is rapid, nonrelapse mortality is limited, excellent disease control can be achieved, and the incidence of chronic GVHD is limited. Thus, haplo-cord achieves high rates of engraftment and encouraging results. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Stem cell transplantation (cord blood transplants).

PubMed

Chao, Nelson J; Emerson, Stephen G; Weinberg, Kenneth I

2004-01-01

Allogeneic stem cell transplantation is an accepted treatment modality for selected malignant and non-malignant diseases. However, the ability to identify suitably matched related or unrelated donors can be difficult in some patients. Alternative sources of stem cells such as cord blood provide a readily available graft for such patients. Data accumulated over the past several years have demonstrated that the use of cord blood is an accepted source of stem cells for pediatric patients. Since the cell numbers of hematopoietic progenitors in cord blood is limited and the collection can occur only in a single occasion, its use in adult patients can be more problematic. Here, new developments in the use of cord blood for adults and studies aimed at expansion of cord blood cells and immune reconstitution are described. In Section I, Dr. Nelson Chao describes the early data in cord blood transplantation in adult patients. The patient outcomes are reviewed and analyzed for various factors such as cell dose, HLA typing, and patient selection that could have contributed to the final outcome of these adult patients. Myeloablative as well as nonmyeloablative approaches are presented. Discussion of the various benefits and risks are presented. More recent data from multiple single institutions as well as larger registry data comparisons are also provided. Analyses of these studies suggest methods to improve on the outcome. These newer data should lead to a logical progression in the use of cord blood cells in adult patients. In Section II, Dr. Stephen Emerson describes the historical efforts associated with expansion of hematopoietic stem cells, specifically with cord blood cells. These efforts to expand cord blood cells continue with novel methods. Moreover, a better understanding of stem cell biology and signaling is critical if we are to be able to effectively expand these cells for clinical use. An alternative, more direct, approach to expanding stem cells could be achieved by specific genetic pathways known or believed to support primitive HSC proliferation such as Notch-1 receptor activation, Wnt/LEF-1 pathway induction, telomerase or the Homeobox (Hox) gene products. The clinical experience with the use of expanded cord blood cells is also discussed. In Section III, Dr. Kenneth Weinberg describes immune reconstitution or lack thereof following cord blood transplantation. One of the hallmarks of successful hematopoietic stem cell transplantation is the ability to fully reconstitute the immune system of the recipient. Thus, the relationship between stem cell source and the development of T lymphocyte functions required for protection of the recipient from infection will be described, and cord blood recipients will be compared with those receiving other sources of stem cells. T cell development is described in detail, tracking from prethymic to postthymic lymphocytes with specific attention to umbilical cord blood as the source of stem cells. Moreover, a discussion of the placenta as a special microenvironment for umbilical cord blood is presented. Strategies to overcome the immunological defects are presented to improve the outcome of these recipients.

Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial design.

PubMed

Bartunek, Jozef; Davison, Beth; Sherman, Warren; Povsic, Thomas; Henry, Timothy D; Gersh, Bernard; Metra, Marco; Filippatos, Gerasimos; Hajjar, Roger; Behfar, Atta; Homsy, Christian; Cotter, Gad; Wijns, William; Tendera, Michal; Terzic, Andre

2016-02-01

Cardiopoiesis is a conditioning programme that aims to upgrade the cardioregenerative aptitude of patient-derived stem cells through lineage specification. Cardiopoietic stem cells tested initially for feasibility and safety exhibited signs of clinical benefit in patients with ischaemic heart failure (HF) warranting definitive evaluation. Accordingly, CHART-1 is designed as a large randomized, sham-controlled multicentre study aimed to validate cardiopoietic stem cell therapy. Patients (n = 240) with chronic HF secondary to ischaemic heart disease, reduced LVEF (<35%), and at high risk for recurrent HF-related events, despite optimal medical therapy, will be randomized 1:1 to receive 600 × 10(6) bone marrow-derived and lineage-directed autologous cardiopoietic stem cells administered via a retention-enhanced intramyocardial injection catheter or a sham procedure. The primary efficacy endpoint is a hierarchical composite of mortality, worsening HF, Minnesota Living with Heart Failure Questionnaire score, 6 min walk test, LV end-systolic volume, and LVEF at 9 months. The secondary efficacy endpoint is the time to cardiovascular death or worsening HF at 12 months. Safety endpoints include mortality, readmissions, aborted sudden deaths, and serious adverse events at 12 and 24 months. The CHART-1 clinical trial is powered to examine the therapeutic impact of lineage-directed stem cells as a strategy to achieve cardiac regeneration in HF populations. On completion, CHART-1 will offer a definitive evaluation of the efficacy and safety of cardiopoietic stem cells in the treatment of chronic ischaemic HF. NCT01768702. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy

PubMed Central

Law, Man Fai; Ho, Rita; Cheung, Carmen K M; Tam, Lydia H P; Ma, Karen; So, Kent C Y; Ip, Bonaventure; So, Jacqueline; Lai, Jennifer; Ng, Joyce; Tam, Tommy H C

2016-01-01

Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies. PMID:27605883

Rare complications after second hematopoietic stem cell transplantation for thalassemia major.

PubMed

Yanir, Asaf; Yatsiv, Ido; Braun, Jacques; Zilkha, Amir; Brooks, Rebecca; Bouhanna, Dalia; Weintraub, Michael; Stepensky, Polina

2012-07-01

We describe an 11-year-old girl with thalassemia major who underwent a second hematopoietic stem cell transplantation from a matched related donor and who subsequently developed posttransplant lymphoproliferative disorder complicated by severe ascending paralysis resembling Guillian-Barré syndrome. Six months later she developed a massive pericardial effusion. She received a multimodal treatment for these complications and currently, 18 months after transplantation, she is in a good clinical condition, is transfusion independent, with no evidence of graft-versus-host disease and off all treatment. This case highlights the dilemma surrounding second hematopoietic stem cell transplantations in hemoglobinopathies and the need for a careful, well informed, and collaborative decision-making process by patients, families, and medical professionals.

[Multiple myeloma: Maintenance therapy after autologous hematopoietic stem cell transplantation, depending on minimal residual disease].

PubMed

Solovyev, M V; Mendeleeva, L P; Pokrovskaya, O S; Nareyko, M V; Firsova, M V; Galtseva, I V; Davydova, Yu O; Kapranov, N M; Kuzmina, L A; Gemdzhian, E G; Savchenko, V G

To determine the efficiency of maintenance therapy with bortezomib in patients with multiple myeloma (MM) who have achieved complete remission (CR) after autologous hematopoietic stem cell (auto-HSCT), depending on the presence of minimal residual disease (MRD). In January 2014 to February 2016, fifty-two MM patients (19 men and 33 women) aged 24 to 66 years (median 54 years), who had achieved CR after auto-HSCT, were randomized to perform maintenance therapy with bortezomib during a year. On day 100 after auto-HSCT, all the patients underwent immunophenotyping of bone marrow plasma cells by 6-color flow cytometry to detect MRD. Relapse-free survival (RFS) was chosen as a criterion for evaluating the efficiency of maintenance therapy. After auto-HSCT, MRD-negative patients had a statistically significantly higher 2-year RFS rate than MRD-positive patients: 52.9% (95% confidence interval (CI), 35.5 to 70.5%) versus 37.2% (95% CI, 25.4 to 49.3%) (p=0.05). The presence of MRD statistically significantly increased the risk of relapse (odds ratio 1.7; 95% CI, 1.2 to 3.4; p=0.05). Two-year cumulative risk of relapse (using the Kaplan-Meier) after auto-HSCT did not statistically significantly differ in MRD-negative patients receiving (n=15) and not receiving (n=10) maintenance therapy with bortezomib (p=0.58). After completion of maintenance treatment, 42% of the MRD-positive patients achieved a negative status. In the MRD-positive patients who had received maintenance therapy, the average time to recurrence was 5 months longer than that in the naïve patients: 17.3 versus 12.3 months. The MRD status determined in MM patients who have achieved CR after auto-HSCT is an important factor for deciding on the use of maintenance therapy.

Relationship of BK polyoma virus (BKV) in the urine with hemorrhagic cystitis and renal function in recipients of T Cell-depleted peripheral blood and cord blood stem cell transplantations.

PubMed

Lee, Yeon Joo; Zheng, Junting; Kolitsopoulos, Yovanna; Chung, Dick; Amigues, Isabelle; Son, Tammy; Choo, Kathleen; Hester, Jeff; Giralt, Sergio A; Glezerman, Ilya G; Jakubowski, Ann A; Papanicolaou, Genovefa A

2014-08-01

Hematopoietic stem cell transplant (HSCT) recipients are at significant risk for BK virus (BKV) reactivation, hemorrhagic cystitis (HC), and renal dysfunction. We prospectively monitored 98 patients who had received HSCT by serial BKV PCR in the urine through day (D) +100 to analyze the relationship between BK viruria and HC, serum creatinine (Cr), and creatinine clearance (CrCl) through D +180 or death. Patients, median age 52 years (range, 20 to 73), received T cell-depleted (50%) or cord blood allografts (21%). Median pre-HSCT BKV IgG titers were 1:10,240. Incremental increase in BKV IgG titers correlated with developing BK viruria ≥ 10(7) copies/mL. By D +100, 53 (54%) patients had BK viruria. BKV load in the urine increased at engraftment and persisted throughout D +100. HC developed in 10 patients (10%); 7 of 10 with BK viruria. In competing risk analyses, BK viruria ≥ 10(7) copies/mL, older age, cytomegalovirus reactivation, and foscarnet use were risk factors for HC. Cr and CrCl at 2, 3, and 6 months after HSCT were similar between patients with and without BK viruria. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Full myeloablative conditioning and an unrelated HLA mismatched donor increase the risk for BK virus-positive hemorrhagic cystitis in allogeneic hematopoetic stem cell transplanted patients.

PubMed

Dalianis, Tina; Ljungman, Per

2011-03-01

BK virus (BKV)-associated hemorrhagic cystitis (HC), varying from mild hematuria with or without dysuria to life-threating bleeding and clots that may cause urinary obstruction and renal failure, causes significant morbidity and mortality in haematopoetic stem cell transplanted (HSCT) patients. Unfortunately, its development is difficult to predict since BK viruria is very common after HSCT and can be present in patients with and without HC. There is therefore the need to identify risk factors that may increase the risk of developing HC after HSCT. The viral load of BK-viruria, as well as BK viremia, has been monitored for this purpose. Moreover, having full myeoblative conditioning (MC) versus reduced intensity conditioning (RIC) prior to HSCT and an HLA-matched or -mismatched graft from an unrelated donor in contrast to an HLA-matched graft from a related donor have been studied as risk factors for HC. In addition, graft versus host disease has been examined, but has not been defined as a definite risk factor for HC. We conclude that the present evidence suggests that HSCT patients with BK viruria, receiving MC and an unrelated donor graft that is HLA-mismatched have an increased risk for developing HC in comparison to patients receiving RIC and an HLA-matched related donor graft.

Multicenter analysis of treatment outcomes in adult patients with lymphoblastic lymphoma who received hyper-CVAD induction followed by hematopoietic stem cell transplantation.

PubMed

Jeong, Seong Hyun; Moon, Joon Ho; Kim, Jin Seok; Yang, Deok-Hwan; Park, Yong; Cho, Seok Goo; Kwak, Jae-Yong; Eom, Hyeon Seok; Won, Jong Ho; Hong, Jun Shik; Oh, Sung Yong; Lee, Ho Sup; Kim, Seok Jin

2015-04-01

The hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) regimen has been widely used for lymphoblastic lymphoma (LBL) as a primary treatment. However, there is few data about its treatment outcome in Asian patients. Thus, we conducted this study to evaluate the efficacy of hyper-CVAD induction and stem cell transplantation (SCT) consolidation in LBL patients. The treatment responses of 49 patients treated with the hyper-CVAD regimen were retrospectively analyzed in 13 institutions. Given 24 patients who responded to hyper-CVAD underwent consolidation treatment with SCT, overall survival (OS) and progression-free survival (PFS) of patients who received SCT were compared with patients who did not. The overall response rate was 79 %: 73 % (36/49) complete responses, 6 % (3/49) partial responses, and 4 % (2/49) induction deaths. The major limitation for the delivery of the planned hyper-CVAD cycles was hematological toxicity. Among 39 responders, 24 patients underwent autologous (n = 16) and allogeneic SCT (n = 8) consolidation. Their 3-year OS and PFS rates were 76 and 78 %, respectively, and there was no difference in survival outcomes between autologous and allogeneic SCT. However, 15 patients without SCT consolidation showed poorer PFS even though they all achieved complete response. Thus, only seven patients maintained their response at the time of analysis. In conclusion, the hyper-CVAD regimen is effective for remission induction in LBL, and SCT consolidation after hyper-CVAD induction produced better clinical outcomes than did continuation of hyper-CVAD.

Alterations of the bone marrow stromal microenvironment in adult patients with acute myeloid and lymphoblastic leukemias before and after allogeneic hematopoietic stem cell transplantation.

PubMed

Shipounova, Irina N; Petinati, Nataliya A; Bigildeev, Alexey E; Drize, Nina J; Sorokina, Tamara V; Kuzmina, Larisa A; Parovichnikova, Elena N; Savchenko, Valeri G

2017-02-01

Bone marrow (BM) derived adult multipotent mesenchymal stromal cells (MMSCs) and fibroblast colony-forming units (CFU-Fs) of 20 patients with acute myeloid leukemia (AML) and 15 patients with acute lymphoblastic leukemia (ALL) before and during 1 year after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) were studied. The growth characteristics of MMSCs of all patients before allo-HSCT were not altered; however, relative expression level (REL) of some genes in MMSCs, but not in CFU-Fs, from AML and ALL patients significantly changed. After allo-HSCT, CFU-F concentration and MMSC production were significantly decreased for 1 year; REL of several genes in MMSCs and CFU-F-derived colonies were also significantly downregulated. Thus, chemotherapy that was used for induction of remission did not impair the function of stromal precursors, but gene expression levels were altered. Allo-HSCT conditioning regimens significantly damaged MMSCs and CFU-Fs, and the effect lasted for at least 1 year.

Epidemiologic Profile of Patients Transplanted With Hematopoietic Stem Cells in a Reference Service in the State of Rio Grande do Norte, Brazil.

PubMed

Campos de Azevedo, I; Ferreira Júnior, M A; Pereira de Aquino, L A; de Oliveira, A A; Cruz, G K P; de Queiroz Cardoso, A I; Ivo, M L; Santos, V E P

2018-04-01

Hematopoietic stem cell transplantation (HSCT) consists of the intravenous infusion of healthy hematopoietic stem cells to restore the medullary and immunologic function of patients affected by a series of hematologic, oncologic, immunologic, malignant and nonmalignant inherited or acquired diseases, with the possibility of cure or increase of disease-free survival. To characterize the epidemiologic profile and the cases of death of patients who underwent HSCT. This is a cohort quantitative study, nested with a retrospective, descriptive, and analytical study of a hospital-based cohort that included the patients who underwent HSCT at a referral service in the state of Rio Grande do Norte, a region of northeastern Brazil. There was a slight male prevalence (52.94%), the age of the patients ranged from 2 to 73 years old, 18.38% were brown, 47.06% were married, 15.07% were students, 78.31% had a diagnosis of multiple myeloma, 93.38% developed gastrointestinal toxicities, all patients received chemotherapeutic treatment, 54.78% had allogeneic HSCT, and the cause of the most recorded deaths was septic shock (48.19%). This study showed relevant scientific evidence on the clinical and epidemiologic profile of patients who underwent HSCT. In general, sociodemographic data are similar to national and international research results. Copyright © 2018 Elsevier Inc. All rights reserved.

Alpha/Beta T-Cell Depleted Grafts as an Immunological Booster to Treat Graft Failure after Hematopoietic Stem Cell Transplantation with HLA-Matched Related and Unrelated Donors

PubMed Central

Rådestad, E.; Wikell, H.; Engström, M.; Watz, E.; Sundberg, B.; Thunberg, S.; Uzunel, M.; Mattsson, J.; Uhlin, M.

2014-01-01

Allogeneic hematopoietic stem cell transplantation is associated with several complications and risk factors, for example, graft versus host disease (GVHD), viral infections, relapse, and graft rejection. While high levels of CD3+ cells in grafts can contribute to GVHD, they also promote the graft versus leukemia (GVL) effect. Infusions of extra lymphocytes from the original stem cell donor can be used as a treatment after transplantation for relapse or poor immune reconstitution but also they increase the risk for GVHD. In peripheral blood, 95% of T-cells express the αβ T-cell receptor and the remaining T-cells express the γδ T-cell receptor. As αβ T-cells are the primary mediators of GVHD, depleting them from the graft should reduce this risk. In this pilot study, five patients transplanted with HLA-matched related and unrelated donors were treated with αβ T-cell depleted stem cell boosts. The majority of γδ T-cells in the grafts expressed Vδ2 and/or Vγ9. Most patients receiving αβ-depleted stem cell boosts increased their levels of white blood cells, platelets, and/or granulocytes 30 days after infusion. No signs of GVHD or other side effects were detected. A larger pool of patients with longer follow-up time is needed to confirm the data in this study. PMID:25371909

Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant

ClinicalTrials.gov

2018-01-02

HIV Infection; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Plasmablastic Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Follicular Lymphoma; Stage III Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

A randomized study on migration of the Spectron EF and the Charnley flanged 40 cemented femoral components using radiostereometric analysis at 2 years.

PubMed

Kadar, Thomas; Hallan, Geir; Aamodt, Arild; Indrekvam, Kari; Badawy, Mona; Havelin, Leif Ivar; Stokke, Terje; Haugan, Kristin; Espehaug, Birgitte; Furnes, Ove

2011-10-01

We performed a randomized study to determine the migration patterns of the Spectron EF femoral stem and to compare them with those of the Charnley stem, which is regarded by many as the gold standard for comparison of implants due to its extensive documentation. 150 patients with a mean age of 70 years were randomized, single-blinded, to receive either a cemented Charnley flanged 40 monoblock, stainless steel, vaquasheen surface femoral stem with a 22.2-mm head (n = 30) or a cemented Spectron EF modular, matte, straight, collared, cobalt-chrome femoral stem with a 28-mm femoral head and a roughened proximal third of the stem (n = 120). The patients were followed with repeated radiostereometric analysis for 2 years to assess migration. At 2 years, stem retroversion was 2.3° and 0.7° (p < 0.001) and posterior translation was 0.44 mm and 0.17 mm (p = 0.002) for the Charnley group (n = 26) and the Spectron EF group (n = 74), respectively. Subsidence was 0.26 mm for the Charnley and 0.20 mm for the Spectron EF (p = 0.5). The Spectron EF femoral stem was more stable than the Charnley flanged 40 stem in our study when evaluated at 2 years. In a report from the Norwegian arthroplasty register, the Spectron EF stem had a higher revision rate due to aseptic loosening beyond 5 years than the Charnley. Initial stability is not invariably related to good long-term results. Our results emphasize the importance of prospective long-term follow-up of prosthetic implants in clinical trials and national registries and a stepwise introduction of implants.

Clinical and virological factors associated with hepatitis B virus reactivation in HBsAg-negative and anti-HBc antibodies-positive patients undergoing chemotherapy and/or autologous stem cell transplantation for cancer.

PubMed

Borentain, P; Colson, P; Coso, D; Bories, E; Charbonnier, A; Stoppa, A M; Auran, T; Loundou, A; Motte, A; Ressiot, E; Norguet, E; Chabannon, C; Bouabdallah, R; Tamalet, C; Gérolami, R

2010-11-01

We studied clinical outcome and clinico-virological factors associated with hepatitis B virus reactivation (HBV-R) following cancer treatment in hepatitis B virus surface antigen (HBsAg)-negative/anti-hepatitis B core antibodies (anti-HBcAb)-positive patients. Between 11/2003 and 12/2005, HBV-R occurred in 7/84 HBsAg-negative/anti-HBcAb-positive patients treated for haematological or solid cancer. Virological factors including HBV genotype, core promoter, precore, and HBsAg genotypic and amino acid (aa) patterns were studied. Patients presenting with reactivation were men, had an hepatitis B virus surface antibody (HBsAb) titre <100 IU/L and underwent >1 line of chemotherapy (CT) significantly more frequently than controls. All were treated for haematological cancer, 3/7 received haematopoietic stem cell transplantation (HSCT), and 4/7 received rituximab. Using multivariate analysis, receiving >1 line of CT was an independent risk factor for HBV-R. Fatal outcome occurred in 3/7 patients (despite lamivudine therapy in two), whereas 2/4 survivors had an HBsAg seroconversion. HBV-R involved non-A HBV genotypes and core promoter and/or precore HBV mutants in all cases. Mutations known to impair HBsAg antigenicity were detected in HBV DNA from all seven patients. HBV DNA could be retrospectively detected in two patients prior cancer treatment and despite HBsAg negativity. HBV-R is a concern in HBsAg-negative/anti-HBcAb-positive patients undergoing cancer therapy, especially in males presenting with haematological cancer, a low anti-HBsAb titre and more than one chemotherapeutic agent. HBV DNA testing is mandatory to improve diagnosis and management of HBV-R in these patients. The role of specific therapies such as rituximab or HSCT as well as of HBV aa variability deserves further studies. © 2009 Blackwell Publishing Ltd.

Optimizing the pretransplant regimen for autologous stem cell transplantation in acute myelogenous leukemia: Better outcomes with busulfan and melphalan compared with busulfan and cyclophosphamide in high risk patients autografted in first complete remission: A study from the acute leukemia working party of the EBMT.

PubMed

Gorin, Norbert Claude; Labopin, Myriam; Blaise, Didier; Dumas, Pierre-Yves; Pabst, Thomas; Trisolini, Silvia Maria; Arcese, William; Houhou, Mohamed; Mohty, Mohamad; Nagler, Arnon

2018-04-12

Autologous stem cell transplantation remains a clinical option to consolidate some adult patients with acute myelogenous leukemia (AML) in first complete remission (CR1). In a small cohort of patients, we have previously shown better outcomes following Busulfan and Melphalan (BUMEL) over Busulfan and Cyclophosphamide (BUCY). To identify the subpopulations that might get the highest benefit with BUMEL, we designed a larger study. All adult patients with primary AML and available cytogenetics, autografted from January 2000 to December 2016 in CR1, were included: 1137 patients received BUCY and 512 BUMEL. All factors differing in distribution between the 2 conditioning groups were introduced in multivariate analyzes. In a primary analysis, we found an interaction between conditioning and the poor risk group defined as poor cytogenetics and/or presence of the FLT3-ITD mutation. During analysis of the poor risk group, 176 patients received BUCY and 62 BUMEL. BUMEL was associated with a lower RI at 5 years (53% versus 69%, HR: 0.52, P = .002), a better Leukaemia-free survival (LFS) (42% versus 25%, HR: 0.54, P = .002) and a better OS (54% versus 36%, HR: 0.61, P = .02). During analysis of the non poor risk group, 961 patients received BUCY and 450 BUMEL. At 5 years, the RI was 50% and 47%, the LFS 45% and 48% and the OS 56% and 60% respectively, with no significant difference. We conclude that BUMEL is the preferable conditioning regimen for the poor risk leukemic patients, while in AML patients without poor risk cytogenetics or FLT3 both conditioning regimens are valid. © 2018 Wiley Periodicals, Inc.

A Randomized, Placebo-Controlled Trial of Human Umbilical Cord Blood Mesenchymal Stem Cell Infusion for Children With Cerebral Palsy

PubMed Central

Huang, Li; Zhang, Che; Gu, Jiaowei; Wu, Wei; Shen, Zhujun; Zhou, Xihui; Lu, Haixia

2018-01-01

Cerebral palsy (CP) is a common disability which results in permanent chronic motor disability appearing in early childhood. Recently human umbilical cord blood mesenchymal stem cell (hUCB-MSC) infusion has emerged as a promising therapeutic strategy for CP, and the treatment efficacy remains to be confirmed by clinical trials. All 54 patients received basic rehabilitation as a background treatment. The infusion group comprising 27 patients received 4 infusions of hUCB-MSCs (intravenous infusions at a fixed dose of 5 × 107) and basic rehabilitation treatment, whereas 27 patients in the control group received 0.9% normal saline and basic rehabilitation treatment. Several indices were tested from baseline up to 24 months posttreatment regarding efficacy and safety evaluations, including the gross motor function measurement 88 (GMFM-88) scores, the comprehensive function assessment (CFA), lab tests, electroencephalogram (EEG), routine magnetic resonance imaging (MRI), and adverse events. The changes in the total proportion of GMFM-88 and total scores of CFA in the hUCB-MSC infusion group were significantly higher than that in control group at 3, 6, 12, 24 months posttreatment. Less diffuse slow waves were noticed after hUCB-MSC infusion in patients with slowing of EEG background rhythms at baseline. Based on the routine MRI exams, improvements in cerebral structures were rare after treatment. Serious adverse events were not observed during the whole study period. The results of the study indicated that hUCB-MSC infusion with basic rehabilitation was safe and effective in improving gross motor and comprehensive functions in children with CP. PMID:29637820

The effect of red ginseng extract on inflammatory cytokines after chemotherapy in children.

PubMed

Lee, Jae Min; Hah, Jeong Ok; Kim, Hee Sun

2012-10-01

Ginseng has been used as an herbal medicine, widely used in Asian countries, for long time. Recently, beneficial effects for immune functions of Korean red ginseng (KRG) have been reported in adults. This study was performed to investigate the effects of ginseng on immune functions in children after cessation of chemotherapy or stem cell transplantation for advanced cancer. Thirty patients, who were diagnosed and treated for leukemia and solid cancer at the department of pediatrics and adolescence of the Yeungnam University Hospital from June 2004 to June 2009, were enrolled for the study. The study group consisted of 19 patients who received KRG extract (60 mg/kg/d) for 1 yr and 11 patients who did not receive KRG extract were the control group. Blood samples were collected every 6 mo. Immune assays included circulating lymphocyte subpopulation, serum cytokines (IL- 2, IL-10, IL-12, TNF-alpha, and IFN-gamma), and total concentrations of serum IgG, IgA, and IgM subclasses. Age at diagnosis ranged from 2 mo to 15 yr (median 5 yr). Nine patients received stem cell transplantation. The cytokines of the KRG treated group were decreasing more rapidly than that of the control group. Lymphocyte subpopulations (T cell, B cell, NK cell, T4, T8, and T4/ T8 ratio) and serum immunoglobulin subclasses (IgG, IgA, and IgM) did not show significant differences between the study and the control groups. This study suggests that KRG extract might have a stabilizing effect on the inflammatory cytokines in children with cancer after chemotherapy.

Return to work for patients with diffuse large B-cell lymphoma and transformed indolent lymphoma undergoing autologous stem cell transplantation

PubMed Central

Arboe, Bente; Olsen, Maja Halgren; Goerloev, Jette Soenderskov; Duun-Henriksen, Anne Katrine; Johansen, Christoffer; Dalton, Susanne Oksbjerg; Brown, Peter de Nully

2017-01-01

Background Autologous stem cell transplantation (ASCT) is the standard treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL) or transformed indolent lymphoma (TIL). The treatment is mainly considered for younger patients still available for the work market. In this study, social outcomes after ASCT in terms of return to work (RTW) are described. Patients and methods Information from national administrative registers was combined with clinical information on patients, who received ASCT for relapse of DLBCL or TIL between 2000 and 2012. A total of 164 patients were followed until RTW, disability or old-age pension, death, or December 31, 2015, whichever came first. A total of 205 patients were followed with disability pension as the event of interest. Cox models were used to determine cause-specific hazards. Results During follow-up, 82 (50%) patients returned to work. The rate of returning to work in the first year following ASCT was decreased for patients being on sick leave at the time of relapse (hazard ratio [HR] 0.3 [0.2;0.5]) and increased for patients aged ≥55 years (HR 1.9 [1.1;3.3]). In all, 56 (27%) patients were granted disability pension. Being on sick leave at the time of relapse was positively associated with receiving a disability pension in the first 2 years after ASCT (HR 3.7 [1.8;7.7]). Conclusion Patients on sick leave at the time of relapse have a poorer prognosis regarding RTW and have a higher rate of disability pension. Furthermore, patients >55 are more likely to RTW compared to younger patients. These results indicate an unmet need for focused social rehabilitation. PMID:28652814

Adoptive Immunotherapy for Primary Immunodeficiency Disorders with Virus-Specific T-lymphocytes

PubMed Central

Naik, Swati; Nicholas, Sarah K; Martinez, Caridad A; Leen, Ann M; Hanley, Patrick J; Gottschalk, Steven M; Rooney, Cliona M; Hanson, I Celine; Krance, Robert A; Cruz, Conrad R; Amrolia, Persis; Lucchini, Giovanna; Bunin, Nancy; Heimall, Jennifer; Klein, Orly R; Gennery, Andrew R; Slatter, Mary A; Vickers, Mark A; Orange, Jordan S; Heslop, Helen E; Bollard, Catherine M; Keller, Michael D

2016-01-01

Background Viral infections are a leading fatal complication for patients with primary immunodeficiency (PID) who require hematopoietic stem cell transplantation (HSCT). Use of virus-specific T-lymphocytes (VST) has been successful for treatment and prevention of viral infections after HSCT for malignant and non-malignant conditions. Here, we describe the clinical use of VST in PID at four centers. Objective To evaluate the safety and efficacy of VST for treatment of viral infections in patients with PID. Methods Patients with PID who have received VST therapy on previous or current protocols were reviewed in aggregate. Clinical information including transplantation details, viral infections, and use of antiviral and immunosuppressive pharmacotherapy were evaluated. Data regarding VST production, infusions, and adverse reactions were compared. Results Thirty-six patients with twelve classes of PID diagnoses received 37 VST products before or after HSCT. Twenty-six patients (72%) had been diagnosed with infections with cytomegalovirus, Epstein-Barr virus, adenovirus, BK virus, and/or human herpesvirus 6 (HHV6). Two patients were treated prior to HSCT due to EBV-associated lymphoproliferative disease (LPD). Partial or complete responses against targeted viruses occurred in 81% of patients overall. Time to response varied from two weeks to three months (median 28 days). Overall survival at six months after therapy was 80%. Four patients developed graft versus host disease (GVHD) in the 45 days following VST infusion, which in most cases was therapy-responsive. Interpretation VST derived from either stem cell donors or third-party donors are likely safe and effective for treatment of viral infections in patients with PID. PMID:26920464

Use of biosimilar filgrastim compared with lenograstim in autologous haematopoietic stem-cell transplant and in sibling allogeneic transplant

PubMed Central

Uddin, Shab; Russell, Pippa; Farrell, Maresa; Davy, Barbara; Taylor, Joe

2015-01-01

Objectives: Biosimilar filgrastim was compared with lenograstim for autologous haematopoietic stem-cell transplant (HSCT) in patients with haematological malignancies. Data from a separate group of sibling donors who underwent allogeneic HSCT are also reported. Methods: Patients with lymphoma or multiple myeloma (MM) who underwent autologous HSCT with biosimilar filgrastim were compared with a historical control group of patients who received lenograstim. Peripheral blood (PB) cells counts were monitored after 7–8 consecutive days of granulocyte-colony stimulating factor (G-CSF) injection and apheresis was performed on day 8 if PB CD34+ cell count was ⩾10 cells/µl. The target PB CD34+ cell doses were ⩾2.0 × 106/kg (lymphoma), ⩾4.0 × 106/kg (MM ⩾60 years old) or ⩾8.0 × 106/kg (MM <60 years old). Results: A total of 259 patients were included in the autologous HSCT comparison (biosimilar filgrastim, n = 104; lenograstim, n = 155). In patients with lymphoma and older MM patients (⩾60 years old), no significant differences were observed between groups with regard to stem-cell mobilization parameters. However, in MM patients <60 years old, all parameters were significantly superior in the biosimilar filgrastim group, including the need for 1 rather than 2 apheresis procedures. No significant differences were observed between groups in median number of days to absolute neutrophil count (ANC) or platelet recovery. In the allogeneic setting, 47 sibling donors received biosimilar filgrastim. Mean CD34+ count at the first apheresis was 6.1 × 106/kg. A total of 13 donors needed a second apheresis and 4 required a third. Among recipients, median days to ANC recovery was 16 (10–28) and to platelet recovery was 13 (9–54). Conclusions: Biosimilar filgrastim is as effective as lenograstim for autologous HSCT in patients with lymphoma or MM patients ⩾60 years old. However, mobilization with biosimilar filgrastim appeared to be superior to that with lenograstim in younger MM patients. PMID:25830013

Budesonide/Formoterol for bronchiolitis obliterans after hematopoietic stem cell transplantation.

PubMed

Bergeron, Anne; Chevret, Sylvie; Chagnon, Karine; Godet, Cendrine; Bergot, Emmanuel; Peffault de Latour, Régis; Dominique, Stéphane; de Revel, Thierry; Juvin, Karine; Maillard, Natacha; Reman, Oumedaly; Contentin, Nathalie; Robin, Marie; Buzyn, Agnès; Socié, Gérard; Tazi, Abdellatif

2015-06-01

Systemic steroids are the standard treatment for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) despite their poor efficacy and disabling side effects. To evaluate the effectiveness and tolerance of budesonide/formoterol as an alternative treatment for BOS after HSCT. In this randomized, double-blind, placebo-controlled study, we randomly assigned 32 HSCT recipients with mild/severe BOS to receive budesonide/formoterol or placebo for 6 months. The primary outcome was the change in the FEV1 after 1 month of treatment (M1) compared with the baseline value. Patients were unblinded at M1 if there was no improvement in the FEV1. Those who had initially received placebo were switched to budesonide/formoterol. Intention-to-treat analysis was performed to assess the primary outcome. Additional analyses took scheduled treatment contamination into account. At M1, the median FEV1 increased by 260 ml in the budesonide/formoterol arm compared with 5 ml in the placebo arm (P = 0.012). The median increases in the FEV1 at M1 relative to the baseline value for the treated and placebo groups were 13 and 0%, respectively (P = 0.019). Twenty-five patients received budesonide/formoterol during the study. The median difference in the FEV1 between the baseline and after 1 month of treatment for these patients was +240 ml (P = 0.0001). The effect of budesonide/formoterol on the FEV1 was maintained in the 13 patients who completed 6 months of treatment. Budesonide/formoterol administration led to a significant improvement in the FEV1 in patients with mild/severe BOS after allogeneic HSCT. Clinical trial registered with www.clinicaltrials.gov (NCT00624754).

Association between bortezomib dose intensity and overall survival in mantle cell lymphoma patients on frontline VR-CAP in the phase 3 LYM-3002 study.

PubMed

Robak, Tadeusz; Huang, Huiqiang; Jin, Jie; Zhu, Jun; Liu, Ting; Samoilova, Olga; Pylypenko, Halyna; Verhoef, Gregor; Siritanaratkul, Noppadol; Osmanov, Evgenii; Pereira, Juliana; Mayer, Jiri; Hong, Xiaonan; Okamoto, Rumiko; Pei, Lixia; Rooney, Brendan; van de Velde, Helgi; Cavalli, Franco

2017-06-05

The pivotal LYM-3002 study compared frontline rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with bortezomib, rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients for whom stem cell transplantation was not an option. This post hoc subanalysis of the VR-CAP data from LYM-3002 evaluated the effect of bortezomib dose intensity on OS in patients who completed ≥6 cycles of treatment. From the end of cycle 6, patients receiving ≥4.6 mg/m 2 /cycle of bortezomib had significantly longer OS (but not PFS) compared with those receiving <4.6 mg/m 2 /cycle by univariate analysis (HR 0.43 [95% CI: 0.23-0.80]; p = .0059). This association remained significant in multivariate analysis adjusting for baseline patient and disease characteristics (HR 0.40 [95% CI: 0.20-0.79]; p = .008]. Higher bortezomib dose intensity was the strongest predictor of OS in newly diagnosed MCL patients receiving VR-CAP. Clinicaltrials.gov identifier: NCT00722137.

Epidemiology, Clinico-Haematological Profile and Management of Aplastic Anaemia: AIIMS Experience.

PubMed

Mahapatra, M; Singh, P K; Agarwal, M; Prabhu, M; Mishra, P; Seth, T; Tyagi, S; Patil, H P; Saxena, R

2015-03-01

The incidence of aplastic anaemia (AA) is higher in Asia than in the West. The precise incidence of AA in India is not known due to lack of epidemiological study. 20-40% of pancytopenic patients in referral centres are of aplastic anaemia. This was an analysis of 1501 patients diagnosed with aplastic anaemia over a period of seven and half years (January 2007- June 2014) attending the Aplastic clinic of department of haematology of All India Institute of Medical Sciences, New Delhi. The details regarding medical history, physical examination, complete blood count, bone marrow aspirate and biopsy, treatment received, were retrieved. Inherited bone marrow failure was screened in patients below 35 years. Treatment response was analysed for various treatment modalities. 1501 patients of AA from 20 different states of India were analysed. The bulk of patients were from Uttar Pradesh (28.7%), Bihar (23.6%), Delhi/NCR (20%) and Haryana (7%).The average number of new aplastic anaemia patients enrolled per year 214 (range: 101 -263). The median age at presentation was 25 years (range 2-83),with M;F - 2.3:1. Severity of AA revealed: severe (SAA): 75%, very severe (VSAA): 15%, non-severe (NSAA): 10%. Inherited bone marrow failure syndromes constituted 5% (75 patients) of all aplastic anaemia patients. The most common clinical presentations were pallor (97%), bleeding manifestations (69.6%) and fever (54%). The haematological parameters showed: median level of haemoglobin level: 5.9 gm/dL, WBC: 2700/mm3, ANC: 380/mm3, platelet: 1 0000/mm3. PNH clone was present in 13.5% of patients. 107 patients (7%) were lost to follow up or expired before any treatment was initiated. Only 69 patients (4.5%) received treatment with HLA-matched sibling stem cell transplantation and another 232 (15.5%) patients received ATG plus cyclosporine as immunosuppressive therapy. Seven hundred thirteenpatients (47.5%) received cyclosporine. The overall response to various treatment modalities was: HLA matched sibling haematopoietic stem cell transplant: 75.3%, Anti-thymocyte globulin plus cyclosporine: 58.7%, cyclosporine plus androgen: 45.6%, cyclosporine alone: 32.2%. Management of AA is a real challenge in developing countries.This is one of the largest case series from a single centre from India. It is our endeavour to reduce the detrimental outcome by increasing awareness among patients and referring physicians to reduce the delay between diagnosis and treatment.

The use of anthracycline at first-line compared to alkylating agents or nucleoside analogs improves the outcome of salvage treatments after relapse in follicular lymphoma The REFOLL study by the Fondazione Italiana Linfomi.

PubMed

Rossi, Giuseppe; Marcheselli, Luigi; Dondi, Alessandra; Bottelli, Chiara; Tucci, Alessandra; Luminari, Stefano; Arcaini, Luca; Merli, Michele; Pulsoni, Alessandro; Boccomini, Carola; Puccini, Benedetta; Micheletti, Moira; Martinelli, Giovanni; Rossi, Andrea; Zilioli, Vittorio Ruggero; Bozzoli, Valentina; Balzarotti, Monica; Bolis, Silvia; Cabras, Maria Giuseppina; Federico, Massimo

2015-01-01

Follicular lymphoma (FL) patients experience multiple remissions and relapses and commonly receive multiple treatment lines. A crucial question is whether anthracyclines should be used at first-line or whether they would be better "reserved" for relapse and whether FL outcome can be optimized by definite sequences of treatments. Randomized trials can be hardly designed to address this question. In this retrospective multi-institutional study, time-to-next-treatment after first relapse was analyzed in 510 patients who had received either alkylating agents- or anthracycline- or nucleoside analogs-based chemotherapy with/without rituximab at first-line and different second-line therapies. After a median of 42 months, median time-to-next-treatment after relapse was 41 months (CI95%:34-47 months). After adjustment for covariates, first-line anthracycline-based chemotherapy with/without rituximab was associated with better time-to-next-treatment after any salvage than alkylating agents-based chemotherapy with/without rituximab or nucleoside analogs-based chemotherapy with/without rituximab (HR:0.74, P = 0.027). The addition of rituximab to first-line chemotherapy had no significant impact (HR:1.22, P = 0.140). Autologs stem cell transplantation performed better than any other salvage treatment (HR:0.53, P < 0.001). First-line anthracycline-based chemotherapy significantly improved time-to-next-treatment even in patients receiving salvage autologs stem cell transplantation (P = 0.041). This study supports the concept that in FL previous treatments significantly impact on the outcome of subsequent therapies. The outcome of second-line treatments, either with salvage chemoimmunotherapy or with autologs stem cell transplantation, was better when an anthracycline-containing regimen was used at first-line. © 2014 Wiley Periodicals, Inc.

Osteonecrosis of the jaw: effect of bisphosphonate type, local concentration, and acidic milieu on the pathomechanism.

PubMed

Otto, Sven; Pautke, Christoph; Opelz, Christine; Westphal, Ines; Drosse, Inga; Schwager, Joanna; Bauss, Frieder; Ehrenfeld, Michael; Schieker, Matthias

2010-11-01

Osteonecrosis of the jaw has been reported in patients receiving high doses of intravenous nitrogen-containing bisphosphonates (N-BPs) because of malignant disease. The exact pathomechanisms have been elusive and questions of paramount importance remain unanswered. Recent studies have indicated toxic effects of bisphosphonates on different cell types, apart from osteoclast inhibition. Multipotent stem cells play an important role in the processes of wound healing and bone regeneration, which seem to be especially impaired in the jaws of patients receiving high doses of N-BPs. Therefore, the aim of the present study was to investigate the effects of different bisphosphonate derivatives and dose levels combined with varying pH levels on the mesenchymal stem cells in vitro. The effect of 2 N-BPs (zoledronate and ibandronate) and 1 non-N-BP (clodronate) on immortalized mesenchymal stem cells was tested at different concentrations, reflecting 1, 3, and 6 months and 1, 3, 5, and 10 years of exposure to standard oncology doses of the 2 N-BPs and equimolar concentrations of clodronate at different pH values (7.4, 7.0, 6.7, and 6.3). Cell viability and activity were analyzed using a WST assay. Cell motility was investigated using scratch wound assays and visualized using time-lapse microscopy. Both types of bisphosphonates revealed remarkable differences. Zoledronate and ibandronate showed a dose- and pH-dependent cellular toxicity. Increasing concentrations of both N-BPs and an acidic milieu led to a significant decrease in cell viability and activity (P < .01), with more pronounced effects for zoledronate. Equimolar concentrations of clodronate did not affect the cell survival or activity significantly, apart from the effect of pH reduction itself, which was also detectable in the patients in the control group who did not receive bisphosphonates. Our results have shown that high concentrations of N-BPs and a local acidic milieu, which is commonly present in infections of the jaw, might play a key role in the pathogenesis of osteonecrosis of the jaw in patients receiving high doses of N-BPs for malignant diseases. Also the potency of N-BPs might be different, suggesting a greater risk of osteonecrosis of the jaw with zoledronate. Copyright © 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

BK virus-associated hemorrhagic cystitis in pediatric cancer patients receiving high-dose cyclophosphamide.

PubMed

Cheerva, Alexandra C; Raj, Ashok; Bertolone, Salvatore J; Bertolone, Kathy; Silverman, Craig L

2007-09-01

Hemorrhagic cystitis (HC) is a known complication of oxazophosphorine chemotherapy. BK virus (BKV) has been commonly found to be associated with hematuria in stem cell transplant patients; however, it has rarely been reported after cyclophosphamide chemotherapy alone. The authors present 3 cases of BK viruria with HC in nontransplant pediatric oncology patients. The 3 patients with BKV had more prolonged hematuria (14 to 16 wk) compared with 1 patient with BKV-negative HC (10 wk). The HC necessitated chemotherapy delays and also prolonged supportive care. One patient was treated with intravenous cidofovir with resolution of BK viruria and hematuria. BKV may have an association with the development of HC in nonstem cell transplant patients receiving high-dose oxazophosphorine chemotherapy. HC may present early and be more prolonged in patients with BK viruria. Patients with HC after cyclophosphamide or ifosfamide with negative bacterial cultures should be studied for BKV. Cidofovir may be beneficial in certain patients with BK viruria and HC; however, definitive data will require a clinical trial.

Relatively favorable outcome after allogeneic stem cell transplantation for BCR-ABL1-positive AML: A survey from the acute leukemia working party of the European Society for blood and marrow transplantation (EBMT).

PubMed

Lazarevic, Vladimir Lj; Labopin, Myriam; Depei, Wu; Yakoub-Agha, Ibrahim; Huynh, Anne; Ljungman, Per; Schaap, Nicolaas; Cornelissen, Jan J; Maillard, Natacha; Pioltelli, Pietro; Gedde-Dahl, Tobias; Lenhoff, Stig; Houhou, Mohamed; Esteve, Jordi; Mohty, Mohamad; Nagler, Arnon

2018-01-01

The aim of the study was to assess the role of allogeneic stem cell transplantation (SCT) in patients diagnosed with BCR-ABL1-positive acute myeloid leukemia (AML). Fifty-seven patients (median age, 48 years, range: 19-67) with BCR-ABL1 positive AML undergoing SCT were identified. The majority of the patients (70%) received a TKI before the transplant. At SCT 48 patients were in CR (45 in CR1), while 9 patients were transplanted in a more advanced stage of the disease. MRD was negative (BCR-ABL1/ABL < 10 4 ) at time of SCT in 36.1% (14/40). After SCT, 16 (61.5%) out of 26 patients with MRD positive at transplantation reached MRD negativity. After a median follow-up of 6.3 years (0.7-14.2), NRM, RI, LFS, OS, and GRFS at 5 years were 18.1%, 37%, 44.2%, 53.8%, and 32.1%, respectively. The cumulative incidence of acute GvHD grade II-IV was 16.4%, incidence of chronic GvHD 24.9%, and of extensive cGvHD 21.4%, respectively. In patients who received SCT in CR1, 5-yr NRM, RI, LFS, OS, and GRFS were 15.9%, 36.4%, 46.5%, 59.4%, and 34.9%, respectively. Univariate analysis showed that age (<50 vs. ≥50 years) was associated with RI (5-yr: 22.7 vs. 50%), LFS (5-yr: 61.9 vs. 31.8%), and GRFS (5-yr: 52.4 vs. 18.2%), whereas MRD-negative status before SCT was associated with an improved GRFS (38.9 vs. 16.7%). We conclude that the outcome of patients <50 years of age with BCR-ABL1-positive AML receiving allogeneic SCT in CR is relatively favorable, possibly reflecting the beneficial effect of the use of TKI. © 2017 Wiley Periodicals, Inc.

Epstein-Barr-Virus-Positive B-Cell Lymphoma of Recipient Origin Despite of the Elimination of Clonally EBV-Infected T Cells by Allogeneic Stem Cell Transplantation in a Patient with Chronic Active EBV Infection

PubMed Central

Nagasawa, Masayuki

2012-01-01

A 20-year-old patient with chronic active EBV infection (CAEBV) received peripheral blood stem cell transplantation (PBSCT) from HLA-one-locus-mismatched mother. Although EB-virus-infected T cells were eliminated after PBSCT, she developed EB-virus-positive B-cell lymphoma of recipient origin in the brain. By reducing the immunosuppressive therapy, the initial lesion disappeared. However, another lesion in the opposite lateral brain appeared later and was resistant to further reduction of immunosuppressive therapy. EBV-DNA was persistently negative after PBSCT in the peripheral blood. This case is suggestive in management of EBV reactivation after SCT and understanding alloimmune response to EBV. PMID:23213608

Mesenchymal Stem Cells: Time to Change the Name!

PubMed Central

2017-01-01

Summary Mesenchymal stem cells (MSCs) were officially named more than 25 years ago to represent a class of cells from human and mammalian bone marrow and periosteum that could be isolated and expanded in culture while maintaining their in vitro capacity to be induced to form a variety of mesodermal phenotypes and tissues. The in vitro capacity to form bone, cartilage, fat, etc., became an assay for identifying this class of multipotent cells and around which several companies were formed in the 1990s to medically exploit the regenerative capabilities of MSCs. Today, there are hundreds of clinics and hundreds of clinical trials using human MSCs with very few, if any, focusing on the in vitro multipotential capacities of these cells. Unfortunately, the fact that MSCs are called “stem cells” is being used to infer that patients will receive direct medical benefit, because they imagine that these cells will differentiate into regenerating tissue‐producing cells. Such a stem cell treatment will presumably cure the patient of their medically relevant difficulties ranging from osteoarthritic (bone‐on‐bone) knees to various neurological maladies including dementia. I now urge that we change the name of MSCs to Medicinal Signaling Cells to more accurately reflect the fact that these cells home in on sites of injury or disease and secrete bioactive factors that are immunomodulatory and trophic (regenerative) meaning that these cells make therapeutic drugs in situ that are medicinal. It is, indeed, the patient's own site‐specific and tissue‐specific resident stem cells that construct the new tissue as stimulated by the bioactive factors secreted by the exogenously supplied MSCs. Stem Cells Translational Medicine 2017;6:1445–1451 PMID:28452204

[Molecular diagnosis and hematopoietic stem cell transplantation in 17 children with inherited bone marrow failure syndrome].

PubMed

Li, Qian; Li, Benshang; Luo, Changying; Wang, Jianmin; Luo, Chengjuan; Ding, Lixia; Chen, Jing

2015-11-01

To enrich our national database with data of rare diseases by analyzing molecular diagnosis and hematopoietic stem cell transplantation (HSCT) in children with inherited bone marrow failure syndromes (IBMFS). Next-generation sequencing (NGS)-based genetic diagnosis panel was applied for the clinical diagnosis and management of IBMFS. Retrospective analysis was performed on clinical and genetic data of 17 consecutive children who received HSCT over a long time interval (November. 2005-June 2015). Three patients were diagnosed only by clinical manifestation before 2012. After that NGS-based genetic diagnosis panel was used to identify IBMFS-related genes in 12/14.IBMFS patients (except two Diamond-Blackfan anemia (DBA) patients). Two Fanconi anemia (FA) patients were confirmed to be new variations through family-genotype-analysis and 3 families accepted prenatal diagnosis to avoid birth of affected fetuses. Seventeen IBMFS patients (10 FA,5 DBA and 2 dyskeratosis congenital (DKC)) were treated with HSCT from matched sibling donors (n=2), matched unrelated donors (n=8) or mismatched unrelated donors (n=7). The source of stem cells for transplantation included peripheral blood (n=12) and cord blood (n=5). With regard to the conditioning regimens, FA and DKC patients received fludarabine-based reduced intensity conditioning, while DBA patients received classical busulfan-based myeloablative conditioning. Median age at the time of HSCT was 36 months (7-156 months). The number of infused mononuclear cells and CD34⁺ cells was (10.6 ± 6.7) × 10⁸ and (5.9 ± 7.0) × 10⁶ per kilogram of recipient body weight, respectively. The median number of days to neutrophil recovery was 13 days after HSCT (range: 10-19 days). Platelet recovery was faster in the PBSCT group than in the CBT group ((16.3 ± 6.0) days vs. (30.0 ± 17.1) days,t=-2.487,P=0.026). During a median follow-up of 17 months (range: 2-114 months), except one FA patient who was transplanted with HLA-matched unrelated cord blood (CB) died from pneumonia and heart failure because of engraftment failure, other 16 children are alive after the successful HSCT. The failure-free survival rate of the patients three years after HSCT was 94%. NGS-based molecular diagnosis technology and effective HSCT have significantly facilitated the treatment of children with IBMFS in our country, and our national database about this rare disease is to be further exploited.

Enteric nervous system abnormalities are present in human necrotizing enterocolitis: potential neurotransplantation therapy

PubMed Central

2013-01-01

Introduction Intestinal dysmotility following human necrotizing enterocolitis suggests that the enteric nervous system is injured during the disease. We examined human intestinal specimens to characterize the enteric nervous system injury that occurs in necrotizing enterocolitis, and then used an animal model of experimental necrotizing enterocolitis to determine whether transplantation of neural stem cells can protect the enteric nervous system from injury. Methods Human intestinal specimens resected from patients with necrotizing enterocolitis (n = 18), from control patients with bowel atresia (n = 8), and from necrotizing enterocolitis and control patients undergoing stoma closure several months later (n = 14 and n = 6 respectively) were subjected to histologic examination, immunohistochemistry, and real-time reverse-transcription polymerase chain reaction to examine the myenteric plexus structure and neurotransmitter expression. In addition, experimental necrotizing enterocolitis was induced in newborn rat pups and neurotransplantation was performed by administration of fluorescently labeled neural stem cells, with subsequent visualization of transplanted cells and determination of intestinal integrity and intestinal motility. Results There was significant enteric nervous system damage with increased enteric nervous system apoptosis, and decreased neuronal nitric oxide synthase expression in myenteric ganglia from human intestine resected for necrotizing enterocolitis compared with control intestine. Structural and functional abnormalities persisted months later at the time of stoma closure. Similar abnormalities were identified in rat pups exposed to experimental necrotizing enterocolitis. Pups receiving neural stem cell transplantation had improved enteric nervous system and intestinal integrity, differentiation of transplanted neural stem cells into functional neurons, significantly improved intestinal transit, and significantly decreased mortality compared with control pups. Conclusions Significant injury to the enteric nervous system occurs in both human and experimental necrotizing enterocolitis. Neural stem cell transplantation may represent a novel future therapy for patients with necrotizing enterocolitis. PMID:24423414

Clinical Characteristics of Monomorphic Post-transplant Lymphoproliferative Disorders

PubMed Central

Park, Byeong-Bae; Suh, Cheolwon; Won, Jong-Ho; Lee, Won-Sik; Shin, Ho-Jin

2010-01-01

Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of lymphoproliferative disorders associated with immunosuppression and Epstein-Barr virus infection. PTLD is classified into three major categories: early lesions, polymorphic PTLD, and monomorphic PTLD. The majority of monomorphic PTLD cases are non-Hodgkin's lymphoma of B-cell origin. This retrospective study was conducted to investigate the incidence, clinical manifestation, treatment, and outcomes of monomorphic PTLD among 5,817 recipients of solid organ or allogeneic hematopoietic stem cell transplantation from five institutions. Fourteen patients with monomorphic PTLD were identified (male:female 11:3; median age 42.6 yr, range 24-60). The overall incidence rate was 0.24%. The most common disease type was diffuse large B cell lymphoma (n=7). The median time between the transplant and diagnosis of PTLD was 85.8 months. However, all cases of PTLD after allogeneic hematopoietic stem cell transplantation occurred within 1 yr after transplantation. Ten of the 14 patients had EBV-positive tumor. Fourteen patients received combination systemic chemotherapy and four patients were treated with radiation therapy. Ten patients achieved a complete response (CR) and two patients a partial response (PR). The median follow-up period for surviving patients was 36.6 months. Nine patients remain alive (eight CR, one PR). Nine of 11 solid organ transplantations preserved graft function. The present study indicates a lower incidence rate and a longer median time before the development of PTLD than those of previous reports. Careful monitoring was needed after allogeneic hematopoietic stem cell transplantation for PTLD. PMID:20357991

Successful hematopoietic stem cell transplantation following a cyclophosphamide-containing preparative regimen with concomitant phenobarbital administration.

PubMed

Weber, Catherine; Kasberg, Heather; Copelan, Edward

2012-01-01

Cyclophosphamide is an immunosuppressive agent and an anticancer prodrug which requires bioactivation catalyzed primarily by cytochrome P450 enzymes in order to be transformed into its active alkylating compounds. Concomitant administration of drugs known to inhibit or induce this enzyme system is a clinical concern. Herein, we present the case of a chronically ill 21-year-old patient who received high-dose cyclophosphamide, equine antithymocyte globulin (eATG), and total body irradiation (TBI) followed by an allogeneic hematopoietic stem cell transplant (HSCT) for severe aplastic anemia. Throughout her hospitalization, she continued to receive quadruple anticonvulsant therapy including phenobarbital for her long-standing seizure history. The preparative regimen was tolerated well aside from a hypersensitivity reaction to eATG, and minimal cyclophosphamide-related toxicities. Safe and effective administration of high-dose cyclophosphamide was possible with multidisciplinary care consisting of physician, nursing, pharmacy, neurology consultation, as well as social work and case management.

CD20 positivity and white blood cell count predict treatment outcomes in Philadelphia chromosome-negative acute lymphoblastic leukemia patients ineligible for pediatric-inspired chemotherapy.

PubMed

Isshiki, Yusuke; Ohwada, Chikako; Sakaida, Emiko; Onoda, Masahiro; Aotsuka, Nobuyuki; Tanaka, Hiroaki; Fukazawa, Motoharu; Cho, Ryuko; Sugawara, Takeaki; Kawaguchi, Takeharu; Hara, Satoru; Yokota, Akira

2017-11-01

The efficacy of conventional chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been controversial as post-remission therapies for adult Philadelphia chromosome-negative acute lymphoblastic leukemia patients. We retrospectively analyzed 96 adolescent and adult cases of Philadelphia chromosome-negative acute lymphoblastic leukemia to evaluate whether allo-HSCT should be performed after first complete remission (1CR). In total, 34 patients received chemotherapy followed by allo-HSCT (HSCT group) and 62 received chemotherapy alone (chemotherapy group). No significant differences in the event-free survival (EFS) or overall survival were observed between the two groups. In the chemotherapy group, use of pediatric regimens was significantly associated with favorable EFS, while high white blood cell (WBC) count and CD20 positivity were associated with poor outcome. In patients who received pediatric regimens, subsequent allo-HSCT did not influence EFS. In patients who received conventional chemotherapy (adult regimen), subsequent allo-HSCT did not improve EFS. High WBC count and CD20 positivity were also significantly associated with poor EFS in patients who received adult regimens. Patients with low WBC count and absence of CD20 who received adult regimens did not benefit from allo-HSCT. Allo-HSCT may not be required in the pediatric regimen-eligible patients; however, pediatric regimen-ineligible patients with either CD20 positivity or high WBC count should receive allo-HSCT after achieving 1CR. This study was registered at http://www.umin.ac.jp/ctr/ as #C000016287. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Allogeneic stem cell transplantation benefits for patients ≥ 60 years with acute myeloid leukemia and FLT3 internal tandem duplication: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

PubMed Central

Poiré, Xavier; Labopin, Myriam; Polge, Emmanuelle; Passweg, Jakob; Craddock, Charles; Blaise, Didier; Cornelissen, Jan J.; Volin, Liisa; Russell, Nigel H.; Socié, Gérard; Michallet, Mauricette; Fegueux, Nathalie; Chevallier, Patrice; Brecht, Arne; Hunault-Berger, Mathilde; Mohty, Mohamad; Esteve, Jordi; Nagler, Arnon

2018-01-01

Intermediate-risk cytogenetic acute myeloid leukemia with an internal tandem duplication of FLT3 (FLT3-ITD) is associated with a high risk of relapse, and is now a standard indication for allogeneic stem cell transplantation. Nevertheless, most studies supporting this strategy have been performed in young patients. To address the benefit of allogeneic transplantation in the elderly, we made a selection from the European Society for Blood and Marrow Transplantation registry of de novo intermediate-risk cytogenetic acute myeloid leukemia harboring FLT3-ITD in patients aged 60 or over and transplanted from a related or unrelated donor between January 2000 and December 2015. Two hundred and ninety-one patients were identified. Most patients received a reduced-intensity conditioning (82%), while donors consisted of an unrelated donor in 161 (55%) patients. Two hundred and twelve patients received their transplantation in first remission, 37 in second remission and 42 in a more advanced stage of the disease. The 2-year leukemia-free survival rate was 56% in patients in first remission, 22% in those in second remission and 10% in patients with active disease, respectively (P<0.005). Non-relapse mortality for the entire cohort was 20%. In multivariate analysis, disease status at transplantation was the most powerful predictor of worse leukemia-free survival, graft-versus-host disease and relapse-free survival, and overall survival. In this elderly population, age was not associated with outcome. Based on the current results, allogeneic transplantation translates into a favorable outcome in fit patients ≥ 60 with FLT3-ITD acute myeloid leukemia in first remission, similarly to current treatment recommendations for younger patients. PMID:29242299

Resurfacing shoulder arthroplasty for the treatment of severe rheumatoid arthritis: outcome in 167 patients from the Danish Shoulder Registry.

PubMed

Voorde, Pia C Ten; Rasmussen, Jeppe V; Olsen, Bo S; Brorson, Stig

2015-06-01

There is no consensus on which type of shoulder prosthesis should be used in patients with rheumatoid arthritis (RA). We describe patients with RA who were treated with shoulder replacement, regarding patient-reported outcome, prosthesis survival, and causes of revision, and we compare outcome after resurfacing hemi-arthroplasty (RHA) and stemmed hemi-arthroplasty (SHA). We used data from the national Danish Shoulder Arthroplasty Registry and included patients with RA who underwent shoulder arthroplasty in Denmark between 2006 and 2010. Patient-reported outcome was obtained 1-year postoperatively using the Western Ontario Osteoarthritis of the Shoulder index (WOOS), and rates of revision were calculated by checking revisions reported until December 2011. The patient-reported outcome of RHA was compared to that of SHA using regression analysis with adjustment for age, sex, and previous surgery. During the study period, 167 patients underwent shoulder arthroplasty because of rheumatoid arthritis, 80 (48%) of whom received RHA and 34 (26%) of whom received SHA. 16 patients were treated with total stemmed shoulder arthroplasty (TSA), and 24 were treated with reverse shoulder arthroplasty (rTSA). 130 patients returned a completed questionnaire, and the total mean WOOS score was 63. The cumulative 5-year revision rate was 7%. Most revisions occurred after RHA, with a revision rate of 14%. Mean WOOS score was similar for RHA and for SHA. This study shows that shoulder arthroplasty, regardless of design, is a good option in terms of reducing pain and improving function in RA patients. The high revision rate in the RHA group suggests that other designs may offer better implant survival. However, this should be confirmed in larger studies.

The impact of stem cell transplantation on the natural course of peripheral T-cell lymphoma: a real-world experience.

PubMed

Rohlfing, Sarah; Dietrich, Sascha; Witzens-Harig, Mathias; Hegenbart, Ute; Schönland, Stefan; Luft, Thomas; Ho, Anthony D; Dreger, Peter

2018-07-01

The role of autologous stem cell transplantation (autoSCT) as consolidating treatment for peripheral T-cell lymphoma (PTCL) is unsettled. The aim of this analysis was to investigate the impact of autoSCT in the upfront setting by intent-to-treat and to study salvage strategies after relapse. Retrospective follow-up of all patients aged 18-70 years and treated at our institution for ALK-PTCL diagnosed between 2001 and 2014. Of 117 eligible patients, diagnosis was PTCL-NOS in 34, ALCL ALK- in 31, AITL in 28, and other PTCL in 24 patients. Disregarding 20 patients who received first-line treatment externally, upfront autoSCT was not intended in 34 due to comorbidity, higher age, low IPI, physician's decision or unknown reasons (nITT), while intent-to-transplant (ITT) was documented in 63 patients. ITT was not associated with significant benefits for 5-year progression-free survival (PFS) and overall survival (OS) with 46 and 23% in the ITT group vs. 42 and 25% in the nITT group, even after multivariate adjustment for confounders. Altogether, 91 of all 117 patients relapsed or progressed. Thirty-one patients managed to proceed to salvage allografting and achieved a 5-year OS of 52%. In contrast, all 7 patients receiving salvage autoSCT relapsed and died, and only 3 of the 51 patients not eligible for SCT salvage survived. In this study, a significant benefit of intending first-line autoSCT over non-transplant induction in patients with ALK-PTCL did not emerge. Most patients fail first-line treatment and have a poor outlook if salvage alloSCT cannot be performed.

Haploidentical hematopoietic stem cell transplant with umbilical cord-derived multipotent mesenchymal cell infusion for the treatment of high-risk acute leukemia in children.

PubMed

Zhu, Ling; Wang, Zhidong; Zheng, Xiaoli; Ding, Li; Han, Dongmei; Yan, Hongmin; Guo, Zikuan; Wang, Hengxiang

2015-05-01

In this study, 25 children with high-risk acute leukemia received haploidentical hematopoietic stem cell transplant (haplo-HSCT) with co-transfusion of umbilical cord multipotent mesenchymal cells (UC-MSCs). Adverse effects, hematopoietic recovery, complications and outcome were observed during a median follow-up of 12.8 months (range: 3-25 months). Myeloid engraftment was rapid, and the median time to neutrophil and platelet recovery was 15.12 days and 20.08 days, respectively. Eight patients developed grade I skin acute graft-versus-host disease (aGVHD) that responded well to standard steroid therapy. Of note, cytomegalovirus viremia was observed in most patients (23/25 cases). Patients died mainly of leukemia relapse and pulmonary complication. Fourteen patients are currently alive and remain with full donor chimerism at the time of reporting. The present results suggest further clinical trials to testify the effectiveness of UC-MSCs to prevent aGVHD in haplo-HSCT for treating children with high-risk leukemia.

An individualised risk-adapted protocol of pre- and post transplant zoledronic acid reduces bone loss after allogeneic stem cell transplantation: results of a phase II prospective trial.

PubMed

Grigg, A; Butcher, B; Khodr, B; Bajel, A; Hertzberg, M; Patil, S; D'Souza, A B; Ganly, P; Ebeling, P; Wong, E

2017-09-01

Bone loss occurs frequently following allogeneic haematopoietic stem cell transplantation (alloSCT). The Australasian Leukaemia and Lymphoma Group conducted a prospective phase II study of pretransplant zoledronic acid (ZA) and individualised post-transplant ZA to prevent bone loss in alloSCT recipients. Patients received ZA 4 mg before conditioning. Administration of post-transplant ZA from days 100 to 365 post alloSCT was determined by a risk-adapted algorithm based on serial bone density assessments and glucocorticoid exposure. Of 82 patients enrolled, 70 were alive and without relapse at day 100. A single pretransplant dose of ZA prevented femoral neck bone loss at day 100 compared with baseline (mean change -2.6±4.6%). Using the risk-adapted protocol, 42 patients received ZA between days 100 and 365 post alloSCT, and this minimised bone loss at day 365 compared with pretransplant levels (mean change -2.9±5.3%). Femoral neck bone loss was significantly reduced in ZA-treated patients compared with historical untreated controls at days 100 and 365. This study demonstrates that a single dose of ZA pre-alloSCT prevents femoral neck bone loss at day 100 post alloSCT, and that a risk-adapted algorithm is able to guide ZA administration from days 100 to 365 post transplant and minimise further bone loss.

Risk of sinusoidal obstruction syndrome in allogeneic stem cell transplantation after prior gemtuzumab ozogamicin treatment: a retrospective study from the Acute Leukemia Working Party of the EBMT.

PubMed

Battipaglia, G; Labopin, M; Candoni, A; Fanin, R; El Cheikh, J; Blaise, D; Michallet, M; Ruggeri, A; Contentin, N; Ribera, J M; Stadler, M; Sierra, J; von dem Borne, P A; Bloor, A; Socié, G; Nagler, A; Mohty, M

2017-04-01

Gemtuzumab ozogamicin (GO) may increase the risk of sinusoidal obstruction syndrome (SOS) when used prior to allogeneic stem cell transplantation (HSCT). We assessed SOS incidence and outcomes after HSCT of 146 adults, with a median age of 50 years, previously receiving GO. SOS prophylaxis was used in 69 patients (heparin n=57, ursodeoxycholic acid n=8, defibrotide n=4). Cumulative incidence (CI) of SOS was 8% (n=11), with death in 3 patients. Median interval between last GO dose and HSCT was 130 days. Overall survival (OS) and SOS incidence did not differ for patients receiving GO ⩽3.5 months before HSCT and the others. CI of acute and chronic GVHD was 31% and 25%, respectively. Probability of OS and leukemia-free survival (LFS) at 5 years was 40% and 37%, respectively. Relapse incidence and non-relapse mortality were 42% and 21%, respectively. In multivariate analysis, active disease at HSCT was associated with relapse and worse LFS and OS (P<0.03). Liver abnormalities before HSCT correlated with worse OS (P<0.03). Use of low-dose GO prior to HSCT is associated with an acceptable SOS incidence. Prospective studies investigating the role and the utility of SOS prophylaxis are warranted.

Aplastic anemia as a feature of systemic lupus erythematosus: a case report and literature review.

PubMed

Chalayer, Émilie; Ffrench, Martine; Cathébras, Pascal

2015-06-01

Peripheral cytopenias are common in systemic lupus erythematosus, but bone marrow involvement is rarely reported. Aplastic anemia is the result of immune-mediated destruction of hematopoietic stem cells causing pancytopenia and characterized by an empty bone marrow. This rare but serious disease has been described as an unusual manifestation of systemic lupus erythematosus. We reviewed the 25 cases published in the English language literature and discuss the clinical presentation, outcome, treatment, and pathophysiology of aplastic anemia as a complication of systemic lupus erythematosus. We report here the first case of aplastic anemia associated with systemic lupus erythematosus treated with an allogeneic hematopoietic stem cell transplant. Over one half of patients received concomitantly the diagnoses of systemic lupus erythematosus and aplastic anemia. No clinical or histological features can distinguish primary aplastic anemia from aplastic anemia occurring in systemic lupus erythematosus patients. The overall mortality is about 15% and corticosteroid-based therapy alone or in combination with other immunomodulatory drugs can restore bone marrow function. Systemic lupus erythematosus may be complicated by bone marrow involvement. The diagnosis of peripheral cytopenias should be confirmed by bone marrow aspiration. All these patients should receive cortisone as a first treatment. Plasma exchanges seem to have some efficacy. Other different immunomodulatory therapies were used with variable results.

Effective chemomobilization with etoposide and cytarabine (EC regimen) in lymphoma patients: a single-center, retrospective, observational study.

PubMed

Koyama, Daisuke; Nishiwaki, Satoshi; Harada, Yasuhiko; Yamamoto, Satomi; Kurahashi, Shingo; Sugimoto, Takumi; Iwasaki, Toshihiro; Sugiura, Isamu

2017-09-01

Autologous stem cell transplantation is an important strategy for patients with relapsed or refractory lymphoma. Although various regimens for peripheral blood stem cell collection have been used, the optimal regimen has not yet been established. We aimed to evaluate the mobilization efficacy and safety of the regimen consisted of etoposide and cytarabine (EC regimen). We retrospectively analyzed the clinical data of 46 lymphoma patients who received peripheral blood stem cell mobilization with the EC regimen [etoposide (100 mg/m2/day, days 1-4) and cytarabine (100 mg/m2/day, days 1-4)] at Toyohashi municipal hospital from 2004 to 2013. The median age of the patients was 55 years. The most common underlying diseases were diffuse large B-cell lymphoma (46%) and follicular lymphoma (26%). Three-quarters of patients were in their second complete or partial remission. The median total number of collected CD34+ cells was 10.6 × 106 kg-1. Forty-two patients (91%) yielded at least 2 × 106 kg-1 CD34+ cells within a median of 2 apheresis days, and 33 patients (72%) achieved it with only one apheresis. Successful mobilization was observed in five of six patients who failed to mobilize previously. Although febrile neutropenia occurred in 22 patients (48%), no fatal infection was observed. The EC regimen was highly effective in lymphoma patients, including patients who mobilized poorly with other regimens. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Long-term survival of sorafenib-treated FLT3-ITD-positive acute myeloid leukaemia patients relapsing after allogeneic stem cell transplantation.

PubMed

Metzelder, S K; Schroeder, T; Lübbert, M; Ditschkowski, M; Götze, K; Scholl, S; Meyer, R G; Dreger, P; Basara, N; Fey, M F; Salih, H R; Finck, A; Pabst, T; Giagounidis, A; Kobbe, G; Wollmer, E; Finke, J; Neubauer, A; Burchert, A

2017-11-01

Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukaemia (AML) relapsing after allogeneic stem cell transplantation (allo-SCT) has a dismal prognosis with limited therapeutic options. FLT3-ITD kinase inhibition is a reasonable but palliative experimental treatment alternative in this situation. Information on long-term outcome is not available. We performed a long-term follow-up analysis of a previously reported cohort of 29 FLT3-ITD-positive AML patients, which were treated in relapse after allo-SCT with sorafenib monotherapy. With a median follow-up of 7.5 years, 6 of 29 patients (21%) are still alive. Excluding one patient who received a second allo-SCT, five patients (17%) achieved sustained complete remissions with sorafenib. Four of these patients are in treatment-free remission for a median of 4.4 years. Sorafenib may enable cure of a proportion of very poor risk FLT3-ITD-positive AML relapsing after allo-SCT. Copyright © 2017 Elsevier Ltd. All rights reserved.

CMV monitoring after peripheral blood stem cell and bone marrow transplantation by pp65 antigen and quantitative PCR.

PubMed

Schulenburg, A; Watkins-Riedel, T; Greinix, H T; Rabitsch, W; Loidolt, H; Keil, F; Mitterbauer, M; Kalhs, P

2001-10-01

We prospectively monitored 74 consecutive allogeneic and 50 autologous patients after bone marrow/stem cell transplantation from May 1999 to October 2000 at our institution with quantitative CMV PCR and pp65 antigen assay once weekly from conditioning therapy to days 120 and 80 after transplantation, respectively. Written informed consent was obtained from every patient. CMV prophylaxis consisted of acyclovir during transplant. Additionally all patients received only platelet products from CMV-negative donors. In the case of CMV infection preemptive therapy with gancyclovir was applied. In the case of CMV disease high-dose immunoglobulin was given as well. In the allogeneic setting 16 out of 74 (22%) patients developed a positive PCR. Seven episodes of a positive pp65 antigen assay occurred in six allograft recipients. In the autologous setting no positive assay was found during the whole observation period. Additionally, in 6/16 patients a lymphoproliferative assay was performed during CMV infection. Two patients showed a positive (15 and 5.4) and four a negative (2,1.6,1,1.8) stimulation index.

Oligoclonal and monoclonal bands after single autologous stem cell transplant in patients with multiple myeloma: impact on overall survival and progression-free survival.

PubMed

Jimenez-Zepeda, Victor H; Reece, Donna E; Trudel, Suzanne; Franke, Norman; Winter, Andrew; Chen, Christine; Tiedemann, Rodger; Kukreti, Vishal

2014-10-01

Abstract Recently, the occurrence of oligoclonal and monoclonal bands (OB/MB) unrelated to the original clone has been reported in patients with multiple myeloma who undergo autologous stem cell transplant (ASCT) and/or receive treatment with novel agents. The aim of our study was to assess the impact of OB/MB occurrence on overall (OS) and progression-free survival (PFS) for patients with MM undergoing single ASCT at our institution. All consecutive patients with documented MM undergoing single ASCT from January 2000 to December 2012 were evaluated. Ninety-nine patients (11.8%) developed OB/MB at day 100 post-ASCT (32.3%, OB and 67.7%, MB). Multivariate analysis identified the development of OBs/MBs as an independent favorable prognostic factor for OS and PFS (p = 0.008 and 0.012, respectively). In conclusion, the occurrence of OB/MB is an important prognostic factor in patients with MM who undergo ASCT. Its impact on clinical outcomes should be prospectively validated and its biological significance further elucidated.

Breaking the Blood-Brain Barrier With Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain.

PubMed

Tajiri, Naoki; Lee, Jea Young; Acosta, Sandra; Sanberg, Paul R; Borlongan, Cesar V

2016-01-01

Blood-brain barrier (BBB) permeabilizers, such as mannitol, can facilitate peripherally delivered stem cells to exert therapeutic benefits on the stroke brain. Although this BBB permeation-aided stem cell therapy has been demonstrated in the acute stage of stroke, such BBB permeation in the chronic stage of the disease remains to be examined. Adult Sprague-Dawley rats initially received sham surgery or experimental stroke via the 1-h middle cerebral artery occlusion (MCAo) model. At 1 month after the MCAo surgery, stroke animals were randomly assigned to receive human umbilical cord stem cells only (2 million viable cells), mannitol only (1.1 mol/L mannitol at 4°C), combined human umbilical cord stem cells (200,000 viable cells) and mannitol (1.1 mol/L mannitol at 4°C), and vehicle (phosphate-buffered saline) only. Stroke animals that received human umbilical cord blood cells alone or combined human umbilical cord stem cells and mannitol exhibited significantly improved motor performance and significantly better brain cell survival in the peri-infarct area compared to stroke animals that received vehicle or mannitol alone, with mannitol treatment reducing the stem cell dose necessary to afford functional outcomes. Enhanced neurogenesis in the subventricular zone accompanied the combined treatment of human umbilical cord stem cells and mannitol. We showed that BBB permeation facilitates the therapeutic effects of a low dose of peripherally transplanted stem cells to effectively cause functional improvement and increase neurogenesis in chronic stroke.

Epithelial expression of cytokeratins 15 and 19 in vitiligo.

PubMed

Saleh, Fatma Y; Awad, Sherif S; Nasif, Ghada A; Halim, Christein

2016-12-01

Cytokeratins (CK) belong to the family of intermediate filament proteins, and among them specific epithelial keratins are considered markers for stem cells activation. This study aims to investigate the expression of CK15 and CK19 as possible stem cell markers in vitiligo during phototherapy. The study was conducted on vitiligo patients receiving narrow-band ultraviolet therapy. Immunohistochemical staining for CK15 and CK19 was carried out, and clinical follow-up continued for 4 weeks. Of 28 patients, CK15 expression was demonstrated in 17 cases (61%) while CK19 expression was demonstrated in 11 cases (39%). Cells expressing positive staining were demonstrated in follicular and interfollicular epithelium. Expression was clearly demonstrated in patients younger than 20 years old, with shorter disease duration, with disease stability, and with normally pigmented hairs. Expression of cytokeratins was significantly correlated to improvement of vitiligo lesions. CK15 and CK19 are expressed in vitiligo during UV repigmentation in the follicular and interfollicular epithelium. This expression of cytokeratins was significantly correlated to improvement and can be considered valuable tool to monitor stem cells stimulation for the sake of the repigmentation process in vitiligo. © 2016 Wiley Periodicals, Inc.

Imatinib use immediately before stem cell transplantation in children with Philadelphia chromosome-positive acute lymphoblastic leukemia: Results from Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Study Ph(+) ALL04.

PubMed

Manabe, Atsushi; Kawasaki, Hirohide; Shimada, Hiroyuki; Kato, Itaru; Kodama, Yuichi; Sato, Atsushi; Matsumoto, Kimikazu; Kato, Keisuke; Yabe, Hiromasa; Kudo, Kazuko; Kato, Motohiro; Saito, Tomohiro; Saito, Akiko M; Tsurusawa, Masahito; Horibe, Keizo

2015-05-01

Incorporation of imatinib into chemotherapeutic regimens has improved the prognosis of children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). We investigated a role of imatinib immediately before hematopoietic stem cell transplantation (HSCT). Children with Ph(+) ALL were enrolled on JPLSG Ph(+) ALL 04 Study within 1 week of initiation of treatment for ALL. Treatment regimen consisted of Induction phase, Consolidation phase, Reinduction phase, 2 weeks of imatinib monotherapy phase, and HSCT phase (Etoposide+CY+TBI conditioning). Minimal residual disease (MRD), the amount of BCR-ABL transcripts, was measured with the real-time PCR method. The study was registered in UMIN-CTR: UMIN ID C000000290. Forty-two patients were registered and 36 patients (86%) achieved complete remission (CR). Eight of 17 patients (47%) who had detectable MRD at the beginning of imatinib monotherapy phase showed disappearance or decrease in MRD after imatinib treatment. Consequently, 26 patients received HSCT in the first CR and all the patients had engraftment and no patients died because of complications of HSCT. The 4-year event-free survival rates and overall survival rates among all the 42 patients were 54.1 ± 7.8% and 78.1 ± 6.5%, respectively. Four of six patients who did achieve CR and three of six who relapsed before HSCT were salvaged with imatinib-containing chemotherapy and subsequently treated with HSCT. The survival rate was excellent in this study although all patients received HSCT. A longer use of imatinib concurrently with chemotherapy should eliminate HSCT in a subset of patients with a rapid clearance of the disease. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Treatment of primary acute myeloid leukemia: results of a prospective multicenter trial including high-dose cytarabine or stem cell transplantation as post-remission strategy.

PubMed

Brunet, Salut; Esteve, Jordi; Berlanga, Joan; Ribera, Josep M; Bueno, Javier; Martí, Josep M; Bargay, Joan; Guardia, Ramon; Juliá, Antoni; Granena, Albert; Montserrat, Emili; Sierra, Jorge

2004-08-01

To evaluate a regimen of induction and consolidation chemotherapy, followed by a post-remission therapy which depended on age and cytogenetics, in patients with primary acute myeloid leukemia. Two hundred patients up to 60 years old received idarubicin, standard dose cytarabine and etoposide as induction chemotherapy and one consolidation course including intermediate dose cytarabine and mitoxantrone. Subsequently, patients with favorable cytogenetics, [i.e., t(8;21), inv(16)] were scheduled to receive 2 courses of high-dose cytarabine. The remainder were scheduled for allogeneic stem cell transplantation (SCT), if 50 years old or lacking a donor. In patients with favorable cytogenetics the 4-year probabilities of survival and leukemia-free survival (LFS) were 62+/-9% and 41+/-10%, respectively. The results were better in patients with t(8;21). LFS at 4 years in patients 50 years old assigned to auto-SCT had a 4-year LFS of 17+/-9%. Adverse cytogenetics and white blood cell count >or= 20 yen 109/L at diagnosis were associated with lower probability of survival and leukemia-free survival. We confirmed that high-dose cytarabine seems a good option for patients with t(8;21). Autologous and allogeneic SCT led to similar leukemia-free survival in patients

Second neoplasms in adult patients submitted to haematopoietic stem cell transplantation.

PubMed

Torrent, Anna; Ferrá, Christelle; Morgades, Mireia; Jiménez, María-José; Sancho, Juan-Manuel; Vives, Susana; Batlle, Montserrat; Moreno, Miriam; Xicoy, Blanca; Oriol, Albert; Ibarra, Gladys; Ribera, Josep-Maria

2018-06-08

Patients submitted to haematopoietic stem cell transplantation (HSCT) are at increased risk of late complications, such as second neoplasm (SN). The incidence and risk factors of SN in patients receiving HSCT at a single centre were analysed. The follow-up of adult patients who received a first HSCT (autologous [auto-HSCT] or allogeneic [allo-HSCT]) between January 2000 and December 2015 was reviewed. We collected their demographic characteristics, the primary disease and type of HSCT, and analysed the cumulative incidence of SN and their risk factors. Of 699 transplanted patients (auto-HSCT, n=451; allo-HSCT, n=248), 42 (6%) developed SN (17 haematological and 25 solid), 31 post-auto-HSCT and 11 post-allo-HSCT. Haematologic SN were more frequent after auto-HSCT than after allo-HSCT. The median time between HSCT and SN was 4.09 years [range 0.07-13.15], with no differences between auto-HSCT and allo-HSCT. The cumulative incidence of SN was 5% (95% CI 3-6) at 5 years, 7% (95% CI 5-10) at 10 years and 11% (95% CI 8-15) at 15 years, without differences according to the type of HSCT. Only the age over 40 years correlated with an increased risk of SN. In this series, the incidence of post-HSCT SN was similar to that previously described. Patients submitted to an auto-HSCT showed a higher frequency of haematologic SN. A higher incidence of SN was detected in patients older than 40 at the time of HSCT. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Allogeneic hematopoietic stem cell transplantation for Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disease in Japan.

PubMed

Sato, Emiko; Ohga, Shouichi; Kuroda, Hiroshi; Yoshiba, Fumiaki; Nishimura, Miki; Nagasawa, Masayuki; Inoue, Masami; Kawa, Keisei

2008-09-01

Epstein-Barr virus (EBV)-associated T/NK-cell lymphoproliferative disease (LPD) has been linked to several different disorders. Its prognosis is generally poor and a treatment strategy has yet to be established. There are reports, however, that hematopoietic stem cell transplantation (HSCT) can cure this disease. To clarify the current situation regarding allogeneic hematopoietic stem cell transplantation (allo-HSCT) for EBV-associated T/NK-LPD, a nationwide survey was performed in Japan. Data for 74 patients were collected. There were 42 cases of chronic active EBV infection (CAEBV), 10 cases of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), and 22 cases of EBV-associated lymphoma/leukemia (EBV-lymphoma/leukemia). Of those with CAEBV, 54% had the EBV-infected T-cell type and 59% with EBV-lymphoma/leukemia had the EBV-infected NK-cell type. Most patients with EBV-HLH and EBV-lymphoma/leukemia received allo-HSCT within 1 year after onset compared to only 14% of patients with CAEBV. The event-free survival (EFS) rate following allo-HSCT was 0.561 +/- 0.086 for CAEBV, 0.614 +/- 0.186 for EBV-HLH, and 0.309 +/- 0.107 for EBV-lymphoma/leukemia. The EFS of allo-HSCT with conventional conditioning was 0.488 +/- 0.074 and with reduced-intensity conditioning was 0.563 +/- 0.124. Thus, in a substantial number of cases, EBV-associated T/NK-LPD can be cured by either allogeneic conventional stem cell transplantation or reduced-intensity stem cell transplantation. Copyright 2008 Wiley-Liss, Inc.

Upfront plerixafor plus G-CSF versus cyclophosphamide plus G-CSF for stem cell mobilization in multiple myeloma: efficacy and cost analysis study.

PubMed

Afifi, S; Adel, N G; Devlin, S; Duck, E; Vanak, J; Landau, H; Chung, D J; Lendvai, N; Lesokhin, A; Korde, N; Reich, L; Landgren, O; Giralt, S; Hassoun, H

2016-04-01

Cyclophosphamide plus G-CSF (C+G-CSF) is one of the most widely used stem cell (SC) mobilization regimens for patients with multiple myeloma (MM). Plerixafor plus G-CSF (P+G-CSF) has demonstrated superior SC mobilization efficacy when compared with G-CSF alone and has been shown to rescue patients who fail mobilization with G-CSF or C+G-CSF. Despite the proven efficacy of P+G-CSF in upfront SC mobilization, its use has been limited, mostly due to concerns of high price of the drug. However, a comprehensive comparison of the efficacy and cost effectiveness of SC mobilization using C+G-CSF versus P+G-CSF is not available. In this study, we compared 111 patients receiving C+G-CSF to 112 patients receiving P+G-CSF. The use of P+G-CSF was associated with a higher success rate of SC collection defined as ⩾5 × 10(6) CD34+ cells/kg (94 versus 83%, P=0.013) and less toxicities. Thirteen patients in the C+G-CSF arm were hospitalized owing to complications while none in the P+G-CSF group. C+G-CSF was associated with higher financial burden as assessed using institutional-specific costs and charges (P<0.001) as well as using Medicare reimbursement rates (P=0.27). Higher rate of hospitalization, increased need for salvage mobilization, and increased G-CSF use account for these differences.

Immunization of Children Receiving Immunosuppressive Therapy for Cancer or Hematopoietic Stem Cell Transplantation

PubMed Central

Shetty, Avinash K.; Winter, Mary A.

2012-01-01

In the past 3 decades, the number of immunocompromised children has increased steadily because of dramatic improvement in survival rates in certain malignancies as a result of intensive curative treatment regimens and an increase in the number of children undergoing life-saving hematopoietic stem cell transplantation (HSCT). Children receiving immunosuppressive therapy for cancer, as well as HSCT recipients, will benefit from vaccination but warrant close evaluation for a variety of reasons, such as the risk of developing severe infections, serious adverse events following certain vaccines, and decreased vaccine efficacy caused by poor immune response to vaccination. Various professional organizations have published vaccination guidelines for immunocompromised patients. Given their heterogeneity, recommendations for the immunization of immunocompromised patients may not be universally applicable. The safety of many commonly used vaccines has not been established in immunocompromised children. In addition, no large-scale vaccine studies have evaluated the clinical outcome of disease prevention in this population. All killed vaccines are generally safe, while live vaccines may be administered to immunocompromised children in select circumstances, depending on the degree of altered immunocompetence and the underlying primary condition. Healthcare providers should be knowledgeable about the indications, contraindications, and precautions for vaccine administration in immunocompromised patients. To protect immunocompromised patients, all family, household contacts, and healthcare workers should also be immunized with all routinely recommended vaccines. Pediatricians play a crucial role in identifying and effectively communicating the risks and benefits of vaccines to immunocompromised patients and their parents. PMID:23049460

A natural stem cell therapy? How novel findings and biotechnology clarify the ethics of stem cell research

PubMed Central

Patel, P

2006-01-01

The natural replacement of damaged cells by stem cells occurs actively and often in adult tissues, especially rapidly dividing cells such as blood cells. An exciting case in Boston, however, posits a kind of natural stem cell therapy provided to a mother by her fetus—long after the fetus is born. Because there is a profound lack of medical intervention, this therapy seems natural enough and is unlikely to be morally suspect. Nevertheless, we feel morally uncertain when we consider giving this type of therapy to patients who would not naturally receive it. Much has been written about the ethics of stem cell research and therapy; this paper will focus on how recent advances in biotechnology and biological understandings of development narrow the debate. Here, the author briefly reviews current stem cell research practices, revisits the natural stem cell therapy case for moral evaluation, and ultimately demonstrates the importance of permissible stem cell research and therapy, even absent an agreement about the definition of when embryonic life begins. Although one promising technology, blighted ovum utilisation, uses fertilised but developmentally bankrupt eggs, it is argued that utilisation of unfertilised eggs to derive totipotent stem cells obviates the moral debate over when life begins. There are two existing technologies that fulfil this criterion: somatic cell nuclear transfer and parthenogenic stem cell derivation. Although these technologies are far from therapeutic, concerns over the morality of embryonic stem cell derivation should not hinder their advancement. PMID:16574879

Hematopoietic stem cell transplantation from unrelated donors in children with DOCK8 deficiency.

PubMed

Uygun, Dilara Fatma K; Uygun, Vedat; Reisli, İsmail; Keleş, Sevgi; Özen, Ahmet; Yılmaz, Mustafa; Sayar, Esra H; Daloğlu, Hayriye; Öztürkmen, Seda I; Çakı, Suar; Karasu, Gülsün T; Yeşilipek, Akif

2017-11-01

DIDS is a unique form of combined immune deficiency characterized by an unusual susceptibility to cutaneous viral infections, severe allergies with eosinophilia and elevated immunoglobulin E titers, autoimmunity, and cancer. HSCT is considered the standard of care for this deadly disease. We have retrospectively analyzed the outcome of allogeneic HSCT from unrelated donors in patients with DIDS. Data from four patients, with five transplants, are presented. All patients received transplants from unrelated donors' BM, except for one patient who received a cord blood transplant. The conditioning regimens were based on myeloablative protocols for BM derived transplants; a NM regimen was pursued for the patient who received a cord blood transplant, which resulted in graft rejection. Although recurrent pneumonia and skin infections resolved immediately after transplantation, all patients subsequently developed human herpesvirus infection, including cutaneous herpetic lesions, cytomegalovirus reactivation, and zona zoster, which could be attributed to the use of ATG. Despite the presence of serious morbidities prior to transplantation, all patients recovered successfully. DIDS can be successfully treated with allogeneic HSCT from unrelated donors following a myeloablative conditioning regimen, with a reasonable safety profile. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Late-Onset Cerebral Toxoplasmosis After Allogeneic Hematopoietic Stem Cell Transplantation

PubMed Central

Khalaf, Ahmed M.; Hashim, Mahmoud A.; Alsharabati, Mohammed; Fallon, Kenneth; Cure, Joel K.; Pappas, Peter; Mineishi, Shin; Saad, Ayman

2017-01-01

Patient: Male, 44 Final Diagnosis: Cerebral toxoplasmosis after HSCT Symptoms: Hemiparesis • muscle weakness Medication: — Clinical Procedure: — Specialty: Hematology Objective: Unusual clinical course Background: Toxoplasmosis is an uncommon but potentially fatal complication following allogeneic hematopoietic stem cell transplantation (HCT). Post-transplant toxoplasmosis is often a reactivation of prior infection and typically occurs within the first 6 months of transplant. Herein, we report that cerebral toxoplasmosis may occur 22 months after allogeneic hematopoietic stem cell transplantation. Case Report: We describe a case of cerebral toxoplasmosis that occurred 22 months after an allogeneic HCT while the patient was on aerosolized pentamidine for Pneumocystis jiroveci pneumonia (PCP) prophylaxis. The disease was only diagnosed after brain biopsy because of atypical MRI appearance of the cerebral lesion and negative Toxoplasma gondii IgG antibody test result in the cerebrospinal fluid (CSF). The patient received pyrimethamine and sulfadiazine treatment, with dramatic improvement after several months. The patient is alive 2 years after infection diagnosis, with no evidence of disease and is off Toxoplasma prophylaxis. Conclusions: Cerebral toxoplasmosis can occur late after allogeneic HCT while patients are on immunosuppression therapy, with atypical features on imaging studies and negative Toxoplasma gondii IgG antibody test result in the CSF. Pre-transplant serologic screening for T. gondii antibodies in allogeneic transplant candidates is warranted. Brain biopsy can be a helpful diagnostic tool for cerebral lesions. PMID:28280256

Intermediate dose of imatinib in combination with chemotherapy followed by allogeneic stem cell transplantation improves early outcome in paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL): results of the Spanish Cooperative Group SHOP studies ALL-94, ALL-99 and ALL-2005.

PubMed

Rives, Susana; Estella, Jesús; Gómez, Pedro; López-Duarte, Mónica; de Miguel, Purificación García; Verdeguer, Amparo; Moreno, Maria José; Vivanco, José Luis; Couselo, José Miguel; Fernández-Delgado, Rafael; Maldonado, Marisol; Tasso, María; López-Ibor, Blanca; Lendínez, Francisco; López-Almaraz, Ricardo; Uriz, Javier; Melo, Montserrat; Fernández-Teijeiro, Ana; Rodríguez, Isidoro; Badell, Isabel

2011-09-01

Philadelphia-chromosome acute lymphoblastic leukaemia (Ph+ ALL) is a subgroup of ALL with very high risk of treatment failure. We report here the results of the Sociedad Española de Hematología y Oncología Pediátricas (SEHOP/SHOP) in paediatric Ph+ ALL treated with intermediate-dose imatinib concurrent with intensive chemotherapy. The toxicities and outcome of these patients were compared with historical controls not receiving imatinib. Patients with Ph+ ALL aged 1-18years were enrolled in three consecutive ALL/SHOP trials (SHOP-94/SHOP-99/SHOP-2005). In the SHOP-2005 trial, imatinib (260mg/m(2) per day) was given on day-15 of induction. Allogeneic haematopoietic stem-cell transplantation (HSCT) from a matched related or unrelated donor was scheduled in first complete remission (CR1). Forty-three patients were evaluable (22 boys, median age 6·8years, range, 1·2-15). Sixteen received imatinib whereas 27 received similar chemotherapy without imatinib. Seventeen of 27 and 15 of 16 patients in the non-imatinib and imatinib cohort, respectively, underwent HSCT in CR1. With a median follow-up of 109 and 39months for the non-imatinib and imatinib cohorts, the 3-year event-free survival (EFS) was 29·6% and 78·7%, respectively (P=0·01). These results show that, compared to historical controls, intermediate dose of imatinib given concomitantly with chemotherapy and followed by allogeneic HSCT markedly improved early EFS in paediatric Ph+ ALL. © 2011 Blackwell Publishing Ltd.

Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure.

PubMed

Spencer, Andrew; Prince, H Miles; Roberts, Andrew W; Prosser, Ian W; Bradstock, Kenneth F; Coyle, Luke; Gill, Devinder S; Horvath, Noemi; Reynolds, John; Kennedy, Nola

2009-04-10

Thalidomide is effective in the treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM). However, the role of thalidomide in the post-autologous stem cell transplantation (ASCT) context remains unclear. This study assessed whether the addition of thalidomide consolidation following ASCT would improve the durability of responses achieved and overall survival. Between January 2002 and March 2005, 269 patients with newly diagnosed MM who achieved disease stabilization or better with conventional induction chemotherapy received a single high-dose melphalan conditioned ASCT. Post-ASCT, 129 patients were randomly assigned to receive indefinite prednisolone maintenance therapy (control group) and 114 to receive the same in addition to 12 months of thalidomide consolidation (thalidomide group). The primary study end points were progression-free survival (PFS) and overall survival (OS). The secondary end point was tolerability. After a median follow-up of 3 years, the postrandomization 3-year PFS rates were 42% and 23% (P < .001; hazard ratio [HR], 0.5; 95% CI, 0.35 to 0.71) and the OS rates were 86% and 75% (P = .004; HR, 0.41; 95% CI, 0.22 to 0.76) in the thalidomide and control groups, respectively. There was no difference in survival between groups 12 months after disease progression (79% v 77%; P = .237). Neurological toxicities were more common in the thalidomide arm but there were no differences between arms for thromboembolic events. Consolidation therapy with 12 months of thalidomide combined with prednisolone prolongs survival when used after a single high-dose therapy supported ASCT in patients with newly diagnosed MM. Furthermore, thalidomide consolidation therapy did not adversely impact on survival in the subsequent salvage setting.

The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT registry.

PubMed

Michallet, M; Sobh, M; Milligan, D; Morisset, S; Niederwieser, D; Koza, V; Ruutu, T; Russell, N H; Verdonck, L; Dhedin, N; Vitek, A; Boogaerts, M; Vindelov, L; Finke, J; Dubois, V; van Biezen, A; Brand, R; de Witte, T; Dreger, P

2010-10-01

We analyzed 368 chronic lymphocytic leukemia patients who underwent allogeneic hematopoietic stem cell transplantation reported to the EBMT registry between 1995 and 2007. There were 198 human leukocyte antigen (HLA)-identical siblings; among unrelated transplants, 31 were well matched in high resolution ('well matched' unrelated donor, WMUD), and 139 were mismatched (MM), including 30 matched in low resolution; 266 patients (72%) received reduced-intensity conditioning and 102 (28%) received standard. According to the EBMT risk score, 11% were in scores 1-3, 23% in score 4, 40% in score 5, 22% in score 6 and 4% in score 7. There was no difference in overall survival (OS) at 5 years between HLA-identical siblings (55% (48-64)) and WMUD (59% (41-84)), P=0.82. In contrast, OS was significantly worse for MM (37% (29-48) P=0.005) due to a significant excess of transplant-related mortality. Also OS worsened significantly when EBMT risk score increased. HLA matching had no significant impact on relapse (siblings: 24% (21-27); WMUD: 35% (26-44), P=0.11 and MM: 21% (18-24), P=0.81); alemtuzumab T-cell depletion and stem cell source (peripheral blood) were associated with an increased risk. Our findings support the use of WMUD as equivalent alternative to HLA-matched sibling donors for allogeneic HSCT in CLL, and justify the application of EBMT risk score in this disease.

Diagnosis and Clinical Management of Human Papilloma Virus-Related Gingival Squamous Cell Carcinoma in a Patient With Leukemia: A Case Report.

PubMed

Yassin, Alaa; Dixon, Douglas R; Oda, Dolphine; London, Robert M

2016-02-01

Close clinical inspection for intraoral lesions in patients with leukemia that develop chronic graft-versus-host disease (cGVHD) is critical. Additionally, neoplasias developing in bone marrow transplant patients after treatment for leukemia represent a significant obstacle for long-term patient survival, necessitating lifetime follow-up by health care providers. This case report describes the identification, diagnosis, and treatment of gingival squamous cell carcinoma (SCC) in a patient with leukemia who was treated previously with a stem cell transplant and referred for routine periodontal care. A 53-year-old male was referred to the Department of Periodontics for an assessment of tooth #10 with 2+ mobility and associated cross-bite occlusion. The patient was diagnosed with acute myeloid leukemia at age 39 years, received hematopoietic stem cell transplantation (HSCT), and later developed cGVHD followed by human papilloma virus (HPV) infections. During the periodontal evaluation, a large, non-painful, exophytic, alveolar gingival mass was identified and later diagnosed as SCC. It is unusual that oral SCC presents as an exophytic, gingival swelling. The patient received comprehensive periodontal management in coordination with his otolaryngology team before and during the diagnosis of SCC secondary to cGVHD and HPV infection. Patients with a history of HSCT treatment for leukemia and subsequent cGVHD are at a high risk of developing second primary oral malignancies, including SCC. Exposure to oncogenic HPV infection may compound this risk. Therefore, it is important for dentists to be aware of special treatment concerns and to frequently screen these patients to achieve early diagnosis and treatment of these neoplasms.

In vitro toxicity assay of cisplatin on mouse acute lymphoblastic leukaemia and spermatogonial stem cells.

PubMed

Shabani, R; Ashtari, K; Behnam, B; Izadyar, F; Asgari, H; Asghari Jafarabadi, M; Ashjari, M; Asadi, E; Koruji, M

2016-06-01

Testicular cancer is the most common cancer affecting men in reproductive age, and cisplatin is one of the major helpful chemotherapeutic agents for treatment of this cancer. In addition, exposure of testes cancer cells to cisplatin could potentially eliminate tumour cells from germ cells in patients. The aim of this study was to evaluate the effect of cisplatin on viability of mouse acute lymphoblastic leukaemia cell line (EL-4) and neonatal mouse spermatogonial cells in vitro. In this study, the isolated spermatogonial stem cells (SSC) and EL-4 were divided into six groups including control (received medium), sham (received DMSO in medium) and experimental groups which received different doses of cisplatin (0.5, 5, 10 and 15 μg ml(-1) ). Cells viability was evaluated with MTT assay. The identity of the cultured cells was confirmed by the expression of specific markers. Our finding showed that viability of both SSC and EL-4 cells was reduced with the dose of 15 μg/ml when compared to the control group (P ≤ 0.05). Also, the differences between the IC50 in doses 10 and 15 μg/ml at different time were significant (P ≤ 0.05). The number of TUNEL-positive cells was increased, and the BAX and caspase-3 expressions were upregulated in EL4 cells for group that received an effective dose of cisplatin). In conclusion, despite the dramatic effects of cisplatin on both cells, spermatogonial stem cells could form colony in culture. © 2015 Blackwell Verlag GmbH.

Lower hospital mortality and complications after pediatric hematopoietic stem cell transplantation.

PubMed

Bratton, Susan L; Van Duker, Heather; Statler, Kimberly D; Pulsipher, Michael A; McArthur, Jennifer; Keenan, Heather T

2008-03-01

To assess protective and risk factors for mortality among pediatric patients during initial care after hematopoietic stem cell transplantation (HSCT) and to evaluate changes in hospital mortality. Retrospective cohort using the 1997, 2000, and 2003 Kids Inpatient Database, a probabilistic sample of children hospitalized in the United States with a procedure code for HSCT. Hospitalized patients in the United States submitted to the database. Age, <19 yrs. None. Hospital mortality significantly decreased from 12% in 1997 to 6% in 2003. Source of stem cells changed with increased use of cord blood. Rates of sepsis, graft versus host disease, and mechanical ventilation significantly decreased. Compared with autologous HSCT, patients who received an allogenic HSCT without T-cell depletion were more likely to die (adjusted odds ratio, 2.4; 95% confidence interval, 1.5, 3.9), while children who received cord blood HSCT were at the greatest risk of hospital death (adjusted odds ratio, 4.8; 95% confidence interval, 2.6, 9.1). Mechanical ventilation (adjusted odds ratio, 26.32; 95% confidence interval, 16.3-42.2), dialysis (adjusted odds ratio, 12.9; 95% confidence interval, 4.7-35.4), and sepsis (adjusted odds ratio, 3.9; 95% confidence interval, 2.5-6.1) were all independently associated with death, while care in 2003 was associated with decreased risk (adjusted odds ratio, 0.4; 95% confidence interval, 0.2-0.7) of death. Hospital mortality after HSCT in children decreased over time as did complications including need for mechanical ventilation, graft versus host disease, and sepsis. Prevention of complications is essential as the need for invasive support continues to be associated with high mortality risk.

Hematopoietic Stem Cell Transplantation in Multiple Myeloma: A Retrospective Study of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

PubMed

Beaussant, Yvan; Daguindau, Etienne; Pugin, Aurore; Mohty, Mohamad; Avet-Loiseau, Hervé; Roos-Weil, Damien; Michallet, Mauricette; Chevalier, Patrice; Raus, Nicole; El-Cheikh, Jean; Tabrizi, Reza; Huyn, Anne; Buzyn, Agnès; Socié, Gérard; Vincent, Laure; Guilhot, François; Yakoub-Agha, Ibrahim; Lenain, Pascal; François, Sylvie; Beckerich, Florence; Lioure, Bruno; Bulabois, Claude-Eric; Deconinck, Eric

2015-08-01

Because the indication of allograft (allogeneic stem cell transplantation [alloSCT]) for multiple myeloma (MM) has widened in recent years, thanks to the development of reduced-intensity conditionings (RIC), it is still unclear if myeloablative conditioning (MAC) remains appropriate. This study compares retrospectively outcomes of patients undergoing either RIC or MAC regimens for MM. Based on the SFGM-TC registry, we included 446 MM patients receiving alloSCT between 1999 and 2009 for whom a minimal data set was available. Median follow-up for the entire cohort was 33.6 months (range, 0 to 164.5). RIC and MAC populations were different regarding age (53.5 versus 47.1 years, respectively), number of prior autologous (auto)SCTs (93.2% versus 79.6% had at least 2 autoSCTs), and stem cell source (90.2% versus 61.2% received peripheral blood). For RIC and MAC populations the nonrelapse mortality at 2 years was 24.6% and 22.4%, respectively, progression-free survival 35.5% and 51.1%, and overall survival 59.5% and 66.7% (not significant). These outcomes were not affected by conditioning intensity either on univariate or multivariate analysis. Despite some limitations in the study design, these results indicate that MAC should remain a valuable option in alloSCT for MM, especially for young and less-treated patient with no comorbidity. The constant progress in induction treatments of MM and supportive care after alloSCT could improve these results in the near future. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Wireless capsule endoscopy for diagnosis of acute intestinal graft-versus-host disease.

PubMed

Neumann, Susanne; Schoppmeyer, Konrad; Lange, Thoralf; Wiedmann, Marcus; Golsong, Johannes; Tannapfel, Andrea; Mossner, Joachim; Niederwieser, Dietger; Caca, Karel

2007-03-01

The small intestine is the most common location of intestinal graft-versus-host disease (GVHD). EGD with duodenal biopsies yields the highest diagnostic sensitivity, but the jejunum and ileum are not accessible by regular endoscopy. In contrast, wireless capsule endoscopy (WCE) is a noninvasive imaging procedure offering complete evaluation of the small intestine. The objective was to compare the diagnostic value of EGD, including biopsies, with the results of WCE in patients with acute intestinal symptoms who received allogeneic blood stem cell transplantation and to analyze the appearance and distribution of acute intestinal GVHD lesions in these patients. An investigator-blinded, single-center prospective study. Patients with acute intestinal symptoms after allogeneic stem cell transplantation underwent both EGD and WCE within 24 hours. Clinical data were recorded during 2 months of follow-up. Fourteen consecutive patients with clinical symptoms of acute intestinal GVHD were recruited. In 1 patient, the capsule remained in the stomach and was removed endoscopically. In 7 of 13 patients who could be evaluated, acute intestinal GVHD was diagnosed by EGD with biopsies, but 3 of these would have been missed by EGD alone. In all 7 patients with histologically confirmed acute intestinal GVHD, WCE revealed typical signs of GVHD. Lesions were scattered throughout the small intestine, but were most accentuated in the ileum. This study had a small number of patients. WCE, which is less invasive than EGD with biopsies, showed a comparable sensitivity and a high negative predictive value for diagnosing acute intestinal GVHD. It may be helpful to avoid repeated endoscopic procedures in patients who have undergone stem cell transplantation.

Ovarian tissue cryopreservation in girls undergoing haematopoietic stem cell transplant: experience of a single centre.

PubMed

Biasin, E; Salvagno, F; Berger, M; Nesi, F; Quarello, P; Vassallo, E; Evangelista, F; Marchino, G L; Revelli, A; Benedetto, C; Fagioli, F

2015-09-01

Fertility after childhood haemopoietic stem cell transplant (HSCT) is a major concern. Conditioning regimens before HSCT present a high risk (>80%) of ovarian failure. Since 2000, we have proposed cryopreservation of ovarian tissue to female patients undergoing HSCT at our centre, to preserve future fertility. After clinical and haematological evaluation, the patients underwent ovarian tissue collection by laparoscopy. The tissue was analysed by histologic examination to detect any tumour contamination and then frozen following the slow freezing procedure and cryopreserved in liquid nitrogen. From August 2000 to September 2013, 47 patients planned to receive HSCT, underwent ovarian tissue cryopreservation. The median age at diagnosis was 11.1 years and at the time of procedure it was 13 years, respectively. Twenty-four patients were not pubertal at the time of storage, whereas 23 patients had already experienced menarche. The median time between laparoscopy and HSCT was 25 days. Twenty-six out of 28 evaluable patients (93%) developed hypergonadotropic hypogonadism at a median time of 23.3 months after HSCT. One patient required autologous orthotopic transplantation that resulted in one live birth. Results show a very high rate of iatrogenic hypergonadotropic hypogonadism, highlighting the need for fertility preservation in these patients.

Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism

PubMed Central

2013-01-01

Background Autism is a pervasive neurodevelopmental disorder. At present there are no defined mechanisms of pathogenesis and therapy is mostly limited to behavioral interventions. Stem cell transplantation may offer a unique treatment strategy for autism due to immune and neural dysregulation observed in this disease. This non-randomized, open-label, single center phase I/II trial investigated the safety and efficacy of combined transplantation of human cord blood mononuclear cells (CBMNCs) and umbilical cord-derived mesenchymal stem cells (UCMSCs) in treating children with autism. Methods 37 subjects diagnosed with autism were enrolled into this study and divided into three groups: CBMNC group (14 subjects, received CBMNC transplantation and rehabilitation therapy), Combination group (9 subjects, received both CBMNC and UCMSC transplantation and rehabilitation therapy), and Control group (14 subjects, received only rehabilitation therapy). Transplantations included four stem cell infusions through intravenous and intrathecal injections once a week. Treatment safety was evaluated with laboratory examinations and clinical assessment of adverse effects. The Childhood Autism Rating Scale (CARS), Clinical Global Impression (CGI) scale and Aberrant Behavior Checklist (ABC) were adopted to assess the therapeutic efficacy at baseline (pre-treatment) and following treatment. Results There were no significant safety issues related to the treatment and no observed severe adverse effects. Statistically significant differences were shown on CARS, ABC scores and CGI evaluation in the two treatment groups compared to the control at 24 weeks post-treatment (p < 0.05). Conclusions Transplantation of CBMNCs demonstrated efficacy compared to the control group; however, the combination of CBMNCs and UCMSCs showed larger therapeutic effects than the CBMNC transplantation alone. There were no safety issues noted during infusion and the whole monitoring period. Trial registration ClinicalTrials.gov: NCT01343511, Title “Safety and Efficacy of Stem Cell Therapy in Patients with Autism”. PMID:23978163

Autologous transplantation of blood stem cells mobilized with filgrastim alone in 93 patients with malignancies: the number of CD34+ cells reinfused is the only factor predicting both granulocyte and platelet recovery.

PubMed

Faucher, C; Le Corroller, A G; Chabannon, C; Viens, P; Stoppa, A M; Bouabdallah, R; Camerlo, J; Vey, N; Gravis, G; Gastaut, J A; Novakovitch, G; Mannoni, P; Bardou, V J; Moatti, J P; Maraninchi, D; Blaise, D

1996-12-01

High-dose chemotherapy (HDC) supported by autologous transplantation of blood stem cells (BSC) is used increasingly for patients with poor-risk malignancies. We report our experience with 93 consecutive patients who were mobilized with recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone. They received a fixed dose of G-CSF for 5 or 6 days, and BSC were collected by leukapheresis. Aphereses were evaluated for MNC, CD34+ cells, and CFU-GM counts and cryopreserved. All patients received a conditioning regimen without TBI. Engraftment was assessed as the first of 2 consecutive days on which patients achieved 0.5 and 1 x 10(9)/L neutrophils and an unsupported platelet count of 25 x 10(9)/L. Multivariate analysis was performed to study patients and graft characteristics that could influence reconstitution. The G-CSF priming regimen was well tolerated and allowed collection of BSC for all patients, 66% of them achieving >3 x 10(6)/kg CD34+ cells, and 86% achieving >10 x 10(4) CFU-GM/kg. The numbers of collected CD34 and CFU-GM cells were highly correlated. The number of courses of chemotherapy prior to collection, a diagnosis of breast cancer, the use of rhG-CSF posttransplant, and the numbers of CFU-GM and CD34+ cells reinfused were correlated with hematologic recovery. In a multivariate analysis, however, the number of CD34+ cells was the only factor independently influencing both granulocyte and platelet recovery. Patients who received at least 3 x 10(6)/kg CD34+ cells achieved granulocyte reconstitution on day 11 after reinfusion (range 8-15) and an unsupported platelet count of 25 x 10(9)/l on day 14 (range 12-180), significantly earlier than patients who received fewer cells (p < 0.001). In addition, G-CSF administration postreinfusion independently enhanced granulocyte reconstitution but not platelet recovery. In conclusion, CD34+ cell number appears to be the only factor predicting both granulocyte and platelet reconstitution. Based on this study, the collection of a minimal number of 3 x 10(6)/kg CD34+ cells appears desirable.

Autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation: analysis of 533 adult patients who underwent transplantation at King's College Hospital.

PubMed

Wang, Meng; Wang, Wenjia; Abeywardane, Ayesha; Adikarama, Malinthi; McLornan, Donal; Raj, Kavita; de Lavallade, Hugues; Devereux, Stephen; Mufti, Ghulam J; Pagliuca, Antonio; Potter, Victoria T; Mijovic, Aleksandar

2015-01-01

Autoimmune hemolytic anemia (AIHA) is a recognized complication of hematopoietic stem cell transplantation (HSCT); it is often refractory to treatment and carries a high mortality. To improve understanding of the incidence, risk factors, and clinical outcome of post-transplantation AIHA, we analyzed 533 patients who received allogeneic HSCT, and we identified 19 cases of AIHA after HSCT (overall incidence, 3.6%). The median time to onset, from HSCT to AIHA, was 202 days. AIHA was associated with HSCT from unrelated donors (hazard ratio [HR], 5.28; 95% confidence interval [CI], 1.22 to 22.9; P = .026). In the majority (14 of 19; 74%) of AIHA patients, multiple agents for treatment were required, with only 9 of 19 (47%) patients achieving complete resolution of AIHA. Patients with post-transplantation AIHA had a higher overall mortality (HR, 2.48; 95% CI, 1.33 to 4.63; P = .004), with 36% (4 of 11 cases) of deaths attributable to AIHA. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Addition of doxycycline to ciprofloxacin for infection prophylaxis during autologous stem cell transplants for multiple myeloma.

PubMed

Sivik, J M; Davidson, J; Hale, C M; Drabick, J J; Talamo, G

2018-03-21

The most commonly used antibacterial prophylaxis during autologous stem cell transplants (ASCT) for multiple myeloma (MM) involves a fluoroquinolone, such as ciprofloxacin or levofloxacin. We assessed the impact of adding doxycycline to ciprofloxacin as routine antibacterial prophylaxis in these patients. We retrospectively reviewed electronic medical records and our ASCT database to analyze rates and types of bacterial infections in MM patients who underwent ASCT in our institution. Among 419 patients, 118 received ciprofloxacin alone (cipro group), and 301 ciprofloxacin and doxycycline (cipro-doxy group). Neutropenic fever (NF) developed in 63 (53%) and 108 (36%) patients of the cipro and cipro-doxy groups, respectively (p = 0.010). The number of documented bacteremic episodes was 13 (11%) and 14 (4.7%) in the two groups, respectively (p = 0.017). Antimicrobial resistance and Clostridium difficile infections were uncommon. Transplant-related mortality was 1% in both groups. The addition of doxycycline to standard prophylaxis with ciprofloxacin seems to reduce the number of NF episodes and documented bacterial infections in patients with MM undergoing ASCT, without increasing rate of serious complications.

Establishing an Inpatient Gym for Recipients of Stem Cell Transplantation: A Multidisciplinary Collaborative.

PubMed

Blackburn, Roxann; Presson, Kimberly; Laufman, Robin; Tomczak, Nancy; Brassil, Kelly J

2016-02-01

Evidence suggests that exercise can have a profound impact on physiologic and quality-of-life outcomes for patients undergoing hematopoietic stem cell transplantation (HSCT). Despite this, implementation of a gym on inpatient HSCT units may be limited because of space, infrastructure, and budget. This article presents the design, implementation, and evaluation of the gym and highlights its use for individual and group patient activities. An interprofessional team at a National Cancer Institute-designated comprehensive cancer center collaborated to design and implement gym space on an inpatient HSCT unit servicing as many as 86 beds. Informal feedback from patients, as well as metrics on use of the space, indicates that the gym is well received and frequently used. Limitations include the absence of a designated physical therapy technician to supervise individual activity, which may limit patient access when a staff member is unavailable. The cost associated with the implementation of such space may be offset by benefits to patients, including enhanced conditioning, quality of life, and time to discharge, as evidenced in the literature.

Outcomes of autologous or allogeneic stem cell transplantation for non-Hodgkin lymphoma.

PubMed

Reddy, Nishitha M; Oluwole, Olalekan; Greer, John P; Engelhardt, Brian G; Jagasia, Madan H; Savani, Bipin N

2014-01-01

Transplant outcomes of autologous or allogeneic stem cell transplantation (SCT) have not been elucidated as a single cohort in non-Hodgkin lymphoma (NHL). We analyzed the outcomes of 270 adult recipients receiving autologous (auto) SCT (n = 198) or allogeneic (allo) SCT (n = 72) for NHL between the years 2000 and 2010. Five-year overall survival rates for B and T cell NHL were 58% and 50%, respectively (allo-SCT 51% vs. 54% for B and T-cell NHL, and auto-SCT 60% vs. 47% for B and T cell lymphoma, respectively). In multivariate analysis, the number of chemotherapy regimens and disease status pre-SCT were independently associated with long-term outcome after SCT (for both auto- and allo-SCT). We conclude that the type of transplantation offered to patients, based on patient selection and disease-related factors, can achieve long-term survival, highlighting the importance of further improvement in disease control and reducing procedure-related mortality. The role of transplantation needs to be reevaluated in the era of targeted therapy. Copyright © 2014 ISEH - Society for Hematology and Stem Cells. All rights reserved.

Rationale and design of a randomized controlled trial of allogeneic mesenchymal stem cells in patients with nonischemic cardiomyopathy.

PubMed

Greene, Stephen J; Epstein, Stephen E; Kim, Raymond J; Quyyumi, Arshed A; Cole, Robert T; Anderson, Allen S; Wilcox, Jane E; Skopicki, Hal A; Sikora, Sergey; Verkh, Lev; Tankovich, Nikolai I; Gheorghiade, Mihai; Butler, Javed

2017-04-01

This article describes an ongoing study investigating the safety and efficacy of ischemia-tolerant mesenchymal stem cell (MSC) therapy in patients with nonischemic heart failure and dysfunctional viable myocardium without scarring. This study will follow principles of the previously described mechanistic translational-phase concept whereby the effect of the study agent on laboratory and imaging markers of cardiac structure and function will be tested in a small homogenous cohort with the goal to enhance the understanding of the effect of interventions on cardiac remodeling and performance. This single-blind, placebo-controlled, crossover, multicenter, randomized study will assess the safety, tolerability, and preliminary efficacy of a single intravenous (i.v.) dose of allogeneic ischemia-tolerant MSCs in individuals with heart failure of nonischemic cause, ejection fraction 40% or less, and dysfunctional viable myocardium who have been receiving guideline-directed medical therapy. Eligible patients will have no evidence of baseline replacement scarring on delayed-enhancement cardiac magnetic resonance (CMR). Approximately 20 patients will be randomized in a 1 : 1 ratio to receive an i.v. infusion of ischemia-tolerant MSCs or placebo. At 90 days, the two groups will undergo crossover and received the alternative treatment. The primary endpoint is safety, as evaluated through at least 1-year post-MSC infusion. Additional efficacy endpoints will include measures of cardiac structure and function, as evaluated by serial cine-CMR and transthoracic echocardiography at 90 and 180 days post-initial infusion. This pilot study will explore the safety and effects on cardiac structure and function of i.v. injection of ischemia-tolerant MSCs in a small homogenous cohort of nonischemic heart failure patients with reduced ejection fraction and absent replacement scarring on CMR. This study also represents a prospective mechanistic translational-phase study using baseline and serial CMR imaging in heart failure patients and serves as a potential model for design of future heart failure trials (ClinicalTrials.gov identifier: NCT02467387).

Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation

PubMed Central

Amrolia, Persis J.; Muccioli-Casadei, Giada; Huls, Helen; Adams, Stuart; Durett, April; Gee, Adrian; Yvon, Eric; Weiss, Heidi; Cobbold, Mark; Gaspar, H. Bobby; Rooney, Cliona; Kuehnle, Ingrid; Ghetie, Victor; Schindler, John; Krance, Robert; Heslop, Helen E.; Veys, Paul; Vitetta, Ellen; Brenner, Malcolm K.

2006-01-01

Poor T lymphocyte reconstitution limits the use of haploidentical stem cell transplantation (SCT) because it results in a high mortality from viral infections. One approach to overcome this problem is to infuse donor T cells from which alloreactive lymphocytes have been selectively depleted, but the immunologic benefit of this approach is unknown. We have used an anti-CD25 immunotoxin to deplete alloreactive lymphocytes and have compared immune reconstitution after allodepleted donor T cells were infused at 2 dose levels into recipients of T-cell–depleted haploidentical SCT. Eight patients were treated at 104 cells/kg/dose, and 8 patients received 105 cells/kg/dose. Patients receiving 105 cells/kg/dose showed significantly improved T-cell recovery at 3, 4, and 5 months after SCT compared with those receiving 104 cells/kg/dose (P < .05). Accelerated T-cell recovery occurred as a result of expansion of the effector memory (CD45RA–CCR-7-) population (P < .05), suggesting that protective T-cell responses are likely to be long lived. T-cell–receptor signal joint excision circles (TRECs) were not detected in reconstituting T cells in dose-level 2 patients, indicating they are likely to be derived from the infused allodepleted cells. Spectratyping of the T cells at 4 months demonstrated a polyclonal Vβ repertoire. Using tetramer and enzyme-linked immunospot (ELISPOT) assays, we have observed cytomegalovirus (CMV)– and Epstein-Barr virus (EBV)–specific responses in 4 of 6 evaluable patients at dose level 2 as early as 2 to 4 months after transplantation, whereas such responses were not observed until 6 to 12 months in dose-level 1 patients. The incidence of significant acute (2 of 16) and chronic graft-versus-host disease (GVHD; 2 of 15) was low. These data demonstrate that allodepleted donor T cells can be safely used to improve T-cell recovery after haploidentical SCT and may broaden the applicability of this approach. PMID:16741253

Outcomes using wedge stem with full hydroxiapatite coverage with a minimum of 5 years' follow-up.

PubMed

Godoy-Monzon, D; Buttaro, M; Comba, F; Zanotti, G; Piccaluga, F; Neira-Borrajo, I

Total Hip Arthroplsty (THA) using uncemented stems is a popular practice in the last decades. The implant survivorship is crtitical and a less than 10% revision at 10 years is been propesed for commercialization and use. To analyse the clinicoradiological results of an uncemented hydroxiapatite covered wedge stem with a 5 years minimum follow up. Prospective study, patients aged from 21-75years were included. All patients received an Element stem (Exactech) and uncemented cup with crosslink poly and 32 mm metal head, and posterior approach with piriformis retention was used. Scheduled clinical and radiographic evaluation at 3 weeks, 3-6 month, year and subsequent years using Harris Hip Score and Merle d'Aubigné Postel. Intraoperative and during follow up complications were recorded. One hundred and fourteen total hip replacements in 104 patients: 54 females and 50 males (52%/48%). Follow-up of 5.7 years (range, 5-6.2years). Average age 56.8years (range, 42-75years). Clinical evaluation the Merle d'Aubigné score improved 6.8 points and from the initianl Harris Hip Score 47.3 to 93.1 points at last follow up. Radiographic evaluation shows osteointegration in all stems. And in 6 cases (5.3% at 3 months subsidence was detected, average 1.4 mm (range 0-2.6 mm) with no clinical manifestation, 3 cases of subsidence were associated to intraoperative fractures (1 greater trochanter and 2 in the calcar area, all resolved with wire cerclaje). Subjective evaluation: 86 cases (82.6%) excellent, 9 patients (8.6%) good, 6 cases (5.9%) satisfactory and 3 cases (2.9%) poor. All poor results linked to the intraoperative complications. No patient lost during follow up period. No femoral pain dislocation or aseptic or loosening detected. All implants were in situ at last follow up. The radiological results confirm the benefits of this type of stem with good osteointegration. The clinical and subjective results are promising. With good surgical technical and without complications the risk of aseptic loosening should be absent or minimal. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Mycoplasma detection and elimination are necessary for the application of stem cell from human dental apical papilla to tissue engineering and regenerative medicine.

PubMed

Kim, Byung-Chul; Kim, So Yeon; Kwon, Yong-Dae; Choe, Sung Chul; Han, Dong-Wook; Hwang, Yu-Shik

2015-01-01

Recently, postnatal stem cells from dental papilla with neural crest origin have been considered as one of potent stem cell sources in regenerative medicine regarding their multi-differentiation capacity and relatively easy access. However, almost human oral tissues have been reported to be infected by mycoplasma which gives rise to oral cavity in teeth, and mycoplasma contamination of ex-vivo cultured stem cells from such dental tissues and its effect on stem cell culture has received little attention. In this study, mycoplama contamination was evaluated with stem cells from apical papilla which were isolated from human third molar and premolars from various aged patients undergoing orthodontic therapy. The ex-vivo expanded stem cells from apical papilla were found to express stem cell markers such as Stro-1, CD44, nestin and CD133, but mycoplama contamination was detected in almost all cell cultures of the tested 20 samples, which was confirmed by mycoplasma-specific gene expression and fluorescence staining. Such contaminated mycoplasma could be successfully eliminated using elimination kit, and proliferation test showed decreased proliferation activity in mycoplasma-contaminated cells. After elimination of contaminated mycoplasma, stem cells from apical papilla showed osteogenic and neural lineage differentiation under certain culture conditions. Our study proposes that the evaluation of mycoplasma contamination and elimination process might be required in the use of stem cells from apical papilla for their potent applications to tissue engineering and regenerative medicine.

Implications of Cancer Stem Cell Theory for Cancer Chemoprevention by Natural Dietary Compounds

PubMed Central

Li, Yanyan; Wicha, Max S.; Schwartz, Steven J.; Sun, Duxin

2011-01-01

The emergence of cancer stem cell theory has profound implications for cancer chemoprevention and therapy. Cancer stem cells give rise to the tumor bulk through continuous self-renewal and differentiation. Understanding the mechanisms that regulate self-renewal is of greatest importance for discovery of anti-cancer drugs targeting cancer stem cells. Naturally-occurring dietary compounds have received increasing attention in cancer chemoprevention. The anti-cancer effects of many dietary components have been reported for both in vitro and in vivo studies. Recently, a number of studies have found that several dietary compounds can directly or indirectly affect cancer stem cell self-renewal pathways. Herein we review the current knowledge of most common natural dietary compounds for their impact on self-renewal pathways and potential effect against cancer stem cells. Three pathways (Wnt/β-catenin, Hedgehog, and Notch) are summarized for their functions in self-renewal of cancer stem cells. The dietary compounds, including curcumin, sulforaphane, soy isoflavone, epigallocatechin-3-gallate, resveratrol, lycopene, piperine, and vitamin D3, are discussed for their direct or indirect effect on these self-renewal pathways. Curcumin and piperine have been demonstrated to target breast cancer stem cells. Sulforaphane has been reported to inhibit pancreatic tumor initiating cells and breast cancer stem cells. These studies provide a basis for preclinical and clinical evaluation of dietary compounds for chemoprevention of cancer stem cells. This may enable us to discover more preventive strategies for cancer management by reducing cancer resistance and recurrence and improving patient survival. PMID:21295962

Effects of two doses of anti-T lymphocyte globulin-Fresenius given after full-match sibling stem cell transplantation in acute myeloblastic leukemia patients who underwent myeloablative fludarabine/busulfan conditioning.

PubMed

Boga, Can; Yeral, Mahmut; Gereklioglu, Ciğdem; Asma, Suheyl; Maytalman, Erkan; Aytan, Pelin; Kozanoglu, Ilknur; Sariturk, Cagla; Ozdogu, Hakan

2018-02-20

Anti-T lymphocyte globulin Fresenius (rATG-F; ATG-Fresenius) and antithymocyte globulin (thymoglobulin), which are included in transplant protocols, are used to reduce the risk of chronic graft-versus-host disease (cGVHD) or suppress allograft rejection. Available clinical studies have been conducted in heterogenous patient populations and with different administration protocols including stem cell sources. Additionally, the pharmacokinetics of ATG is variable, and the clinically effective dose of rATG-F, in particular, is not exactly known. The aim of the study was to investigate the clinical outcomes of acute myeloid leukemia (AML) patients who underwent hemopoietic peripheral stem cell transplantation from full-matched sibling donors and given two different doses of r-ATG-F. This was a single-center, retrospective chart review conducted between July 2005 and July 2016. Sixty-nine consecutive AML patients who underwent transplant with fludarabine- and busulfan-based conditioning were included in the study. Patients in Group 1 received 15 mg/kg body weight rATG-F to 2013 (n = 46), and Group 2 received 30 mg/kg of rATG-F dose begining in 2013 to reduce to cGVHD (n = 23). Cyclosporine and methotrexate were used to treat acute GVHD (aGVHD) prophylaxis. Outcome parameters were compared between the groups. Although the recommended dose r-ATG-F had led to a decrease in the cumulative incidence of cGVHD (27 [58.7%] vs. 8 [34.8%]; p = .03), it also increased the infection rate at 1 year (3 [6.5%] vs. 4 [17.4%]; p = .02). The two groups were similar in terms of engraftment time, aGVHD, relapse, nonrelapse mortality, and rATG-F-related toxicity. A Cox regression model revealed that aGVHD III-IV was associated with increased nonrelapse mortality at 1 year (hazard ratio = 18.2; 95% confidence interval, 1.667-199.255; p = <.02). No patients developed rATG-F-related severe adverse events (Common Terminology Criteria grade 4 or 5). Dose difference of rATG-F did not influence survival parameters; however, increasing the dose to 30 mg/kg seems to be effective for reducing cGVHD with an increase in infection rate requiring close monitoring of infections in AML patients who received myeloablative fludarabine/busulfan conditioning. Copyright © 2018 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

A nationwide survey of deep fungal infections and fungal prophylaxis after hematopoietic stem cell transplantation in Japan.

PubMed

Imataki, O; Kami, M; Kim, S-W; Gotoh, M; Komaba, S; Kasai, M; Hashino, S; Naito, K; Masuda, M; Anan, K; Teshima, H; Togitani, K; Inoue, T; Nishimura, M; Adachi, Y; Fukuhara, T; Yamashita, T; Uike, N; Kobayashi, Y; Hamaguchi, M; Higuchi, M; Kawakami, K; Takaue, Y

2004-06-01

We conducted a nationwide survey to define incidence of deep fungal infections and fungal prophylaxis practices after HSCT. In all, 63 institutions responded. Total number of in-patient transplantations was 935: 367 autologous, 414 allogeneic myeloablative, and 154 allogeneic reduced-intensity (RIST) (n=154). Number of patients who were cared for in a clean room at transplant was 261 (71%) in autologous, 409 (99%) in conventional and 93 (66%) in RIST, respectively. All patients received prophylactic antifungal agents; 89% fluconazole. Number of patients who received the dosage recommended in the CDC guidelines (400 mg/day) was 135 (42%) in conventional transplant and 34 (30%) in RIST (P=0.037). Number of patients who received fluconazole until engraftment and beyond day 75 in conventional transplant vs RIST was, respectively, 324 (100%) vs 109 (97%), and 39 (12%) vs 18 (16%), with no significant difference between the two groups. A total of 37 patients (4.0%) were diagnosed with deep fungal infections; autologous transplantation (0.03%), conventional transplantation (6.0%) and RIST (7.1%). Wide variations in antifungal prophylaxis practice according to the type of transplant and the institutions, and deep fungal infection remain significant problems in RIST.

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation.

PubMed

Gilis, L; Morisset, S; Billaud, G; Ducastelle-Leprêtre, S; Labussière-Wallet, H; Nicolini, F-E; Barraco, F; Detrait, M; Thomas, X; Tedone, N; Sobh, M; Chidiac, C; Ferry, T; Salles, G; Michallet, M; Ader, F

2014-05-01

BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P=0.028), unrelated donor (P=0.0178), stem cell source (P=0.0001), HLA mismatching (P=0.0022) and BU in conditioning regimen (P=0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P=0.0005) and peripheral blood stem cells (P=0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P=0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (P<0.0001), more RBC (P=0.0003) and platelet transfusions (P<0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at \\[euro]2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

Recent advances in treatment of aplastic anemia

PubMed Central

Shin, Seung Hwan; Lee, Sung Eun

2014-01-01

Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line treatment option for younger patients with severe or very severe AA, whereas immunosuppressive treatment (IST) is an alternative option for others. Horse anti-thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST regimen with acceptable response rate. Recently, horse ATG had been not available and replaced with rabbit ATG in most countries. Subsequently, recent comparative studies showed that the outcomes of patients who received rabbit ATG/CsA were similar or inferior compared to those who received horse ATG/CsA. Therefore, further studies to improve the outcomes of IST, including additional eltrombopag, are necessary. On the other hand, the upper age limit of patients who are able to receive MSD-SCT as first-line treatment is a current issue because of favorable outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In addition, further studies to improve the outcomes of patients who receive allogeneic SCT from alternative donors are needed. In this review, current issues and the newly emerging trends that may improve their outcomes in near futures will be discussed focusing the management of patients with AA. PMID:25378968

Similar outcome of allogeneic stem cell transplantation after myeloablative and sequential conditioning regimen in patients with refractory or relapsed acute myeloid leukemia: A study from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire.

PubMed

Decroocq, Justine; Itzykson, Raphaël; Vigouroux, Stéphane; Michallet, Mauricette; Yakoub-Agha, Ibrahim; Huynh, Anne; Beckerich, Florence; Suarez, Felipe; Chevallier, Patrice; Nguyen-Quoc, Stéphanie; Ledoux, Marie-Pierre; Clement, Laurence; Hicheri, Yosr; Guillerm, Gaëlle; Cornillon, Jérôme; Contentin, Nathalie; Carre, Martin; Maillard, Natacha; Mercier, Mélanie; Mohty, Mohamad; Beguin, Yves; Bourhis, Jean-Henri; Charbonnier, Amandine; Dauriac, Charles; Bay, Jacques-Olivier; Blaise, Didier; Deconinck, Eric; Jubert, Charlotte; Raus, Nicole; Peffault de Latour, Regis; Dhedin, Nathalie

2018-03-01

Patients with acute myeloid leukemia (AML) in relapse or refractory to induction therapy have a dismal prognosis. Allogeneic hematopoietic stem cell transplantation is the only curative option. In these patients, we aimed to compare the results of a myeloablative transplant versus a sequential approach consisting in a cytoreductive chemotherapy followed by a reduced intensity conditioning regimen and prophylactic donor lymphocytes infusions. We retrospectively analyzed 99 patients aged 18-50 years, transplanted for a refractory (52%) or a relapsed AML not in remission (48%). Fifty-eight patients received a sequential approach and 41 patients a myeloablative conditioning regimen. Only 6 patients received prophylactic donor lymphocytes infusions. With a median follow-up of 48 months, 2-year overall survival was 39%, 95% confidence interval (CI) (24-53) in the myeloablative group versus 33%, 95% CI (21-45) in the sequential groups (P = .39), and 2-year cumulative incidence of relapse (CIR) was 57% versus 50% respectively (P = .99). Nonrelapse mortality was not higher in the myeloablative group (17% versus 15%, P = .44). In multivariate analysis, overall survival, CIR and nonrelapse mortality remained similar between the two groups. However, in multivariate analysis, sequential conditioning led to fewer acute grade II-IV graft versus host disease (GVHD) (HR for sequential approach = 0.37; 95% CI: 0.21-0.65; P < .001) without a significant impact on chronic GVHD (all grades and extensive). In young patients with refractory or relapsed AML, myeloablative transplant and sequential approach offer similar outcomes except for a lower incidence of acute GvHD after a sequential transplant. © 2018 Wiley Periodicals, Inc.

Late-Onset Hepatic Veno-Occlusive Disease after Allografting: Report of Two Cases with Atypical Clinical Features Successfully Treated with Defibrotide.

PubMed

Castellino, Alessia; Guidi, Stefano; Dellacasa, Chiara Maria; Gozzini, Antonella; Donnini, Irene; Nozzoli, Chiara; Manetta, Sara; Aydin, Semra; Giaccone, Luisa; Festuccia, Moreno; Brunello, Lucia; Maffini, Enrico; Bruno, Benedetto; David, Ezio; Busca, Alessandro

2018-01-01

Hepatic Veno-Occlusive Disease (VOD) is a potentially severe complication of hematopoietic stem cell transplantation (HSCT). Here we report two patients receiving an allogeneic HSCT who developed late onset VOD with atypical clinical features. The two patients presented with only few risk factors, namely, advanced acute leukemia, a myeloablative busulphan-containing regimen and received grafts from an unrelated donor. The first patient did not experience painful hepatomegaly and weight gain and both patients showed only a mild elevation in total serum bilirubin level. Most importantly, the two patients developed clinical signs beyond day 21 post-HSCT. Hepatic transjugular biopsy confirmed the diagnosis of VOD. Intravenous defibrotide was promptly started leading to a marked clinical improvement. Based on our experience, liver biopsy may represent a useful diagnostic tool when the clinical features of VOD are ambiguous. Early therapeutic intervention with defibrotide represents a crucial issue for the successful outcome of patients with VOD.

Late-Onset Hepatic Veno-Occlusive Disease after Allografting: Report of Two Cases with Atypical Clinical Features Successfully Treated with Defibrotide

PubMed Central

Castellino, Alessia; Guidi, Stefano; Dellacasa, Chiara Maria; Gozzini, Antonella; Donnini, Irene; Nozzoli, Chiara; Manetta, Sara; Aydin, Semra; Giaccone, Luisa; Festuccia, Moreno; Brunello, Lucia; Maffini, Enrico; Bruno, Benedetto; David, Ezio; Busca, Alessandro

2018-01-01

Hepatic Veno-Occlusive Disease (VOD) is a potentially severe complication of hematopoietic stem cell transplantation (HSCT). Here we report two patients receiving an allogeneic HSCT who developed late onset VOD with atypical clinical features. The two patients presented with only few risk factors, namely, advanced acute leukemia, a myeloablative busulphan-containing regimen and received grafts from an unrelated donor. The first patient did not experience painful hepatomegaly and weight gain and both patients showed only a mild elevation in total serum bilirubin level. Most importantly, the two patients developed clinical signs beyond day 21 post-HSCT. Hepatic transjugular biopsy confirmed the diagnosis of VOD. Intravenous defibrotide was promptly started leading to a marked clinical improvement. Based on our experience, liver biopsy may represent a useful diagnostic tool when the clinical features of VOD are ambiguous. Early therapeutic intervention with defibrotide represents a crucial issue for the successful outcome of patients with VOD. PMID:29326798

Implications of Parkinson's disease pathophysiology for the development of cell replacement strategies and drug discovery in neurodegenerative diseases.

PubMed

Pan-Montojo, Francisco; Funk, Richard H W

2012-11-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder traditionally characterized by the loss of dopaminergic neurons in the substantia nigra (SN) at the midbrain. The potential use of adult or embryonic stem cells, induced pluriputent stem (iPS) cells and endogenous neurogenesis in cell replacement strategies has lead to numerous studies and clinical trials in this direction. It is now possible to differentiate stem cells into dopaminergic neurons in vitro and clinical trials have shown an improvement in PD-related symptoms after intra-striatal embryonic transplants and acceptable cell survival rates on the mid term. However, clinical improvement is transitory and associated with a strong placebo effect. Interestingly, recent pathological studies in PD patients who received embryonic stem cells show that in PD patients, grafted neurons show PD-related pathology. In this manuscript we review the latest findings regarding PD pathophysiology and give an outlook on the implications of these findings in how cell replacement strategies for PD treatment should be tested. These include changes in the type of animal models used, the preparation/conditioning of the cells before intracerebral injection, specially regarding backbone chronic diseases in iPS cells and determining the optimal proliferation, survival, differentiation and migration capacity of the grafted cells.

Efficacy and safety of leflunomide for the treatment of BK virus-associated hemorrhagic cystitis in allogeneic hematopoietic stem cell transplantation recipients.

PubMed

Chen, Xin-Chuan; Liu, Ting; Li, Jian-Jun; He, Chuan; Meng, Weng-Tong; Huang, Rui

2013-01-01

BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation. So far, no specific antiviral drug with proven efficacy has been approved for treating BKV-HC. Leflunomide is an immunosuppressive drug with antiviral activity and has been used in treating BKV-associated nephropathy after renal transplantation. This is the first report on the efficacy and safety of leflunomide in the treatment of BKV-HC. From January 2006 to January 2009, 89 patients received allogeneic hematopoietic stem cell transplantation, and among them, 18 patients were identified as having BKV-HC, with a 20% cumulative incidence. Fourteen patients were treated with oral leflunomide. Three days of 100 mg/day leflunomide was used as loading doses and followed by maintenance doses of 20 mg/day. The urinary BKV-DNA load was monitored weekly by real-time quantitative PCR. The efficacy was evaluated on day 20 after leflunomide treatment. Seven patients (50%) achieved complete remission, 5 patients (35.7%) achieved partial remission, and 2 patients (14.3%) had more than a 1-log reduction in urinary BKV-DNA loads after treatment. During the leflunomide treatment, the graft-versus-host disease of the patients did not progress, and the dosages of the immunosuppressant were reduced simultaneously. One patient discontinued treatment because of intolerable gastrointestinal symptoms. Neutropenia occurred in 2 cases. These preliminary data suggest that leflunomide may be a potentially effective medication for treating BKV-HC without significant toxicity, but evidence supporting its use requires randomized controlled trials. Copyright © 2013 S. Karger AG, Basel.

Improvement over the years of long-term survival in high-risk lymphoma patients treated with hematopoietic stem cell transplantation as consolidation or salvage therapy.

PubMed

Calderón-Cabrera, C; Márquez-Malaver, F J; de la Cruz-Vicente, F; Falantes, F; Carrillo, E; Parody, R; Montero, I; González Campos, J; Martino, M L; Carmona, M; Pérez-Simón, J A; Espigado, I

2013-01-01

The role of hemopoietic stem cell transplantation (HSCT) is not well established in certain types of lymphoma, such as those with a high relapse risk or relapsing after initial therapy. New chemotherapeutic schemes and immunotherapy have improved survival of these patients. Nevertheless, there is not enough evidence regarding whether transplantation is the best therapeutic approach. Moreover, published data on long-term follow-up of high-risk lymphoma patients treated with HSCT are scarce. We analyzed 177 consecutive patients diagnosed with a high risk of relapse or with relapsed lymphoma who underwent HSCT after induction with standard chemotherapy in a tertiary academic center from 1989 to 2013. The median age was 40 years. Diagnoses were Hodgkin disease (n = 56), diffuse large B-cell lymphoma (n = 44), follicular lymphoma (n = 29), mantle cell lymphoma (n = 15), T-cell lymphoma (n = 18), and others (n = 15). Patients received either an autologous graft (n = 154) in first complete remission (1CR; n = 59) or more advanced stages (AS; n = 95), or an allogeneic graft (n = 23) in 1CR (n = 4) or AS (n = 19). In the autologous group, overall survival (OS) at 5 years was 57% and 75% in the periods 1989-2001 and 2002-2013, respectively (P = .05). Patients receiving an allogeneic graft presented an OS of 25% and 43% in the 2 periods. With a mean follow-up of 5 years (95% confidence interval 3.5-6.6), for patients receiving a transplant in 1CR, OS at 5 years was 80%, and for those receiving a transplant in AS it was 59% (P = .003). Nonrelapse mortality (NRM) at 5 years was 3.1% in the autologous group and 27.9% in the allogeneic group (P < .001). The main cause of NRM was infection (44%) in the whole cohort. All this leads to the conclusion that transplantation, as a therapeutic strategy, has shown a high long-term OS in this subgroup of patients with such a poor prognosis. OS improved over the years and reaching 1CR was a good prognostic feature. Infections were the main cause of NRM. Copyright © 2013 Elsevier Inc. All rights reserved.

Stem cells in cardiac repair.

PubMed

Henning, Robert J

2011-01-01

Myocardial infarction is the leading cause of death among people in industrialized nations. Although the heart has some ability to regenerate after infarction, myocardial restoration is inadequate. Consequently, investigators are currently exploring the use of human embryonic stem cells (hESCs), skeletal myoblasts and adult bone marrow stem cells to limit infarct size. hESCs are pluripotent cells that can regenerate myocardium in infarcted hearts, attenuate heart remodeling and contribute to left ventricle (LV) systolic force development. Since hESCs can form heart teratomas, investigators are differentiating hESCs toward cardiac progenitor cells prior to transplantation into hearts. Large quantities of hESCs cardiac progenitor cells, however, must be generated, immune rejection must be prevented and grafts must survive over the long term to significantly improve myocardial performance. Transplanted autologous skeletal myoblasts can survive in infarcted myocardium in small numbers, proliferate, differentiate into skeletal myofibers and increase the LV ejection fraction. These cells, however, do not form electromechanical connections with host cardiomyocytes. Consequently, electrical re-entry can occur and cause cardiac arrhythmias. Autologous bone marrow mononuclear cells contain hematopoietic and mesenchymal stem cells. In several meta-analyses, patients with coronary disease who received autologous bone marrow cells by intracoronary injection show significant 3.7% (range: 1.9-5.4%) increases in LV ejection fraction, decreases in LV end-systolic volume of -4.8 ml (range: -1.4 to -8.2 ml) and reductions in infarct size of 5.5% (-1.9 to -9.1%), without experiencing arrhythmias. Bone marrow cells appear to release biologically active factors that limit myocardial damage. Unfortunately, bone marrow cells from patients with chronic diseases propagate poorly and can die prematurely. Substantial challenges must be addressed and resolved to advance the use of stem cells in cardiac repair including identifying the optimal stem cell(s) that permit transplantation without requirements for host immune suppression; timing of stem cell transplantation that maximizes chemoattraction of stem cells to infarcts; and determining the optimal technique for injecting stem cells for cardiac repair. Techniques must be developed to enhance survival and propagation of stem cells in the myocardium. These studies will require close cooperation and interaction of scientists and clinicians. Cell-based cardiac repair in the 21st century will offer new hope for millions of patients worldwide with myocardial infarctions who, otherwise, would suffer from the relentless progression of heart disease to heart failure and death.

Donor Vδ1+ γδ T cells expand after allogeneic hematopoietic stem cell transplantation and show reactivity against CMV-infected cells but not against progressing B-CLL.

PubMed

Prinz, Immo; Thamm, Kristina; Port, Matthias; Weissinger, Eva M; Stadler, Michael; Gabaev, Ildar; Jacobs, Roland; Ganser, Arnold; Koenecke, Christian

2013-05-11

γδ T lymphocytes play an important role in immune reactions towards infections and malignancies. In particular, Vγ9-Vδ1+ T lymphocytes are thought to play protective antiviral roles in human CMV infection. Recently, Vδ1+ T lymphocytes were proposed to also have anti- B-CLL reactivity. Here we report a case of 48-year-old man who received allogeneic stem cell transplantation for progressive B-CLL. Within one year after transplantation, lymphoma relapsed despite a dramatic increase of Vδ1+ T cells in the patient's blood. In vitro killing assays revealed activity of patient's γδ cells against CMV target cells, but not against the relapsing lymphoma-cells. This argues for a contribution of Vδ1+ cells in the immune reaction against CMV reactivation, but does not support a strong correlation of expanded Vδ1+ T cells and favorable disease outcome in B-CLL patients.

Application of adipocyte-derived stem cells in treatment of cutaneous radiation syndrome.

PubMed

Riccobono, Diane; Agay, Diane; Scherthan, Harry; Forcheron, Fabien; Vivier, Mylène; Ballester, Bruno; Meineke, Viktor; Drouet, Michel

2012-08-01

Cutaneous radiation syndrome caused by local high dose irradiation is characterized by delayed outcome and incomplete healing. Recent therapeutic management of accidentally irradiated burn patients has suggested the benefit of local cellular therapy using mesenchymal stem cell grafting. According to the proposed strategy of early treatment, large amounts of stem cells would be necessary in the days following exposure and hospitalization, which would require allogeneic stem cells banking. In this context, the authors compared the benefit of local autologous and allogeneic adipocyte-derived stem cell injection in a large animal model. Minipigs were locally irradiated using a 60Co gamma source at a dose of 50 Gy and divided into three groups. Two groups were grafted with autologous (n = 5) or allogeneic (n = 5) adipocyte-derived stem cells four times after the radiation exposure, whereas the control group received the vehicle without cells (n = 8). A clinical score was elaborated to compare the efficiency of the three treatments. All controls exhibited local inflammatory injuries leading to a persistent painful necrosis, thus mimicking the clinical evolution in human victims. In the autologous adipocyte-derived stem cells group, skin healing without necrosis or uncontrollable pain was observed. In contrast, the clinical outcome was not significantly different in the adipocyte-derived stem cell allogeneic group when compared with controls. This study suggests that autologous adipocyte-derived stem cell grafting improves cutaneous radiation syndrome wound healing, whereas allogeneic adipocyte derived stem cells do not. Further studies will establish whether manipulation of allogeneic stem cells will improve their therapeutic potential.

The Effect of In Vivo Mobilization of Bone Marrow Stem Cells on the Pancreas of Diabetic Albino Rats (A Histological & Immunohistochemical Study)

PubMed Central

Ismail, Zeinab Mohamed Kamel; Kamel, Ashraf Mahmoud Fawzy; Yacoub, Mira Farouk Youssef; Aboulkhair, Alshaymaa Gamal

2013-01-01

Background and Objectives The rapidly increasing number of diabetic patients across the world drew the attention to develop more effective therapeutic approaches. Recent investigations on newly differentiated insulin producing cells (IPCs) revealed that they could be derived from embryonic, adult mesenchymal and hematopoietic stem cells. This work was planned to evaluate the role of StemEnhance (Aphanizomenon flos-aquae [AFA] plant extract) in mobilizing naturally occurring bone marrow stem cells as well as in improving streptozotocin-induced diabetic rats. Methods and Results Twenty adult male albino rats were divided into four groups namely the control, the diabetic, the positive control-StemEnhance and the diabetic-StemEnhance groups. After diabetes induction by streptozotocin (STZ), rats received StemEnhance for four weeks. The mean number of blood CD34 immunopositive cells was measured by flowcytometry and random blood sugar was measured weekly. The pancreas was removed from the sacrificed rats and processed for staining with H&E and immunohistochemical staining for CD34+ve and insulin +ve cells. CD34+ve cells increased in the blood after introduction of StemEnhance. CD34+ve cells were observed in the pancreas and the insulin producing cells in the islets of Langerhans were increased from the second to the fourth week of treatment. Blood glucose level improved but it was still higher than the control level after four weeks of StemEnhance treatment. Conclusions This work points to the significant role of StemEnhance in stem cell mobilization and the improvement of diabetes mellitus. PMID:24298369

[MMC conditioning regimen (Melphalan, MeCCNU and cyclophosphamide) followed by allogeneic peripheral blood stem cells transplantation for chronic myeloid leukemia].

PubMed

Liu, T; Jia, Y; Wang, H; Lu, Z; Meng, W; Yang, Y; Wu, J; Deng, C

1998-12-01

This paper reports 3 cases of allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) for the patients with chronic myeloid leukemia (CML). The patients received MMC preparative regimen with high dose chemotherapy (Melphalan 170 mg/m2, p.o. on Day-5, MeCCNU 400 mg/m2, p.o. on Day-4, and Cyclophosphomide 60 mg/kg/day, i.v. on Days-3 and -2). The HLA-identical sibling donors received filgrastim (rhG-CSF) for mobilization at a dose of 300 micrograms/day for 6 days. Leukaphereses were done at the 6th day of mobilization. A median of 8000 ml (2 times total blood volume) of blood was processed the collecting: 2.5-4.5 x 10(8)/kg MNC, 12.8-20.0 x 10(6)/kg CD34+ cells (including 4.8-7.5 x 10(6)/kg CD34+CD33-, 8.0-13.0 x 10(6)/kg CD34+CD33+), and 3.5-4.3 x 10(5)/kg CFU-GM. Cyclosporin A and methotrexate were used for GVHD prophylaxis. Hematopoitic function recovered as for 14-20 days to > 0.5 x 10(9)/L of neutrophil count, and for 16-34 days to > 20 x 10(9)/L of platelet count. At day + 100, chromosome analysis of bone marrow cells showed that complete chimera without ph1 positive chromosome in Cases 1 and 3, and a partial chimera with 73% donor karyotype in Case 2. All patients now are in disease free survival. No episode of acute graft versus host disease (GVHD) developed. It was concluded that HLA matched sibling allogeneic PBSCT result in rapid hematopoitic reconstitution and the MMC conditioning regimen is effective both in leukemic cells eradication and in immunosuppression for stem cells engraftment, and the drug related toxicity could be tolerated by patients.

Impact of Thymoglobulin by Stem Cell Source (Peripheral Blood Stem Cell or Bone Marrow) After Myeloablative Stem Cell Transplantation From HLA 10/10-Matched Unrelated Donors: A Report From the Société Française de Greffe de Moelle et de Thérapie Cellulaire.

PubMed

Ravinet, Aurelie; Cabrespine, Aurelie; Socié, Gerard; Milpied, Noël; Yakoub Agha, Ibrahim; Nguyen, Stephanie; Michallet, Mauricette; Menard, Anne Lise; Maillard, Natacha; Mohty, Mohamad; Suarez, Felipe; Huynh, Anne; Marchand, Tony; Deteix, Clémence; Cassuto, Jill Patrice; Maury, Sebastien; Chevallier, Patrice; Reman, Oumedaly; Peffault de Latour, Régis; Bay, Jacques Olivier

2016-08-01

The impact of antithymocyte globulin (ATG) in the setting of a myeloablative conditioning transplantation remains controversial, especially when using bone marrow (BM) as the stem cell source. We therefore conducted a retrospective analysis to investigate the impact of ATG in patients with acute myeloid leukemia or myelodysplastic syndrome receiving myeloablative conditioning followed by a matched 10 of 10 unrelated donor transplant from BM or peripheral blood stem cells (PBSCs). Our study included 356 patients conditioned with cyclophosphamide associated with fractionated total body irradiation or busulfan. Median follow-up was 17.6 months (range, 0-156). The ATG and PBSCs were the only variables that independently decreased the cumulative incidence (CI) of chronic graft-versus-host disease (GvHD) (hazards ratio [HR], 0.4; 95% CI, 0.21-0.73; P < 0.01; and HR, 0.53; 95% CI, 0.30-0.90; P = 0.02, respectively). The ATG had no impact on overall survival, disease-free survival, relapse, and nonrelapse mortality. In the PBSC group (n = 139), ATG was associated with a lower CI of both grades III to IV acute GvHD (HR, 0.17; 95% CI, 0.03-0.91; P = 0.04), chronic GvHD (HR, 0.31; 95% CI, 0.11-0.87; P = 0.03), and GvHD-free/relapse-free survival (HR, 0.48; 95% CI, 0.29-0.80; P < 0.01), whereas these correlations were not significant in the group of patients (n = 217) receiving BM (HR, 0.36; 95% CI, 0.11-1.93; P = 0.06 for grade III-IV acute GvHD; HR, 0.49; 95% CI, 0.22-1.06; P = 0.08 for chronic GvHD; and HR, 0.69; 95% CI, 0.46-1.01; P = 0.06 for GvHD-free/relapse-free survival). Although our results confirm the recommendation for ATG to be added after PBSC transplantation, no obvious benefit was identified using this approach in the setting of BM transplantation. Only prospective studies may yield definitive answers to this question.

Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell-depleted stem cell transplantation.

PubMed

Broers, A E; van Der Holt, R; van Esser, J W; Gratama, J W; Henzen-Logmans, S; Kuenen-Boumeester, V; Löwenberg, B; Cornelissen, J J

2000-04-01

We evaluated the efficacy, toxicity, and outcome of preemptive ganciclovir (GCV) therapy in 80 cytomegalovirus (CMV)-seropositive patients allografted between 1991 and 1996 and compared their outcome to 35 seronegative patients allografted during the same period. Both cohorts were comparable with respect to diagnosis and distribution of high- versus standard-risk patients. All patients received a stem cell graft from an HLA-identical sibling donor, and grafts were partially depleted of T cells in 109 patients. Patients were monitored for CMV antigenemia by leukocyte expression of the CMV-pp65 antigen. Fifty-two periods of CMV reactivation occurring in 30 patients were treated preemptively with GCV. A favorable response was observed in 48 of 50 periods, and only 2 patients developed CMV disease: 1 with esophagitis and 1 with pneumonia. Ten of 30 treated patients developed GCV-related neutropenia (less than 0.5 x 10(9)/L), which was associated with a high bilirubin at the start of GCV therapy. Overall survival at 5 years was 64% in the CMV-seronegative cohort and 40% in the CMV-seropositive cohort (P =.01). Increased treatment-related mortality accounted for inferior survival. CMV seropositivity proved an independent risk factor for developing acute graft-versus-host disease, and acute graft-versus-host disease predicted for higher treatment-related mortality and worse overall survival in a time-dependent analysis. We conclude that, although CMV disease can effectively be prevented by preemptive GCV therapy, CMV seropositivity remains a strong adverse risk factor for survival following partial T-cell-depleted allogeneic stem cell transplantation.

Clinical Observation of Factors in the Efficacy of Blood Component Transfusion in Patients following Hematopoietic Stem Cell Transplantation

PubMed Central

Zhang, Xi; Xiao, Yanni; Ran, Qian; Liu, Yao; Duan, Qianbi; Duan, Huiling; Ye, Xingde; Li, Zhongjun

2012-01-01

Background Factors affecting the efficacy of platelet and red blood cell (RBC) transfusion in patients undergoing hematopoietic stem cell transplantation (HSCT) have not been studied extensively. We aimed to evaluate platelet and RBC transfusion efficacy by measuring the platelet corrected count increment and the hemoglobin increment, respectively, 24 h after transfusion in 105 patients who received HSCT. Methodology/Principal Findings Using retrospective analysis, we studied whether factors, including gender, time of transplantation, the compatibility of ABO group between HSC donors and recipients, and autologous or allogenic transplantation, influence the efficacy of blood component transfusion. We found that the infection rate of HSCT patients positively correlated with the transfusion amount, and the length of stay in the laminar flow room was associated with transfusion. We found that platelet transfusion performed during HSCT showed significantly better efficacy than that performed before HSCT. The effect of platelet transfusion in auto-transplantation was significantly better than that in allo-transplantation. The efficacy of RBC transfusion during HSCT was significantly lower than that performed before HSCT. The efficacy of RBC transfusion in auto-transplantation was significantly higher than that in allo-transplantation. Allo-transplantation patients who received HSCs from compatible ABO groups showed significantly higher efficacy during both platelet and RBC transfusion. Conclusions We conclude that the efficacy of platelet and RBC transfusions does not correlate with the gender of patients, while it significantly correlates with the time of transplantation, type of transplantation, and ABO compatibility between HSC donors and recipients. During HSCT, the infection rate of patients positively correlates with the transfusion amount of RBCs and platelets. The total volume of RBC units transfused positively correlates with the length of the patients’ stay in the laminar flow room. PMID:22701516

Treatment of BK virus-associated hemorrhagic cystitis in pediatric hematopoietic stem cell transplant recipients with cidofovir: a single-center experience.

PubMed

Kwon, H J; Kang, J H; Lee, J W; Chung, N-G; Kim, H-K; Cho, B

2013-12-01

BK virus (BKV)-associated hemorrhagic cystitis (BKV-HC) is a severe complication after hematopoietic stem cell transplantation (HSCT). Cidofovir (CDV) has emerged as an effective agent for the treatment of BKV nephropathy, but its use for BKV-HC in pediatric HSCT recipients has not yet been established as a standard therapy. We retrospectively investigated the efficacy and safety of CDV therapy for patients with BKV-HC at a single institution and analyzed the clinical management outcomes. From April 2009 to July 2011, 12 patients developed BKV-HC at a median of 37 days after transplant (range 15-59 days). The cumulative incidence was 9% and the median peak of the urine BKV load was 2.5 × 10(10) copies/mL (range 1.4 × 10(9) -1.2 × 10(11) copies/mL). Eleven patients received intravenous CDV (5 mg/kg/dose, with probenecid), whereas 1 patient received CDV (5 mg/kg/dose, without probenecid) intravesically. The median duration of therapy was 25 days (range 9-73 days), and a median of 2 doses was given (range 1-4). A reduction of ≥ 1 log in the BKV load was found in 11 patients, while 1 patient did not have any significant change in BKV load. Clinical improvement was observed in all cases, and no HC-related death was observed. CDV-related toxicity occurred in 1 patient (8%) and spontaneously resolved. CDV appears to be an effective and safe treatment for BKV-HC in pediatric HSCT recipients, but prospective trials are warranted to support its use. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The incidence, risk factors, and outcomes of primary poor graft function after unmanipulated haploidentical stem cell transplantation.

PubMed

Sun, Yu-Qian; He, Gan-Lin; Chang, Ying-Jun; Xu, Lan-Ping; Zhang, Xiao-Hui; Han, Wei; Chen, Huan; Chen, Yu-Hong; Wang, Yu; Wang, Feng-Rong; Wang, Jing-Zhi; Liu, Kai-Yan; Huang, Xiao-Jun

2015-10-01

Primary poor graft function (PGF) is a severe complication after allogeneic stem cell transplantation (SCT). The incidence, risk factors, and outcomes of PGF have not been well described, especially in the haploidentical SCT setting. We retrospectively reviewed patients who received haploidentical SCT at Peking University Institute of Hematology between January 1, 2011, and December 31, 2012. PGF was defined as persistent neutropenia (≤0.5 × 10(9) L(-1)), thrombocytopenia (platelets ≤20 × 10(9) L(-1)), and/or hemoglobin ≤70 g L(-1) after engraftment with hypocellular bone marrow and full donor chimerism, without concurrent graft-versus-host disease or disease relapse. Incidence was calculated from all patients. Of the 464 total patients, 26 (5.6 %) developed primary PGF. The risk factors were analyzed and compared with control patients with good graft function who were selected using the case-pair method. Finally, 104 patients were selected as a control group according to the matching conditions: (1) the type (acute leukemia, myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML)) and status (standard risk, high risk) of underlying disease, (2) sex, (3) year in which the transplantation was received, and (4) a 1:4 ratio of case-control. No factors were found to be associated with primary PGF. Compared to cases with good graft function, patients with primary PGF experienced poor overall survival (34.6 vs. 82.7 %, p < 0.001). Of the 26 primary PGF patients, only nine achieved hematopoietic recovery and survived. In conclusion, primary PGF is a rare but life-threatening complication after haploidentical SCT, and effective therapies need to be explored.

Self-transcendence in stem cell transplantation recipients: a phenomenologic inquiry.

PubMed

Williams, Barbara J

2012-01-01

To understand the meaning of self-transcendence, or the ability to go beyond the self, for patients who have had a stem cell transplantation. A phenomenologic investigation guided by the interpretive philosophy of Heidegger. A cancer center in a major urban academic medical center. 4 men and 4 women ages 45-63 who had received a stem cell transplantation in the previous year. Two or three unstructured, open-ended interviews were conducted with each participant. Data were extracted, analyzed, and interpreted according to the Colaizzi method. Self-transcendence. Self-transcendence emerged as a process that was triggered by the suffering the participants experienced as they lived through the physical effects of the treatment, faced death, drew strength from within themselves, and perceived a spiritually influenced turning point. The experience of a human connection lessened their feelings of vulnerability in the process. As the participants recovered, they described being transformed both physically and personally. The findings from this study highlight the power inherent in patients to not only meet the challenges they face, but to grow from their experiences. The findings also highlight patients' deep need for a human connection and the power that nurses and other healthcare professionals have to provide that connection. The caring connections established by health-care professionals can ease the ability of patients to access the inner resource of self-transcendence and reduce their feelings of vulnerability.

Prevention of veno-occlusive disease with defibrotide after allogeneic stem cell transplantation.

PubMed

Chalandon, Yves; Roosnek, Eddy; Mermillod, Bernadette; Newton, Anita; Ozsahin, Hulya; Wacker, Pierre; Helg, Claudine; Chapuis, Bernard

2004-05-01

Veno-occlusive disease (VOD) of the liver occurs in 10% to 50% of patients after allogeneic stem cell transplantation, ranging from mild reversible disease to severe disease, with a mortality rate almost always close to 100%. Recently, promising results in the treatment of established VOD with defibrotide were reported. Therefore, defibrotide may be used as a prophylactic regimen for hepatic VOD in stem cell transplantation for hematologic malignancies. Fifty-two successive patients who underwent transplantation between October 1999 and June 2002 received defibrotide prophylaxis intravenously from day -7 to day +20 after transplantation in addition to heparin and were compared with historical controls who underwent transplantation successively between February 1997 and September 1999. In the defibrotide group, the maximum total bilirubin levels and the number of patients with serum levels exceeding 50 micromol/L were significantly lower than in the control group (5 of 52 versus 18 of 52, respectively; P =.004). None of the 52 patients developed VOD (Baltimore criteria), and no side effects occurred. These results were significantly different (P =.001) from controls (10/52 [19%] with VOD, 3 of whom died of severe VOD). In addition, day 100 event-free survival was significantly higher in the study group (P =.02), with a trend toward better day 100 overall survival (P =.07). These results suggest that defibrotide given in addition to heparin may be an efficient prophylaxis for VOD.

Long-term survivorship of the Corail™ standard stem.

PubMed

Louboutin, L; Viste, A; Desmarchelier, R; Fessy, M-H

2017-11-01

The Corail™ stem, which was first introduced in 1986, has since been modified twice: first to make the neck thinner and then to change the location of the laser markings. The survival and complications of the first-generation straight, titanium, hydroxyapatite-coated stem are known; however, there is little specific information about the latest-generation stem. This led us to conduct a retrospective study to determine the: (1) long-term survival; (2) clinical and radiographic outcomes; (3) complications; and (4) risk factors for revision of the newest Corail™ stem. The newest Corail™ AMT (Articul/EZE™ Mini Taper) standard stem has comparable survival to prior models. This single-center, retrospective study included 133 patients (140 hips), who underwent primary total hip arthroplasty (THA), between January and December 2004, in which a Corail™ Standard stem was implanted using a posterolateral approach. Patients who underwent revision THA, THA due to femoral neck fracture or who received lateralized (offset) stems were excluded. The mean age at the time of THA was 69±13 years [35-92] in 85 men (61%) and 55 women (39%) who had a mean BMI of 27kg/m 2 ±11 [16-39]. At the latest follow-up, 32 patients (32 hips) had died and 8 patients (8 hips) had less than 3 years' follow-up, thus were not included in the clinical evaluation. The Merle d'Aubigné (PMA) score was collected. The stem's survivorship was calculated using the Kaplan-Meier method with revision for aseptic loosening and revision or implant removal for any reason as the end-points. The Cox model was used to analyze risk factors for revision. The mean follow-up was 10±3 years [3-12]. The PMA score was 12±2.6 [5-17] preoperatively and 16±2.7 [7-18] at the last follow-up (P<0.00001). Eighteen complications (12.8%) were recorded at the last follow-up. There were 15 early complications: 6 dislocations, 5 calcar fractures (4 treated by wire cerclage and 1 by stem change plus wire cerclage), 2 greater trochanter fractures (treated non-surgically) and 2 cases of sciatic nerve palsy. There were 3 late complications: 2 cases of iliopsoas irritation and 1 ceramic insert fracture. Stem survival for surgical revision due to aseptic loosening was 98% (95% CI: [0.96-1]). At 12 years, 95% of stems had not been revised or removed (95% CI: [0.92-0.99]). Being less than 58 years of age at the time of surgery was the only risk factor significantly associated with stem revision for any reason (P=0.04). Survival of the Corail™ Standard stem is similar to that of previous generation stems. The changes made in this stem solved the neck failure problem and did not induce new complications. Level IV (retrospective study). Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Invasive Mechanical Ventilation and Mortality in Pediatric Hematopoietic Stem Cell Transplantation: A Multicenter Study.

PubMed

Rowan, Courtney M; Gertz, Shira J; McArthur, Jennifer; Fitzgerald, Julie C; Nitu, Mara E; Loomis, Ashley; Hsing, Deyin D; Duncan, Christine N; Mahadeo, Kris M; Smith, Lincoln S; Moffet, Jerelyn; Hall, Mark W; Pinos, Emily L; Cheifetz, Ira M; Tamburro, Robert F

2016-04-01

To establish the current respiratory practice patterns in pediatric hematopoietic stem cell transplant patients and investigate their associations with mortality across multiple centers. Retrospective cohort between 2009 and 2014. Twelve children's hospitals in the United States. Two hundred twenty-two pediatric allogeneic hematopoietic stem cell transplant recipients with acute respiratory failure using invasive mechanical ventilation. None. PICU mortality of our cohort was 60.4%. Mortality at 180 days post PICU discharge was 74%. Length of PICU stay prior to initiation of invasive mechanical ventilation was significantly lower in survivors, and the odds of mortality increased for longer length of PICU stay prior to intubation. A total of 91 patients (41%) received noninvasive ventilation at some point during their PICU stay prior to intubation. Noninvasive ventilation use preintubation was associated with increased mortality (odds ratio, 2.1; 95% CI, 1.2-3.6; p = 0.010). Patients ventilated longer than 15 days had higher odds of death (odds ratio, 2.4; 95% CI, 1.3-4.2; p = 0.004). Almost 40% of patients (n = 85) were placed on high-frequency oscillatory ventilation with a mortality of 76.5% (odds ratio, 3.3; 95% CI, 1.7-6.5; p = 0.0004). Of the 20 patients who survived high-frequency oscillatory ventilation, 18 were placed on high-frequency oscillatory ventilation no later than the third day of invasive mechanical ventilation. In this subset of 85 patients, transition to high-frequency oscillatory ventilation within 2 days of the start of invasive mechanical ventilation resulted in a 76% decrease in the odds of death compared with those who transitioned to high-frequency oscillatory ventilation later in the invasive mechanical ventilation course. This study suggests that perhaps earlier more aggressive critical care interventions in the pediatric hematopoietic stem cell transplant patient with respiratory failure requiring invasive mechanical ventilation may offer an opportunity to improve outcomes.

Growth after Hematopoietic Stem Cell Transplantation in Children with Acute Myeloid Leukemia

PubMed Central

Chung, Seung Joon; Park, Seung Wan; Kim, Min Kyoung; Kang, Min Jae; Lee, Young Ah; Lee, Seong Yong; Yang, Sei Won; Kang, Hyoung Jin; Park, Kyung Duk; Shin, Hee Young; Ahn, Hyo Seop

2013-01-01

Previous studies have shown that hematopoietic stem cell transplantation (HSCT) may result in growth impairment. The purpose of this study was to evaluate the growth during 5 yr after HSCT and to determine factors that influence final adult height (FAH). We retrospectively reviewed the medical records of acute myeloid leukemia (AML) patients who received HSCT. Among a total of 37 eligible patients, we selected 24 patients who began puberty at 5 yr after HSCT (Group 1) and 19 patients who reached FAH without relapse (Group 2). In Group 1, with younger age at HSCT, sex, steroid treatment, hypogonadism and hypothyroidism were not significantly associated with growth impairment 5 yr after HSCT. History of radiotherapy (RT) significantly impaired the 5 yr growth after HSCT. Chronic graft-versus-host disease (cGVHD) only temporarily impaired growth after HSCT. In Group 2, with younger age at HSCT, steroid treatment and hypogonadism did not significantly reduce FAH. History of RT significantly reduced FAH. Growth impairment after HSCT may occur in AML patients, but in patients without a history of RT, growth impairment seemed to be temporary and was mitigated by catch-up growth. PMID:23341720

High-dose therapy and autologous stem cell transplantation for extra-nodal NK/T lymphoma in patients from the Western hemisphere: a study from the European Society for Blood and Marrow Transplantation.

PubMed

Fox, Christopher P; Boumendil, Ariane; Schmitz, Norbert; Finel, Herve; Luan, Jian J; Sucak, Gülsan; Blaise, Didier; Finke, Jürgen; Pflüger, Karl-Heinz; Veelken, Hendrik; Gorin, Norbert-Claude; Poiré, Xavier; Ganser, Arnold; Dreger, Peter; Sureda, Anna

2015-01-01

Extra-nodal NK/T lymphoma (ENKTL) is rare and more frequently encountered in East Asia. The role of high-dose therapy and autologous stem cell transplantation (HDT-ASCT) for ENKTL is unclear. Twenty-eight evaluable patients who had undergone HDT-ASCT in Europe from 2000-2009 were studied. The median age was 47 years and patients had received a median of two lines of prior therapy. Some 57% of patients were not in complete remission or beyond first complete remission at HDT-ASCT. The 1-year non-relapse mortality (NRM) was 11%; 2-year progression-free survival (PFS) and overall survival (OS) rates were 41% and 52%, respectively. Notably, the 2-year PFS and OS for those with stage III/IV disease were 33% and 40%, respectively, with no relapses beyond 1-year post-HDT-ASCT. This is the largest analysis of HDT-ASCT for patients with ENKTL reported from the Western hemisphere. Survival is comparable to East Asian cohorts and outcomes are encouraging for patients with advanced disease.

Music therapy improves the mood of patients undergoing hematopoietic stem cells transplantation (controlled randomized study).

PubMed

Dóro, Carlos Antonio; Neto, José Zanis; Cunha, Rosemyriam; Dóro, Maribel Pelaez

2017-03-01

The allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a therapeutic medical treatment for various neoplastic hematologic, congenital, genetic, or acquired disorders. In this procedure which combines high-dose chemotherapy and/or radiotherapy and has a high degree of cytotoxicity, the patient experiences solitary confinement, which causes psychological distress, pain, anxiety, mood disorders and can lead him/her to depression. Music therapy was applied with the purpose of decreasing this social confinement. This is a randomized controlled trial. Patients (n = 100) were selected randomly. Patients (n = 50) were selected for the Experimental Music Therapy Group (EMG) and n = 50 for the control group (CG) who received the standard treatment. The intervention of live music was applied using music therapy techniques. Assessment and quantification were made using the visual analog scale (VAS). The dependent variables were pain, anxiety, and mood of patients. The Mann-Whitney test (p < 0.05) applied was considered statistically significant when comparing the groups, improving mood significantly (EMG). Music therapy proved to be a strong ally in the treatment of patients undergoing allo-HSCT, providing bio-psychosocial welfare.

Thalidomide, clarithromycin, lenalidomide and dexamethasone therapy in newly diagnosed, symptomatic multiple myeloma.

PubMed

Mark, Tomer M; Bowman, Isaac A; Rossi, Adriana C; Shah, Manan; Rodriguez, Melissa; Quinn, Ryann; Pearse, Roger N; Zafar, Faiza; Pekle, Karen; Jayabalan, David; Ely, Scott; Coleman, Morton; Chen-Kiang, Selina; Niesvizky, Ruben

2014-12-01

We studied T-BiRD (thalidomide [Thalomid(®)], clarithromycin [Biaxin(®)], lenalidomide [Revlimid(®)] and dexamethasone) in symptomatic, newly diagnosed multiple myeloma. In 28-day cycles, patients received dexamethasone 40 mg/day on days 1, 8, 15, 22, clarithromycin 500 mg twice daily on days 1-28; lenalidomide 25 mg/day on days 1-21; and thalidomide 100 mg/day (50 mg/day on days 1-7 of cycle 1 only) on days 1-28. Twenty-six patients received a median of 6 cycles (range 0-41). Overall response rate (ORR) was 80% for the group and 100% in 11 patients who underwent autologous stem cell transplantation as part of first-line therapy. The 4-year overall survival rate was 74.9%, and the median progression-free survival was 35.6 months. Eight patients discontinued due to regimen toxicity. Grade 3 non hematologic toxicity affected 12 patients (46.2%). T-BiRD is a highly active regimen with potential toxicity limitations. ClinicalTrials.gov identifier: NCT00538733.

Comprehensive evaluation of nutritional status before and after hematopoietic stem cell transplantation in 170 patients with hematological diseases.

PubMed

Liu, Peng; Wang, Boshi; Yan, Xia; Cai, Jingjing; Wang, Yu

2016-12-01

To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation (HSCT), and explore optimal methods for assessing nutritional status in patients with hematological diseases. This cohort study enrolled 170 patients who were diagnosed with hematological diseases and underwent allogeneic HSCT in the Department of Hematology, Peking University People's Hospital between May 2011 and April 2013. We used fixed-point continuous sampling and four nutritional screening tools, Nutritional Risk Screening 2002 (NRS-2002), Mini Nutritional Assessment (MNA), Subjective Global Assessment (SGA) and Malnutrition Universal Screening Tools (MUST), in combination with body measurements, to extensively screen and evaluate nutritional risks and status in patients receiving HSCT before entering and after leaving laminar air flow rooms. After HSCT, patients had significant reduction in weight, hip circumference, waist-hip ratio, calf circumference, mid-upper arm circumference, and suprailiac skinfold thickness compared with pre-HSCT measurements. Before HSCT, NRS-2002 identified that 21.2% of patients were at nutritional risks, compared with 100% after HSCT. MUST indicated that before HSCT, 11.77% of patients were at high nutritional risk, compared with 59.63% after HSCT. MNA assessed that 0.06% of patients were malnourished before HSCT, compared with 19.27% after HSCT. SGA identified that before HSCT, 1.76% of patients had mild to severe malnutrition, which increased to 83.3% after HSCT. There is a significant increase in the nutritional risk and malnutrition in patients who received HSCT. Before HSCT, some patients already had nutritional risk or nutritional deficiencies, and prompt and close nutritional screening or assessment should be performed. The nutritional status of patients after HSCT was generally deteriorated compared with that before transplantation. Body measurements should be taken more frequently during the subsequent treatment window in the laminar air flow rooms. After HSCT, it is recommended to combine MNA and SGA to fully evaluate the nutritional status, and thus provide timely and reasonable nutritional support.

Ciprofloxacin vs levofloxacin for prophylaxis during hematopoietic stem-cell transplantation.

PubMed

Copeland, Vanessa; McLaughlin, Milena; Trifilio, Steven

2018-01-01

The objective of the current retrospective study was to compare differences in rate of breakthrough infections for ciprofloxacin vs levofloxacin prophylaxis in autologous hematopoietic stem-cell transplant (HSCT) patients treated for multiple myeloma. This was a retrospective, cohort study comparing autologous HSCT recipients treated for multiple myeloma who received ciprofloxacin prophylaxis vs levofloxacin prophylaxis. A total of 297 patients, 143 levofloxacin- and 154 ciprofloxacin-treated were included. There was a significantly higher incidence of bloodstream infections in the ciprofloxacin group (24/154) compared to the levofloxacin group (10/143), P = .03, primarily caused by a statistically higher incidence of gram-positive bloodstream infections (ciprofloxacin [21/154] vs levofloxacin [8/143]; P < .01). Clinically relevant differences exist between fluoroquinolone agents used for prophylaxis. Levofloxacin prophylaxis was more effective than ciprofloxacin prophylaxis to reduce the incidence of bloodstream infections in this study. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Late relapse of progressive multifocal leucoencephalopathy postallogenic transplant in a young patient with CLL.

PubMed

Sanchez-Quintana, Ana; Breña-Atienza, Joaquín; Marrero-Santos, Carmen; Alvarez-Acosta, Luis

2013-08-05

We describe a case of progressive multifocal leucoencephalopathy (PML) in a 39-year-old patient diagnosed with chronic lymphocytic leukaemia (CLL) who underwent two allogenic matched-sibling stem cell transplantations. PML was confirmed just after the first transplantation with cerebral MRI and by PCR in the cerebrospinal fluid. After immunosuppression withdrawal and cidofovir treatment, he achieved a reversal of clinical symptoms, John Cunningham (JC) virus positivity and MRI lesions regression. He remained asymptomatic for 5 years with no signs of infection activity, even though he received three new chemotherapy regimens due to a CLL relapse. However, after the second stem cell transplantation, new neurological symptoms began and a reactivation of the JC virus infection was detected. This time, treatment with mefloquine was started, but he experienced a progressive neurological deterioration and died 1 month after the symptoms began.

Real world treatment patterns in chronic myeloid leukemia patients newly initiated on tyrosine kinase inhibitors in an U.S. integrated healthcare system.

PubMed

Rashid, Nazia; Koh, Han A; Lin, Kathy J; Stwalley, Brian; Felber, Eugene

2018-06-01

Purpose To evaluate treatment patterns in patients diagnosed with incident chronic myelogenous leukemia (CML) newly initiating therapy with imatinib, dasatinib, or nilotinib. Patients were followed to determine switching and discontinuation rates. Factors associated with switching or discontinuation from index TKI therapy, reasons for discontinuation based on electronic chart notes, and frequency of laboratory monitoring were assessed during the follow-up period. Methods A retrospective cohort study was conducted in chronic myelogenous leukemia patients aged ≥ 18 years who were identified from the Kaiser Permanente Southern California (KPSC) Cancer Registry database during the study time period of 1 January 2007 to 12 December 2013. The index date was defined as the date of the first TKI prescription (imatinib, dasatinib, or nilotinib) identified during the study time period with no prior history of TKI use within 12 months. Patients had to have continuous membership with drug benefit eligibility and no prior history of stem cell transplant (SCT) or other cancers during the 12 months prior to the index date. Baseline characteristics were identified during 12 months prior to the index date and outcomes were identified during the follow-up period after the index date. All patients were followed from index TKI therapy until end of study time period (12 December 2014), death, stem cell transplant, or disenrollment from the health plan unless one of the following occurred first: a patient switched their index therapy, or a patient discontinued their index therapy. Forward stepwise selection multivariable logistic regression models were used to evaluate factors associated with patients who continued therapy compared to those who switched or discontinued therapy with the index TKI. Chart notes were reviewed 30 days prior and 30 days post index TKI discontinuation to evaluate reasons for discontinuation. Molecular and cytogenetic testing frequency was also assessed during the follow-up period among the different patient groups. Results Two hundred sixteen patients were identified with incident chronic myelogenous leukemia and use of TKI therapy: 189 (87.5%) received imatinib, 19 (8.8%) received dasatinib, and 8 (3.7%) received nilotinib. The mean age on index date was 53 years and 63% were male; 103 patients (48%) continued on their index therapy, while 62 patients (28%) switched, and 51 patients (24%) discontinued.

Safety and effects of prophylactic defibrotide for sinusoidal obstruction syndrome in hematopoietic stem cell transplantation.

PubMed

Park, Meerim; Park, Hyeon Jin; Eom, Hyeon-Seok; Kwon, Young Joo; Park, Jeong A; Lim, Yeon Jung; Yoon, Jong Hyung; Kong, Sun-Young; Ghim, Thad T; Lee, Hye Won; Yun, Tak; Park, Byung-Kiu

2013-01-28

Sinusoidal obstruction syndrome (SOS) is a serious complication of hematopoietic stem cell transplantation (HSCT), with a mortality rate of up to 90%. We report our experience on the use of defibrotide for SOS prophylaxis in HSCT. We retrospectively reviewed data of 49 patients who received defibrotide as SOS prophylaxis during the course of HSCT at the National Cancer Center, Goyang, Korea, between August 2005 and July 2008. Thirty-four patients (69.4%) were classified as a high-risk group for developing SOS. Defibrotide was well-tolerated, without any grade 3 or 4 toxicity. The median value of maximum total bilirubin within 100 days after HSCT was within the normal range. SOS was diagnosed in only 1 patient, who underwent autologous HSCT due to relapsed medulloblastoma. There was no day 100 treatment-related mortality in our study. Defibrotide appears to be a safe prophylaxis for SOS. This study suggests that it could be effective to use prophylactic defibrotide in advance to improve HSCT outcomes in patients at risk of SOS.

Newly identified poor prognostic factors for adult T-cell leukemia-lymphoma treated with allogeneic hematopoietic stem cell transplantation.

PubMed

Tokunaga, Masahito; Uto, Hirofumi; Takeuchi, Shogo; Nakano, Nobuaki; Kubota, Ayumu; Tokunaga, Mayumi; Takatsuka, Yoshifusa; Seto, Masao; Ido, Akio; Utsunomiya, Atae

2017-01-01

To explore pre-transplantation prognostic factors for adult T-cell leukemia-lymphoma (ATL), we retrospectively analyzed allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 70 patients at our institute (63 acute type and seven lymphoma type patients). Forty-five patients died after HSCT and the three-year overall survival (OS) rate was 35.2%. By univariate analysis, the adverse prognostic factors for OS were performance status ≥2, hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score ≥3, European Group for Blood and Marrow Transplantation (EBMT) risk score ≥5, HSCT from an HLA-mismatched donor, serum soluble interleukin-2 receptor (sIL-2R) level ≥10,000 U/mL, lymphocyte count ≥4000/μL, and hemoglobin <9 g/dL at the time of HSCT. EBMT risk score and sIL-2R were identified as significant adverse prognostic factors using multivariate analysis. This analysis clearly demonstrates for the first time that HCT-CI and EBMT risk scores are reliable prognostic factors for ATL patients receiving allo-HSCT.

Terminal Complement Blockade after Hematopoietic Stem Cell Transplantation Is Safe without Meningococcal Vaccination.

PubMed

Jodele, Sonata; Dandoy, Christopher E; Danziger-Isakov, Lara; Myers, Kasiani C; El-Bietar, Javier; Nelson, Adam; Wallace, Gregory; Teusink-Cross, Ashley; Davies, Stella M

2016-07-01

Eculizumab inhibits terminal complement-mediated intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and complement-mediated thrombotic microangiopathy (TMA) in patients with atypical hemolytic uremic syndrome and is now used as a first-line therapy in these diseases. Eculizumab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) because of an increased risk of meningococcal infections in persons without adequate functional complement. Administration of meningococcal vaccine is required at least 2 weeks before administering the first dose of eculizumab, and this advice is included in the product label. Eculizumab use for treatment of TMA in hematopoietic stem cell transplantation (HSCT) recipients brings a significant dilemma regarding REMS required meningococcal vaccination. TMA after HSCT usually occurs within the first 100 days after transplantation when patients are severely immunocompromised and are not able to mount a response to vaccines. We evaluated 30 HSCT recipients treated with eculizumab for high-risk TMA without meningococcal vaccine. All patients received antimicrobial prophylaxis adequate for Neisseria meningitides during eculizumab therapy and for 8 weeks after discontinuation of the drug. Median time to TMA diagnosis was 28 days after transplant (range, 13.8 to 48.5). Study subjects received a median of 14 eculizumab doses (range, 2 to 38 doses) for HSCT-associated TMA therapy. There were no incidences of meningococcal infections. The incidences of bacterial and fungal bloodstream infections were similar in patients treated with eculizumab (n = 30) as compared with those with HSCT-associated TMA who did not receive any complement blocking therapy (n = 39). Our data indicate that terminal complement blockade in the early post-transplant period can be performed without meningococcal vaccination while using appropriate antimicrobial prophylaxis until complement function is restored after therapy completion. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Feasibility and Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant High-Dose Cyclophosphamide for Children and Adolescents with Hematologic Malignancies: An AIEOP-GITMO Retrospective Multicenter Study.

PubMed

Berger, Massimo; Lanino, Edoardo; Cesaro, Simone; Zecca, Marco; Vassallo, Elena; Faraci, Maura; De Bortoli, Massimiliano; Barat, Veronica; Prete, Arcangelo; Fagioli, Franca

2016-05-01

Post-transplant high-dose cyclophosphamide (PTCy) is a novel approach to prevent graft-versus-host disease (GVHD) and rejection in patients given haploidentical hematopoietic stem cell transplantation (HSCT). Thirty-three patients with high-risk hematologic malignancies and lacking a match-related or -unrelated donor were treated with PTCy haploidentical HSCT in 5 Italian AIEOP centers. Nineteen patients had a nonmyeloablative preparative regimen (57%), and 14 patients received a full myeloablative conditioning regimen (43%). No patients received serotherapy; GVHD prophylaxis was based on PTCy (50 mg/kg on days +3 and +4) combined with mycophenolate plus tacrolimus or cyclosporine A. Neutrophil and platelet engraftment was achieved on days +17 (range, 14 to 37) and +27 (range, 16 to 71). One patient had autologous reconstitution for anti-HLA antibodies. Acute GVHD grades II to IV and III to IV and chronic GVHD developed in 22% (95% CI, 11 to 42), 3% (95% CI, 0 to 21), and 4% (95% CI, 0 to 27) of cases, respectively. The 1-year overall survival rate was 72% (95% CI, 56 to 88), progression-free survival rate was 61% (95% CI, 43 to 80), cumulative incidence of relapse was 24% (95% CI, 13 to 44), and transplant-related mortality was 9% (95% CI, 3 to 26). The univariate analysis for risk of relapse incidence showed how 3 significant variables, mother as donor (P = .02), donor gender as female (P = .04), and patient gender as female (P = .02), were significantly associated with a lower risk of relapse. Disease progression was the main cause of death. PTCy is a safe procedure also for children and adolescents who have already received several lines of chemotherapy. Among the different diseases, a trend for better 1-year rates of overall survival was obtained for nonacute leukemia patients. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial.

PubMed

Corbacioglu, Selim; Cesaro, Simone; Faraci, Maura; Valteau-Couanet, Dominique; Gruhn, Bernd; Rovelli, Attilio; Boelens, Jaap J; Hewitt, Annette; Schrum, Johanna; Schulz, Ansgar S; Müller, Ingo; Stein, Jerry; Wynn, Robert; Greil, Johann; Sykora, Karl-Walter; Matthes-Martin, Susanne; Führer, Monika; O'Meara, Anne; Toporski, Jacek; Sedlacek, Petr; Schlegel, Paul G; Ehlert, Karoline; Fasth, Anders; Winiarski, Jacek; Arvidson, Johan; Mauz-Körholz, Christine; Ozsahin, Hulya; Schrauder, Andre; Bader, Peter; Massaro, Joseph; D'Agostino, Ralph; Hoyle, Margaret; Iacobelli, Massimo; Debatin, Klaus-Michael; Peters, Christina; Dini, Giorgio

2012-04-07

Hepatic veno-occlusive disease is a leading cause of morbidity and mortality after haemopoietic stem-cell transplantation (HSCT). We aimed to assess whether defibrotide can reduce the incidence of veno-occlusive disease in this setting. In our phase 3 open-label, randomised controlled trial, we enrolled patients at 28 European university hospitals or academic medical centres. Eligible patients were younger than 18 years, had undergone myeloablative conditioning before allogeneic or autologous HSCT, and had one or more risk factor for veno-occlusive disease based on modified Seattle criteria. We centrally assigned eligible participants on the basis of a computer-generated randomisation sequence (1:1), stratified by centre and presence of osteopetrosis, to receive intravenous defibrotide prophylaxis (treatment group) or not (control group). The primary endpoint was incidence of veno-occlusive disease by 30 days after HSCT, adjudicated by a masked, independent review committee, in eligible patients who consented to randomisation (intention-to-treat population), and was assessed with a competing risk approach. Patients in either group who developed veno-occlusive disease received defibrotide for treatment. We assessed adverse events to 180 days after HSCT in all patients who received allocated prophylaxis. This trial is registered with ClinicalTrials.gov, number NCT00272948. Between Jan 25, 2006, and Jan 29, 2009, we enrolled 356 eligible patients to the intention-to-treat population. 22 (12%) of 180 patients randomly allocated to the defibrotide group had veno-occlusive disease by 30 days after HSCT compared with 35 (20%) of 176 controls (risk difference -7·7%, 95% CI -15·3 to -0·1; Z test for competing risk analysis p=0·0488; log-rank test p=0·0507). 154 (87%) of 177 patients in the defibrotide group had adverse events by day 180 compared with 155 (88%) of 176 controls. Defibrotide prophylaxis seems to reduce incidence of veno-occlusive disease and is well tolerated. Thus, such prophylaxis could present a useful clinical option for this serious complication of HSCT. Gentium SpA, European Group for Blood and Marrow Transplantation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Feasibility and Efficacy of Intra‐Arterial Administration of Mesenchymal Stem Cells in an Animal Model of Double Toxin‐Induced Multiple System Atrophy

PubMed Central

Na Kim, Ha; Yeol Kim, Dong; Hee Oh, Se; Sook Kim, Hyung; Suk Kim, Kyung

2017-01-01

Abstract Multiple system atrophy (MSA) is a sporadic neurodegenerative disease of the central and autonomic nervous system. Because no drug treatment consistently benefits MSA patients, neuroprotective strategy using mesenchymal stem cells (MSCs) has a lot of concern for the management of MSA. In this study, we investigated the safety and efficacy of intra‐arterial administration of MSCs via internal carotid artery (ICA) in an animal model of MSA. The study was composed of feasibility test using a ×10 and ×50 of a standard dose of MSCs (4 × 107 MSCs) and efficacy test using a ×0.2, ×2, and ×20 of the standard dose. An ultrasonic flow meter and magnetic resonance imaging (MRI) showed that no cerebral ischemic lesions with patent ICA blood flow was were observed in animals receiving a ×10 of the standard dose of MSCs. However, no MSA animals receiving a ×50 of the standard dose survived. In efficacy test, animals injected with a ×2 of the standard dose increased nigrostriatal neuronal survival relative to a ×0.2 or ×20 of the standard dose. MSA animals receiving MSCs at ×0.2 and ×2 concentrations of the standard dose exhibited a significant reduction in rotation behavior relative to ×20 of the standard dose of MSCs. Cerebral ischemic lesions on MRI were only observed in MSA animals receiving a ×20 of the standard dose. The present study revealed that if their concentration is appropriate, intra‐arterial injection of MSCs is safe and exerts a neuroprotective effect on striatal and nigral neurons with a coincidental improvement in motor behavior. Stem Cells Translational Medicine 2017;6:1424–1433 PMID:28296268

[Effect of a dehydrated extract of nopal (Opuntia ficus indica Mill.) on blood glucose].

PubMed

Frati-Munari, A C; de León, C; Ariza-Andraca, R; Bañales-Ham, M B; López-Ledesma, R; Lozoya, X

1989-01-01

To assess if a dehydrated extract of nopal stems retains the effect on glycemia of the entire nopal stems two experiments were performed. A. Six patients with type II diabetes mellitus in fasting condition received 30 capsules containing 10.1 +/- 0.3 g of the extract, and serum glucose levels were measured hourly from 0 to 180 minutes. B. Six healthy volunteers received 30 capsules with the extract followed by 74 g of dextrose orally. Serum glucose measurements were made in a similar fashion. In each experiment a control test with empty capsules was performed. Nopal extract did not reduce fasting glycemia in diabetic subjects. Nevertheless, the extract diminished the increase of serum glucose which followed a dextrose load. Peak serum glucose was 20.3 +/- 18.2 mg/dl (X +/- SD) lower in the test with nopal than in the control one (P less than 0.025). Dehydrated extract of nopal (Opuntia ficus-indica Mill) did not show acute hypoglycemic effect, although could attenuate postprandial hyperglycemia.

Development of a modified prognostic index for patients with aggressive adult T-cell leukemia-lymphoma aged 70 years or younger: possible risk-adapted management strategies including allogeneic transplantation.

PubMed

Fuji, Shigeo; Yamaguchi, Takuhiro; Inoue, Yoshitaka; Utsunomiya, Atae; Moriuchi, Yukiyoshi; Uchimaru, Kaoru; Owatari, Satsuki; Miyagi, Takashi; Taguchi, Jun; Choi, Ilseung; Otsuka, Eiichi; Nakachi, Sawako; Yamamoto, Hisashi; Kurosawa, Saiko; Tobinai, Kensei; Fukuda, Takahiro

2017-07-01

Adult T-cell leukemia-lymphoma is a distinct type of peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type I. Although allogeneic stem cell transplantation after chemotherapy is a recommended treatment option for patients with aggressive adult T-cell leukemia-lymphoma, there is no consensus about indications for allogeneic stem cell transplantation because there is no established risk stratification system for transplant eligible patients. We conducted a nationwide survey of patients with aggressive adult T-cell leukemia-lymphoma in order to construct a new, large database that includes 1,792 patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who were diagnosed between 2000 and 2013 and received intensive first-line chemotherapy. We randomly divided patients into two groups (training and validation sets). Acute type, poor performance status, high soluble interleukin-2 receptor levels (> 5,000 U/mL), high adjusted calcium levels (≥ 12 mg/dL), and high C-reactive protein levels (≥ 2.5 mg/dL) were independent adverse prognostic factors used in the training set. We used these five variables to divide patients into three risk groups. In the validation set, median overall survival for the low-, intermediate-, and high-risk groups was 626 days, 322 days, and 197 days, respectively. In the intermediate- and high-risk groups, transplanted recipients had significantly better overall survival than non-transplanted patients. We developed a promising new risk stratification system to identify patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who may benefit from upfront allogeneic stem cell transplantation. Prospective studies are warranted to confirm the benefit of this treatment strategy. Copyright© 2017 Ferrata Storti Foundation.

Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study.

PubMed

Hernigou, Philippe; Flouzat Lachaniette, Charles Henri; Delambre, Jerome; Zilber, Sebastien; Duffiet, Pascal; Chevallier, Nathalie; Rouard, Helene

2014-09-01

The purpose of this study was to evaluate the efficiency of biologic augmentation of rotator cuff repair with iliac crest bone marrow-derived mesenchymal stem cells (MSCs). The prevalence of healing and prevention of re-tears were correlated with the number of MSCs received at the tendon-to-bone interface. Forty-five patients in the study group received concentrated bone marrow-derived MSCs as an adjunct to single-row rotator cuff repair at the time of arthroscopy. The average number of MSCs returned to the patient was 51,000 ± 25,000. Outcomes of patients receiving MSCs during their repair were compared to those of a matched control group of 45 patients who did not receive MSCs. All patients underwent imaging studies of the shoulder with iterative ultrasound performed every month from the first postoperative month to the 24th month. The rotator cuff healing or re-tear was confirmed with MRI postoperatively at three and six months, one and two years and at the most recent follow up MRI (minimum ten-year follow-up). Bone marrow-derived MSC injection as an adjunctive therapy during rotator cuff repair enhanced the healing rate and improved the quality of the repaired surface as determined by ultrasound and MRI. Forty-five (100 %) of the 45 repairs with MSC augmentation had healed by six months, versus 30 (67 %) of the 45 repairs without MSC treatment by six months. Bone marrow concentrate (BMC) injection also prevented further ruptures during the next ten years. At the most recent follow-up of ten years, intact rotator cuffs were found in 39 (87 %) of the 45 patients in the MSC-treated group, but just 20 (44 %) of the 45 patients in the control group. The number of transplanted MSCs was determined to be the most relevant to the outcome in the study group, since patients with a loss of tendon integrity at any time up to the ten-year follow-up milestone received fewer MSCs as compared with those who had maintained a successful repair during the same interval. This study showed that significant improvement in healing outcomes could be achieved by the use of BMC containing MSC as an adjunct therapy in standard of care rotator cuff repair. Furthermore, our study showed a substantial improvement in the level of tendon integrity present at the ten-year milestone between the MSC-treated group and the control patients. These results support the use of bone marrow-derived MSC augmentation in rotator cuff repair, especially due to the enhanced rate of healing and the reduced number of re-tears observed over time in the MSC-treated patients.

Application of stem cell-derived retinal pigmented epithelium in retinal degenerative diseases: present and future.

PubMed

Luo, Mingyue; Chen, Youxin

2018-01-01

As a constituent of blood-retinal barrier and retinal outer segment (ROS) scavenger, retinal pigmented epithelium (RPE) is fundamental to normal function of retina. Malfunctioning of RPE contributes to the onset and advance of retinal degenerative diseases. Up to date, RPE replacement therapy is the only possible method to completely reverse retinal degeneration. Transplantation of human RPE stem cell-derived RPE (hRPESC-RPE) has shown some good results in animal models. With promising results in terms of safety and visual improvement, human embryonic stem cell-derived RPE (hESC-RPE) can be expected in clinical settings in the near future. Despite twists and turns, induced pluripotent stem cell-derived RPE (iPSC-RPE) is now being intensely investigated to overcome genetic and epigenetic instability. By far, only one patient has received iPSC-RPE transplant, which is a hallmark of iPSC technology development. During follow-up, no major complications such as immunogenicity or tumorigenesis have been observed. Future trials should keep focusing on the safety of stem cell-derived RPE (SC-RPE) especially in long period, and better understanding of the nature of stem cell and the molecular events in the process to generate SC-RPE is necessary to the prosperity of SC-RPE clinical application.

Implications of cancer stem cell theory for cancer chemoprevention by natural dietary compounds.

PubMed

Li, Yanyan; Wicha, Max S; Schwartz, Steven J; Sun, Duxin

2011-09-01

The emergence of cancer stem cell theory has profound implications for cancer chemoprevention and therapy. Cancer stem cells give rise to the tumor bulk through continuous self-renewal and differentiation. Understanding the mechanisms that regulate self-renewal is of greatest importance for discovery of anticancer drugs targeting cancer stem cells. Naturally occurring dietary compounds have received increasing attention in cancer chemoprevention. The anticancer effects of many dietary components have been reported for both in vitro and in vivo studies. Recently, a number of studies have found that several dietary compounds can directly or indirectly affect cancer stem cell self-renewal pathways. Herein we review the current knowledge of most common natural dietary compounds for their impact on self-renewal pathways and potential effect against cancer stem cells. Three pathways (Wnt/β-catenin, Hedgehog and Notch) are summarized for their functions in self-renewal of cancer stem cells. The dietary compounds, including curcumin, sulforaphane, soy isoflavone, epigallocatechin-3-gallate, resveratrol, lycopene, piperine and vitamin D(3), are discussed for their direct or indirect effect on these self-renewal pathways. Curcumin and piperine have been demonstrated to target breast cancer stem cells. Sulforaphane has been reported to inhibit pancreatic tumor-initiating cells and breast cancer stem cells. These studies provide a basis for preclinical and clinical evaluation of dietary compounds for chemoprevention of cancer stem cells. This may enable us to discover more preventive strategies for cancer management by reducing cancer resistance and recurrence and improving patient survival. Copyright © 2011 Elsevier Inc. All rights reserved.

“Anatomy of an Illness”: Control from a caregiver’s perspective

PubMed Central

Laudenslager, Mark L.

2013-01-01

Caregivers of loved ones with chronic illnesses experience an uncontrollable challenge with potentially negative behavioral and medical consequences. Extensive research has demonstrated immune and endocrine regulation can be significantly disrupted by negative behavioral factors based on both animal models and human studies. However, fewer studies have focused on how psychosocial interventions might reverse the negative consequences of stressors such as caregiving. The distress of caring for individuals with cancer has only recently begun to receive attention. These interventions addressing caregiver distress are rare overall and caregivers of patients receiving hematopoietic stem cell transplants (HSCT) have received even less attention. HSCT caregivers report feelings of loss of control. Animal studies suggest that control over aversive events can mitigate the negative consequences of stressors. Caregivers of allogeneic HSCT patients for blood cancers must be available 24/7 for three months or longer following stem cell infusion to closely monitor the recipients’ health and well-being. Does establishing a greater sense of control have positive impacts on caregivers? A randomized control trial of a cognitive behavioral stress management intervention for allogeneic HSCT caregivers is briefly described. A model of caregiver mental health which may potentially impact the patient’s quality of life is proposed. These relationships exist in a complex system that includes genetic influences, sex, social environment, and prior experience. This system fits well within recent formulations of a “complexity science” approach to health and well-being. PMID:24012646

Safety and tolerability of allogeneic dendritic cell vaccination with induction of Wilms tumor 1-specific T cells in a pediatric donor and pediatric patient with relapsed leukemia: a case report and review of the literature.

PubMed

Saito, Shoji; Yanagisawa, Ryu; Yoshikawa, Kentaro; Higuchi, Yumiko; Koya, Terutsugu; Yoshizawa, Kiyoshi; Tanaka, Miyuki; Sakashita, Kazuo; Kobayashi, Takashi; Kurata, Takashi; Hirabayashi, Koichi; Nakazawa, Yozo; Shiohara, Masaaki; Yonemitsu, Yoshikazu; Okamoto, Masato; Sugiyama, Haruo; Koike, Kenichi; Shimodaira, Shigetaka

2015-03-01

A 15-year-old girl with acute lymphoblastic leukemia received allogeneic dendritic cell vaccination, pulsed with Wilms tumor 1 (WT1) peptide, after her third hematopoietic stem cell transplantation (HSCT). The vaccines were generated from the third HSCT donor, who was her younger sister, age 12 years. The patient received 14 vaccines and had no graft-versus-host disease or systemic adverse effect, aside from grade 2 skin reaction at the injection site. WT1-specific immune responses were detected after vaccination by both WT1-tetramer analysis and enzyme-linked immunosorbent spot assay. This strategy may be safe, tolerable and even feasible for patients with a relapse after HSCT. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Evaluation of the efficacy and safety of original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) in CD34(+) peripheral hematopoietic stem cell mobilization procedures for allogeneic hematopoietic stem cell transplant donors.

PubMed

Sivgin, Serdar; Karakus, Esen; Keklik, Muzaffer; Zararsiz, Gokmen; Solmaz, Musa; Kaynar, Leylagul; Eser, Bulent; Cetin, Mustafa; Unal, Ali

2016-06-01

In this study, we aimed to compare the potency of different G-CSF agents including original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) on CD34(+) cell mobilization in patients that underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). The data of 243 donors for alloHSCT recipients diagnosed with mostly acute leukemia and myelodsyplastic syndromes (MDS) were analyzed, retrospectively. Data for stem cell mobilization have been recorded from patients' files. Donors who received Filgrastim (Neupogen®, Group I), biosimilar Filgrastim (Leucostim®, Group II) and Lenograstim (Granocyte®, Group III) were analyzed for total CD34(+) cell count at the end of mobilization procedures. A total of 243 donors and patients for alloHSCT were analyzed retrospectively. The diagnosis of the patients were; acute myeloid leukemia (AML) (110 patients, 45.2%), acute lymphoid leukemia (ALL) (61 patients, 25.1%), aplastic anemia (AA) (38 patients, 15.6%), lymphomas (14 patients, 5.7%) and others (20 patients, 8.4%). The median number of total collected PB CD34(+) cells (×10(6)/kg) was 7.12 (min-max: 5.38-7.90) in the Neupogen® group, 7.27 (min-max: 6.79-7.55) in the Leucostim® group and 7.15 (min-max: 5.34-7.58) in the Granocyte® group. There was no statistically significant difference among groups in terms of total collected PB CD34(+) cells (p = 0.919). The median doses of G-CSF agents (µg/kg/day) in PBSC collection in Neupogen® group was; 11.00 (10.00-12.00) in Leucostim® group10.35 (min-max: 10.00-11.10) and in Granocyte® group11.00 (min-max: 10.00-11.00). There was no statistical significance among groups (p = 0.215). Biosimilar filgrastim (Leucostim®) was found comparable to original Filgrastim (Neupogen®) and Lenograstim (Granocyte®) for PBSC mobilization in donors of the patients that underwent alloHSCT. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intravenous busulfan for autologous stem cell transplantation in adult patients with acute myeloid leukemia: a survey of 952 patients on behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

PubMed Central

Nagler, Arnon; Labopin, Myriam; Gorin, Norbert-Claude; Ferrara, Felicetto; Sanz, Miguel A; Wu, Depei; Gomez, Antonio Torres; Lapusan, Simona; Irrera, Giuseppe; Guimaraes, Jose E; Sousa, Aida Botelho; Carella, Angelo M.; Vey, Norbert; Arcese, William; Shimoni, Avichai; Berger, Raanan; Rocha, Vanderson; Mohty, Mohamad

2014-01-01

Oral busulfan is the historical backbone of the busulfan+cyclophosphamide regimen for autologous stem cell transplantation. However intravenous busulfan has more predictable pharmacokinetics and less toxicity than oral busulfan; we, therefore, retrospectively analyzed data from 952 patients with acute myeloid leukemia who received intravenous busulfan for autologous stem cell transplantation. Most patients were male (n=531, 56%), and the median age at transplantation was 50.5 years. Two-year overall survival, leukemia-free survival, and relapse incidence were 67±2%, 53±2%, and 40±2%, respectively. The non-relapse mortality rate at 2 years was 7±1%. Five patients died from veno-occlusive disease. Overall leukemia-free survival and relapse incidence at 2 years did not differ significantly between the 815 patients transplanted in first complete remission (52±2% and 40±2%, respectively) and the 137 patients transplanted in second complete remission (58±5% and 35±5%, respectively). Cytogenetic risk classification and age were significant prognostic factors: the 2-year leukemia-free survival was 63±4% in patients with good risk cytogenetics, 52±3% in those with intermediate risk cytogenetics, and 37 ± 10% in those with poor risk cytogenetics (P=0.01); patients ≤50 years old had better overall survival (77±2% versus 56±3%; P<0.001), leukemia-free survival (61±3% versus 45±3%; P<0.001), relapse incidence (35±2% versus 45±3%; P<0.005), and non-relapse mortality (4±1% versus 10±2%; P<0.001) than older patients. The combination of intravenous busulfan and high-dose melphalan was associated with the best overall survival (75±4%). Our results suggest that the use of intravenous busulfan simplifies the autograft procedure and confirm the usefulness of autologous stem cell transplantation in acute myeloid leukemia. As in allogeneic transplantation, veno-occlusive disease is an uncommon complication after an autograft using intravenous busulfan. PMID:24816236

A double-blind, randomized, controlled trial on N-acetylcysteine for the prevention of acute kidney injury in patients undergoing allogeneic hematopoietic stem cell transplantation.

PubMed

Ataei, Sara; Hadjibabaie, Molouk; Moslehi, Amirhossein; Taghizadeh-Ghehi, Maryam; Ashouri, Asieh; Amini, Elham; Gholami, Kheirollah; Hayatshahi, Alireza; Vaezi, Mohammad; Ghavamzadeh, Ardeshir

2015-06-01

Acute kidney injury (AKI) is one of the complications of hematopoietic stem cell transplantation and is associated with increased mortality. N-acetylcysteine (NAC) is a thiol compound with antioxidant and vasodilatory properties that has been investigated for the prevention of AKI in several clinical settings. In the present study, we evaluated the effects of intravenous NAC on the prevention of AKI in allogeneic hematopoietic stem cell transplantation patients. A double-blind randomized placebo-controlled trial was conducted, and 80 patients were recruited to receive 100 mg/kg/day NAC or placebo as intermittent intravenous infusion from day -6 to day +15. AKI was determined on the basis of the Risk-Injury-Failure-Loss-End-stage renal disease and AKI Network criteria as the primary outcome. We assessed urine neutrophil gelatinase-associated lipocalin (uNGAL) on days -6, -3, +3, +9 and +15 as the secondary outcome. Moreover, transplant-related outcomes and NAC adverse reactions were evaluated during the study period. Statistical analysis was performed using appropriate parametric and non-parametric methods including Kaplan-Meier for AKI and generalized estimating equation for uNGAL. At the end of the trial, data from 72 patients were analysed (NAC: 33 patients and placebo: 39 patients). Participants of each group were not different considering baseline characteristics. AKI was observed in 18% of NAC recipients and 15% of placebo group patients, and the occurrence pattern was not significantly different (p = 0.73). Moreover, no significant difference was observed between groups for uNGAL measures (p = 0.10). Transplant-related outcomes were similar for both groups, and all patients had successful engraftment. Three patients did not tolerate NAC because of abdominal pain, shortness of breath and rash with pruritus and were dropped from the intervention group before transplantation. However, the frequency of adverse reactions was not significantly different between groups. In conclusion, our findings could not show any clinical benefits from high-dose NAC particularly for AKI prevention in allogeneic hematopoietic stem cell transplantation patients. Copyright © 2014 John Wiley & Sons, Ltd.

Clinical Cold Welding of the Modular Total Hip Arthroplasty Prosthesis.

PubMed

Whittaker, Robert K; Zaghloul, Ahmed M; Hothi, Harry S; Siddiqui, Imran A; Blunn, Gordon W; Skinner, John A; Hart, Alister J

2017-02-01

A head that is "clinically cold welded" to a stem is one of the commonest reasons for unplanned removal of the stem. It is not clear which hip designs are at greatest risk of clinical cold welding. This was a case-control study of consecutively received hip implant retrievals; we chose the design of hip that had the greatest number of truly cold-welded heads (n = 11). For our controls, we chose retrieved hips of the same design but without cold welding of the head (n = 35). We compared the clinical variables between these 2 groups using nonparametric Mann-Whitney tests to investigate the significance of differences between the cold-welded and non-cold-welded groups. The design that most commonly caused cold welding was a combination of a Ti stem and Ti taper: 11 out of 48 (23%) were truly cold welded. Comparison of the clinical data showed that no individual factor could be used to predict this preoperatively with none of the 4 predictors tested showing any significance: (1) time to revision (P = .687), (2) head size (P = .067), (3) patient age at primary (P = .380), and (4) gender (P = .054). We have shown that clinical cold welding is most prevalent in Ti-Ti combinations of the stem and taper; approximately 25% of cases received at our center were cold welded. Analysis of clinical variables showed that it is not possible to predict which will be cold welded preoperatively. Surgeons should be aware of this potential complication when revising a Ti-Ti stem/head junction. Copyright © 2016 Elsevier Inc. All rights reserved.

Effectiveness of Visual Methods in Information Procedures for Stem Cell Recipients and Donors

PubMed Central

Sarıtürk, Çağla; Gereklioğlu, Çiğdem; Korur, Aslı; Asma, Süheyl; Yeral, Mahmut; Solmaz, Soner; Büyükkurt, Nurhilal; Tepebaşı, Songül; Kozanoğlu, İlknur; Boğa, Can; Özdoğu, Hakan

2017-01-01

Objective: Obtaining informed consent from hematopoietic stem cell recipients and donors is a critical step in the transplantation process. Anxiety may affect their understanding of the provided information. However, use of audiovisual methods may facilitate understanding. In this prospective randomized study, we investigated the effectiveness of using an audiovisual method of providing information to patients and donors in combination with the standard model. Materials and Methods: A 10-min informational animation was prepared for this purpose. In total, 82 participants were randomly assigned to two groups: group 1 received the additional audiovisual information and group 2 received standard information. A 20-item questionnaire was administered to participants at the end of the informational session. Results: A reliability test and factor analysis showed that the questionnaire was reliable and valid. For all participants, the mean overall satisfaction score was 184.8±19.8 (maximum possible score of 200). However, for satisfaction with information about written informed consent, group 1 scored significantly higher than group 2 (p=0.039). Satisfaction level was not affected by age, education level, or differences between the physicians conducting the informative session. Conclusion: This study shows that using audiovisual tools may contribute to a better understanding of the informed consent procedure and potential risks of stem cell transplantation. PMID:27476890

[Therapeutic effect of human mesenchymal stem cells in skin after radiation damage].

PubMed

Bensidhoum, Morad; Gobin, Stéphanie; Chapel, Alain; Lemaitre, Gilles; Bouet, Stéphan; Waksman, Gilles; Thierry, Dominique; Martin, Michèle T

2005-01-01

Over 50% of all cancer patients presently receive radiotherapy at one stage in their treatment course. Inevitably skin is one of the most frequently damaged tissue due to its localization and constant turn-over. Our present goal is to reduce radiation-induced complications in human skin through stem cell therapy, particulary in human epidermis. Mesenchymal Stem Cells (MSCs) have been shown to be multipotent cells able to engraft in many tissues after injury. Herein, we isolated human MSCs and tested their capability to improve skin wound healing after irradiation. This potential was assessed in NOD/SCID mice which received 30 Gy locally on the thigh. This dose caused within 3 weeks local epidermis necrosis which was repaired within 13 weeks. MSCs were intravenously injected in irradiated mice 24 hours after exposure. Clinical scoring throughout 6 weeks gave indications that human MSCs reduced the extent of damage and accelerated the wound healing process. We show by quantitative qPCR and histological studies the presence of human MSCs derived cells into the scar. Human MSCs homed to the damaged skin and participated to the wound healing process. These results open prospects for cellular therapy by MSCs in irradiated epithelial tissues and could be extended to the whole general field of cutaneous cicatrization, particularly after burns.

Allogeneic stem cell transplantation benefits for patients ≥ 60 years with acute myeloid leukemia and FLT3 internal tandem duplication: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

PubMed

Poiré, Xavier; Labopin, Myriam; Polge, Emmanuelle; Passweg, Jakob; Craddock, Charles; Blaise, Didier; Cornelissen, Jan J; Volin, Liisa; Russell, Nigel H; Socié, Gérard; Michallet, Mauricette; Fegueux, Nathalie; Chevallier, Patrice; Brecht, Arne; Hunault-Berger, Mathilde; Mohty, Mohamad; Esteve, Jordi; Nagler, Arnon

2018-02-01

Intermediate-risk cytogenetic acute myeloid leukemia with an internal tandem duplication of FLT3 ( FLT3 -ITD) is associated with a high risk of relapse, and is now a standard indication for allogeneic stem cell transplantation. Nevertheless, most studies supporting this strategy have been performed in young patients. To address the benefit of allogeneic transplantation in the elderly, we made a selection from the European Society for Blood and Marrow Transplantation registry of de novo intermediate-risk cytogenetic acute myeloid leukemia harboring FLT3 -ITD in patients aged 60 or over and transplanted from a related or unrelated donor between January 2000 and December 2015. Two hundred and ninety-one patients were identified. Most patients received a reduced-intensity conditioning (82%), while donors consisted of an unrelated donor in 161 (55%) patients. Two hundred and twelve patients received their transplantation in first remission, 37 in second remission and 42 in a more advanced stage of the disease. The 2-year leukemia-free survival rate was 56% in patients in first remission, 22% in those in second remission and 10% in patients with active disease, respectively ( P <0.005). Non-relapse mortality for the entire cohort was 20%. In multivariate analysis, disease status at transplantation was the most powerful predictor of worse leukemia-free survival, graft- versus -host disease and relapse-free survival, and overall survival. In this elderly population, age was not associated with outcome. Based on the current results, allogeneic transplantation translates into a favorable outcome in fit patients ≥ 60 with FLT3 -ITD acute myeloid leukemia in first remission, similarly to current treatment recommendations for younger patients. Copyright© 2018 Ferrata Storti Foundation.

[Hematopoietic Reconstitution and Prognosis of HLA Matched and Haploidentical Hematopoietic Stem Cell Transplantation Using Modified FC/ATG Conditioning for Treatment of Severe Aplastic Anemia].

PubMed

Wang, Li; Wu, Ya-Mei; Cao, Yong-Bin; Li, Xiao-Hong; Xu, Li-Xin; Wang, Hai-Tao; Gao, Ya-Hui; Wu, Xiao-Xiong

2016-12-01

To analyse the feasibility and compare differences between hematopoietic reconstitution and prognosis of patients with severe aplastic anemia(SAA) after matched sibling donor (MSD) or haploidentical family donor (HFD) hematopoietic stem cell transplantation (HSCT) using the modified FC/ATG conditioning. The clinical data of 56 patients with SAA who received HSCT in First Affiliated Hospital of Chinese PLA General Hospital from January 2011 to June 2016 were analyzed retrospectively. The hematopoietic reconstitution, graft verus host disease (GVHD), transplantation related toxicity (TRT) and prognosis after transplantation were compared. Furthermore, the modifed conditioning FC/ATG included low-dose cyclophosphamide (total dose 100 mg/kg), infustion of third-party donor-derived mesenchymal stem cells. All 56 patients with MSD-HSCT or HFD-HSCT achieved hematopoietic reconstitution. Among them, not only the recovery of neutrophils and platelets, but also the incidences of III-IV aGVHD, extensive cGVHD and TRT were not significantly different (the P value were 0.58, 0.61, 0.73, 0.73 and 0.67, respectively). After following-up for 32(2-66) months, 48 patients alive well, the 1-year overall survival rates were 86% in HFD-HSCT group and 89% in MSD-HSCT group, respectively (P=0.58). After HSCT using the modifed FC/ATG conditioning, patients with SAA achieved stable engraftment, low toxicity, mild GVHD and excellent outcomes. Furthermore, the HFD-HSCT achieved comparable outcomes to MSD-HSCT and may be served as an alternate therapy for patients with SAA.

Haploidentical Stem Cell Transplantation for Refractory/Relapsed Neuroblastoma.

PubMed

Illhardt, Toni; Toporski, Jacek; Feuchtinger, Tobias; Turkiewicz, Dominik; Teltschik, Heiko-Manuel; Ebinger, Martin; Schwarze, Carl-Philipp; Holzer, Ursula; Lode, Holger N; Albert, Michael H; Gruhn, Bernd; Urban, Christian; Dykes, Josefina H; Teuffel, Oliver; Schumm, Michael; Handgretinger, Rupert; Lang, Peter

2018-05-01

Pediatric patients with refractory or relapsed metastatic neuroblastoma (NBL) have a poor prognosis despite autologous stem cell transplantation (SCT). Allogeneic SCT from a haploidentical donor has a remarkable alloreactive effect in patients with leukemia; thus, we evaluated this approach in children with very high-risk NBL. We analyzed data from 2 prospective phase I/II trials. A total of 26 patients with refractory (n = 5), metastatic relapsed (n = 20), or locally relapsed MYCN-positive (n = 1) NBL received a median of 17 × 10 6 /kg T/B cell-depleted CD34 + stem cells with 68 × 10 3 /kg residual T cells and 107 × 10 6 /kg natural killer cells. The conditioning regimen comprised melphalan, fludarabine, thiotepa, OKT3, and a short course of mycophenolate mofetil post-transplantation. Engraftment occurred in 96% of the patients. Event-free survival and overall survival at 5 years were 19% and 23%, respectively. No transplantation-related mortality was observed, and the single death was due to progression/subsequent relapse. The median duration of follow-up was 8.1 years. Patients in complete remission before SCT had a significantly better prognosis than those with residual tumor load (P < .01). All patients with progressive disease before SCT relapsed within 1 year. Grade II and grade III acute graft-versus-host disease (GVHD) occurred in 31% and 12% of the patients, respectively. Chronic limited and extensive GVHD occurred in 28% and 10%, respectively. Our data indicate that haploidentical SCT is a feasible treatment option that can induce long-term remission in some patients with NBL with tolerable side effects, and may enable the development of further post-transplantation therapeutic strategies based on the donor-derived immune system. Copyright © 2018. Published by Elsevier Inc.

Expression of intracellular reactive oxygen species (ROS) in haematopoietic stem cells (HSCs) correlates with time to neutrophil and platelet engraftment in patients undergoing autologous bone marrow transplantation.

PubMed

Bai, Lijun; Best, Giles; Xia, Wei; Peters, Lyndsay; Wong, Kelly; Ward, Christopher; Greenwood, Matthew

2018-06-19

Reactive oxygen species (ROS) play important roles in haematopoiesis and regulate the self-renewal, migration and myeloid differentiation of haemopoeitic stem cells (HSCs). This study was conducted to determine whether ROS levels in donor HSCs correlate with neutrophil and platelet engraftment in patients following bone marrow transplantation. Cryopreserved HSCs samples from 51 patients who underwent autologous transplantation were studied. Levels of intracellular ROS were assessed by flow cytometry using 2',7' dichlorodihydrofluorescein diacetate (H 2 DCFDA) in the CD45 + /CD34 + HSC population. Colony forming unit (CFU) assays were performed on HSCs isolated from the ROS high and ROS low populations to assess the differentiation potential of these two cell subsets. Distinct populations of ROS high and ROS low cells were evident in all patient samples. The median percentage of ROS high expressing HSCs in the study cohort was 75.8% (range 2% - 95.2%). A significant correlation was identified between the percentage of ROS high stem cells present in the HPC(A) product infused and the time to neutrophil engraftment (p < 0.001, R= - 0.54) as well as time to plt20, plt50 and plt100 (p < 0.001, R = - 0.55, - 0.59 and - 0.56 respectively). The dose of CD34 + / ROS high /kg infused also inversely correlated with a shorter time to neutrophil engraftment; time to engraftment for patients receiving > or ≤ 3 × 10 6 cells/kg was 11.5 (range 9 - 23) days vs. 14 (10 - 28) days respectively (p = 0.02). The dose of ROS high HSCs delivered did not correlate with platelet engraftment. Collectively, these data suggest that the dose of ROS high stem cells delivered to patients may predict time to neutrophil engraftment following autologous transplantation. Copyright © 2018. Published by Elsevier Inc.

Impact of Donor Epstein-Barr Virus Serostatus on the Incidence of Graft-Versus-Host Disease in Patients With Acute Leukemia After Hematopoietic Stem-Cell Transplantation: A Study From the Acute Leukemia and Infectious Diseases Working Parties of the European Society for Blood and Marrow Transplantation.

PubMed

Styczynski, Jan; Tridello, Gloria; Gil, Lidia; Ljungman, Per; Hoek, Jennifer; Iacobelli, Simona; Ward, Katherine N; Cordonnier, Catherine; Einsele, Hermann; Socie, Gerard; Milpied, Noel; Veelken, Hendrik; Chevallier, Patrice; Yakoub-Agha, Ibrahim; Maertens, Johan; Blaise, Didier; Cornelissen, Jan; Michallet, Mauricette; Daguindau, Etienne; Petersen, Eefke; Passweg, Jakob; Greinix, Hildegard; Duarte, Rafael F; Kröger, Nicolaus; Dreger, Peter; Mohty, Mohamad; Nagler, Arnon; Cesaro, Simone

2016-07-01

We investigated the effect of Epstein-Barr virus (EBV) serostatus on the overall outcome of allogeneic hematopoietic stem-cell transplantation (allo-HSCT). The study included 11,364 patients who underwent allogeneic peripheral-blood or bone marrow transplantation for acute leukemia between 1997 and 2012. We analyzed the impact of donor and recipient EBV serologic status on overall survival, relapse-free survival, relapse incidence, nonrelapse mortality, and incidence of graft-versus-host disease (GVHD) after allo-HSCT. Patients receiving grafts from EBV-seropositive donors had the same overall survival as patients who received grafts from EBV-seronegative donors (hazard ratio [HR], 1.05; 95% CI, 0.97 to 1.12; P = .23). Seropositive donors also had no influence on relapse-free survival (HR, 1.04; 95% CI, 0.97 to 1.11; P = 0.31), relapse incidence (HR, 1.03; 95% CI, 0.94 to 1.12; P = .58), and nonrelapse mortality (HR, 1.05; 95% CI, 0.94 to 1.17; P = .37). However, in univariate analysis, recipients receiving grafts from seropositive donors had a higher risk of chronic GVHD than those with seronegative donors (40.8% v 31.0%, respectively; P < .001; HR, 1.42; 95% CI, 1.30 to 1.56). When adjusting for confounders, higher risk was identified for both acute and chronic GVHD. In seronegative patients with seropositive donors, the HR for chronic GVHD was 1.30 (95% CI, 1.06 to 1.59; P = .039). In seropositive patients with seropositive donors, the HR was 1.24 (95% CI, 1.07 to 1.45; P = .016) for acute GVHD and 1.43 (95% CI, 1.23 to 1.67; P < .001) for chronic GVHD. Seropositive patients with seronegative donors did not have an increased risk of GVHD. Our data suggest that donor EBV status significantly influences development of acute and chronic GVHD after allo-HSCT. © 2016 by American Society of Clinical Oncology.

Stem cell bioprocessing: fundamentals and principles

PubMed Central

Placzek, Mark R.; Chung, I-Ming; Macedo, Hugo M.; Ismail, Siti; Mortera Blanco, Teresa; Lim, Mayasari; Min Cha, Jae; Fauzi, Iliana; Kang, Yunyi; Yeo, David C.L.; Yip Joan Ma, Chi; Polak, Julia M.; Panoskaltsis, Nicki; Mantalaris, Athanasios

2008-01-01

In recent years, the potential of stem cell research for tissue engineering-based therapies and regenerative medicine clinical applications has become well established. In 2006, Chung pioneered the first entire organ transplant using adult stem cells and a scaffold for clinical evaluation. With this a new milestone was achieved, with seven patients with myelomeningocele receiving stem cell-derived bladder transplants resulting in substantial improvements in their quality of life. While a bladder is a relatively simple organ, the breakthrough highlights the incredible benefits that can be gained from the cross-disciplinary nature of tissue engineering and regenerative medicine (TERM) that encompasses stem cell research and stem cell bioprocessing. Unquestionably, the development of bioprocess technologies for the transfer of the current laboratory-based practice of stem cell tissue culture to the clinic as therapeutics necessitates the application of engineering principles and practices to achieve control, reproducibility, automation, validation and safety of the process and the product. The successful translation will require contributions from fundamental research (from developmental biology to the ‘omics’ technologies and advances in immunology) and from existing industrial practice (biologics), especially on automation, quality assurance and regulation. The timely development, integration and execution of various components will be critical—failures of the past (such as in the commercialization of skin equivalents) on marketing, pricing, production and advertising should not be repeated. This review aims to address the principles required for successful stem cell bioprocessing so that they can be applied deftly to clinical applications. PMID:19033137

Stem cell bioprocessing: fundamentals and principles.

PubMed

Placzek, Mark R; Chung, I-Ming; Macedo, Hugo M; Ismail, Siti; Mortera Blanco, Teresa; Lim, Mayasari; Cha, Jae Min; Fauzi, Iliana; Kang, Yunyi; Yeo, David C L; Ma, Chi Yip Joan; Polak, Julia M; Panoskaltsis, Nicki; Mantalaris, Athanasios

2009-03-06

In recent years, the potential of stem cell research for tissue engineering-based therapies and regenerative medicine clinical applications has become well established. In 2006, Chung pioneered the first entire organ transplant using adult stem cells and a scaffold for clinical evaluation. With this a new milestone was achieved, with seven patients with myelomeningocele receiving stem cell-derived bladder transplants resulting in substantial improvements in their quality of life. While a bladder is a relatively simple organ, the breakthrough highlights the incredible benefits that can be gained from the cross-disciplinary nature of tissue engineering and regenerative medicine (TERM) that encompasses stem cell research and stem cell bioprocessing. Unquestionably, the development of bioprocess technologies for the transfer of the current laboratory-based practice of stem cell tissue culture to the clinic as therapeutics necessitates the application of engineering principles and practices to achieve control, reproducibility, automation, validation and safety of the process and the product. The successful translation will require contributions from fundamental research (from developmental biology to the 'omics' technologies and advances in immunology) and from existing industrial practice (biologics), especially on automation, quality assurance and regulation. The timely development, integration and execution of various components will be critical-failures of the past (such as in the commercialization of skin equivalents) on marketing, pricing, production and advertising should not be repeated. This review aims to address the principles required for successful stem cell bioprocessing so that they can be applied deftly to clinical applications.

Hypoglycemic effect of Opuntia streptacantha Lemaire in NIDDM.

PubMed

Frati-Munari, A C; Gordillo, B E; Altamirano, P; Ariza, C R

1988-01-01

To assess the hypoglycemic effect of the nopal Opuntia streptacantha Lemaire (O. streptacantha Lem.), three groups of patients with non-insulin-dependent diabetes mellitus (NIDDM) were studied. Group one (16 patients) ingested 500 g of broiled nopal stems. Group 2 (10 patients) received only 400 ml of water as a control test. Three tests were performed on group 3 (6 patients): one with nopal, a second with water, and a third with ingestion of 500 g broiled squash. Serum glucose and insulin levels were measured at 0, 60, 120, and 180 min. After the intake of O. streptacantha Lem., serum glucose and serum insulin levels decreased significantly in groups 1 and 3, whereas no similar changes were noticed in group 2. The mean reduction of glucose reached 17.6 +/- 2.2% of basal values at 180 min in group 1 and 16.2 +/- 1.8% in group 3; the reduction of serum insulin at 180 min reached 50.2 +/- 8.0% in group 1 and 40.3 +/- 12.4% in group 3. This study shows that the stems of O. streptacantha Lem. cause a hypoglycemic effect in patients with NIDDM. The mechanism of this effect is unknown, but an increased insulin sensitivity is suggested.

Immune Reconstitution Reactions in Human Immunodeficiency Virus–Negative Patients

PubMed Central

Scharschmidt, Tiffany C.; Amerson, Erin H.; Rosenberg, Oren S.; Jacobs, Richard A.; McCalmont, Timothy H.; Shinkai, Kanade

2013-01-01

Background Immune reconstitution inflammatory syndrome (IRIS) is a phenomenon initially described in patients with human immunodeficiency virus. Upon initiation of combination antiretroviral therapy, recovery of cellular immunity triggers inflammation to a preexisting infection or antigen that causes paradoxical worsening of clinical disease. A similar phenomenon can occur in human immunodeficiency virus–negative patients, including pregnant women, neutropenic hosts, solidorgan or stem cell transplant recipients, and patients receiving tumor necrosis factor inhibitors. Observations We report a case of leprosy unmasking and downgrading reaction after stem cell transplantation that highlights some of the challenges inherent to the diagnosis of IRIS, especially in patients without human immunodeficiency virus infection, as well as review the spectrum of previously reported cases of IRIS reactions in this population. Conclusions The mechanism of immune reconstitution reactions is complex and variable, depending on the underlying antigen and the mechanism of immunosuppression or shift in immune status. Use of the term IRIS can aid our recognition of an important phenomenon that occurs in the setting of immunosuppression or shifts in immunity but should not deter us from thinking critically about the distinct processes that underlie this heterogeneous group of conditions. PMID:23324760

Serum growth differentiation factor 15 levels in newly diagnosed multiple myeloma patients.

PubMed

Tarkun, Pinar; Birtas Atesoglu, Elif; Mehtap, Ozgur; Musul, Mahmut Mert; Hacihanefioglu, Abdullah

2014-01-01

Multiple myeloma (MM) is a hematological cancer associated with increased clonal malignant plasma cells. Growth differentiation factor 15 (GDF 15) is a protein that is highly expressed in the bone marrow mesenchymal stem cells of patients with MM. This study investigated whether the clinical stage of the disease, treatment response and survival are affected by pretreatment serum GDF 15 levels. Serum GDF 15 levels were measured in 35 newly diagnosed MM patients and 27 healthy controls. The correlation between serum GDF 15 levels and various clinical and laboratory parameters was analyzed. The study demonstrated significantly higher levels of GDF 15 in MM patients. There was a negative correlation between GDF 15 levels, hemoglobin and albumin levels, and a positive correlation between GDF 15 levels, CRP, creatinine, β-2-microglobulin and stage. GDF 15 levels were lower in patients who could receive autologous stem cell transplantation compared to other groups, representing a statistically significant difference. However, in the survival analyses, GDF 15 level did not have an impact on survival. High serum levels of GDF 15 may indicate a poor treatment response. Our study supports the prognostic value of GDF 15 in MM. © 2013 S. Karger AG, Basel.

[Role of long-term follow-up in management of late-onset post-hematopoietic stem cell transplant complications].

PubMed

Asano-Mori, Yuki

As the number of long-term survivors after allogeneic hematopoietic stem cell transplantation (HSCT) has increased owing to advances in transplantation and supportive care techniques, the health and welfare of these survivors have come into focus. However, they are still at risks for various complications, including chronic graft-versus-host disease, infectious diseases, and secondary cancers even in the late period, which can not only interfere with the patient's quality of life (QOL) but also lead to death. The importance of long-term follow-up (LTFU) and management have been recently recognized, and nationwide systems to promote LTFU care in patients receiving HSCT, such as medical fee revision, publication of a LTFU guideline unique to Japan, and preparation of patient pocketbook, is under consideration. The number of medical facilities at LTFU outpatient clinic is also increasing; therefore, an optimal comprehensive support system may be established sooner or later. However, self-management by patients is essential to overcome late complications as well as to improve QOL after HSCT. Healthcare professionals should collaborate and continue to make the greatest possible efforts to educate patients regarding the risks of late complications and their prevention.

Late Complications in acute Leukemia patients following HSCT: A single center experience.

PubMed

Vaezi, Mohammad; Gharib, Cyrous; Souri, Maryam; Ghavamzadeh, Ardeshir

2016-01-01

Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for acute leukemia. As HSCT improves the long-term survival, it is necessary to assess the late-onset complications affecting the quality of life following HSCT. The study included 122 patients (65 male, 57 female) with leukemia (72 AML and 50 ALL) who received transplants from fully- matched siblings, unrelated donors and unrelated cord blood donors between February 2013 and August 2014 in Shariati Hospital. All study participants were over 18 years of age and had the minimum and maximum survival of 2 and 5 years, respectively. Patients who received HLA-haploidentical SCT were excluded from the study. All allogeneic recipients received busulfan and cyclophosphamide as conditioning regimen. Nobody received TBI-based conditioning regimen in this study. Patients were evaluated for cardiovascular, vision, psychological, endocrine, fertility problems and secondary malignancies one year after transplantation. Results : Data were analyzed using SPSS 15.0. Mitral and tricuspid regurgitation (TR/MR) were the most common cardiac complications (n=12, 10.5%).Thirty-nine percent of patients had psychological problems, especially depression (34%). Cataract was observed in 13% of patients and 34% complained of dry eye. Symptomatic pulmonary changes were found in 13 patients (10.6%). None of the HSCT survivors had experienced fertility before study entry. According to LH and FSH levels, 15% and 9% of females had ovarian failure, respectively. Testosterone level was less than normal in 49(84%) men and, according to their FSH and LH level, 20 (41%) had secondary hypogonadism and 29 (59%) had primary gonadal dysfunction. The results showed that patients who received Bu/Cy conditioning regimen experienced fewer late side effects such as cataract formation and hypothyroidism, compared to previous studies using TBI-based conditioning regimen.

Late Complications in acute Leukemia patients following HSCT: A single center experience

PubMed Central

Vaezi, Mohammad; Gharib, Cyrous; Souri, Maryam; Ghavamzadeh, Ardeshir

2016-01-01

Background: Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for acute leukemia. As HSCT improves the long-term survival, it is necessary to assess the late-onset complications affecting the quality of life following HSCT. Subjects and Methods: The study included 122 patients (65 male, 57 female) with leukemia (72 AML and 50 ALL) who received transplants from fully- matched siblings, unrelated donors and unrelated cord blood donors between February 2013 and August 2014 in Shariati Hospital. All study participants were over 18 years of age and had the minimum and maximum survival of 2 and 5 years, respectively. Patients who received HLA-haploidentical SCT were excluded from the study. All allogeneic recipients received busulfan and cyclophosphamide as conditioning regimen. Nobody received TBI-based conditioning regimen in this study. Patients were evaluated for cardiovascular, vision, psychological, endocrine, fertility problems and secondary malignancies one year after transplantation. Results : Data were analyzed using SPSS 15.0. Mitral and tricuspid regurgitation (TR/MR) were the most common cardiac complications (n=12, 10.5%).Thirty-nine percent of patients had psychological problems, especially depression (34%). Cataract was observed in 13% of patients and 34% complained of dry eye. Symptomatic pulmonary changes were found in 13 patients (10.6%). None of the HSCT survivors had experienced fertility before study entry. According to LH and FSH levels, 15% and 9% of females had ovarian failure, respectively. Testosterone level was less than normal in 49(84%) men and, according to their FSH and LH level, 20 (41%) had secondary hypogonadism and 29 (59%) had primary gonadal dysfunction. Conclusion: The results showed that patients who received Bu/Cy conditioning regimen experienced fewer late side effects such as cataract formation and hypothyroidism, compared to previous studies using TBI-based conditioning regimen. PMID:27047644

High-dose ifosfamide in combination with etoposide and epirubicin (IVE) in the treatment of relapsed/refractory Hodgkin's disease and non-Hodgkin's lymphoma: a report on toxicity and efficacy.

PubMed

Proctor, S J; Taylor, P R; Angus, B; Wood, K; Lennard, A L; Lucraft, H; Carey, P J; Stark, A; Iqbal, A; Haynes, A; Russel, N; Leonard, R C; Culligan, D; Conn, J; Jackson, G H

2001-07-01

One hundred and seven patients (61 with diffuse large B-cell non-Hodgkin's lymphomas and 46 with Hodgkin's disease) in relapse or following of primary therapy received ifosfamide 3 g/m2 i.v. daily for 3 days in combination with epirubicin 50 mg/m2 i.v. day 1 and etoposide 200 mg/m2 i.v. days 1-3. Of the 46 patients with Hodgkin's disease (28 male, 18 female, and a median age of 28 years) 85% of patients had a response to treatment, with 17 achieving complete remission and 11 good partial remission. Twenty-eight proceeded to autologous bone marrow or peripheral blood stem cell transplantation. Twenty-three patients remain alive in continuous remission with a follow-up of 12-61 months. The median overall survival time for all patients in this group is 36 months. Haematological toxicity, particularly WHO Grade IV neutropenia, occurred in all patients but improved over the three courses of treatment. There was no major non-haematological toxicity. Further trials of this regimen in this clinical situation are indicated. The patients with non-Hodgkin's lymphomas in this study had diffuse large B-cell lymphomas and had only received first-line treatment. Twenty had primarily refractory disease, 15 had only achieved partial remissions (PR), and 26 had developed relapse following primary treatment. The overall response rate was 43%; it was 60% for those who had achieved initial PR, 58% for those in relapse after an initial CR or very good PR following initial therapy, but only 10% for those with primarily refractory disease. Tolerance to the regimen was similar to that observed in treatment of the patients with Hodgkin's disease and many were able to undergo stem cell collection, following mobilization with this regimen. The 2-year overall survival result was 22% for patients with some response to first-line treatment but 0% for primary refractory patients.

Impact of pre-transplantation minimal residual disease determined by multiparameter flow cytometry on the outcome of AML patients with FLT3-ITD after allogeneic stem cell transplantation.

PubMed

Zhao, Xiaosu; Wang, Zhidong; Ruan, Guorui; Liu, Yanrong; Wang, Yu; Zhang, Xiaohui; Xu, Lanping; Huang, Xiaojun; Chang, Yingjun

2018-06-01

In this study, using multiparameter flow cytometry (FCM), we investigate the impact of minimal residual disease prior to transplantation (pre-MRD) on the transplant outcomes of AML patients with fms-related tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutation. A total of 20 patients who received HLA-matched sibling donor transplantation (MSDT) and 63 patients who received unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT) were enrolled. Patients were classified into four groups based on the status of pre-FCM: group 1 with positive pre-FCM before MSDT, group 2 with negative pre-FCM before MSDT, group 3 with positive pre-FCM before haplo-HSCT, and group 4 with positive pre-FCM before haplo-HSCT. The results showed that patients in group 1 had the highest cumulative incidence of relapse (2-year CIR, 75.0%), the lowest leukemia-free survival (2-year LFS, 33.3%), and the overall survival (2-year OS, 25.0%) among all four groups. The other three groups of patients had comparable CIR (2-year CIR: group 2 vs. 3 vs. 4, 12.5% vs. 31.3% vs. 22.2%, P > 0.05) and LFS (2-year LFS: group 2 vs. 3 vs. 4, 87.5% vs. 62.5% vs. 66.5%, P > 0.05). Multivariate analysis indicated that disease status (> CR) and pre-MRD were associated with a higher CIR and a lower LFS when patients were classified by pre-MRD and transplant type. Our results suggested that AML patients with FLT3-ITD were able to be separated into high-risk and low-risk relapse groups based on pre-MRD, as determined by multiparameter FCM. Haplo-HSCT might overcome the negative impact of pre-MRD on patient outcomes compared to MSDT. These results require further investigation in prospective study with large numbers of cases.

Treatment of advanced gastrointestinal cancer with genetically modified autologous mesenchymal stem cells - TREAT-ME-1 - a phase I, first in human, first in class trial.

PubMed

von Einem, Jobst C; Peter, Sylvia; Günther, Christine; Volk, Hans-Dieter; Grütz, Gerald; Salat, Christoph; Stoetzer, Oliver; Nelson, Peter J; Michl, Marlies; Modest, Dominik P; Holch, Julian W; Angele, Martin; Bruns, Christiane; Niess, Hanno; Heinemann, Volker

2017-10-06

This phase I, first in human, first in class clinical study aimed at evaluating the safety, tolerability and efficacy of treatment with genetically modified mesenchymal stromal cells (MSC) in combination with ganciclovir (GCV). MSC_apceth_101 are genetically modified autologous MSCs used as vehicles for a cell-based gene therapy in patients with advanced gastrointestinal adenocarcinoma. The study design consisted of a dose-escalation 3 + 3 design. All patients ( n = 6) were treated with up to three applications of MSC_apceth_101, followed by GCV infusions given on three consecutive days starting 48 hours after injection of MSC_apceth_101. Three of six patients received a total dose of 1.5 × 10 6 cells/kg. Two patients received three doses of 1 × 10 6 cells/kg, while one patient received only two doses of 1 × 10 6 cells/kg due to a SADR. Six patients received MSC_apceth_101. No IMP-related serious adverse events occurred. Adverse-events related to IMP-injection were increased creatinine, cough, fever, and night sweat. TNF, IL-6, IL-8, IL-10 and sE-Selectin, showed that repeated application is immunologically safe, but induces a switch of the functional properties of monocytes to an inflammatory phenotype. Treatment induced stable disease in 4/6 patients, and progressive disease in 2/6 patients. Treatment with MSC_apceth_101 in combination with GCV demonstrated acceptable safety and tolerability in patients with advanced gastrointestinal adenocarcinoma.

Treatment of advanced gastrointestinal cancer with genetically modified autologous mesenchymal stem cells - TREAT-ME-1 - a phase I, first in human, first in class trial

PubMed Central

von Einem, Jobst C.; Peter, Sylvia; Günther, Christine; Volk, Hans-Dieter; Grütz, Gerald; Salat, Christoph; Stoetzer, Oliver; Nelson, Peter J.; Michl, Marlies; Modest, Dominik P.; Holch, Julian W.; Angele, Martin; Bruns, Christiane

2017-01-01

Purpose This phase I, first in human, first in class clinical study aimed at evaluating the safety, tolerability and efficacy of treatment with genetically modified mesenchymal stromal cells (MSC) in combination with ganciclovir (GCV). MSC_apceth_101 are genetically modified autologous MSCs used as vehicles for a cell-based gene therapy in patients with advanced gastrointestinal adenocarcinoma. Experimental design The study design consisted of a dose-escalation 3 + 3 design. All patients (n = 6) were treated with up to three applications of MSC_apceth_101, followed by GCV infusions given on three consecutive days starting 48 hours after injection of MSC_apceth_101. Three of six patients received a total dose of 1.5 × 106 cells/kg. Two patients received three doses of 1 × 106 cells/kg, while one patient received only two doses of 1 × 106 cells/kg due to a SADR. Results Six patients received MSC_apceth_101. No IMP-related serious adverse events occurred. Adverse-events related to IMP-injection were increased creatinine, cough, fever, and night sweat. TNF, IL-6, IL-8, IL-10 and sE-Selectin, showed that repeated application is immunologically safe, but induces a switch of the functional properties of monocytes to an inflammatory phenotype. Treatment induced stable disease in 4/6 patients, and progressive disease in 2/6 patients. Conclusion Treatment with MSC_apceth_101 in combination with GCV demonstrated acceptable safety and tolerability in patients with advanced gastrointestinal adenocarcinoma. PMID:29113291

Clinical characteristics of 15 children with juvenile myelomonocytic leukaemia who developed blast crisis: MDS Committee of Japanese Society of Paediatric Haematology/Oncology.

PubMed

Honda, Yuko; Tsuchida, Masahiro; Zaike, Yuji; Masunaga, Atsuko; Yoshimi, Ayami; Kojima, Seiji; Ito, Masafumi; Kikuchi, Akira; Nakahata, Tatsutoshi; Manabe, Atsushi

2014-06-01

Juvenile myelomonocytic leukaemia (JMML) is a rare haematopoietic stem cell disease of early childhood, which can progress to blast crisis in some children. A total of 153 children diagnosed with JMML were reported to the Myelodysplastic Syndrome Committee in Japan between 1989 and 2007; 15 of them (9·8%) had 20% or more blasts in the bone marrow (blast crisis) during the disease course. Blast crisis occurred during observation without therapy (n = 3) or with oral 6-mercaptopurine treatment (n = 9) and in relapse after haematopoietic stem cell transplantation (HSCT; n = 3). Six patients had a complex karyotype (5 including monosomy 7) and an additional three patients had isolated monosomy 7 at blast crisis. Seven patients received HSCT after blast crisis and four of them achieved remission. Eleven out of the 15 patients died; the cause of death was disease progression in 10 patients and transplant-related complication in one patient. In summary, patients with blast crisis have poor prognosis and can be cured only by HSCT. The emergence of monosomy 7 and complex karyotype may be characteristic of blast crisis in a substantial subset of children. © 2014 John Wiley & Sons Ltd.

The use of stem cells in regenerative medicine for Parkinson's and Huntington's Diseases.

PubMed

Lescaudron, L; Naveilhan, P; Neveu, I

2012-01-01

Cell transplantation has been proposed as a means of replacing specific cell populations lost through neurodegenerative processes such as that seen in Parkinson's or Huntington's diseases. Improvement of the clinical symptoms has been observed in a number of Parkinson and Huntington's patients transplanted with freshly isolated fetal brain tissue but such restorative approach is greatly hampered by logistic and ethical concerns relative to the use of fetal tissue, in addition to potential side effects that remain to be controlled. In this context, stem cells that are capable of self-renewal and can differentiate into neurons, have received a great deal of interest, as demonstrated by the numerous studies based on the transplantation of neural stem/progenitor cells, embryonic stem cells or mesenchymal stem cells into animal models of Parkinson's or Huntington's diseases. More recently, the induction of pluripotent stem cells from somatic adult cells has raised a new hope for the treatment of neurodegenerative diseases. In the present article, we review the main experimental approaches to assess the efficiency of cell-based therapy for Parkinson's or Huntington's diseases, and discuss the recent advances in using stem cells to replace lost dopaminergic mesencephalic or striatal neurons. Characteristics of the different stem cells are extensively examined with a special attention to their ability of producing neurotrophic or immunosuppressive factors, as these may provide a favourable environment for brain tissue repair and long-term survival of transplanted cells in the central nervous system. Thus, stem cell therapy can be a valuable tool in regenerative medicine.

Ten-Year Outcome of Serum Metal Ion Levels After Primary Total Hip Arthroplasty

PubMed Central

Levine, Brett R.; Hsu, Andrew R.; Skipor, Anastasia K.; Hallab, Nadim J.; Paprosky, Wayne G.; Galante, Jorge O.; Jacobs, Joshua J.

2013-01-01

Abstract: We previously reported on the metal ion concentrations of cobalt, chromium, and titanium that were found in the serum of patients three years after they had undergone primary total hip arthroplasty as compared with the concentrations found in the serum of control patients who did not have an implant. This study is a concise update on the serum metal levels found in a cohort of these patients ten years after the time of hip implantation. Of the original seventy-five subjects, metal ion levels were available for forty patients (53%). Ten patients (hybrid group) had received a hybrid total hip replacement that consisted of a modular cobalt-alloy femoral stem with a cobalt-alloy femoral head that had been inserted with cement and a titanium acetabular socket that had been inserted without cement. Nine patients (cobalt-chromium [CoCr] group) had received an implant with an extensively porous-coated modular cobalt-alloy femoral stem and femoral head along with a titanium acetabular socket; the femoral and acetabular components had each been inserted without cement. Eight patients (titanium group) had undergone insertion of a proximally porous-coated modular titanium-alloy femoral stem with a cobalt-alloy femoral head and a titanium acetabular socket; the femoral and acetabular components had each been inserted without cement. Thirteen patients (control group) from the original control group of patients who had not received an implant served as control subjects. Serum metal levels were measured with use of high-resolution sector field inductively coupled plasma mass spectrometry. The hybrid total hip arthroplasty group had mean cobalt levels that were 3.2 times higher at 120 months than they were at baseline, and the cobalt levels in that group were significantly higher than those in the titanium total hip arthroplasty group at thirty-six, sixty, eighty-four, ninety-six, and 120 months (p < 0.01). The hybrid group had mean chromium levels that were 3.9 times higher at 120 months than they were at baseline, and the CoCr total hip arthroplasty group had chromium levels that were 3.6 times higher at 120 months than they were at baseline. The serum titanium levels were higher in the titanium group at all follow-up time intervals as compared with the levels in all other groups, and the level in the titanium group at 120 months was eighteen times higher than it was at baseline (p < 0.01). Patients with well-functioning primary metal-on-polyethylene total hip replacements had elevated serum metal levels for as many as ten years postoperatively. Furthermore, metal release at the modular femoral head-neck junctions, rather than passive dissolution from porous ingrowth surfaces, was likely the dominant source of serum cobalt and chromium. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID:23515985

Systemic irradiation for selected stage IV and recurrent pediatric solid tumors: method, toxicity, and preliminary results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wharam, M.D.; Kaizer, H.; Leventhal, B.G.

1980-02-01

Eight patients with advanced pediatric solid tumors received either sequential upper and lower half-body irradiation (HBI) (7.5 rad/min to 500 rad total) or total body irradiation (TBI) (7.5 rad/min to 800 rad total) as part of two multimodality treatment regimens. All patients received combination chemotherapy; drugs were determined by the tumor type. The TBI regimen was selected for two patients who had progression of disease with conventional chemotherapy and for two patients with stage IV neuroblastoma. This intensive regimen consisted of bone marrow harvesting, followed by local radiation to gross disease, marrow-ablative chemotherapy, TBI, and re-infusion of the cryopreserved autologousmore » marrow. Significant acute toxicity was followed by hematologic reconstitution in each patient within seven weeks. At this writing, two patients survived, one of whom is disease free two and one half years without maintenance chemotherapy. A less intensive, outpatient regimen was selected for four patients; three had a complete or good partial response to chemotherapy. The fourth patient had tumor-involved bone marrow not responsive to chemotherapy and was therefore ineligible for marrow cryopreservation and TBI. Each of these four patients received HBI after chemotherapy and local radiation to the primary and/or metastatic sites. Acute toxicity was limited to nausea and vomiting. Significant leukopenia and thrombocytopenia occurred in three patients. All four patients were alive 10 to 26 months post HBI. This pilot study demonstrates that chemotherapy can be integrated with local fractionated radiation, and systemic radiation given as HBI or TBI with acceptable toxicity; sufficient bone marrow stem cells can be harvested after conventional chemotherapy and then cryopreserved to permit hematologic reconstitution of the patient who receives marrow ablative therapy.« less

A TAD better for myeloma therapy?

PubMed

Giralt, Sergio

2010-02-11

In this issue of Blood, Lokhorst and colleagues report on the results of HOVON-50, a phase 3 randomized trial designed to evaluate the effects of thalidomide during induction treatment and as maintenance in patients with multiple myeloma. There were 556 patients randomly assigned either to 3 cycles of VAD or to TAD. All patients were to receive high-dose melphalan with autologous stem cell support followed by maintenance with interferon for the VAD arm or thalidomide for the TAD arm.(1) This study together with other randomized and nonrandomized trials establish a definitive role for thalidomide as induction therapy in conjunction with dexamethasone, anthracyclines, and alkylating agents.

Feasibility, toxicity and response of upfront metaiodobenzylguanidine therapy therapy followed by German Pediatric Oncology Group Neuroblastoma 2004 protocol in newly diagnosed stage 4 neuroblastoma patients.

PubMed

Kraal, K C J M; Bleeker, G M; van Eck-Smit, B L F; van Eijkelenburg, N K A; Berthold, F; van Noesel, M M; Caron, H N; Tytgat, G A M

2017-05-01

Radiolabelled meta-iodobenzylguanidine (MIBG) is an effective option in treatment of neuroblastoma (NBL) tumours. We studied feasibility, toxicity and efficacy of upfront 131 I-MIBG and induction treatment in stage 4 NBL patients. Retrospective, multi-centre (AMC and EMC) pilot regimen (1/1/2005-2011). Newly diagnosed stage 4 NBL patients, were treated with 2 courses of 131 I-MIBG, GPOH 2004 NBL protocol, myeloablative therapy (MAT) and autologous stem cell rescue (ASCT). 131 I-MIBG was administered in a fixed dose. Response rate (RR) was defined as complete remission, very good partial response and partial response. Thirty-two patients, (median age [range] 2.9 [0-11.4] years), 21 received 131 I-MIBG therapy, 11 did not because of: MIBG non-avid (N = 5) and poor clinical condition (N = 6). In 95% of eligible patients 131 I-MIBG treatment was feasible within 2 weeks from diagnosis. Interval between chemotherapy courses was 25 days ( 131 I-MIBG group) versus 22 days (chemotherapy group). No stem cell support was needed after 131 I-MIBG therapy. Stem cell harvest in both groups was feasible, neutrophil recovery was comparable, but platelet recovery post MAT, ASCT was slower for 131 I-MIBG-treated patients. RR post 131 I-MIBG was 38%, post MAT + ASCT was 71% ( 131 I-MIBG group), 36% (chemotherapy group) and overall 59%. Induction therapy with 131 I-MIBG before the HR GPOH NB 2004 protocol is feasible, tolerable and effective in newly diagnosed stage 4 NBL patients. 131 I-MIBG upfront therapy induces early responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Peripheral blood stem cell mobilization and engraftment after autologous stem cell transplantation with biosimilar rhG-CSF.

PubMed

Reményi, Péter; Gopcsa, László; Marton, Imelda; Réti, Marienn; Mikala, Gábor; Pető, Mónika; Barta, Anikó; Bátai, Arpád; Farkas, Zita; Borbényi, Zita; Csukly, Zoltán; Bodó, Imre; Fábián, János; Király, Agnes; Lengyel, Lilla; Piukovics, Klára; Torbágyi, Eva; Masszi, Tamás

2014-04-01

Biosimilar versions of filgrastim [recombinant human granulocyte colony-stimulating factor (rhG-CSF)] are now widely available. To date, biosimilar rhG-CSF has demonstrated a comparable quality, safety and efficacy profile to the originator product (filgrastim [Neupogen(®)], Amgen Inc., CA, USA) in the prevention and management of neutropenia. Biosimilar rhG-CSFs have also been used to induce peripheral blood stem cell (PBSC) mobilization in patients undergoing autologous stem cell transplantation (AHSCT). The authors have examined the effectiveness of a biosimilar rhG-CSF (Zarzio(®), Sandoz Biopharmaceuticals, Holzkirchen, Germany) in two retrospective studies across two medical centers in Hungary. In Study 1, 70 patients with hematological malignancies scheduled to undergo AHSCT received chemotherapy followed by biosimilar rhG-CSF (2 × 5 μg) for facilitating neutrophil, leukocyte, and platelet engraftment. In study 2, 40 additional patients with lymphoid malignancies and planned AHSCT received chemotherapy followed by biosimilar rhG-CSF for PBSC mobilization. The effectiveness of treatment was assessed by the average yield of cluster of differentiation (CD) 34+ cells and the number of leukaphereses required. In Study 1 (patients undergoing AHSCT), the median age was 56 years and most patients were male (60%). The conditioning regimens were mainly high-dose melphalan (n = 41) and carmustine (BiCNU(®), Bristol-Myers Squibb, NJ, USA), etoposide, cytarabine and melphalan BEAM (n = 21). Median times to absolute neutrophil and leukocyte engraftment were 9 (range 8-11 days) and 10 (8-12) days, respectively. Median time to platelet engraftment was 10.5 days (7-19 days). In Study 2, the patients' median age was 54 years and the majority (57.5%) were female. The median time interval between day 1 of mobilizing chemotherapy and first leukapheresis was 12 (9-27) days. In the autologous PBSC grafts, the median number of CD34+ cells harvested was 5.2 × 10(6)/kg (2.22-57.07 × 10(6)/kg). The median yield of CD34+ cells per leukapheresis product was 2.47 × 10(6)/kg. In total, 58 leukaphereses were performed in 40 successfully harvested patients. In line with previous studies with originator rhG-CSF, the findings of this study indicate that biosimilar rhG-CSF following AHSCT is effective and generally well tolerated in the engraftment setting. In addition, biosimilar rhG-CSF is comparable to the originator rhG-CSF in terms of kinetics of PBSC mobilization and yield of CD34+ cells. In conclusion, the authors have demonstrated that the use of biosimilar rhG-CSF is effective and safe in autologous PBSC mobilization and engraftment after AHSCT.

Nature and incidence of severe limbal stem cell deficiency in Australia and New Zealand.

PubMed

Bobba, Samantha; Di Girolamo, Nick; Mills, Richard; Daniell, Mark; Chan, Elsie; Harkin, Damien G; Cronin, Brendan G; Crawford, Geoffrey; McGhee, Charles; Watson, Stephanie

2017-03-01

This study aimed to determine the nature and incidence of severe limbal stem cell deficiency (LSCD) in Australia and New Zealand. A 1-year pilot surveillance study with a 1-year follow-up period was conducted in association with the Australian and New Zealand Ophthalmic Surveillance Unit. The study included patients reported by practising ophthalmologists on the Surveillance Unit's database. Ophthalmologists were provided with a definition of severe limbal stem cell deficiency, contacted on a monthly basis by the Unit and asked to report newly diagnosed cases. Severe LSCD was defined as at least 6 clock hours of whorl-like epitheliopathy, an opaque epithelium arising from the limbus, late fluorescein staining of the involved epithelium and superficial corneal neovascularization or conjunctivalization. On average, 286 report cards were sent by the Surveillance Unit to practising ophthalmologists each month (total 3429 over 12 months) and the Unit received an average of 176 responses per month (total 2111; 62% response rate). During the 1-year study period from April 2013 to March 2014, 14 positive cases were reported to the Unit. A range of underlying aetiologies were implicated, with contact lens over-wear and cicatrizing conjunctivitis being the most common (n = 3). This surveillance study is the first worldwide to document the incidence of limbal stem cell deficiency; however, because of study design limitations, it is likely to have been under-reported. It provides novel data on the demographics, clinical conditions and management of patients with limbal stem cell deficiency as reported by treating ophthalmologists. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

Differential epitope mapping of antibodies to PDC-E2 in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation and primary biliary cirrhosis.

PubMed

Bellucci, Roberto; Oertelt, Sabine; Gallagher, Meagan; Li, Sigui; Zorn, Emmanuel; Weller, Edie; Porcheray, Fabrice; Alyea, Edwin P; Soiffer, Robert J; Munshi, Nikhil C; Gershwin, M Eric; Ritz, Jerome

2007-03-01

A unique characteristic of the autoimmune liver disease primary biliary cirrhosis (PBC) is the presence of high-titer and extremely specific autoantibodies to the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Autoantibodies to PDC-E2 antigen have only been detected in patients with disease or in those who subsequently develop PBC. One exception has been a subgroup of patients with multiple myeloma (MM) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) and received donor lymphocyte infusions (DLIs) after transplantation. These patients developed high-titer antibodies to a variety of myeloma-associated antigens, including PDC-E2, coincident with rejection of myeloma cells in vivo. To examine the specificity of autoantibodies to PDC in these patients, we screened sera from patients with MM, chronic leukemias, monoclonal gammopathy of unknown significance (MGUS), PBC, and healthy donors. Three of 11 patients with MM (27%) and 2 of 6 patients with chronic leukemias (33%) developed anti-PDC-E2 antibodies in association with DLI response; 2 of 12 (17%) patients in the MGUS pretreatment control population also had detectable anti-PDC responses. Interestingly, the epitope specificity of these PDC-E2 autoantibodies was distinctive, suggesting that the mechanisms leading to loss of tolerance in the transplantation patients are distinct from PBC.

Clinical features and outcomes in patients with disseminated toxoplasmosis admitted to intensive care: a multicenter study.

PubMed

Schmidt, Matthieu; Sonneville, Romain; Schnell, David; Bigé, Naike; Hamidfar, Rebecca; Mongardon, Nicolas; Castelain, Vincent; Razazi, Keyvan; Marty, Antoine; Vincent, François; Dres, Martin; Gaudry, Stephane; Luyt, Charles Edouard; Das, Vincent; Micol, Jean-Baptiste; Demoule, Alexandre; Mayaux, Julien

2013-12-01

Characteristics and outcomes of adult patients with disseminated toxoplasmosis admitted to the intensive care unit (ICU) have rarely been described. We performed a retrospective study on consecutive adult patients with disseminated toxoplasmosis who were admitted from January 2002 through December 2012 to the ICUs of 14 university-affiliated hospitals in France. Disseminated toxoplasmosis was defined as microbiological or histological evidence of disease affecting >1 organ in immunosuppressed patients. Isolated cases of cerebral toxoplasmosis were excluded. Clinical data on admission and risk factors for 60-day mortality were collected. Thirty-eight patients were identified during the study period. Twenty-two (58%) had received an allogeneic hematopoietic stem cell transplant (median, 61 [interquartile range {IQR}, 43-175] days before ICU admission), 4 (10%) were solid organ transplant recipients, and 10 (27%) were infected with human immunodeficiency virus (median CD4 cell count, 14 [IQR, 6-33] cells/µL). The main indications for ICU admission were acute respiratory failure (89%) and shock (53%). The 60-day mortality rate was 82%. Allogeneic hematopoietic stem cell transplant (hazard ratio [HR] = 2.28; 95% confidence interval [CI], 1.05-5.35; P = .04) and systolic cardiac dysfunction (HR = 3.54; 95% CI, 1.60-8.10; P < .01) within 48 hours of ICU admission were associated with mortality. Severe disseminated toxoplasmosis leading to ICU admission has a poor prognosis. Recipients of allogeneic hematopoietic stem cell transplant appear to have the highest risk of mortality. We identified systolic cardiac dysfunction as a major determinant of outcome. Strategies aimed at preventing this fatal opportunistic infection may improve outcomes.

Improved survival with ursodeoxycholic acid prophylaxis in allogeneic stem cell transplantation: long-term follow-up of a randomized study.

PubMed

Ruutu, Tapani; Juvonen, Eeva; Remberger, Mats; Remes, Kari; Volin, Liisa; Mattsson, Jonas; Nihtinen, Anne; Hägglund, Hans; Ringdén, Olle

2014-01-01

We report the long-term results of a prospective randomized study on the use of ursodeoxycholic acid (UDCA) for prevention of hepatic complications after allogeneic stem cell transplantation. Two hundred forty-two patients, 232 with malignant disease, were randomized to receive (n = 123) or not to receive (n = 119) UDCA from the beginning of the conditioning until 90 days post-transplantation. The results were reported after 1-year follow-up. UDCA administration reduced significantly the proportion of patients developing high serum bilirubin levels as well as the incidence of severe acute graft-versus-host disease (GVHD), liver GVHD, and intestinal GVHD. In the UDCA prophylaxis group, nonrelapse mortality (NRM) was lower and overall survival better than in the control group. After a 10-year follow-up, the difference in the survival and NRM in favor of the UDCA-treated group, seen at 1 year, was maintained (survival 48% versus 38%, P = .037; NRM 28% versus 41%, P = .01). A landmark analysis in patients surviving at 1 year post-transplantation showed no significant differences between the study groups in the long-term follow-up in chronic GVHD, relapse rate, NRM, disease-free survival, or overall survival. These long-term results continue to support the useful role of UDCA in the prevention of transplant-related complications in allogeneic transplantation. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial.

PubMed

Choi, Sung Won; Braun, Thomas; Chang, Lawrence; Ferrara, James L M; Pawarode, Attaphol; Magenau, John M; Hou, Guoqing; Beumer, Jan H; Levine, John E; Goldstein, Steve; Couriel, Daniel R; Stockerl-Goldstein, Keith; Krijanovski, Oleg I; Kitko, Carrie; Yanik, Gregory A; Lehmann, Michael H; Tawara, Isao; Sun, Yaping; Paczesny, Sophie; Mapara, Markus Y; Dinarello, Charles A; DiPersio, John F; Reddy, Pavan

2014-01-01

Acute graft-versus-host disease (GVHD) remains a barrier to more widespread application of allogeneic haemopoietic stem-cell transplantation. Vorinostat is an inhibitor of histone deacetylases and was shown to attenuate GVHD in preclinical models. We aimed to study the safety and activity of vorinostat, in combination with standard immunoprophylaxis, for prevention of GVHD in patients undergoing related-donor reduced-intensity conditioning haemopoietic stem-cell transplantation. Between March 31, 2009, and Feb 8, 2013, we did a prospective, single-arm, phase 1/2 study at two centres in the USA. We recruited adults (aged ≥18 years) with high-risk haematological malignant diseases who were candidates for reduced-intensity conditioning haemopoietic stem-cell transplantation and had an available 8/8 or 7/8 HLA-matched related donor. All patients received a conditioning regimen of fludarabine (40 mg/m(2) daily for 4 days) and busulfan (3.2 mg/kg daily for 2 days) and GVHD immunoprophylaxis of mycophenolate mofetil (1 g three times a day, days 0-28) and tacrolimus (0.03 mg/kg a day, titrated to a goal level of 8-12 ng/mL, starting day -3 until day 180). Vorinostat (either 100 mg or 200 mg, twice a day) was initiated 10 days before haemopoietic stem-cell transplantation until day 100. The primary endpoint was the cumulative incidence of grade 2-4 acute GVHD by day 100. This trial is registered with ClinicalTrials.gov, number NCT00810602. 50 patients were assessable for both toxic effects and response; eight additional patients were included in the analysis of toxic effects. All patients engrafted neutrophils and platelets at expected times after haemopoietic stem-cell transplantation. The cumulative incidence of grade 2-4 acute GVHD by day 100 was 22% (95% CI 13-36). The most common non-haematological adverse events included electrolyte disturbances (n=15), hyperglycaemia (11), infections (six), mucositis (four), and increased activity of liver enzymes (three). Non-symptomatic thrombocytopenia after engraftment was the most common haematological grade 3-4 adverse event (nine) but was transient and all cases resolved swiftly. Administration of vorinostat in combination with standard GVHD prophylaxis after related-donor reduced-intensity conditioning haemopoietic stem-cell transplantation is safe and is associated with a lower than expected incidence of severe acute GVHD. Future studies are needed to assess the effect of vorinostat for prevention of GVHD in broader settings of haemopoietic stem-cell transplantation. Merck, Leukemia and Lymphoma Society, National Institutes of Health, St Baldrick's Foundation, Michigan Institute for Clinical and Health Research. Copyright © 2014 Elsevier Ltd. All rights reserved.

[The cord blood bank at the Instituto Mexicano del Seguro Social].

PubMed

Peñaflor-Juárez, Karina; Guillén-Chan, Sonia Marilyn; Romero-Juárez, Yanín; Luna-Bautista, Fernando; Franco-Gutiérrez, Elizabeth; Arellano-Ocampo, Jesús Salvador; Ibáñez-Sánchez, Rocío; de Lourdes Domínguez-Contreras, María; Guerra-Márquez, Angel

2015-01-01

Hematopoietic stem cells have been used for over 50 years in the treatment of diverse diseases. Umbilical cord blood (UCB) has proved to be a viable source of hematopoietic stem cells for transplantation purposes. The aim was to report the contribution of the umbilical cord blood bank over the past 9 years, in the treatment of various diseases. Since 2005 the number of units of blood from the umbilical cord and their use for transplantation in diverse disease were analyzed. A selection of volunteer pregnant women in labor was performed. Umbilical cord blood was obtained from them, which underwent processing, cryopreservation and validation, as well as compatibility test before using for transplantation. Ten thousand and ninety nine candidates to donation were assessed, from whom 2481 unit of UCB were collected. Of these, 893 unit were processed and cryopreserved for transplantation. In 65% of cases there was histocompatibility between the cord cell and the receptors. Transplantation was done in 87 patients, 67% had hematologic neoplasias, who have received 140 units of UCB in 102 transplants. This Bank of UCB ranks second in the world in productivity according to the rate of utility of units in transplantation (3.3%). Our bank of UCB has been able to develop a cell line (hematopoietic stem cells) with international quality standards and has been beneficial for patients served by our institution with need of a transplant mainly in hemato-oncologic patients.

Dental assessment prior to stem cell transplant: treatment need and barriers to care.

PubMed

Durey, K; Patterson, H; Gordon, K

2009-05-09

To assess the treatment needs of patients undergoing pre-haematopoietic stem cell transplant (HSCT) dental assessment, to collate the examination findings and treatment provided and to define the management issues impacting on care. Single centre retrospective analysis. Salaried Primary Care Dental Service, Western General Hospital, Edinburgh, UK. One hundred and sixteen available charts of patients who attended for pre-transplant dental assessment during April 2004-June 2007 were examined. Ninety-four patients, 52 men (55.3%) and 42 women (43.6%), were included. Patients were referred a mean of 31.5 (SD 18.82) days before admission for transplant. Dental assessment occurred, on average, 7.88 days (SD 6.78) following referral. Eighty-eight (93.6%) patients were dentate, while six (6.3%) were edentulous. Eighty-eight (93.6%) patients presented with oral disease; 89 (94.7%) patients received dental care. Issues impacting on care were medical (n = 88, 93.6%), time constraints (n = 73, 77.7%), no GDP (n = 25, 26.7%), dental complexity (n = 5, 5.3%) and anxiety management (n = 1, 1.1%). The majority of patients required dental care, most of which, for healthy adults, would normally be completed within a primary care setting. However, the issues surrounding the care of patients destined for HSCT indicate that there is a place for a dedicated dental service as part of the multidisciplinary team.

The prognostic role of CD68 and FoxP3 expression in patients with primary central nervous system lymphoma.

PubMed

Cho, Hyunsoo; Kim, Se Hoon; Kim, Soo-Jeong; Chang, Jong Hee; Yang, Woo Ick; Suh, Chang-Ok; Cheong, June-Won; Kim, Yu Ri; Lee, Jung Yeon; Jang, Ji Eun; Kim, Yundeok; Min, Yoo Hong; Kim, Jin Seok

2017-07-01

The prognostic role of CD68 and FoxP3 in primary central nervous system lymphoma (PCNSL) has not been evaluated. Thus, we examined the prognostic significance of CD68 and FoxP3 expression in tumor samples of 76 newly diagnosed immunocompetent PCNSL patients. All patients were treated initially with high-dose methotrexate (HD-MTX)-based chemotherapy, and 16 (21.1%) patients received upfront autologous stem cell transplantation (ASCT) consolidation. High expression of CD68 (>55 cells/high-power field) or FoxP3 (>15 cells/high-power field) was observed in 10 patients, respectively. High CD68 expression was associated with inferior overall survival (OS) and progression-free survival (PFS) in multivariate analysis (P = 0.023 and P = 0.021, respectively). In addition, we performed subgroup analysis based on upfront ASCT. High CD68 expression was also associated with inferior OS and PFS in multivariate analysis (P = 0.013 and P < 0.001, respectively) among patients who did not receive upfront ASCT (n = 60), but not in patients who received upfront ASCT. The expression of FoxP3 was not significantly associated with survival. Therefore, we identified a prognostic significance of high CD68 expression in PCNSL, which suggests a need for further clinical trials and biological studies on the role of PCNSL tumor microenvironment.

Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study.

PubMed

Chiappella, Annalisa; Martelli, Maurizio; Angelucci, Emanuele; Brusamolino, Ercole; Evangelista, Andrea; Carella, Angelo Michele; Stelitano, Caterina; Rossi, Giuseppe; Balzarotti, Monica; Merli, Francesco; Gaidano, Gianluca; Pavone, Vincenzo; Rigacci, Luigi; Zaja, Francesco; D'Arco, Alfonso; Cascavilla, Nicola; Russo, Eleonora; Castellino, Alessia; Gotti, Manuel; Congiu, Angela Giovanna; Cabras, Maria Giuseppina; Tucci, Alessandra; Agostinelli, Claudio; Ciccone, Giovannino; Pileri, Stefano A; Vitolo, Umberto

2017-08-01

The prognosis of young patients with diffuse large B-cell lymphoma at high risk (age-adjusted International Prognostic Index [aa-IPI] score 2 or 3) treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) is poor. The aim of this study was to investigate the possible benefit of intensification with high-dose chemotherapy and autologous stem-cell transplantation as part of first-line treatment in these patients. We did a multicentre, open-label, randomised, controlled, phase 3 trial with a 2 × 2 factorial design to compare, at two different R-CHOP dose levels, a full course of rituximab-dose-dense chemotherapy (no transplantation group) versus an abbreviated course of rituximab-dose-dense chemotherapy followed by consolidation with R-MAD (rituximab plus high-dose cytarabine plus mitoxantrone plus dexamethasone) and high-dose BEAM chemotherapy (carmustine, etoposide, cytarabine, and melphalan) plus autologous stem-cell transplantation (transplantation group) in young patients (18-65 years) with untreated high-risk diffuse large B-cell lymphoma (aa-IPI score 2-3). At enrolment, patients were stratified according to aa-IPI score and randomly assigned (1:1:1:1) to receive R-CHOP (intravenous rituximab 375 mg/m 2 , cyclophosphamide 750 mg/m 2 , doxorubicin 50 mg/m 2 , and vincristine 1·4 mg/m 2 on day 1, plus oral prednisone 100 mg on days 1-5) delivered in a 14-day cycle (R-CHOP-14) for eight cycles; high-dose R-CHOP-14 (R-MegaCHOP-14; R-CHOP-14 except for cyclophosphamide 1200 mg/m 2 and doxorubicin 70 mg/m 2 ) for six cycles; R-CHOP-14 for four cycles followed by R-MAD (intravenous rituximab 375 mg/m 2 on day 1 or 4 plus intravenous cytarabine 2000 mg/m 2 and dexamethasone 4 mg/m 2 every 12 h on days 1-3 plus intravenous mitoxantrone 8 mg/m 2 on days 1-3) plus BEAM (intravenous carmustine 300 mg/m 2 on day -7, intravenous cytarabine 200 mg/m 2 twice a day on days -6 to -3, intravenous etoposide 100 mg/m 2 twice a day on days -6 to -3, plus intravenous melphalan 140 mg/m 2 on day -2) and autologous stem-cell transplantation (day 0); or R-MegaCHOP-14 for four cycles followed by R-MAD plus BEAM and autologous stem-cell transplantation. The primary endpoint was failure-free survival at 2 years in the intention-to-treat population. This study is registered with EudraCT (2005-002181-14; 2007-000275-42) and with ClinicalTrials.gov, number NCT00499018. Between Jan 10, 2006, and Sept 8, 2010, 399 patients were randomly assigned to receive transplantation (n=199) or no transplantation (n=200); 203 patients were assigned to receive R-CHOP-14 and 196 were assigned to receive R-MegaCHOP-14. With a median follow-up of 72 months (IQR 57-88), 2-year failure-free survival was 71% (95% CI 64-77) in the transplantation group versus 62% (95% CI 55-68) in the no transplantation group (hazard ratio [HR] 0·65 [95% CI 0·47-0·91]; stratified log-rank test p=0·012). No difference in 5-year overall survival was observed between these groups (78% [95% CI 71-83] versus 77% [71-83]; HR 0·98 [0·65-1·48]; stratified log-rank test p=0·91). Grade 3 or worse haematological adverse events were reported in 183 (92%) of 199 patients in the transplantation group versus 135 (68%) of 200 patients in the no transplantation group. Grade 3 or worse non-haematological adverse events were reported in 90 (45%) versus 31 (16%); the most common grade 3 or worse non-haematological adverse event was gastrointestinal (49 [25%] vs 19 [10%]). Treatment-related deaths occurred in 13 (3%) patients; eight in the transplantation group and five in the no transplantation group. Abbreviated rituximab-dose-dense chemotherapy plus R-MAD plus BEAM and autologous stem-cell transplantation reduced the risk of treatment failure compared with full course rituximab-dose-dense chemotherapy in young patients with diffuse large B-cell lymphoma at high risk. However, these results might not be clinically meaningful, since this improvement did not reflect an improvement in overall survival. These results do not support further consideration of the use of intensification of R-CHOP as an upfront strategy in patients with diffuse large B-cell lymphoma with poor prognosis. Fondazione Italiana Linfomi. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relationship of BK polyoma virus (BKV) in the urine with hemorrhagic cystitis and renal function in recipients of T-cell depleted peripheral blood and cord blood stem cell transplants

PubMed Central

Lee, Yeon Joo; Zheng, Junting; Kolitsopoulos, Yovanna; Chung, Dick; Amigues, Isabelle; Son, Tammy; Choo, Kathleen; Hester, Jeff; Giralt, Sergio A.; Glezerman, Ilya G.; Jakubowski, Ann A.; Papanicolaou, Genovefa A.

2014-01-01

Hematopoietic stem cell transplant (HSCT) recipients are at significant risk for BKV reactivation, hemorrhagic cystitis (HC) and renal dysfunction. We prospectively monitored 98 HSCT by serial BKV PCR in the urine through Day (D) +100 to analyze the relationship between BKV viruria and HC, serum creatinine (Cr) and creatinine clearance (CrCl) through D +180 or death. Patients, median age 52 years, range 20-73, received T-cell depleted (50%) or cord blood allografts (21%). Median pre-HSCT BKV IgG titers were 1:10,240. Incremental increase in BKV IgG titers correlated with developing BKV viruria ≥ 107 copies/mL. By D +100, 53 (54%) patients had BKV viruria. BKV viral load in the urine increased at engraftment and persisted throughout D +100. HC developed in 10 patients (10%); 7/10 with BKV viruria. In competing risk analyses, BKV viruria ≥ 107 copies/mL, older age, CMV reactivation and foscarnet use were risk factors for HC. Cr and CrCl at 2, 3 and 6 months post-HSCT were similar between patients with and without BKV viruria. PMID:24769326

Association between BMI-1 expression, acute graft-versus-host disease, and outcome following allogeneic stem cell transplantation from HLA-identical siblings in chronic myeloid leukemia.

PubMed

Mohty, Mohamad; Szydlo, Richard M; Yong, Agnes S M; Apperley, Jane F; Goldman, John M; Melo, Junia V

2008-09-01

Expression of CD7, ELA-2, PR-3, and the polycomb group gene BMI-1 reflects the intrinsic heterogeneity and predicts prognosis of patients with chronic myeloid leukemia (CML) who were not treated with allogeneic stem cell transplantation (allo-SCT). This study investigated whether expression of these genes determined outcome following allo-SCT in a cohort of 84 patients with chronic-phase (CP) CML. We found that patients expressing BMI-1 at a "high" level before allo-SCT had an improved overall survival (P = .005) related to a reduced transplantation-related mortality. In multivariate analysis, when adjusted for the European Group for Blood and Marrow Transplantation (EBMT)-Gratwohl score and other prog-nostic factors, there was an independent association between BMI-1 expression and grades 2 to 4 acute graft-versus-host disease (relative risk [RR] = 2.85; 95% confidence interval [CI], 1.3-6.4; P = .011), suggesting that BMI-1 measured prior to allo-SCT can serve as a biomarker for predicting outcome in patients with CP-CML receiving allo-SCT, and may thus contribute to better therapeutic decisions.

Pegademase bovine (PEG-ADA) for the treatment of infants and children with severe combined immunodeficiency (SCID).

PubMed

Booth, Claire; Gaspar, H Bobby

2009-01-01

Adenosine deaminase deficiency (ADA) is a rare, inherited disorder of purine metabolism characterized by immunodeficiency, failure to thrive and metabolic abnormalities. A lack of the enzyme ADA allows accumulation of toxic metabolites causing defects of both cell mediated and humoral immunity leading to ADA severe combined immune deficiency (SCID), a condition that can be fatal in early infancy if left untreated. Hematopoietic stem cell transplant is curative but is dependent on a good donor match. Other therapeutic options include enzyme replacement therapy (ERT) with pegademase bovine (PEG-ADA) and more recently gene therapy. PEG-ADA has been used in over 150 patients worldwide and has allowed stabilization of patients awaiting more definitive treatment with hematopoietic stem cell transplant. It affords both metabolic detoxification and protective immune function with patients remaining clinically well, but immune reconstitution is often suboptimal and may not be long lived. We discuss the pharmacokinetics, immune reconstitution, effects on systemic disease and side effects of treatment with PEG-ADA. We also review the long-term outcome of patients receiving ERT and discuss the role of PEG-ADA in the management of infants and children with ADA-SCID, alongside other therapeutic options.

The implication of follicular lymphoma patients receiving allogeneic stem cell transplantation from donors carrying t(14;18)-positive cells.

PubMed

McGregor, D K; Keever-Taylor, C A; Bredeson, C; Schur, B; Vesole, D H; Logan, B; Chang, C-C

2005-06-01

We performed real-time quantitative polymerase chain reaction (RQ-PCR) in peripheral blood (PB) and/or bone marrow (BM) samples collected pre- and post transplant from 23 recipient-donor pairs receiving allogeneic stem cell transplantation (allo-SCT) for follicular lymphoma (FL). Of 23 donors, 11 had a PB and/or BM sample positive for t(14;18) (BCL2/IGH fusion) at low levels (

TOOTH (The Open study Of dental pulp stem cell Therapy in Humans): Study protocol for evaluating safety and feasibility of autologous human adult dental pulp stem cell therapy in patients with chronic disability after stroke.

PubMed

Nagpal, Anjali; Kremer, Karlea L; Hamilton-Bruce, Monica A; Kaidonis, Xenia; Milton, Austin G; Levi, Christopher; Shi, Songtao; Carey, Leeanne; Hillier, Susan; Rose, Miranda; Zacest, Andrew; Takhar, Parabjit; Koblar, Simon A

2016-07-01

Stroke represents a significant global disease burden. As of 2015, there is no chemical or biological therapy proven to actively enhance neurological recovery during the chronic phase post-stroke. Globally, cell-based therapy in stroke is at the stage of clinical translation and may improve neurological function through various mechanisms such as neural replacement, neuroprotection, angiogenesis, immuno-modulation, and neuroplasticity. Preclinical evidence in a rodent model of middle cerebral artery ischemic stroke as reported in four independent studies indicates improvement in neurobehavioral function with adult human dental pulp stem cell therapy. Human adult dental pulp stem cells present an exciting potential therapeutic option for improving post-stroke disability. TOOTH (The Open study Of dental pulp stem cell Therapy in Humans) will investigate the use of autologous stem cell therapy for stroke survivors with chronic disability, with the following objectives: (a) determine the maximum tolerable dose of autologous dental pulp stem cell therapy; (b) define that dental pulp stem cell therapy at the maximum tolerable dose is safe and feasible in chronic stroke; and (c) estimate the parameters of efficacy required to design a future Phase 2/3 clinical trial. TOOTH is a Phase 1, open-label, single-blinded clinical trial with a pragmatic design that comprises three stages: Stage 1 will involve the selection of 27 participants with middle cerebral artery ischemic stroke and the commencement of autologous dental pulp stem cell isolation, growth, and testing in sequential cohorts (n = 3). Stage 2 will involve the transplantation of dental pulp stem cell in each cohort of participants with an ascending dose and subsequent observation for a 6-month period for any dental pulp stem cell-related adverse events. Stage 3 will investigate the neurosurgical intervention of the maximum tolerable dose of autologous dental pulp stem cell followed by 9 weeks of intensive task-specific rehabilitation. Advanced magnetic resonance and positron emission tomography neuro-imaging, and clinical assessment will be employed to probe any change afforded by stem cell therapy in combination with rehabilitation. Nine participants will step-wise progress in Stage 2 to a dose of up to 10 million dental pulp stem cell, employing a cumulative 3 + 3 statistical design with low starting stem cell dose and subsequent dose escalation, assuming that an acceptable probability of dose-limiting complications is between 1 in 6 (17%) and 1 in 3 (33%) of patients. In Stage 3, another 18 participants will receive an intracranial injection with the maximum tolerable dose of dental pulp stem cell. The primary outcomes to be measured are safety and feasibility of intracranial administration of autologous human adult DPSC in patients with chronic stroke and determination of the maximum tolerable dose in human subjects. Secondary outcomes include estimation of the measures of effectiveness required to design a future Phase 2/3 clinical trial. © 2016 World Stroke Organization.

Biomechanical comparisons between a new avascular necrosis of femaral head stem based on Chinese patients with avascular necrosis and two other designs.

PubMed

Zhang, Qiang; Cheng, Cheng-Kung; Wei, Hung-Wen; Dong, Xiang; Chen, Yi-Ting; Lai, Yu-Shu; Wang, Yan

2013-01-01

There is a relatively high failure rate of the femoral component in patients with avascular necrosis at the intermediate-term follow-up. Improving the geometrical fit of the femoral stem against the medullary canal may help to provide long-term survivorship of the hip replacement for patients with avascular necrosis. We designed a specific stem, based on morphometric studies of proximal femoral canals in Chinese avascular necrosis patients and evaluated the stem by finite element analyses, comparing the novel stem with two commercially available and commonly used stems. The morphometric data from avascular necrosis patients showed specific geometric differences in the proximal femoral canal, including profile curves in both the sagittal and coronary planes than the patients with femoral neck fracture. The shorter stemmed prostheses (Fitmore(®) and our stem) performed better than the longer stemmed prosthesis (VerSys(®)). This is the first study to investigate the femoral geometries of Chinese avascular necrosis patients. Our stem provides better stability and is theoretically beneficial to bone ingrowth, which may increase the long-term stability and fixation of the implant.

Prevalence of sarcopenia and relevance of body composition, physiological function, fatigue, and health-related quality of life in patients before allogeneic hematopoietic stem cell transplantation.

PubMed

Morishita, Shinichiro; Kaida, Katsuji; Tanaka, Takashi; Itani, Yusuke; Ikegame, Kazuhiro; Okada, Masaya; Ishii, Shinichi; Kodama, Norihiko; Ogawa, Hiroyasu; Domen, Kazuhisa

2012-12-01

Cachexia in patients with hematological malignancies is often related to sarcopenia. We believe that allogeneic hematopoietic stem cell transplant (allo-HSCT) patients often exhibit sarcopenia prior to transplantation. Here, we aimed to investigate the prevalence of sarcopenia and its relationship with body composition, physiological function, nutrition, fatigue, and health-related quality of life (QOL) in patients before allo-HSCT. We further investigated the confounding factors associated with sarcopenia. We included 164 patients with allo-HSCT in this study. Body composition, handgrip, knee extensor strength, and 6-min walk test were evaluated. Furthermore, fatigue, nutritional status, and health-related QOL were also evaluated. Eighty-three patients (50.6 %) enrolled in our study had sarcopenia prior to allo-HSCT. Patients with sarcopenia experienced decreased muscular strength and increased fatigue compared with patients without sarcopenia (p < 0.05). Patients with sarcopenia showed significantly lower scores in physical functioning, bodily pain, and vitality in health-related QOL than those without sarcopenia. Multivariate regression analysis revealed that only gender and body mass index were significantly related to sarcopenia (gender, odds ratio, 3.09; body mass index, odds ratio, 0.70; p < 0.01). Sarcopenia is common in patients before allo-HSCT and related to low muscle strength, fatigue, and health-related QOL. Male patients may be more susceptible to sarcopenia than female patients before allo-HSCT. Further study of rehabilitation with gender insight is warranted for patients receiving allo-HSCT.

C/EBPβ promotes BCR–ABL-mediated myeloid expansion and leukemic stem cell exhaustion

PubMed Central

Hayashi, Y; Hirai, H; Kamio, N; Yao, H; Yoshioka, S; Miura, Y; Ashihara, E; Fujiyama, Y; Tenen, DG; Maekawa, T

2015-01-01

The BCR–ABL fusion oncoprotein accelerates differentiation and proliferation of myeloid cells during the chronic phase of chronic myeloid leukemia (CP-CML). Here, the role of CCAAT/enhancer binding protein β (C/EBPβ), a regulator for ‘emergency granulopoiesis,’ in the pathogenesis of CP-CML was examined. C/EBPβ expression was upregulated in Lineage− CD34+ CD38− hematopoietic stem cells (HSCs) and myeloid progenitors isolated from bone marrow of patients with CP-CML. In EML cells, a mouse HSC line, BCR–ABL upregulated C/EBPβ, at least in part, through the activation of STAT5. Myeloid differentiation and proliferation induced by BCR–ABL was significantly impaired in C/EBPβ-deficient bone marrow cells in vitro. Mice that were transplanted with BCR–ABL-transduced C/EBPβ knockout bone marrow cells survived longer than mice that received BCR–ABL-transduced wild-type (WT) bone marrow cells. Significantly higher levels of leukemic stem cells were maintained in BCR–ABL-transduced C/EBPβ-deficient cells than in BCR–ABL-transduced WT cells. These results suggest that C/EBPβ is involved in BCR–ABL-mediated myeloid expansion. Further elucidation of the molecular mechanisms underlying the C/EBPβ-mediated stem cell loss might reveal a novel therapeutic strategy for eradication of CML stem cells. PMID:22948537

Early Intervention With Transplantation Recipients to Improve Access to and Knowledge of Palliative Care.

PubMed

Harden, Karen L

2016-08-01

The literature continues to support that patients undergoing hematopoietic stem cell transplantation (HSCT) receive early consultation with palliative care specialists. Nurses can be leaders in this initiative. This quality improvement project was conducted to determine whether patients undergoing HSCT, who were provided an early consultation with palliative care, would report increased knowledge and increased ability to access palliative services. Patients completed a postintervention questionnaire in which the majority of patients reported that they had increased knowledge about palliative care and learned how to access their services. Patient comments were positive about the successful intervention of early palliative care. The palliative care team, however, revealed a different view of the situation, showing that patients were often overwhelmed, anxious, and sometimes did not remember the content of their meetings.

Canopy architecture of a walnut orchard

NASA Technical Reports Server (NTRS)

Ustin, Susan L.; Martens, Scott N.; Vanderbilt, Vern C.

1991-01-01

A detailed dataset describing the canopy geometry of a walnut orchard was acquired to support testing and comparison of the predictions of canopy microwave and optical inversion models. Measured canopy properties included the quantity, size, and orientation of stems, leaves, and fruit. Eight trees receiving 100 percent of estimated potential evapotranspiration water use and eight trees receiving 33 percent of potential water use were measured. The vertical distributions of stem, leaf, and fruit properties are presented with respect to irrigation treatment. Zenith and probability distributions for stems and leaf normals are presented. These data show that, after two years of reduced irrigation, the trees receiving only 33 percent of their potential water requirement had reduced fruit yields, lower leaf area index, and altered allocation of biomass within the canopy.

Comparison of Different Stem Cell Mobilization Regimens in AL Amyloidosis Patients.

PubMed

Lisenko, Katharina; Wuchter, Patrick; Hansberg, Marion; Mangatter, Anja; Benner, Axel; Ho, Anthony D; Goldschmidt, Hartmut; Hegenbart, Ute; Schönland, Stefan

2017-11-01

High-dose melphalan (HDM) and autologous blood stem cell transplantation (ABSCT) is an effective treatment for transplantation-eligible patients with systemic light chain (AL) amyloidosis. Whereas most centers use granulocyte colony-stimulating factor (G-CSF) alone for mobilization of peripheral blood stem cells (PBSC), the application of mobilization chemotherapy might offer specific advantages. We retrospectively analyzed 110 patients with AL amyloidosis who underwent PBSC collection. Major eligibility criteria included age <70 years and cardiac insufficiency New York Heart Association ≤III°. Before mobilization, 67 patients (61%) had been pretreated with induction therapy, including 17 (15%) patients who had received melphalan. Chemo-mobilization was performed with either cyclophosphamide, doxorubicin, dexamethasone (CAD)/G-CSF (n = 78, 71%); ifosfamide/G-CSF (n = 14, 13%); or other regimens (n = 8, 7%). AL amyloidosis patients with predominant heart involvement and/or status post heart transplantation were mobilized with G-CSF only (n = 10, 9%). PBSC collection was successful in 101 patients (92%) at first attempt. The median number of CD34 + cells was 8.7 (range, 2.1 to 45.5) × 10 6 CD34 + /kg collected in a median of 1 leukapheresis (LP) session. Compared with G-CSF-only mobilization, a chemo-mobilization with CAD/G-CSF or ifosfamide/G-CSF had a positive impact on the number of collected CD34 + cell number/kg per LP (P <.001, multivariate). Melphalan-containing previous therapy and higher age had a significant negative impact on quantity of collected CD34 + cells. Median common toxicity criteria (CTC) grade of nonhematologic toxicity was II (range, 0 to IV). Life-threatening CTC grade IV adverse events were observed in 3 patients with no fatalities. Cardiovascular events were observed in 17 patients (22%) upon CAD/G-CSF mobilization (median CTC: grade 3; range, 1 to 4). Toxicity in patients undergoing ifosfamide/G-CSF mobilization was higher than in with those who received G-CSF-only mobilization. HDM and ABSCT were performed in 100 patients. Compared with >6.5 × 10 6 transplanted CD34 + cells/kg, an ABSCT with <3 × 10 6 CD34 + cells/kg was associated with a longer duration to leukocyte reconstitution >1 × 10 9 /L and a reduced platelet count <150 × 10 9 /L 1 year after ASCT. Our results show that CAD chemotherapy is very effective in PBSC mobilization and has a tolerable toxicity profile in AL amyloidosis patients. A further toxicity reduction by omission of doxorubicin might be considered. Because of advanced nonhematologic toxicity, ifosfamide administration cannot be recommended. However, G-CSF mobilization alone is also safe and effective. Considering the hematopoietic reconstitution and long-term stem cell function, our results provide a rationale to collect and transplant as many as >6.5 × 10 6 CD34 + cells/kg, if feasible with reasonable effort. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial.

PubMed

Ferreri, Andrés J M; Cwynarski, Kate; Pulczynski, Elisa; Fox, Christopher P; Schorb, Elisabeth; La Rosée, Paul; Binder, Mascha; Fabbri, Alberto; Torri, Valter; Minacapelli, Eleonora; Falautano, Monica; Ilariucci, Fiorella; Ambrosetti, Achille; Roth, Alexander; Hemmaway, Claire; Johnson, Peter; Linton, Kim M; Pukrop, Tobias; Sønderskov Gørløv, Jette; Balzarotti, Monica; Hess, Georg; Keller, Ulrich; Stilgenbauer, Stephan; Panse, Jens; Tucci, Alessandra; Orsucci, Lorella; Pisani, Francesco; Levis, Alessandro; Krause, Stefan W; Schmoll, Hans J; Hertenstein, Bernd; Rummel, Mathias; Smith, Jeffery; Pfreundschuh, Michael; Cabras, Giuseppina; Angrilli, Francesco; Ponzoni, Maurilio; Deckert, Martina; Politi, Letterio S; Finke, Jürgen; Reni, Michele; Cavalli, Franco; Zucca, Emanuele; Illerhaus, Gerald

2017-11-01

The International Extranodal Lymphoma Study Group-32 (IELSG32) trial is an international randomised phase 2 study that addresses two key clinical questions in the treatment of patients with newly diagnosed primary CNS lymphoma. Results of the first randomisation have demonstrated that methotrexate, cytarabine, thiotepa, and rituximab (called the MATRix regimen) is the induction combination associated with significantly better outcome compared with the other induction combinations tested. Here, we report the results of the second randomisation that addresses the efficacy of myeloablative chemotherapy supported by autologous stem-cell transplantation (ASCT), as an alternative to whole-brain radiotherapy (WBRT), as consolidation after high-dose-methotrexate-based chemoimmunotherapy. HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and an Eastern Cooperative Oncology Group performance status of 0-3 were randomly assigned to receive four courses of methotrexate 3·5 g/m 2 on day 1 plus cytarabine 2 g/m 2 twice daily on days 2 and 3 (group A); or the same combination plus two doses of rituximab 375 mg/m 2 on days -5 and 0 (group B); or the same methotrexate-cytarabine-rituximab combination plus thiotepa 30 mg/m 2 on day 4 (group C), with the three groups repeating treatment every 3 weeks. Patients with responsive or stable disease after induction treatment, with adequate autologous peripheral blood stem-cell collection, and without persistent iatrogenic side-effects, were eligible for the second randomisation between WBRT (photons of 4-10 MeV; five fractions per week; fraction size 180 cGy; started within 4 weeks from the last induction course; group D) and carmustine-thiotepa conditioned ASCT (carmustine 400 mg/m 2 on day -6, and thiotepa 5 mg/kg every 12 h on days -5 and -4, followed by reinfusion of autologous peripheral blood stem cells; group E). A permuted block randomised design was adopted for both randomisations, and a computer-generated randomisation list was used within each stratum. No masking after assignment to intervention was adopted. The primary endpoint was 2-year progression-free survival, with induction group and response to induction chemotherapy as stratification parameters. Analyses were done on a modified intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT01011920. Between Feb 19, 2010, and Aug 27, 2014, 227 patients were recruited from 53 centres in five countries. 219 of 227 enrolled patients were assessable. Of the 122 patients eligible for the second randomisation, 118 patients were randomly assigned to WBRT or ASCT (59 patients per group) and constitute the study population. WBRT and ASCT were both effective, and achieved the predetermined efficacy threshold of at least 40 progression-free survivors at 2 years among the first 52 patients in both groups D and E. There were no significant differences in 2-year progression-free survival between WBRT and ASCT: 80% (95% CI 70-90) in group D and 69% (59-79) in group E (hazard ratio 1·50, 95% CI 0·83-2·71; p=0·17). Both consolidation therapies were well tolerated. Grade 4 non-haematological toxicity was uncommon; as expected, haematological toxicity was more common in patients treated with ASCT than in those who received WBRT. Two toxic deaths (infections) were recorded, both in patients who received ASCT. WBRT and ASCT are both feasible and effective as consolidation therapies after high-dose methotrexate-based chemoimmunotherapy in patients aged 70 years or younger with primary CNS lymphoma. The risks and implications of cognitive impairment after WBRT should be considered at the time of therapeutic decision. Agenzia Italiana del Farmaco, Cancer Research UK, Oncosuisse, and Swiss National Science Foundation. Copyright © 2017 Elsevier Ltd. All rights reserved.

High incidence of chronic graft-versus-host disease after myeloablative allogeneic stem cell transplantation for chronic lymphocytic leukemia in Sweden: graft-versus-leukemia effect protects against relapse.

PubMed

Machaczka, Maciej; Johansson, Jan-Erik; Remberger, Mats; Hallböök, Helene; Lazarevic, Vladimir Lj; Wahlin, Björn Engelbrekt; Omar, Hamdy; Wahlin, Anders; Juliusson, Gunnar; Kimby, Eva; Hägglund, Hans

2013-12-01

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment option for eligible patients with chronic lymphocytic leukemia (CLL). However, it is known that cure of CLL is only possible if a graft-versus-leukemia effect is present. Between 1994 and 2007, 48 adults underwent allo-SCT for poor-risk CLL in Sweden. Of these, ten (21%) patients aged 24-53 years (median: 46 years) received myeloablative conditioning (MAC), based on TBI and cyclophosphamide. All MAC patients had refractory, poorly controlled CLL before allo-SCT (partial remission in 9/10 patients and progressive disease in one). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II-IV was 30%. Nine patients developed chronic GVHD; extensive in four. Rates of nonrelapse mortality at 1, 3 and 10 years were 0, 10 and 20%, respectively. Two patients relapsed 36 and 53 months after transplantation. Six patients were still alive after a median follow-up time of 11.5 years (range 5.9-13.7). The probabilities of relapse-free and overall survival from 1, 3 and 5 years after transplantation were 100, 90 and 70%, and 100, 90 and 80%, respectively. Nevertheless, our analysis of long-term outcome after MAC allo-SCT for CLL suggests that younger patients with poorly controlled CLL may benefit from MAC allo-SCT.

Piperacillin-tazobactam vs. imipenem-cilastatin as empirical therapy in hematopoietic stem cell transplantation recipients with febrile neutropenia.

PubMed

Jing, Yu; Li, Jian; Yuan, Lei; Zhao, Xiaoli; Wang, Quanshun; Yu, Li; Zhou, Daobin; Huang, Wenrong

2016-03-01

This randomized, dual-center study compared the efficacy and safety of piperacillin-tazobactam (PTZ) and imipenem-cilastatin (IMP) in hematopoietic stem cell transplantation (HSCT) recipients with febrile neutropenia. HSCT recipients with febrile neutropenia were randomized into two groups receiving either PTZ or IMP as initial empiric antibiotic. Endpoints were defervescence rate after empiric antibiotic for 48 h, success at end of therapy, and side effects. Defervescence within 48 h after empiric antibiotic was observed in 46 patients with PTZ (75.4%) and 59 patients with IMP (95.2%) (p = 0.002). Ten patients (10/46) in the PTZ group and two patients (2/59) in the IMP group switched empiric antibiotics due to recurrent fever (p = 0.005). Success of initial antibiotic with modification was achieved in 34 patients with PTZ (55.7%) and 53 patients with IMP (85.5%) at the end of therapy (p = 0.001). To treat the bacteremia, seven of 10 patients in the PTZ group and one of eight patients in the IMP group needed to switch the empiric antibiotic (p = 0.025). Compared with PTZ, IMP had more gastrointestinal adverse events (p = 0.045). This study demonstrates that IMP had better efficacy than PTZ as an empiric antibiotic for febrile neutropenia in the HSCT setting, but with more gastrointestinal side reactions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Short stem survival after osteonecrosis of the femoral head.

PubMed

Schnurr, Christoph; Loucif, Anissa; Patzer, Theresa; Schellen, Bernd; Beckmann, Johannes; Eysel, Peer

2018-04-01

Short stems were developed as a bone-conserving alternative especially for the young hip arthroplasty patient. Patients suffering from osteonecrosis of the femoral head are frequently younger than primary arthritis patients. The outcome of short stems in these patients remains unclear. The aim of our study was to compare mid-term survival of short stems after osteonecrosis of the femoral head (ONFH) and primary arthritis. Data on short stem implantations over a 10-year period were collected. Demographic data and X-ray measurements before and after surgery were recorded. Indication for operation was determined from medical records and X-rays. Patients were asked by post about any revision. Reason for revision was identified by analysis of operation protocols. Short stem revision rates were analyzed using Kaplan-Meier charts, comparing 212 ONFH patients (231 operations) and 1284 primary arthritis patients (1455 operations). Follow-up time averaged 5.3 and 6 years and was complete for 92% (ONFH) and 94% (primary arthritis) of the patients. ONFH patients were significantly younger (53 years vs. 59 years, p < 0.001) and more frequently male (55 vs. 42%, p < 0.001). The total revision rate did not differ between the two groups (8 years: 4.2 vs. 5.6%, p = ns). A trend towards more stem revisions was detected for ONFH patients (3 vs. 1.8%, p = ns). The aseptic stem loosening rate was significantly elevated for osteonecrosis patients (8 years: 2.6 vs. 0.7%, p = 0.013). Our study showed elevated short stem loosening rates after ONFH. Similar results are published for classic cementless stems. The question of which stem is best for the young osteonecrosis patient cannot be answered yet. Consecutive studies directly comparing loosening rates of short and classic cementless stems in young osteonecrosis patients are required.

What's missing? Discussing stem cell translational research in educational information on stem cell "tourism".

PubMed

Master, Zubin; Zarzeczny, Amy; Rachul, Christen; Caulfield, Timothy

2013-01-01

Stem cell tourism is a growing industry in which patients pursue unproven stem cell therapies for a wide variety of illnesses and conditions. It is a challenging market to regulate due to a number of factors including its international, online, direct-to-consumer approach. Calls to provide education and information to patients, their families, physicians, and the general public about the risks associated with stem cell tourism are mounting. Initial studies examining the perceptions of patients who have pursued stem cell tourism indicate many are highly critical of the research and regulatory systems in their home countries and believe them to be stagnant and unresponsive to patient needs. We suggest that educational material should include an explanation of the translational research process, in addition to other aspects of stem cell tourism, as one means to help promote greater understanding and, ideally, curb patient demand for unproven stem cell interventions. The material provided must stress that strong scientific research is required in order for therapies to be safe and have a greater chance at being effective. Through an analysis of educational material on stem cell tourism and translational stem cell research from patient groups and scientific societies, we describe essential elements that should be conveyed in educational material provided to patients. Although we support the broad dissemination of educational material on stem cell translational research, we also acknowledge that education may simply not be enough to engender patient and public trust in domestic research and regulatory systems. However, promoting patient autonomy by providing good quality information to patients so they can make better informed decisions is valuable in itself, irrespective of whether it serves as an effective deterrent of stem cell tourism. © 2013 American Society of Law, Medicine & Ethics, Inc.

Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy.

PubMed

Eichler, Florian; Duncan, Christine; Musolino, Patricia L; Orchard, Paul J; De Oliveira, Satiro; Thrasher, Adrian J; Armant, Myriam; Dansereau, Colleen; Lund, Troy C; Miller, Weston P; Raymond, Gerald V; Sankar, Raman; Shah, Ami J; Sevin, Caroline; Gaspar, H Bobby; Gissen, Paul; Amartino, Hernan; Bratkovic, Drago; Smith, Nicholas J C; Paker, Asif M; Shamir, Esther; O'Meara, Tara; Davidson, David; Aubourg, Patrick; Williams, David A

2017-10-26

In X-linked adrenoleukodystrophy, mutations in ABCD1 lead to loss of function of the ALD protein. Cerebral adrenoleukodystrophy is characterized by demyelination and neurodegeneration. Disease progression, which leads to loss of neurologic function and death, can be halted only with allogeneic hematopoietic stem-cell transplantation. We enrolled boys with cerebral adrenoleukodystrophy in a single-group, open-label, phase 2-3 safety and efficacy study. Patients were required to have early-stage disease and gadolinium enhancement on magnetic resonance imaging (MRI) at screening. The investigational therapy involved infusion of autologous CD34+ cells transduced with the elivaldogene tavalentivec (Lenti-D) lentiviral vector. In this interim analysis, patients were assessed for the occurrence of graft-versus-host disease, death, and major functional disabilities, as well as changes in neurologic function and in the extent of lesions on MRI. The primary end point was being alive and having no major functional disability at 24 months after infusion. A total of 17 boys received Lenti-D gene therapy. At the time of the interim analysis, the median follow-up was 29.4 months (range, 21.6 to 42.0). All the patients had gene-marked cells after engraftment, with no evidence of preferential integration near known oncogenes or clonal outgrowth. Measurable ALD protein was observed in all the patients. No treatment-related death or graft-versus-host disease had been reported; 15 of the 17 patients (88%) were alive and free of major functional disability, with minimal clinical symptoms. One patient, who had had rapid neurologic deterioration, had died from disease progression. Another patient, who had had evidence of disease progression on MRI, had withdrawn from the study to undergo allogeneic stem-cell transplantation and later died from transplantation-related complications. Early results of this study suggest that Lenti-D gene therapy may be a safe and effective alternative to allogeneic stem-cell transplantation in boys with early-stage cerebral adrenoleukodystrophy. Additional follow-up is needed to fully assess the duration of response and long-term safety. (Funded by Bluebird Bio and others; STARBEAM ClinicalTrials.gov number, NCT01896102 ; ClinicalTrialsRegister.eu number, 2011-001953-10 .).

STEM Learning Is Everywhere: Summary of a Convocation on Building Learning Systems

ERIC Educational Resources Information Center

Olson, Steve; Labov, Jay

2014-01-01

Science, technology, engineering, and mathematics (STEM) permeate the modern world. The jobs people do, the foods they eat, the vehicles in which they travel, the information they receive, the medicines they take, and many other facets of modern life are constantly changing as STEM knowledge steadily accumulates. Yet STEM education in the United…

Reducing late effects of radiotherapy in average risk medulloblastoma.

PubMed

Ibrahim, Noha Yehia; Abdel Aal, Hisham H; Abdel Kader, Mohamed S; Makaar, Wael S; Shaaban, Ahmed H

2014-03-01

To assess the efficacy and safety in average-risk pediatric medulloblastoma (MB) receiving tumor bed boost irradiation compared to a posterior fossa (PF) boost. Thirty patients were enrolled in the study and divided evenly into two treatment arms of 15. Both arms received 23.4 Gy craniospinal irradiation (CS) and a 32.4 Gy boost. Patients in arm 1 were given PF boosts, and those in arm 2 were given boosts to the gross target volume (GTV). Weekly oncovin was given throughout all radiotherapy (RT). Eight cycles of adjuvant chemotherapy of CCNU, oncovin and platinol were given to all patients after RT. MRI, pure tone audiogram (PTA) and intelligence quotient (IQ) tests were performed before and after RT and every three months thereafter. There were significant differences in the sparing dose to the cochlea and brain stem as well as the volume of the normal brain receiving a 100% dose. There was a significant initial improvement of hearing function in patients given the target volume boost after RT, which was lost after chemotherapy. With a median follow up of 23 months, there was no difference in progression free survival or overall survival between the two arms. Irradiation of the tumor bed after 23.4 Gy craniospinal irradiation for average-risk MB results in similar disease control as a PF boost. Dosimetric sparing for the cochleae and normal tissue is evident in patients receiving tumor bed boosts. The hearing improvement and cognitive function preservation effects of the treatment need more follow up.

Mesenchymal stromal cells in the antimicrobial host response of hematopoietic stem cell recipients with graft-versus-host disease--friends or foes?

PubMed

Balan, A; Lucchini, G; Schmidt, S; Schneider, A; Tramsen, L; Kuçi, S; Meisel, R; Bader, P; Lehrnbecher, T

2014-10-01

Mesenchymal stromal cells (MSCs) are multipotent cells, which exhibit broad immunosuppressive activities. Moreover, they may be administered irrespectively of human leukocyte antigen (HLA) compatibility, without inducing life-threatening immunological reactions, as they express no HLA class II and limited HLA class I antigens under resting conditions. These characteristics have made MSC an appealing candidate for cell therapy after hematopoietic stem cell transplantation (HSCT), for example, for treatment of graft-versus-host disease (GvHD) or for graft rejection prevention/treatment in allogeneic HSCT recipients. Unfortunately, information regarding the effect of MSC infusion on the host response to infectious agents is scarce, and study results on infectious complications in patients receiving MSC are conflicting. The present review focuses on the available data from in vitro studies and animal models regarding the interaction of MSC with bacterial, viral and fungal pathogens. In a clinical part, we present the current information on infectious complications in allogeneic HSCT recipients who had received MSCs as prophylaxis or treatment of GvHD disease.

Palifermin-associated papular eruption.

PubMed

King, Brett; Knopp, Eleanor; Galan, Anjela; Nuovo, Gerard; Tigelaar, Robert; McNiff, Jennifer

2009-02-01

Palifermin is a recombinant human keratinocyte growth factor that is used to reduce the duration and severity of oral mucositis in patients undergoing hematopoietic stem cell transplantation after myelotoxic therapy. Cutaneous adverse reactions associated with keratinocyte growth factor are reported to be rash, pruritus, and erythema. After receiving palifermin following autologous hematopoietic stem cell transplantation and treatment with melphalan, a patient developed erythema and lichenoid papules that were distributed primarily in intertriginous areas. A biopsy specimen of the papules showed a striking resemblance to verrucae, but in situ hybridization studies were negative for human papillomavirus. Immunohistochemical staining with antibodies to Ki-67 and cytokeratin 5/6 showed increased keratinocyte proliferation in lesional skin. After treatment with palifermin, a papular eruption clinically resembling lichen planus or plane warts, with histologic features of verruca plana, and intertriginous erythema may occur. In this case, neither eruption required treatment, and spontaneous resolution was observed over days to weeks. Histopathologic staining patterns of Ki-67 and cytokeratin 5/6 may be useful in identifying adverse reactions to palifermin therapy.

Nano Let‑7b sensitization of eliminating esophageal cancer stem‑like cells is dependent on blockade of Wnt activation of symmetric division.

PubMed

Pang, Yamei; Liu, Jian; Li, Xiang; Zhang, Yiwen; Zhang, Boxiang; Zhang, Jing; Du, Ning; Xu, Chongwen; Liang, Rui; Ren, Hong; Tang, Shou-Ching; Sun, Xin

2017-10-01

The poor therapy response and poor prognosis of esophageal cancer has made it one of the most malignant carcinoma, and the complicated multidisciplinary treatment failed to achieve a long-term disease-free survival. To diagnose esophageal cancer at an earlier stage, and to improve the effect of anticancer therapy would improve the therapeutic efficacy. After retrospective analysis of the cancer samples of patients who received esophagectomy, we found the relevance between ratio of either ALDH1 or CD133-positive cancer stem cells and 2-year recurrence. Higher ratios of cancer stem cells indicated later clinical stages, and Wnt signaling activation was more frequent in later esophageal carcinoma. Further in bench studies, we explored the suppressive roles and the mechanisms involved in Let‑7 on self-renewal in ECA‑109 and ECA‑9706 esophageal cancer stem cells. Isolated cancer stem cells naturally divide symmetrically and are therapy resistant. Therapy of fluorouracil and docetaxel both enriched the stem cells, proving the resistant characteristics of cancer stem cells. Wnt activation stimulated more symmetric division of stem cells, resulting in self-renewal promotion, which could be blocked by Let‑7 overexpression. Furthermore, enforced Let‑7 sensitized the stem cells to chemotherapies in a Wnt pathway inhibition-dependent manner, contributing to Let‑7 sensitization of chemotherapeutic response. Wnt activation weakened the suppressive Let‑7b through the sponge functions of CCAT-1, forming the negative feedback loop of Let‑7b/Wnt/CCAT1. These results identified the crucial participation of stem cells in esophageal cancer occurrence and progression as the potent indicator, and also indicate the potential powerful agent of Let‑7 nano-particles in treatment of cancer.

Allogeneic stem-cell transplantation in patients with NPM1-mutated acute myeloid leukemia: results from a prospective donor versus no-donor analysis of patients after upfront HLA typing within the SAL-AML 2003 trial.

PubMed

Röllig, Christoph; Bornhäuser, Martin; Kramer, Michael; Thiede, Christian; Ho, Anthony D; Krämer, Alwin; Schäfer-Eckart, Kerstin; Wandt, Hannes; Hänel, Mathias; Einsele, Hermann; Aulitzky, Walter E; Schmitz, Norbert; Berdel, Wolfgang E; Stelljes, Matthias; Müller-Tidow, Carsten; Krug, Utz; Platzbecker, Uwe; Wermke, Martin; Baldus, Claudia D; Krause, Stefan W; Stölzel, Friedrich; von Bonin, Malte; Schaich, Markus; Serve, Hubert; Schetelig, Johannes; Ehninger, Gerhard

2015-02-10

The presence of a mutated nucleophosmin-1 gene (NPM1(mut)) in acute myeloid leukemia (AML) is associated with a favorable prognosis. To assess the predictive value with regard to allogeneic stem-cell transplantation (SCT), we compared the clinical course of patients with NPM1(mut) AML eligible for allogeneic SCT in a donor versus no-donor analysis. Of 1,179 patients with AML (age 18 to 60 years) treated in the Study Alliance Leukemia AML 2003 trial, we identified all NPM1(mut) patients with an intermediate-risk karyotype. According to the trial protocol, patients were intended to receive an allogeneic SCT if an HLA-identical sibling donor was available. Patients with no available donor received consolidation or autologous SCT. We compared relapse-free survival (RFS) and overall survival (OS) depending on the availability of a suitable donor. Of 304 eligible patients, 77 patients had a sibling donor and 227 had no available matched family donor. The 3-year RFS rates in the donor and no-donor groups were 71% and 47%, respectively (P = .005); OS rates were 70% and 60%, respectively (P = .114). In patients with normal karyotype and no FLT3 internal tandem duplication (n = 148), the 3-year RFS rates in the donor and no-donor groups were 83% and 53%, respectively (P = .004); and the 3-year OS rates were 81% and 75%, respectively (P = .300). Allogeneic SCT led to a significantly prolonged RFS in patients with NPM1(mut) AML. The absence of a statistically significant difference in OS is most likely a result of the fact that NPM1(mut) patients who experienced relapse responded well to salvage treatment. Allogeneic SCT in first remission has potent antileukemic efficacy and is a valuable treatment option in patients with NPM1(mut) AML with a sibling donor. © 2014 by American Society of Clinical Oncology.

Prognostic Prediction Model for Second Allogeneic Stem-Cell Transplantation in Patients With Relapsed Acute Myeloid Leukemia: Single-Center Report.

PubMed

Park, Sung-Soo; Kim, Hee-Je; Min, Kyoung Il; Min, Gi June; Jeon, Young-Woo; Yoon, Jae-Ho; Yahng, Seung-Ah; Shin, Seung-Hwan; Lee, Sung-Eun; Cho, Byung-Sik; Eom, Ki-Seong; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Cho, Seok-Goo; Kim, Dong-Wook; Lee, Jong Wook; Min, Woo-Sung

2018-04-01

To identify factors affecting survival outcomes and to develop a prognostic model for second allogeneic stem-cell transplantation (allo-SCT2) for relapsed acute myeloid leukemia (AML) after the first autologous or allogeneic stem-cell transplantation. Seventy-eight consecutive adult AML patients who received allo-SCT2 were analyzed in this retrospective study. The 4-year overall survival (OS) rate was 28.7%. In multivariate analysis, poor cytogenetic risk at diagnosis, circulating blast ≥ 20% at relapse, duration from first transplantation to relapse < 9 months, and failure to achieve morphologic complete remission after allo-SCT2 were factors associated with poor OS. A prognostic model was developed with the following score system: intermediate and poor cytogenetic risk at diagnosis (0.5 and 1 point), peripheral blast ≥ 20% at relapse (1 point), duration from the first transplantation to relapse < 9 months (1 point), and failure to achieve morphologic complete remission after allo-SCT2 (1 point). The model identified 2 subgroups according to the 4-year OS rate: 51.3% in the low-risk group (score < 2) and 2.8% in the high-risk group (score ≥ 2) (P < .001). This prognostic model might be useful to make an appropriate decision for allo-SCT2 in relapsed AML after the first autologous or allogeneic stem-cell transplantation. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of effects of busulfan and DMA on SOS in pediatric stem cell recipients.

PubMed

Kerl, Kornelius; Diestelhorst, Christian; Bartelink, Imke; Boelens, Jaap; Trame, Mirjam N; Boos, Joachim; Hempel, Georg

2014-02-01

Busulfan (Bu) is a DNA-alkylating agent used for myeloablative conditioning in stem cell transplantation in children and adults. While the use of intravenous rather than oral administration of Bu has reduced inter-individual variability in plasma levels, toxicity still occurs frequently after hematopoietic stem cell transplantation (HSCT). Toxicity (especially hepatotoxic effects) of intravenous (IV) Bu may be related to both Bu and/or N,N-dimethylacetamide (DMA), the solvent of Bu. In this study, we assessed the relation between the exposure of Bu and DMA with regards to the clinical outcome in children from two cohorts. In a two-centre study Bu and DMA AUC (area under the curve) were correlated in pediatric stem cell recipients to the risk of developing SOS and to the clinical outcome. In patients receiving Bu four times per day Bu levels >1,500 µmol/L minute correlate to an increased risk of developing a SOS. In the collective cohort, summarizing data of all 53 patients of this study, neither high area under the curve (AUC) of Bu nor high AUC of DMA appears to be an independent risk factor for the development of SOS in children. In this study neither Bu nor DMA was observed as an independent risk factor for the development of SOS. To identify subgroups (e.g., infants), in which Bu or DMA might be risk factors for the induction of SOS, larger cohorts have to be evaluated. © 2013 Wiley Periodicals, Inc.

Immunomodulation effects of mesenchymal stromal cells on acute graft-versus-host disease after hematopoietic stem cell transplantation.

PubMed

Zhao, Ke; Lou, Rui; Huang, Fen; Peng, Yanwen; Jiang, Zujun; Huang, Ke; Wu, Xiuli; Zhang, Yu; Fan, Zhiping; Zhou, Hongsheng; Liu, Can; Xiao, Yang; Sun, Jing; Li, Yangqiu; Xiang, Peng; Liu, Qifa

2015-01-01

Refractory acute graft-versus-host disease (aGVHD) is a major cause of death after allogeneic hematopoietic stem cell transplantation. This study evaluated the immunomodulation effects of mesenchymal stromal cells (MSCs) from bone marrow of a third-party donor for refractory aGVHD. Forty-seven patients with refractory aGVHD were enrolled: 28 patients receiving MSC and 19 patients without MSC treatment. MSCs were given at a median dose of 1 × 10(6) cells/kg weekly until patients got complete response or received 8 doses of MSCs. After 125 doses of MSCs were administered, with a median of 4 doses (range, 2 to 8) per patient, overall response rate was 75% in the MSC group compared with 42.1% in the non-MSC group (P = .023). The incidence of cytomegalovirus, Epstein-Barr virus infections, and tumor relapse was not different between the 2 groups during aGVHD treatment and follow-up. The incidence and severity of chronic GVHD in the MSC group were lower than those in the non-MSC group (P = .045 and P = .005). The ratio of CD3(+)CD4(+)/CD3(+)CD8(+) T cells, the frequencies of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), and the levels of signal joint T cell-receptor excision DNA circles (sjTRECs) after MSCs treatment were higher than those pretreatment. MSC-treated patients exhibited higher Tregs frequencies and sjTRECs levels than those in the non-MSC group at 8 and 12 weeks after treatment. MSCs derived from bone marrow of a third-party donor are effective to refractory aGVHD. It might reduce the incidence and severity of chronic GVHD in aGVHD patients by improving thymic function and induction of Tregs but not increase the risks of infections and tumor relapse. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Music therapy for mood disturbance during hospitalization for autologous stem cell transplantation: a randomized controlled trial.

PubMed

Cassileth, Barrie R; Vickers, Andrew J; Magill, Lucanne A

2003-12-15

High-dose therapy with autologous stem cell transplantation (HDT/ASCT) is a commonly used treatment for hematologic malignancies. The procedure causes significant psychological distress and no interventions have been demonstrated to improve mood in these patients. Music therapy has been shown to improve anxiety in a variety of acute medical settings. In the current study, the authors determined the effects of music therapy compared with standard care on mood during inpatient stays for HDT/ASCT. Patients with hematologic malignancy admitted for HDT/ASCT at two sites (Memorial Sloan-Kettering Cancer Center and Ireland Cancer Center in Cleveland, Ohio) were randomized to receive music therapy given by trained music therapists or standard care. Outcome was assessed at baseline and every 3 days after randomization using the Profile of Mood States. Of 69 patients registered in the study, follow-up data were available for 62 (90%). During their inpatient stay, patients in the music therapy group scored 28% lower on the combined Anxiety/Depression scale (P = 0.065) and 37% lower (P = 0.01) on the total mood disturbance score compared with controls. Music therapy is a noninvasive and inexpensive intervention that appears to reduce mood disturbance in patients undergoing HDT/ASCT. Copyright 2003 American Cancer Society.

Fungal osteoarticular infections in patients treated at a comprehensive cancer centre: a 10-year retrospective review.

PubMed

Kumashi, P R; Safdar, A; Chamilos, G; Chemaly, R F; Raad, I I; Kontoyiannis, D P

2006-07-01

This study reviewed retrospectively the clinical characteristics of 28 cancer patients with fungal osteoarticular infections (FOAIs) between 1995 and 2005. Most patients (26; 93%) had haematological malignancies (19 had leukaemia); half (14) were allogeneic stem-cell transplant recipients. Twelve patients (43%) had severe neutropenia (< or = 100/mm3) with a mean duration of 65 days (range 10-500 days), and ten (36%) patients had received a significant dose of corticosteroids. Most (19; 68%) FOAIs were caused by contiguous extension, while nine (32%) were associated with haematogenous spread. Pain, joint instability and local drainage were seen in 28 (100%), six (21%), and seven (25%) patients, respectively. Sixteen (57%) patients had symptoms for < 1 month. The sinuses (ten; 36%) and the vertebral spine (six; 21%) were the most common sites involved. Moulds were the predominant pathogens: Aspergillus fumigatus (two); non-fumigatus Aspergillus spp. (eight); non-specified Aspergillus spp. (three); Fusarium spp. (six); Zygomycetes (five); Scedosporium apiospermum (two); and Exserohilum sp. (one). Candida was the causative pathogen in four cases (including two cases of mixed FOAIs). Arthritis and post-operative FOAIs were both uncommon manifestations, occurring in two patients each. All patients received systemic antifungal therapy (combinations in 20 cases), and 19 cases underwent adjunctive surgery. The crude mortality rates (at 12 weeks) were 44% (9/20) in the patients who underwent surgery and antifungal therapy vs. 33% (2/6) in patients who received antifungal therapy alone (p not significant). FOAI is a rare, yet severe, manifestation of localised or systemic mycoses, caused predominantly by moulds, and is seen typically in patients with haematological malignancies.

[Quantitative real-time PCR--usefulness in detection and monitoring of CMV infection after hematopeietic stem cells transplant].

PubMed

Grabarczyk, Piotr; Brojer, Ewa; Nasiłowska, Barbara; Mariańska, Bozena

2006-09-01

It is recommended that all patients after allogeneic hematopoietic stem cell transplantation (alloHSCT) should be monitored for CMV infection markers. The aim of the study was to check the usefulness of quantitative DNA CMV monitoring after alloHSCT. DNA CMV was tested by real-time PCR in sera and blood samples twice a week until 30th day after alloHSCT thereafter, once a week until 100th day and then, once every 2-3 weeks. 832 samples from 16 patients were tested. All patients were anti-CMV positive or/and received stem cells from seropositive donors. Introduction of antiviral treatment was based on initial viral load and its rate of increase. DNA CMV was detected in 13/16 patients; in 3 before 30h day after allo HSCT (group I) and in 10 (group II) after 30th day. In all patients from group I clinical symptoms were observed and DNA CMV was detected in sera and blood samples. Peak viral load was 2490-34 620 geq/ml. Although antiviral treatment was applied, reinfection was observed and infection lasted from 28 to 91 days. In 6 group II patients, clinical symptoms were observed and DNA CMV in sera and blood was detected for 16-56 days, DNA CMV peak load was 100-8950 geq/ml. In the remaining 4 patients, no clinical symptoms were observed--DNA CMV was detected in blood only for 7 to 14 days. In one patient with peak viral load 10,540 geq/ml, antiviral treatment was applied. In 3 with viral load of 400-2000 geq/ml, treatment was not introduced. The quantitative DNA CMV results were taken into account before the change of antiviral drugs for more effective drugs and the decrease of drug dose due to side effects. Application of quantititative DNA CMV testing allowed to optimise antiviral drug administration in immunosupressed patients after alloHSCT

Outcomes of diffuse large B-cell lymphoma patients relapsing after autologous stem cell transplantation: an analysis of patients included in the CORAL study.

PubMed

Van Den Neste, E; Schmitz, N; Mounier, N; Gill, D; Linch, D; Trneny, M; Bouadballah, R; Radford, J; Bargetzi, M; Ribrag, V; Dührsen, U; Ma, D; Briere, J; Thieblemont, C; Bachy, E; Moskowitz, C H; Glass, B; Gisselbrecht, C

2017-02-01

In the CORAL study, 255 chemosensitive relapses with diffuse large B-cell lymphoma (DLBCL) were consolidated with autologous stem cell transplantation (ASCT), and 75 of them relapsed thereafter. The median time between ASCT and progression was 7.1 months. The median age was 56.1 years; tertiary International Prognosis Index (tIPI) observed at relapse was 0-2 in 71.6% of the patients and >2 in 28.4%. The overall response rate to third-line chemotherapy was 44%. The median overall survival (OS) was 10.0 months (median follow-up: 32.8 months). Thirteen patients received an allogeneic SCT, and three a second ASCT. The median OS was shorter among patients who relapsed <6 months (5.7 months) compared with those relapsing ⩾12 months after ASCT (12.6 months, P=0.0221). The median OS in patients achieving CR, PR or no response after the third-line regimen was 37.7 (P<0.0001), 10.0 (P=0.03) and 6.3 months, respectively. The median OS varied according to tIPI: 0-2: 12.6 months and >2: 5.3 months (P=0.0007). In multivariate analysis, tIPI >2, achievement of response and remission lasting <6 months predicted the OS. This report identifies the prognostic factors for DLBCL relapsing after ASCT and thus helps to select patients for experimental therapy.

Interferon-α salvage treatment is effective for patients with acute leukemia/myelodysplastic syndrome with unsatisfactory response to minimal residual disease-directed donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation.

PubMed

Mo, Xiaodong; Zhang, Xiaohui; Xu, Lanping; Wang, Yu; Yan, Chenhua; Chen, Huan; Chen, Yuhong; Han, Wei; Wang, Fengrong; Wang, Jingzhi; Liu, Kaiyan; Huang, Xiaojun

2018-04-14

The efficacy of salvage interferon-α (IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI) (n = 24). Patients who did not become MRD-negative at 1 month after DLI were those with unsatisfactory response and were eligible to receive salvage IFN-α treatment within 3 months of DLI. Recombinant human IFN-α-2b injections were subcutaneously administered 2-3 times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12.5%) patients became MRD-negative at 1, 2, and > 2 months after the salvage IFN-α treatment, respectively. Two-year cumulative incidences of relapse and non-relapse mortality were 35.9% and 8.3%, respectively. Two-year probabilities of event-free survival, disease-free survival, and overall survival were 51.6%, 54.3%, and 68.0%, respectively. Outcomes of patients subjected to salvage IFN-α treatment after DLI were significantly better than those with persistent MRD without IFN-α treatment. Moreover, clinical outcomes were comparable between the salvage DLI and IFN-α treatment groups. Thus, salvage IFN-α treatment may help improve the outcome of patients with unsatisfactory responses to MRD-directed DLI and could be a potential salvage treatment for these patients after allogeneic hematopoietic stem cell transplantation.

TRX-E-002-1 Induces c-Jun-Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo.

PubMed

Alvero, Ayesha B; Heaton, Andrew; Lima, Eydis; Pitruzzello, Mary; Sumi, Natalia; Yang-Hartwich, Yang; Cardenas, Carlos; Steinmacher, Sahra; Silasi, Dan-Arin; Brown, David; Mor, Gil

2016-06-01

Chemoresistance is a major hurdle in the management of patients with epithelial ovarian cancer and is responsible for its high mortality. Studies have shown that chemoresistance is due to the presence of a subgroup of cancer cells with stemness properties and a high capacity for tumor repair. We have developed a library of super-benzopyran analogues to generate potent compounds that can induce cell death in chemoresistant cancer stem cells. TRX-E-002-1 is identified as the most potent analogue and can induce cell death in all chemoresistant CD44(+)/MyD88(+) ovarian cancer stem cells tested (IC50 = 50 nmol/L). TRX-E-002-1 is also potent against spheroid cultures formed from cancer stem cells, chemosensitive CD44(-)/MyD88(-) ovarian cancer cells, and heterogeneous cultures of ovarian cancer cells. Cell death was associated with the phosphorylation and increased levels of c-Jun and induction of caspases. In vivo, TRX-E-002-1 given as daily intraperitoneal monotherapy at 100 mg/kg significantly decreased intraperitoneal tumor burden compared with vehicle control. When given in combination with cisplatin, animals receiving the combination of cisplatin and TRX-E-002-1 showed decreased tumor burden compared with each monotherapy. Finally, TRX-E-002-1 given as maintenance treatment after paclitaxel significantly delayed disease recurrence. Our results suggest that TRX-E-002-1 may fill the current need for better therapeutic options in the control and management of recurrent ovarian cancer and may help improve patient survival. Mol Cancer Ther; 15(6); 1279-90. ©2016 AACR. ©2016 American Association for Cancer Research.

Bone Marrow Stem Cells Added to a Hydroxyapatite Scaffold Result in Better Outcomes after Surgical Treatment of Intertrochanteric Hip Fractures

PubMed Central

Gutierres, Manuel; Lopes, M. Ascenção; Santos, J. Domingos; Cabral, A. T.; Pinto, R.

2014-01-01

Introduction. Intertrochanteric hip fractures occur in the proximal femur. They are very common in the elderly and are responsible for high rates of morbidity and mortality. The authors hypothesized that adding an autologous bone marrow stem cells concentrate (ABMC) to a hydroxyapatite scaffold and placing it in the fracture site would improve the outcome after surgical fixation of intertrochanteric hip fractures. Material and Methods. 30 patients were randomly selected and divided into 2 groups of 15 patients, to receive either the scaffold enriched with the ABMC (Group A) during the surgical procedure, or fracture fixation alone (Group B). Results. There was a statistically significant difference in favor of group A at days 30, 60, and 90 for Harris Hip Scores (HHS), at days 30 and 60 for VAS pain scales, for bedridden period and time taken to start partial and total weight bearing (P < 0.05). Discussion. These results show a significant benefit of adding a bone marrow enriched scaffold to surgical fixation in intertrochanteric hip fractures, which can significantly reduce the associated morbidity and mortality rates. Conclusion. Bone marrow stem cells added to a hydroxyapatite scaffold result in better outcomes after surgical treatment of intertrochanteric hip fractures. PMID:24955356

Risk of head and neck squamous cell cancer and death in patients with Fanconi anemia who did and did not receive transplants.

PubMed

Rosenberg, Philip S; Socié, Gerard; Alter, Blanche P; Gluckman, Eliane

2005-01-01

Hematopoietic stem cell transplant (SCT) is currently the only therapy that can restore normal hematopoiesis in patients with Fanconi anemia (FA). Patients with FA have a high baseline risk of squamous cell cancers (SCCs) of the head, neck, and esophagus, and SCT conditioning may increase SCC incidence. We evaluated the risks of SCC and death in 145 patients with FA in the North American Survey (NAS) cohort who did not receive transplants, and 117 patients with FA in the Hôpital Saint Louis (SLH) cohort who did receive transplants. The age-specific hazard of SCC was 4.4-fold higher in patients who received transplants than in those who did not (P = .003), and SCCs occurred at significantly younger ages in the former (respective medians, 18 and 33 years, P = .004). Survival after SCC was similarly poor in both cohorts (P = .135, median, 13 months). The hazard of SCC increased at a greater than linear rate, to 4.4% per year by age 40 in NAS and 4.7% per year by 10 years after transplant in SLH. In SLH, the hazard of non-SCC death was biphasic, declining significantly (P = .004) from 7.1% per month during the first 6 months after transplant to 0.13% per month (1.6% per year) after the first year. Acute and chronic graft-versus-host diseases were significant SCC risk factors. Adverse event rates in these cohorts provide historical control rates to assess emerging therapies for FA.

Control of infectious mortality due to carbapenemase-producing Klebsiella pneumoniae in hematopoietic stem cell transplantation.

PubMed

Forcina, A; Baldan, R; Marasco, V; Cichero, P; Bondanza, A; Noviello, M; Piemontese, S; Soliman, C; Greco, R; Lorentino, F; Giglio, F; Messina, C; Carrabba, M; Bernardi, M; Peccatori, J; Moro, M; Biancardi, A; Nizzero, P; Scarpellini, P; Cirillo, D M; Mancini, N; Corti, C; Clementi, M; Ciceri, F

2017-01-01

Carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) infections are an emerging cause of death after hematopoietic stem cell transplantation (HSCT). In allogeneic transplants, mortality rate may rise up to 60%. We retrospectively evaluated 540 patients receiving a transplant from an auto- or an allogeneic source between January 2011 and October 2015. After an Institutional increase in the prevalence of KPC-Kp bloodstream infections (BSI) in June 2012, from July 2012, 366 consecutive patients received the following preventive measures: (i) weekly rectal swabs for surveillance; (ii) contact precautions in carriers (iii) early-targeted therapy in neutropenic febrile carriers. Molecular typing identified KPC-Kp clone ST512 as the main clone responsible for colonization, BSI and outbreaks. After the introduction of these preventive measures, the cumulative incidence of KPC-Kp BSI (P=0.01) and septic shocks (P=0.01) at 1 year after HSCT was significantly reduced. KPC-Kp infection-mortality dropped from 62.5% (pre-intervention) to 16.6% (post-intervention). Day 100 transplant-related mortality and KPC-Kp infection-related mortality after allogeneic HSCT were reduced from 22% to 10% (P=0.001) and from 4% to 1% (P=0.04), respectively. None of the pre-HSCT carriers was excluded from transplant. These results suggest that active surveillance, contact precautions and early-targeted therapies, may efficiently control KPC-Kp spread and related mortality even after allogeneic HSCT.

IMPACT OF PRE-TRANSPLANT RITUXIMAB ON SURVIVAL AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA

PubMed Central

Fenske, Timothy S.; Hari, Parameswaran N.; Carreras, Jeanette; Zhang, Mei-Jie; Kamble, Rammurti T.; Bolwell, Brian J.; Cairo, Mitchell S.; Champlin, Richard E.; Chen, Yi-Bin; Freytes, César O.; Gale, Robert Peter; Hale, Gregory A.; Ilhan, Osman; Khoury, H. Jean; Lister, John; Maharaj, Dipnarine; Marks, David I.; Munker, Reinhold; Pecora, Andrew L.; Rowlings, Philip A.; Shea, Thomas C.; Stiff, Patrick; Wiernik, Peter H.; Winter, Jane N.; Rizzo, J. Douglas; van Besien, Koen; Lazarus, Hillard M.; Vose, Julie M.

2010-01-01

Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens for diffuse large B-cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, many patients develop refractory or recurrent DLBCL and then receive autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes following AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n=176, “+R” group) or was not (n=818, “ −R” group) administered with front-line or salvage therapy prior to AuHCT. The +R group had superior progression-free survival (50% versus 38%, p=0.008) and overall survival (57% versus 45%, p=0.006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Non-relapse mortality (NRM) did not differ significantly between the +R and −R groups. In multivariate analysis, the +R group had improved progression-free survival (relative risk of relapse/progression or death 0.64, p<0.001) and improved overall survival (relative risk of death of 0.74, p=0.039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival following AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM. PMID:19822306

Pre- and postnatal transplantation of fetal mesenchymal stem cells in osteogenesis imperfecta: a two-center experience.

PubMed

Götherström, Cecilia; Westgren, Magnus; Shaw, S W Steven; Aström, Eva; Biswas, Arijit; Byers, Peter H; Mattar, Citra N Z; Graham, Gail E; Taslimi, Jahan; Ewald, Uwe; Fisk, Nicholas M; Yeoh, Allen E J; Lin, Ju-Li; Cheng, Po-Jen; Choolani, Mahesh; Le Blanc, Katarina; Chan, Jerry K Y

2014-02-01

Osteogenesis imperfecta (OI) can be recognized prenatally with ultrasound. Transplantation of mesenchymal stem cells (MSCs) has the potential to ameliorate skeletal damage. We report the clinical course of two patients with OI who received prenatal human fetal MSC (hfMSC) transplantation and postnatal boosting with same-donor MSCs. We have previously reported on prenatal transplantation for OI type III. This patient was retransplanted with 2.8 × 10(6) same-donor MSCs per kilogram at 8 years of age, resulting in low-level engraftment in bone and improved linear growth, mobility, and fracture incidence. An infant with an identical mutation who did not receive MSC therapy succumbed at 5 months despite postnatal bisphosphonate therapy. A second fetus with OI type IV was also transplanted with 30 × 10(6) hfMSCs per kilogram at 31 weeks of gestation and did not suffer any new fractures for the remainder of the pregnancy or during infancy. The patient followed her normal growth velocity until 13 months of age, at which time longitudinal length plateaued. A postnatal infusion of 10 × 10(6) MSCs per kilogram from the same donor was performed at 19 months of age, resulting in resumption of her growth trajectory. Neither patient demonstrated alloreactivity toward the donor hfMSCs or manifested any evidence of toxicities after transplantation. Our findings suggest that prenatal transplantation of allogeneic hfMSCs in OI appears safe and is of likely clinical benefit and that retransplantation with same-donor cells is feasible. However, the limited experience to date means that it is not possible to be conclusive and that further studies are required.

Comparison of clinical outcomes of patients with relapsed acute promyelocytic leukemia induced with arsenic trioxide and consolidated with either an autologous stem cell transplant or an arsenic trioxide-based regimen.

PubMed

Thirugnanam, Rajasekar; George, Biju; Chendamarai, Ezhil; Lakshmi, Kavitha M; Balasubramanian, Poonkuzhali; Viswabandya, Auro; Srivastava, Alok; Chandy, Mammen; Mathews, Vikram

2009-11-01

In patients with relapsed acute promyelocytic leukemia (APL), the best consolidation regimen following induction of remission with arsenic trioxide (ATO) remains to be defined. Since January 2000, 37 patients with relapsed APL were treated at our center. The median age was 34 years (range, 6-57 years), and there were 20 males (54.1%). The median duration of first remission was 20.3 months (range, 2.9-81.2 months). Relapse was treated with single-agent ATO in 22 patients (59.5%), ATO+ATRA in 5 patients (13.5%), and ATO+ATRA + anthracycline in 10 patients (27%). Thirty-three patients (89%) achieved molecular remission after induction and a consolidation course. Fourteen patients opted to undergo autologous stem cell transplantation (SCT), and the remaining 19 patients received monthly cycles of ATO as a single agent (n=13) or ATO+ATRA (n=6) for 6 months. At a median follow-up of 32 months, the 5-year Kaplan-Meier estimate of event-free survival (EFS) was 83.33% +/- 15.21% in those who underwent autologous SCT versus 34.45% +/- 11.24% in those who did not (P=.001; log-rank test). Following remission induction with ATO-based regimens in patients with relapsed APL, consolidation with autologous SCT is associated with a significantly superior clinical outcome compared with ATO- and ATO+ATRA-based maintenance regimens.

Treatment of sinusoidal obstruction syndrome with defibrotide: a single-center experience.

PubMed

Sucak, G T; Aki, Z S; Yagcí, M; Yegin, Z A; Ozkurt, Z N; Haznedar, R

2007-06-01

Sinusoidal obstruction syndrome (SOS) is a frequent, troubling, and potentially fatal complication of hematopoietic stem cell transplantation. Despite promising results with defibrotide (DF), no treatment has been established as standard. DF is a single-stranded polydeoxyribonucleotide, obtained from controlled depolymerization of porcine intestinal mucosal cells. It has antithrombotic, antiischemic, antiinflammatory, and thrombolytic properties without significant side effects. We retrospectively evaluated the charts of 80 consecutive patients, with 89 hematopoietic stem cell transplants for hematologic malignancies. The results of early initiation of DF treatment in 14 patients with SOS are presented in this study. Fourteen patients, 8 males and 6 females % median age 40.5 years (range, 16-46 years) were diagnosed to have SOS. Disease severity was classified as severe in 6 (42.85%), moderate in 4 (28.57%), and mild in 4 (28.57%) patients. We treated 14 patients with DF for a median of 21.5 days (range, 4-39 days). All 14 patients received DF after the diagnosis of SOS. Three patients with severe and all of the patients with mild to moderate SOS responded to treatment with complete resolution of SOS-related signs and symptoms. All patients responding to DF were alive at 100 days posttransplantation. There was no significant drug-related side effect among patients treated with DF. With an overall response rate of 78.56% and a 50% complete response rate in severe SOS cases and minimal side effects, we suggest that DF is the best available agent to treat SOS.

Lactobacillus brevis CD2 lozenges prevent oral mucositis in patients undergoing high dose chemotherapy followed by haematopoietic stem cell transplantation

PubMed Central

Sharma, Atul; Tilak, TVSVGK; Bakhshi, Sameer; Raina, Vinod; Kumar, Lalit; Chaudhary, Surendra Pal; Sahoo, Ranjit Kumar; Gupta, Ritu; Thulkar, Sanjay

2016-01-01

Background Oral mucositis is a common inflammatory complication in patients undergoing high-dose chemotherapy and radiation followed by haematopoietic stem cell transplantation (HSCT). Lactobacillus brevis CD2 has been proven efficacious in preventing chemoradiotherapy-induced oral mucositis in squamous cell carcinoma of head and neck. Methods This phase II study aimed to evaluate the safety and efficacy of L. brevis CD2 lozenges in preventing oral mucositis in patients undergoing HSCT. Eligible patients received four to six lozenges of L. brevis CD2 per day, beginning from 4 to 7 days before initiation of chemotherapy and continuing until resolution of mucositis or till day +24. Results Of 31 patients enrolled, 7 (22.6%) patients did not develop any mucositis, 6 (19.4%) patients developed grade 1, 12 (38.7%) patients developed grade 2, 4 (12.9%) and 2 (6.5%) patients developed grade 3 and grade 4 mucositis, respectively. Median time to onset and for resolution of mucositis were 6 days and 8 days, respectively. No adverse events were reported with usage of study drug. However, one patient died of Klebsiella sepsis. Conclusion Promising results from the study encourage the use of L. brevis CD2 lozenges as a supportive care treatment option; however, a randomised, double-blind, multicentric trial in a larger population is warranted. Trials registration number NCT01480011 at https://www.clinicaltrials.gov/ (Registered on Nov 04, 2011). PMID:28848667

BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma.

PubMed

Niesvizky, Ruben; Jayabalan, David S; Christos, Paul J; Furst, Jessica R; Naib, Tara; Ely, Scott; Jalbrzikowski, Jessica; Pearse, Roger N; Zafar, Faiza; Pekle, Karen; Larow, April; Lent, Richard; Mark, Tomer; Cho, Hearn J; Shore, Tsiporah; Tepler, Jeffrey; Harpel, John; Schuster, Michael W; Mathew, Susan; Leonard, John P; Mazumdar, Madhu; Chen-Kiang, Selina; Coleman, Morton

2008-02-01

This trial determined the safety and efficacy of the combination regimen clarithromycin (Biaxin), lenalidomide (Revlimid), and dexamethasone (BiRD) as first-line therapy for multiple myeloma. Patients received BiRD in 28-day cycles. Dexamethasone (40 mg) was given orally once weekly, clarithromycin (500 mg) was given orally twice daily, and lenalidomide (25 mg) was given orally daily on days 1 to 21. Objective response was defined by standard criteria (ie, decrease in serum monoclonal protein [M-protein] by at least 50%, and a decrease in urine M-protein by at least 90%). Of the 72 patients enrolled, 65 had an objective response (90.3%). A combined stringent and conventional complete response rate of 38.9% was achieved, and 73.6% of the patients achieved at least a 90% decrease in M-protein levels. This regimen did not interfere with hematopoietic stem-cell harvest. Fifty-two patients who did not go on to receive transplants received continued therapy (complete response, 37%; very good partial response, 33%). The major adverse events were thromboembolic events, corticosteroid-related morbidity, and cytopenias. BiRD is an effective regimen with manageable side effects in the treatment of symptomatic, newly diagnosed multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT00151203.

Zoledronate Attenuates Accumulation of DNA Damage in Mesenchymal Stem Cells and Protects Their Function

PubMed Central

Misra, Juhi; Mohanty, Sindhu T.; Madan, Sanjeev; Fernandes, James A.; Hal Ebetino, F.; Russell, R. Graham G.

2015-01-01

Abstract Mesenchymal stem cells (MSCs) undergo a decline in function following ex vivo expansion and exposure to irradiation. This has been associated with accumulation of DNA damage and has important implications for tissue engineering approaches or in patients receiving radiotherapy. Therefore, interventions, which limit accumulation of DNA damage in MSC, are of clinical significance. We were intrigued by findings showing that zoledronate (ZOL), an anti‐resorptive nitrogen containing bisphosphonate, significantly extended survival in patients affected by osteoporosis. The effect was too large to be simply due to the prevention of fractures. Moreover, in combination with statins, it extended the lifespan in a mouse model of Hutchinson Gilford Progeria Syndrome. Therefore, we asked whether ZOL was able to extend the lifespan of human MSC and whether this was due to reduced accumulation of DNA damage, one of the important mechanisms of aging. Here, we show that this was the case both following expansion and irradiation, preserving their ability to proliferate and differentiate in vitro. In addition, administration of ZOL before irradiation protected the survival of mesenchymal progenitors in mice. Through mechanistic studies, we were able to show that inhibition of mTOR signaling, a pathway involved in longevity and cancer, was responsible for these effects. Our data open up new opportunities to protect MSC from the side effects of radiotherapy in cancer patients and during ex vivo expansion for regenerative medicine approaches. Given that ZOL is already in clinical use with a good safety profile, these opportunities can be readily translated for patient benefit. Stem Cells 2016;34:756–767 PMID:26679354

BDNF improves the efficacy ERG amplitude maintenance by transplantation of retinal stem cells in RCS rats.

PubMed

Tian, Chunyu; Weng, Chuan Chuang; Yin, Zheng Qin

2010-01-01

The aim of this study was to evaluate the efficacy of subretinal transplantation of rat retinal stem cell when combined with Brain-derived neurotrophic factor (BDNF) in a rat model of retinal degeneration - Royal College of Surgeons (RCS) rats. Retinal stem cells were derived from embryonic day 17 Long-Evans rats and pre-labeled with fluorescence pigment-DiI prior to transplant procedures. RCS rats received injections of retinal stem cells, stem cells+BDNF, phosphate buffered saline or BNDF alone (n = 3 eyes for each procedure). At 1, 2 and 3 months after transplantation, the electroretinogram (ERG) was assessed and the outer nuclear layer thickness measured. The eyes receiving retinal stem cell and stem cell+BDNF transplants showed better photoreceptor maintenance than the other groups (P < 0.01) at all time points. One month after retina transplantation, the amplitudes of rod-ERG and Max-ERG b waves were significantly higher the eyes with stem cells+BDNF (P < 0.01), however, this difference was not seen at two and three months post transplantation. BDNF treatment alone group (without transplanted cells) had no effect when compared to buffer injections. The present results indicate that BDNF can enhance the short-term efficacy of the retinal stem cell transplantation in treating retinal degenerative disease.

Predictors of Radiation Pneumonitis in Patients Receiving Intensity Modulated Radiation Therapy for Hodgkin and Non-Hodgkin Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinnix, Chelsea C., E-mail: ccpinnix@mdanderson.org; Smith, Grace L.; Milgrom, Sarah

Purpose: Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a singlemore » institution. Methods and Materials: We retrospectively reviewed clinical charts and radiation records of 150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009 through 2013. Clinical and dosimetric predictors associated with RP according to Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified in univariate analysis using the Pearson χ{sup 2} test and logistic multivariate regression. Results: Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grades 1-3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation therapy (10%, P=.019). Several dosimetric parameters predicted RP, including mean lung dose of >13.5 Gy, V{sub 20} of >30%, V{sub 15} of >35%, V{sub 10} of >40%, and V{sub 5} of >55%. The likelihood ratio χ{sup 2} value was highest for V{sub 5} >55% (χ{sup 2} = 19.37). Conclusions: In using IMRT to treat mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with relapsed or refractory lymphoma who received salvage chemotherapy and hematopoietic stem cell transplantation were at higher risk for symptomatic RP.« less

Multiple intravitreal injections of ganciclovir for cytomegalovirus retinitis after stem-cell transplantation.

PubMed

Miao, Heng; Tao, Yong; Jiang, Yan-Rong; Li, Xiao-Xin

2013-07-01

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). Although much effort has been put into dealing with CMV retinitis secondary to acquired immunodeficiency syndrome (AIDS), the few reports which have been published have mainly focused on treatment of CMVR after HSCT. This clinical interventional retrospective study included 14 patients (eight men; mean age 23.89 ± 12.09; 23 eyes) who suffered from CMV retinitis after stem-cell transplantation, in order to evaluate the efficacy and safety of multiple intravitreal injections of ganciclovir (IVG) for patients with CMV retinitis. All patients received 4 injections of IVG of 1 mg at 1 week intervals, and were followed up weekly for at least 2 months with measurement of best-corrected visual acuity (BCVA) and CMV levels in anterior aqueous humor with real-time polymerase chain reaction. Anterior aqueous humor was obtained before each injection. The levels of CMV in anterior aqueous humor showed significant decrease from (6.34 ± 15.78) × 10(5) copies/ml at baseline to (5.22 ± 12.15) × 10(3) copies/ml at 1 month (P < 0.001, Mann-Whitney U test). CMV couldn't be detected in 11 eyes (47.8 %) after two injections, and this rose to 18 eyes (78.3 %) at 1 month. The mean logMAR BCVA was 0.659 ± 0.572 at baseline and 0.680 ± 0.527 at 2 months, which suggested no significant improvement (P = 0.736, Mann-Whitney U test) during the procedure. All patients experienced improved vitreous opacity and diminished area of the lesion under funduscopy after 4 injections of IVG. No severe complications developed. Multiple IVG seemed to be beneficial for patients with CMV retinitis after stem-cell transplantation, in reducing CMV levels in aqueous humor. Further study to optimize the dose of ganciclovir is needed in order to achieve better treatment outcomes.

Prediction of Hematopoietic Stem Cell Transplantation Related Mortality- Lessons Learned from the In-Silico Approach: A European Society for Blood and Marrow Transplantation Acute Leukemia Working Party Data Mining Study.

PubMed

Shouval, Roni; Labopin, Myriam; Unger, Ron; Giebel, Sebastian; Ciceri, Fabio; Schmid, Christoph; Esteve, Jordi; Baron, Frederic; Gorin, Norbert Claude; Savani, Bipin; Shimoni, Avichai; Mohty, Mohamad; Nagler, Arnon

2016-01-01

Models for prediction of allogeneic hematopoietic stem transplantation (HSCT) related mortality partially account for transplant risk. Improving predictive accuracy requires understating of prediction limiting factors, such as the statistical methodology used, number and quality of features collected, or simply the population size. Using an in-silico approach (i.e., iterative computerized simulations), based on machine learning (ML) algorithms, we set out to analyze these factors. A cohort of 25,923 adult acute leukemia patients from the European Society for Blood and Marrow Transplantation (EBMT) registry was analyzed. Predictive objective was non-relapse mortality (NRM) 100 days following HSCT. Thousands of prediction models were developed under varying conditions: increasing sample size, specific subpopulations and an increasing number of variables, which were selected and ranked by separate feature selection algorithms. Depending on the algorithm, predictive performance plateaued on a population size of 6,611-8,814 patients, reaching a maximal area under the receiver operator characteristic curve (AUC) of 0.67. AUCs' of models developed on specific subpopulation ranged from 0.59 to 0.67 for patients in second complete remission and receiving reduced intensity conditioning, respectively. Only 3-5 variables were necessary to achieve near maximal AUCs. The top 3 ranking variables, shared by all algorithms were disease stage, donor type, and conditioning regimen. Our findings empirically demonstrate that with regards to NRM prediction, few variables "carry the weight" and that traditional HSCT data has been "worn out". "Breaking through" the predictive boundaries will likely require additional types of inputs.

UGT2B17 minor histocompatibility mismatch and clinical outcome after HLA-identical sibling donor stem cell transplantation.

PubMed

Santos, N; Rodríguez-Romanos, R; Nieto, J B; Buño, I; Vallejo, C; Jiménez-Velasco, A; Brunet, S; Buces, E; López-Jiménez, J; González, M; Ferrá, C; Sampol, A; de la Cámara, R; Martínez, C; Gallardo, D

2016-01-01

Minor histocompatibility Ags (mHags) have been implicated in the pathogenesis of GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Uridine diphospho-glucuronosyltransferase 2B17 (UGT2B17) gene deletion may act as a mHag and its association with acute GVHD (aGVHD) has been described. We retrospectively studied the clinical impact of a UGT2B17 mismatch in a cohort of 1127 patients receiving a HSCT from an HLA-identical sibling donor. UGT2B17 mismatch was present in 69 cases (6.1%). Incidence of severe aGVHD was higher in the UGT2B17 mismatched pairs (22.7% vs 14.6%), but this difference was not statistically significant (P: 0.098). We did not detect differences in chronic GVHD, overall survival, relapse-free survival, transplant-related mortality or relapse. Nevertheless, when we analyzed only those patients receiving grafts from a male donor (616 cases), aGVHD was significantly higher in the UGT2B17 mismatched group (25.1% vs 12.8%; P: 0.005) and this association was confirmed by the multivariate analysis (P: 0.043; hazard ratio: 2.16, 95% confidence interval: 1.03-4.57). Overall survival was worse for patients mismatched for UGT2B17 (P: 0.005). We conclude that UGT2B17 mismatch has a negative clinical impact in allogeneic HSCT from HLA-identical sibling donors only when a male donor is used. These results should be confirmed by other studies.

Hepatic veno-occlusive disease in pediatric stem cell transplantation: impact of pre-emptive antithrombin III replacement and combined antithrombin III/defibrotide therapy.

PubMed

Haussmann, Ursula; Fischer, Joachim; Eber, Stefan; Scherer, Franziska; Seger, Reinhard; Gungor, Tayfun

2006-06-01

Hepatic veno-occlusive disease (VOD) remains a serious complication after hematopoietic stem cell transplantation (HSCT). Based on a protective effect of antithrombin III (ATIII) on endothelial cells, we assessed the incidence of VOD after pre-emptive ATIII replacement and the outcome of VOD after combined high dose defibrotide (DF) and ATIII therapy. This prospective case series comprised two phases. In the first phase 71 children did not receive any specific VOD prophylaxis or therapy (controls). In the second phase 91 children were given pre-emptive ATIII replacement in case of decreased ATIII activity (< or =70%). If VOD was diagnosed clinically (according to modified Seattle criteria), high dose defibrotide (60 mg/day) and ATIII replacement therapy were combined. The severity of VOD was determined according to the degree of multiple organ dysfunction. The incidence of VOD was similar in both groups (13/71, 18% vs. 14/91, 15%). All 14 patients in the second group who developed VOD showed decreased ATIII activity not more than 1 day prior to the clinical diagnosis of VOD. The resulting short duration of pre-emptive ATIII therapy failed to prevent VOD (OR 0.96). None of the patients (n=72) maintaining normal ATIII levels developed VOD. All 14 patients with VOD who received combined therapy achieved complete remission and 93 % (13/14) survived until day +100, compared to six survivors (46%) in the first group. Pre-emptive ATIII administration did not alter the incidence of VOD. Combination treatment with ATIII and defibrotide was safe and yielded excellent remission and survival rates.

First-in-man mesenchymal stem cells for radiation-induced xerostomia (MESRIX): study protocol for a randomized controlled trial.

PubMed

Grønhøj, Christian; Jensen, David H; Glovinski, Peter V; Jensen, Siri Beier; Bardow, Allan; Oliveri, Roberto S; Specht, Lena; Thomsen, Carsten; Darkner, Sune; Kiss, Katalin; Fischer-Nielsen, Anne; von Buchwald, Christian

2017-03-07

Salivary gland hypofunction and xerostomia are major complications following radiotherapy for head and neck cancer and may lead to debilitating oral disorders and impaired quality of life. Currently, only symptomatic treatment is available. However, mesenchymal stem cell (MSC) therapy has shown promising results in preclinical studies. Objectives are to assess safety and efficacy in a first-in-man trial on adipose-derived MSC therapy (ASC) for radiation-induced xerostomia. This is a single-center, phase I/II, randomized, placebo-controlled, double-blinded clinical trial. A total of 30 patients are randomized in a 1:1 ratio to receive ultrasound-guided, administered ASC or placebo to the submandibular glands. The primary outcome is change in unstimulated whole salivary flow rate. The secondary outcomes are safety, efficacy, change in quality of life, qualitative and quantitative measurements of saliva, as well as submandibular gland size, vascularization, fibrosis, and secretory tissue evaluation based on contrast-induced magnetic resonance imaging (MRI) and core-needle samples. The assessments are performed at baseline (1 month prior to treatment) and 1 and 4 months following investigational intervention. The trial is the first attempt to evaluate the safety and efficacy of adipose-derived MSCs (ASCs) in patients with radiation-induced xerostomia. The results may provide evidence for the effectiveness of ASC in patients with salivary gland hypofunction and xerostomia and deliver valuable information for the design of subsequent trials. EudraCT, Identifier: 2014-004349-29. Registered on 1 April 2015. ClinicalTrials.gov, Identifier: NCT02513238 . First received on 2 July 2015. The trial is prospectively registered.

Ethical and medical management of a pregnant woman with brain stem death resulting in delivery of a healthy child and organ donation.

PubMed

Gopčević, A; Rode, B; Vučić, M; Horvat, A; Širanović, M; Gavranović, Ž; Košec, V; Košec, A

2017-11-01

Maternal brain death during pregnancy remains an exceedingly complex situation that requires not only a well-considered medical management plan, but also careful decision-making in a legally and ethically delicate situation. Management of brain dead pregnant patients needs to adhere to special strategies that support the mother in a way that she can deliver a viable and healthy child. Brain death in pregnant women is very rare, with only a few published cases. We present a case of a pregnant woman with previously diagnosed multiple brain cavernomas that led to intracranial hemorrhage and brain stem death during the 21st week of pregnancy. The condition that can be proven unequivocally, using tests that do not endanger viability of the fetus, is brain stem death, diagnosed through absence of cranial reflexes. The patient was successfully treated until delivery of a healthy female child at 29weeks of gestation. The patient received continuous hormone substitution therapy, fetal monitoring and extrinsic regulation of maternal homeostasis over 64days. After delivery, the final diagnosis of brain death was established through multi-slice computerized tomography pan-angiography. This challenging case discusses ethical and medical circumstances arising from a diagnosis of maternal brain death, while showing that prolongation of somatic life support in a multidisciplinary setting can result in a successful pregnancy outcome. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Usefulness of Diffusion Tensor Imaging and Tractography in Surgery of Brainstem Cavernous Malformations.

PubMed

Januszewski, Jacob; Albert, Lauren; Black, Karen; Dehdashti, Amir R

2016-09-01

Diffusion tensor imaging (DTI) estimates the course and connectivity patterns of white matter tracts. The objective of this study is to evaluate whether findings in the brain stem modify the preoperative surgical trajectory planning or postoperative outcome in patients with brain stem cavernous malformations. Ten patients with symptomatic brainstem cavernous malformation underwent surgical resection. Five patients received preoperative DTI evaluation and the remaining 5 did not. Reconstructed DTI tracts consisted of corticospinal, medial lemnisci, and cerebellar peduncles. The surgical planning and postoperative outcome were evaluated. In 5 patients with no preoperative DTI evaluation, surgical planning was based on anatomic landmark and the 2-point technique. The other 5 patients underwent preoperative DTI, and findings were factored into the selection of the surgical approach. In 3 of the 5 cases with DTI evaluation, the 2-point technique suggested a similar trajectory. In the other 2, the DTI findings suggested a different approach to avoid damage to the white matter tract. Two patients in the group with no DTI had immediate postoperative new or worsened deficit, which improved at long-term follow-up. No patient in the DTI group had a new neurologic deficit. Compared with the standard magnetic resonance imaging, DTI provided improved visualization of cavernous malformation involvement in eloquent fiber tracts of the brainstem. This additional information might help in selecting a more appropriate surgical trajectory in selected lesions. Larger patient cohorts are needed to assess the effect of this modality in patients' outcome. Published by Elsevier Inc.

Evaluation of the immune status against measles, mumps, and rubella in adult allogeneic hematopoietic stem cell transplantation recipients.

PubMed

Kawamura, Koji; Yamazaki, Rie; Akahoshi, Yu; Nakano, Hirofumi; Ugai, Tomotaka; Wada, Hidenori; Yamasaki, Ryoko; Ishihara, Yuko; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-ichi; Kikuchi, Misato; Nakasone, Hideki; Kanda, Junya; Kako, Shinichi; Tanihara, Aki; Nishida, Junji; Kanda, Yoshinobu

2015-03-01

Previous studies have shown that most patients lose immunity to measles, mumps, and rubella (MMR) during long-term follow-up after allogeneic hematopoietic stem cell transplantation (HSCT), and immunizations against them have been investigated. However, these previous studies mainly targeted pediatric patients and information in adult patients is still insufficient. We evaluated the immunity to MMR in 45 adult allogeneic HSCT patients. None of these patients received vaccination after HSCT. The seropositive rates at six years after allogeneic HSCT were estimated to be less than 44% for measles, less than 10% for mumps, and less than 36% for rubella. Thirteen of the 16 female patients who were 16-39 years old were negative or equivocal for rubella. Patients who developed grade II-IV acute graft-versus-host disease tended to become seronegative for measles and rubella at two years after HSCT, although the difference was not statistically significant. This study showed that most adult patients lost immunity to MMR after allogeneic HSCT. Although we did not evaluate the safety and efficacy of vaccination in this study, most HSCT guidelines recommend vaccination for HSCT recipients without active chronic graft-versus-host disease or ongoing immunosuppressive therapy at 24 months after HSCT. Immunization against rubella is especially important for female patients of reproductive age. Further studies will be necessary to evaluate the effect of vaccination on the antibody response in adult allogeneic HSCT recipients.

Perception and Assessment of Verbal and Written Information on Sex and Relationships after Hematopoietic Stem Cell Transplantation.

PubMed

Wendt, Christel

2017-12-01

This study aimed to investigate experiences of verbal and written information about sex and relationships among men and women treated with hematopoietic stem cell transplantation. The study also aimed to investigate the demand for information and assessment of the quality of written patient information material entitled "Sex and relationships in the treatment of blood diseases." Few studies exist that shed any light on the demand for information about sex and relationships on the part of patients with hematological diseases before, during, and after their treatment. A total of 216 patients undergoing treatment for malignant blood diseases between 2000 and 2010 participated in this study. Patients' experiences of information about sex and relationships, and their opinions about the written patient information, were assessed using a questionnaire created specifically for this study. Most patients (81 %) had not received information about sex and relationships from a healthcare professional. Almost 90 % of men felt that verbal information was important, compared with 82 % of women. The majority also held that written information was important. These results indicate that patients, regardless of gender, age, and treatment, consider oral and written information about sex and relationships to be important and that the healthcare system should provide the information. The written patient information was considered to play an important role in creating an opening for a conversation about a sensitive topic such as sexuality, and also as a source of reference and support for the patient and his/her partner.

Allogeneic hematopoietic stem cell transplantation for severe, refractory juvenile idiopathic arthritis

PubMed Central

Ladomenou, Fani; Carpenter, Ben; Chandra, Sharat; Sedlacek, Petr; Formankova, Renata; Grandage, Vicky; Friswell, Mark; Cant, Andrew J.; Nademi, Zohreh; Slatter, Mary A.; Gennery, Andrew R.; Hambleton, Sophie; Flood, Terence J.; Lucchini, Giovanna; Chiesa, Robert; Rao, Kanchan; Amrolia, Persis J.; Brogan, Paul; Wedderburn, Lucy R.; Glanville, Julie M.; Hough, Rachael; Marsh, Rebecca; Abinun, Mario; Veys, Paul

2018-01-01

Patients with juvenile idiopathic arthritis (JIA) can experience a severe disease course, with progressive destructive polyarthritis refractory to conventional therapy with disease-modifying antirheumatic drugs including biologics, as well as life-threatening complications including macrophage activation syndrome (MAS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative immunomodulatory strategy for patients with such refractory disease. We treated 16 patients in 5 transplant centers between 2007 and 2016: 11 children with systemic JIA and 5 with rheumatoid factor–negative polyarticular JIA; all were either refractory to standard therapy, had developed secondary hemophagocytic lymphohistiocytosis/MAS poorly responsive to treatment, or had failed autologous HSCT. All children received reduced toxicity fludarabine-based conditioning regimens and serotherapy with alemtuzumab. Fourteen of 16 patients are alive with a median follow-up of 29 months (range, 2.8-96 months). All patients had hematological recovery. Three patients had grade II-IV acute graft-versus-host disease. The incidence of viral infections after HSCT was high, likely due to the use of alemtuzumab in already heavily immunosuppressed patients. All patients had significant improvement of arthritis, resolution of MAS, and improved quality of life early following allo-HSCT; most importantly, 11 children achieved complete drug-free remission at the last follow-up. Allo-HSCT using alemtuzumab and reduced toxicity conditioning is a promising therapeutic option for patients with JIA refractory to conventional therapy and/or complicated by MAS. Long-term follow-up is required to ascertain whether disease control following HSCT continues indefinitely. PMID:29618462

Stem cell transplantation compared with melphalan plus dexamethasone in the treatment of immunoglobulin light-chain amyloidosis.

PubMed

Gertz, Morie A; Lacy, Martha Q; Dispenzieri, Angela; Buadi, Francis K; Dingli, David; Hayman, Suzanne R; Kumar, Shaji K; Leung, Nelson; Lust, John; Rajkumar, S Vincent; Russell, Stephen J; Suman, Vera J; Le-Rademacher, Jennifer G; Hogan, William J

2016-07-15

Autologous stem cell transplantation (SCT) is a common management strategy for select patients with immunoglobulin light-chain amyloidosis, but no trials have documented improved overall survival. Eighty-nine patients with biopsy-proven immunoglobulin light-chain amyloidosis were allowed to select treatment with melphalan plus dexamethasone (n = 34) or SCT (n = 55); all patients were transplant eligible. Treatment preference resulted in imbalanced study arms. Patients who selected SCT were younger, more frequently had an Eastern Cooperative Oncology Group performance status score less than 2, had lower-stage amyloidosis, and had a lower incidence of cardiac amyloidosis. Patients receiving melphalan plus dexamethasone had a 3-year progression-free survival rate of 29.1% and an overall survival rate of 58.8%. Patients undergoing SCT had a 3-year progression-free survival rate of 51.7% and an overall survival rate of 83.6%. An attempt to match patients between the 2 arms in terms of risk produced 24 matched triplet sets (2 SCT patients for each melphalan-dexamethasone patient); there was no difference in hematologic response, but there was better survival after autologous SCT. A propensity score-matched analysis of the cohorts (melphalan plus dexamethasone vs SCT) showed an overall mortality hazard ratio of 2.56 (P < .01). Although the study had limitations, similar hematologic responses and improved survival were observed after SCT versus melphalan plus dexamethasone. Cancer 2016;122:2197-205. © 2016 American Cancer Society. © 2016 American Cancer Society.

Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study

PubMed Central

Elliott, Martin J; De Coppi, Paolo; Speggiorin, Simone; Roebuck, Derek; Butler, Colin R; Samuel, Edward; Crowley, Claire; McLaren, Clare; Fierens, Anja; Vondrys, David; Cochrane, Lesley; Jephson, Christopher; Janes, Samuel; Beaumont, Nicholas J; Cogan, Tristan; Bader, Augustinus; Seifalian, Alexander M; Hsuan, J Justin; Lowdell, Mark W; Birchall, Martin A

2015-01-01

Summary Background Stem-cell-based, tissue engineered transplants might offer new therapeutic options for patients, including children, with failing organs. The reported replacement of an adult airway using stem cells on a biological scaffold with good results at 6 months supports this view. We describe the case of a child who received a stem-cell-based tracheal replacement and report findings after 2 years of follow-up. Methods A 12-year-old boy was born with long-segment congenital tracheal stenosis and pulmonary sling. His airway had been maintained by metal stents, but, after failure, a cadaveric donor tracheal scaffold was decellularised. After a short course of granulocyte colony stimulating factor, bone marrow mesenchymal stem cells were retrieved preoperatively and seeded onto the scaffold, with patches of autologous epithelium. Topical human recombinant erythropoietin was applied to encourage angiogenesis, and transforming growth factor β to support chondrogenesis. Intravenous human recombinant erythropoietin was continued postoperatively. Outcomes were survival, morbidity, endoscopic appearance, cytology and proteomics of brushings, and peripheral blood counts. Findings The graft revascularised within 1 week after surgery. A strong neutrophil response was noted locally for the first 8 weeks after surgery, which generated luminal DNA neutrophil extracellular traps. Cytological evidence of restoration of the epithelium was not evident until 1 year. The graft did not have biomechanical strength focally until 18 months, but the patient has not needed any medical intervention since then. 18 months after surgery, he had a normal chest CT scan and ventilation-perfusion scan and had grown 11 cm in height since the operation. At 2 years follow-up, he had a functional airway and had returned to school. Interpretation Follow-up of the first paediatric, stem-cell-based, tissue-engineered transplant shows potential for this technology but also highlights the need for further research. Funding Great Ormond Street Hospital NHS Trust, The Royal Free Hampstead NHS Trust, University College Hospital NHS Foundation Trust, and Region of Tuscany. PMID:22841419

Generation of Human Induced Pluripotent Stem Cell‐Derived Bona Fide Neural Stem Cells for Ex Vivo Gene Therapy of Metachromatic Leukodystrophy

PubMed Central

Meneghini, Vasco; Sala, Davide; De Cicco, Silvia; Luciani, Marco; Cavazzin, Chiara; Paulis, Marianna; Mentzen, Wieslawa; Morena, Francesco; Giannelli, Serena; Sanvito, Francesca; Villa, Anna; Bulfone, Alessandro; Broccoli, Vania; Martino, Sabata

2016-01-01

Abstract Allogeneic fetal‐derived human neural stem cells (hfNSCs) that are under clinical evaluation for several neurodegenerative diseases display a favorable safety profile, but require immunosuppression upon transplantation in patients. Neural progenitors derived from patient‐specific induced pluripotent stem cells (iPSCs) may be relevant for autologous ex vivo gene‐therapy applications to treat genetic diseases with unmet medical need. In this scenario, obtaining iPSC‐derived neural stem cells (NSCs) showing a reliable “NSC signature” is mandatory. Here, we generated human iPSC (hiPSC) clones via reprogramming of skin fibroblasts derived from normal donors and patients affected by metachromatic leukodystrophy (MLD), a fatal neurodegenerative lysosomal storage disease caused by genetic defects of the arylsulfatase A (ARSA) enzyme. We differentiated hiPSCs into NSCs (hiPS‐NSCs) sharing molecular, phenotypic, and functional identity with hfNSCs, which we used as a “gold standard” in a side‐by‐side comparison when validating the phenotype of hiPS‐NSCs and predicting their performance after intracerebral transplantation. Using lentiviral vectors, we efficiently transduced MLD hiPSCs, achieving supraphysiological ARSA activity that further increased upon neural differentiation. Intracerebral transplantation of hiPS‐NSCs into neonatal and adult immunodeficient MLD mice stably restored ARSA activity in the whole central nervous system. Importantly, we observed a significant decrease of sulfatide storage when ARSA‐overexpressing cells were used, with a clear advantage in those mice receiving neonatal as compared with adult intervention. Thus, we generated a renewable source of ARSA‐overexpressing iPSC‐derived bona fide hNSCs with improved features compared with clinically approved hfNSCs. Patient‐specific ARSA‐overexpressing hiPS‐NSCs may be used in autologous ex vivo gene therapy protocols to provide long‐lasting enzymatic supply in MLD‐affected brains. Stem Cells Translational Medicine 2017;6:352–368 PMID:28191778

Does hydroxyapatite coating enhance ingrowth and improve longevity of a Zweymuller type stem? A double-blinded randomised RSA trial.

PubMed

Hoornenborg, Daniel; Sierevelt, Inger N; Spuijbroek, Joost A; Cheung, John; van der Vis, Harm M; Beimers, Lijkele; Haverkamp, Daniel

2017-09-11

An ongoing discussion is whether using a hydroxyapatite coating enhances the ingrowth and longevity of a femoral stem in total hip arthroplasty. The best way to predict speed of ingrowth and long-term outcome is by evaluating micromotion by radiostereometric analysis. To study the effect of hydroxyapatite (HA) coating on the migration of the SL-PLUS hip stem, we performed a prospective double blind randomised controlled trial comparing the early migration of the hydroxyapatite (HA)-coated SL-PLUS stem compared to the Standard (non-coated) SL-PLUS stem. 51 patients were randomly assigned to receive either an uncoated or a HA-coated femoral component during total hip replacement. RSA images were obtained direct postoperatively and at 6 weeks, 12 weeks, 6 months, 12 months and 24 months. HOOS scores were obtained preoperative and at final follow-up. RSA evaluation demonstrated significant migration up to 3 months postoperatively in both groups. After initial setting no significant migration was observed. There was no significant difference in migration between the HA-coated group and the uncoated group.Both Harris Hip Score (HHS) and HOOS domain scores (pain and ADL) significantly improved compared to baseline at 24 months after surgery in both treatment groups (p<0.001 for all comparisons). Improvement did not differ significantly between the 2 groups. At 2 years follow-up, the HA-coated and uncoated Zweymuller type, distal fitting stem do not show different migration patterns.

Unresolved issues in hematopoietic stem cell transplantation for severe combined immunodeficiency: Need for safer conditioning and reduced late effects

PubMed Central

Horn, Biljana; Cowan, Morton J.

2017-01-01

In this review we discuss recent outcomes of hematopoietic cell transplantation (HCT) for patients with severe combined immunodeficiency (SCID), including survival, T- and B-cell reconstitution, and late effects, particularly those related to genotype, use of conditioning regimen, and use of alternative donors. We identify the following issues that require additional data, which can be obtained through cooperative studies: outcomes of patients with SCID who did not receive conditioning before alternative donor HCT; outcomes of patients with SCID who did not receive graft-versus-host disease prophylaxis after T cell–replete HCT; late effects of HCT for patients with SCID, including neurocognitive outcomes, growth, and development; and their relationship to genotype and use of alkylating agents for conditioning. Careful follow-up of outcomes of all newborns receiving diagnoses based on newborn screening programs for SCID is essential because data are scarce on the effects of conditioning regimens in very young patients. A consensus on the definition of T- and B-cell recovery, criteria for additional “boosts,” pharmacokinetic data of chemotherapy agents used in young children, and uniformity of the use of various chemotherapy agents are needed to compare results among institutions. Finally, development of new nontoxic conditioning regimens for HCT that can be safely used in very young children is required. PMID:23622119

Improved disease-free-survival after transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical unrelated donors in patients with first chronic phase chronic myeloid leukemia.

PubMed

Elmaagacli, Ahmet H; Basoglu, Semiha; Peceny, Rudolf; Trenschel, Rudolf; Ottinger, Hellmut; Lollert, Andre; Runde, Volker; Grosse-Wilde, Hans; Beelen, Dietrich W; Schaefer, Ulrich W

2002-02-15

Outcomes after peripheral blood stem cell transplantation (PBSCT) for chronic phase chronic myeloid leukemia (n = 37) were compared with outcomes after bone marrow transplantation (BMT) (n = 54) in the HLA-compatible unrelated donor setting. Median follow-up was 17 months after PBSCT and 29 months after BMT. Both neutrophil and platelet recovery were faster after PBSCT (P <.05). PBSCT was associated with improved immune reconstitution, with higher peripheral blood naive (CD4(+)CD45RA(+)) and memory (CD4(+) CD45RO(+)) helper T cells at 3 months and 12 months after transplantation (P <.03). The cumulative incidence of acute (grades II-IV) and chronic graft-versus-host disease (GVHD) were similar, but BMT was associated with a higher cumulative incidence of severe, acute (grade III-IV) GVHD at 24% as compared with 8% with PBSCT (P <.05). Molecular relapse, defined by 2 consecutive positive polymerase chain reaction assays for bcr-abl within a 4-week interval, occurred in 12 of 45 evaluable patients (27%) after BMT and in 4 of 37 (11%) after PBSCT (not significant). Cytogenetic relapse occurred in 5 of 54 patients after BMT (9%) and in 1 of the 37 (3%) patients after PBSCT (not significant). Seventeen of the 54 patients died after BMT (31%), as compared with 2 of 37 patients after PBSCT (5%). Deaths in the BMT group were associated mainly with infections and severe, acute GVHD. The estimated probability of transplant-related mortality (TRM) and disease-free survival at 1000 days after receiving the transplant were 30% and 64% in the BMT group and 5% and 91% in the PBSCT group (P <.03). Overall survival 1000 days after receiving the transplant was 66% after BMT and 94% after PBSCT (P <.02). In the multivariate analysis, only acute GVHD significantly influenced TRM (P <.01).

High-dose sequential epirubicin and cyclophosphamide with peripheral blood stem cell support for advanced breast cancer: results of a phase II study

PubMed Central

Cottu, P H; Extra, J M; Espie, M; Marolleau, J P; Roquancourt, A de; Makke, J; Miclea, J M; Laurence, V; Mayeur, D; Lerebours, F; Cuvier, C; Marty, M

2001-01-01

The aim of this study was to evaluate the feasibility of a high-dose intensity and high-dose density multicycle epirubicin and cyclophosphamide regimen with peripheral blood stem cells (PBSC) and haematopoietic growth factor (G-CSF) support in advanced breast cancer patients. From August 1994 to September 1999, 56 breast cancer patients (8 stage IIIB and 48 stage IV) received 205 courses of cyclophosphamide 3 g m−2and epirubicin 100 mg m−2every 14 days. G-CSF 5 μg kg−1day−1was administered from day 3 to neutrophil recovery. 4 courses were planned. PBSC were collected after course 1, and reinfused after courses 3 and 4, with ≥ 2 × 106CD34+ PBSC kg−1required for each reinfusion. 48 patients (86%) received all 4 planned courses. Early withdrawal was consecutive to infectious complications (n= 4), severe asthenia (n= 3), haemorrhagic cystitis (n= 1). A median number of 10.8 × 106CD34+ PBSC kg−1(range, 3–80) was harvested with 1 or 2 apheresis in 48 patients (94%). Median relative dose intensity was 91.3% (range, 72–102%). Grade 4 neutrophil toxicity was observed in 100% of patients. Febrile neutropenia was observed in 40% of courses (median duration 2 days). Red blood cells and platelets had to be transfused in 54% and 27% of courses, respectively. There were no toxic deaths. Objective response rate was 69% in stage IV patients (31/45 evaluable pts), with a 16% complete response rate. Their median progression-free and overall survivals were 22.5 and 37 months, respectively. This epirubicine-containing high-dose regimen appeared feasible, albeit with high toxicity. Time-related progression parameters exceed commonly reported ones. Controlled studies of upfront sequential high-dose chemotherapy are still needed to evaluate its real benefit. © 2001 Cancer Research Campaign PMID:11720455

Missed strokes using computed tomography imaging in patients with vertigo: population-based cohort study.

PubMed

Grewal, Keerat; Austin, Peter C; Kapral, Moira K; Lu, Hong; Atzema, Clare L

2015-01-01

The purpose of this study was to determine the proportion of emergency department (ED) patients with a diagnosis of peripheral vertigo who received computed tomography (CT) head imaging in the ED and to examine whether strokes were missed using CT imaging. This population-based retrospective cohort study assessed patients who were discharged from an ED in Ontario, Canada, with a diagnosis of peripheral vertigo, April 2006 to March 2011. Patients who received CT imaging (exposed) were matched by propensity score methods to patients who did not (unexposed). If performed, CT imaging was presumed to be negative for stroke because brain stem/cerebellar stroke would result in hospitalization. We compared the incidence of stroke within 30, 90, and 365 days subsequent to ED discharge between groups, to determine whether the exposed group had a higher frequency of early strokes than the matched unexposed group. Among 41 794 qualifying patients, 8596 (20.6%) received ED head CT imaging, and 99.8% of these patients were able to be matched to a control. Among exposed patients, 25 (0.29%) were hospitalized for stroke within 30 days when compared with 11 (0.13%) among matched nonexposed patients. The relative risk of a 30- and 90-day stroke among exposed versus unexposed patients was 2.27 (95% confidence interval, 1.12-4.62) and 1.94 (95% confidence interval, 1.10-3.43), respectively. There was no difference between groups at 1 year. Strokes occurred at a median of 32.0 days (interquartile range, 4.0-33.0 days) in exposed patients, compared with 105 days (interquartile range, 11.5-204.5) in unexposed patients. One fifth of patients diagnosed with peripheral vertigo in Ontario received imaging that is not recommended in guidelines, and that imaging was associated with missed strokes. © 2014 American Heart Association, Inc.

Tracking the rise of stem cell tourism.

PubMed

Ryan, Kirsten A; Sanders, Amanda N; Wang, Dong D; Levine, Aaron D

2010-01-01

Driven by hype surrounding stem cell research, a number of clinics around the world currently offer 'stem cell therapies' to patients. These unproven interventions have attracted policy interest owing to the risks they may pose to patients and to the progress of legitimate translational stem cell research, yet remarkably little data exists about the patients who undergo these unproven therapies or their experiences. We sought to characterize this patient population. We developed a comprehensive data set of blogs written by patients (or their caretakers) about their experiences with unproven stem cell therapies. Analyzing these data suggests that unproven stem cell therapies are increasing rapidly in popularity and are attracting a wide range of patients--both young and old and with a diverse collection of medical conditions. These results should help clinicians advise individual patients and help policymakers devise strategies to mitigate the risks these treatments pose.

Travelling activity and travel-related risks after allogeneic haematopoietic stem cell transplantation - a single centre survey.

PubMed

Hollenstein, Yvonne; Elzi, Luigia; Hatz, Christoph; Passweg, Jakob; Weisser, Maja; Stöckle, Marcel; Halter, Joerg P; Egli, Adrian

2015-01-01

Travel activity and travel-related risks of patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT) remain largely unknown. The aim of our study was to examine travel activity after allo-HSCT including travel behaviour and travel patterns. We analysed travel characteristics of allo-HSCT recipients by using a retrospective cross-sectional survey. Allo-HSCT patients were asked to complete a questionnaire during their annual health visits from 2010 to 2012. Overall, 118/153 (77%) participating patients reported travel activity for a total of 201 travelling episodes. Travellers versus non-travellers were receiving immunosuppressive treatment in 35.6% versus 65.7% (p=0.002), and had graft-versus-host-disease (GvHD) in 52.5% versus 62.9% (p=0.17). In a multivariate analysis, the time between the transplantation and the survey was the only factor associated with travel activity (p<0.0001) and taking pretravel advice (p<0.0001). In 34.8% of travel episodes pretravel advice was sought. Patients with pretravel advice reported travel-related symptoms more frequently. Minor respiratory (27/201) and gastrointestinal (23/201) symptoms were most frequently indicated. Four percent (8/201) of the patients were hospitalised while travelling. We conclude that travelling after allo-HSCT is frequent and linked to the time since transplantation. We could not define specific risks for any destination. Nevertheless, pretravel advice and preparation are highly recommended for immunosuppressed patients.

Invasive Aspergillosis in Hematological Patients.

PubMed

Kimura, Shun-Ichi

2016-01-01

Invasive aspergillosis (IA) is still one of the leading causes of morbidity and mortality in hematological patients, although its outcome has been improving. Prolonged and profound neutropenia in patients receiving intensive chemotherapy for acute leukemia and stem cell transplantation is a major risk factor for IA. Allogeneic stem cell transplant recipients with graft-versus-host disease and corticosteroid use are also at high risk. Management in a protective environment with high efficiency particular air (HEPA) filter is generally recommended to prevent aspergillosis in patients with prolonged and profound neutropenia. Antifungal prophylaxis against Aspergillus species should be considered in patients with past history of aspergillosis or colonization of Aspergillus species, at facilities with high incidence of IA and those without a protective environment. Early diagnosis and prompt antifungal treatment is important to improve outcome. Imaging studies such as computed tomography and biomarkers such as galactomannan antigen and β-D-glucan are useful for early diagnosis. Empirical antifungal treatment based on persistent or recurrent fever during neutropenia despite broad-spectrum antibiotic therapy is generally recommended in high-risk patients. Alternatively, a preemptive treatment strategy has recently been proposed in the context of progress in the early diagnosis of IA based on the results of imaging studies and biomarkers. Voriconazole is recommended for initial therapy for IA. Liposomal amphotericin B is considered as alternative initial therapy. Combination antifungal therapy of echinocandin with voriconazole or liposomal amphotericin B could be a choice for refractory cases.

Role of Salvage Radiation Therapy for Patients With Relapsed or Refractory Hodgkin Lymphoma Who Failed Autologous Stem Cell Transplant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goda, Jayant S.; Massey, Christine; Kuruvilla, John

2012-11-01

Purpose: To analyze, through chart review, the efficacy of salvage radiation therapy (sRT) for relapsed or progressive Hodgkin lymphoma (HL) patients who failed autologous stem cell transplant (ASCT). Patients and Methods: Among 347 patients with recurrent/refractory HL who received ASCT from 1986-2006, 163 had post-ASCT progression or relapse. Of these, 56 received sRT and form the basis of this report. Median age at sRT was 30 years (range, 17-59 years). Disease was confined to lymph nodes in 27 patients, whereas 24 had both nodal and extranodal disease. Salvage radiation therapy alone was given in 34 patients (61%), and sRT plusmore » chemotherapy was given in 22 (39%). Median interval from ASCT to sRT was 0.8 years (range, 0.1-5.6 years). The median dose was 35 Gy (range, 8-40.3 Gy). The sRT technique was extended-field in 14 patients (25%) and involved-field in 42 (75%). Results: The median follow-up from sRT was 31.3 months (range, 0.2-205.5 months). Overall response rate was 84% (complete response: 36%; partial response: 48%). The median overall survival was 40.8 months (95% confidence interval, 34.2-56.3 months). The 5-year overall survival was 29% (95% confidence interval, 14%-44%). The 2-year progression-free survival (PFS) was 16%; the 2-year local PFS was 65%, whereas the 2-year systemic PFS was 17%. The 1-year PFS was higher in patients in whom all diseased sites were irradiated (49%) compared with those in whom only the symptomatic site was treated (22%, P=.07). Among 20 alive patients, 5 were disease free (at 6.4, 6.8, 7.4, 7.9, and 17.1 years). Conclusion: For patients with HL who fail ASCT, a selective use of RT provides a durable local control rate of 65% at 2 years and should be considered as part of the standard management plan for the palliation of incurable HL. Occasionally irradiation of truly localized disease can lead to long-term survival.« less

Total Body Irradiation Compared With BEAM: Long-Term Outcomes of Peripheral Blood Autologous Stem Cell Transplantation for Non-Hodgkin's Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Hong-Wei; University of Manitoba, Winnipeg, MB; Seftel, Matthew D.

Purpose: The optimal preparative regimen for non-Hodgkin's lymphoma patients undergoing autologous peripheral blood stem cell transplantation (PBSCT) is unknown. We compared a total body irradiation (TBI)-based regimen with a chemotherapy-alone regimen. Methods and Materials: A retrospective cohort study was performed at a Canadian cancer center. The TBI regimen consisted of cyclophosphamide, etoposide, and TBI 12 Gy in six fractions (CY/E/TBI). The chemotherapy-alone regimen consisted of carmustine, etoposide, cytarabine, and melphalan (BEAM). We compared the acute and long-term toxicities, disease relapse-free survival, and overall survival (OS). Results: Of 73 patients, 26 received CY/E/TBI and 47 received BEAM. The median follow-up formore » the CY/E/TBI group was 12.0 years and for the BEAM group was 7.3 years. After PBSCT, no differences in acute toxicity were seen between the two groups. The 5-year disease relapse-free survival rate was 50.0% and 50.7% in the CY/E/TBI and BEAM groups, respectively (p = .808). The 5-year OS rate was 53.9% and 63.8% for the CY/E/TBI and BEAM groups, respectivey (p = .492). The univariate analysis results indicated that patients with Stage IV, with chemotherapy-resistant disease, and who had received PBSCT before 2000 had inferior OS. A three-way categorical analysis revealed that transplantation before 2000, rather than the conditioning regimen, was a more important predictive factor of long-term outcome (p = .034). Conclusion: A 12-Gy TBI-based conditioning regimen for PBSCT for non-Hodgkin's lymphoma resulted in disease relapse-free survival and OS similar to that after BEAM. PBSCT before 2000, and not the conditioning regimen, was an important predictor of long-term outcomes. TBI was not associated with more acute toxicity or pneumonitis. We found no indication that the TBI regimen was inferior or superior to BEAM.« less

Current anti-myeloma therapies in renal manifestations of monoclonal light chain-associated Fanconi syndrome: a retrospective series of 49 patients.

PubMed

Vignon, M; Javaugue, V; Alexander, M P; El-Karoui, K; Karras, A; Roos-Weil, D; Royer, B; Asli, B; Knebelmann, B; Touchard, G; Jaccard, A; Arnulf, B; Bridoux, F; Leung, N; Fermand, J P

2017-01-01

We retrospectively reviewed 49 patients with light chain (LC) Fanconi syndrome (FS). Patients presented with chronic kidney disease (median estimated glomerular filtration rate (eGFR) of 33 ml/min/1.73 m 2 ) and tubular proteinuria. All patients tested had elevated fractional excretion of phosphate, uric acid, generalized aminoaciduria and/or normoglycemic glycosuria. Thirty-eight patients had monoclonal gammopathy of renal significance and eleven patients had an overt hematological malignancy. The monoclonal LC isotype was kappa in 46/49 cases. Kidney biopsy in 39 patients showed various proximal tubular lesions and characteristic LC intracytoplasmic crystalline inclusions in 24 patients. Forty-two patients received chemotherapy. Patients with plasma cell proliferation (n=38) received bortezomib-based regimens (n=11), immunomodulatory agents (n=7) or alkylating agents (n=6). High-dose melphalan (HDM) followed by autologous stem cell transplantation was performed in 14 patients. Hematological response was obtained in 90% of evaluable patients, assessed on serum free light chains (FLC). GFR remained stable as long as hematological response was maintained and declined when serum FLC level rebounded. Improvement in proximal tubule function occurred in 13 patients. In patients with LC-associated FS, chemotherapy using HDM and/or new generation anti-myeloma agents can stabilize renal function and improve proximal tubule function. Serum FLC should be used to assess the hematological response, related to renal outcome.

Umbilical Cord Blood Transplantation Corrects Very Early-Onset Inflammatory Bowel Disease in Chinese Patients With IL10RA-Associated Immune Deficiency.

PubMed

Peng, Kaiyue; Qian, Xiaowen; Huang, Zhiheng; Lu, Junping; Wang, Yuhuan; Zhou, Ying; Wang, Huijun; Wu, Bingbing; Wang, Ying; Chen, Lingli; Zhai, Xiaowen; Huang, Ying

2018-05-18

Hematopoietic stem cell transplantation is considered the only curative therapy for very early-onset inflammatory bowel disease with specific immune defects, such as interleukin-10 receptor deficiency. We performed reduced-intensity conditioning before umbilical cord blood transplantation in patients with interleukin-10 receptor-A deficiency. We enrolled 9 very early-onset inflammatory bowel disease patients with typical manifestations. We diagnosed the patients with interleukin-10 receptor-A deficiency by whole-exome sequencing. Umbilical cord blood transplantation was performed in all 9 patients. Eight patients received the reduced-intensity conditioning regimen, and 1 patient received the myeloablative conditioning regimen. All 9 patients received transplantation between the ages of 6 months to 43 months (average, 16.8 months) with body weights ranging from 3 to 10.4 kg (average, 6.6 kg). The patients displayed complete chimerism at 2-8 weeks after transplantation; 6 patients achieved complete remission without evidence of graft-vs-host disease or infections; 1 patient died of chronic lung graft-vs-host disease at 6 months post-transplantation; and the other 2 patients died of sepsis post-transplantation because of unsuccessful engraftments. Severe malnutrition and growth retardation associated with interleukin-10 receptor-A deficiency were significantly improved post-transplantation. We recommend umbilical cord blood transplantation as a potential treatment for very early-onset inflammatory bowel disease with a defined monogenic immunodeficiency, and we suggest that reduced-intensity conditioning chemotherapy is more suitable than myeloablative conditioning for patients with severe malnutrition and bowel disease. We have demonstrated success with reduced-intensity conditioning for interleukin-10 receptor-A deficiency in pediatric patients with severe clinical conditions. 10.1093/ibd/izy028_video1izy028.video15786489183001.

Clinical analysis of eight patients with blunt main stem bronchial injuries.

PubMed

Lei, Jie; Zhao, Jinbo; Tian, Feng; Wang, Xiaoping; Zhou, Yongan; Li, Xiaofei; Wang, Jian

2017-01-01

Blunt main stem bronchial injuries are rare but potentially life-threatening injuries in clinical. The aim of this study was to sum up the experience on diagnosis and treatment of blunt main stem bronchial injuries. This report retrospective1y analyzed eight cases of main stem bronchial injuries induced by blunt chest trauma between 2013 and 2016 in Tangdu Hospital, Fourth Military Medical University. There were eight patients, including four men and four women. The definitive diagnosis was confirmed by fibrobronchoscopy. Mean time between injury and treatment in our hospital was 4.25 days (range, 1-12 days). Mean length of airway tear was 1.04 cm (range, 0.5-2 cm). In four patients there was an injury to the left main stem bronchus, in three patients to the right main stem bronchus and in one patient to the ambilateral main stem bronchus. Emergent operation was performed in two patients and elective operation in six patients. End to end bronchial anastomosis was performed via right thoracotomy in two patients and via left thoracotomy in three patients, and primary repair was performed via right thoracotomy in two patients and via left thoracotomy in the remaining one patient. There was no death in this group. Seven patients had no complications and were able to take part in normal activities. One patient suffered from anastomotic stricture after operation was healed by granulation tissue resection and cryotherapy under fibrobronchoscopy. Fibrobronchoscopy is able to define the blunt main stem bronchial injuries precisely and surgical approach is the preferred method for patients with these life-threatening complications.

Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis.

PubMed

Lu, Zhengqi; Zhang, Bingjun; Qiu, Wei; Kang, Zhuang; Shen, Liping; Long, Youming; Huang, Junqi; Hu, Xueqiang

2011-01-01

Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS). To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS. Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral. Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases.

Comparative Brain Stem Lesions on MRI of Acute Disseminated Encephalomyelitis, Neuromyelitis Optica, and Multiple Sclerosis

PubMed Central

Kang, Zhuang; Shen, Liping; Long, Youming; Huang, Junqi; Hu, Xueqiang

2011-01-01

Background Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS). Objectives To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS. Methods Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. Results Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral. Conclusions Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases. PMID:21853047

Bendamustine added to allogeneic conditioning improves long-term outcomes in patients with CLL.

PubMed

Khouri, I F; Sui, D; Jabbour, E J; Samuels, B I; Turturro, F; Alatrash, G; Anderlini, P; Ahmed, S; Oran, B; Ciurea, S O; Marin, D; Olson, A; Patel, K K; Popat, U R; Ledesma, C; Kadia, T M; Ferrajoli, A; Burger, J A; Jorgensen, J L; Medeiros, L J; Bassett, R L; Gulbis, A M

2017-01-01

Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=<0.001). The 3-year overall survival estimates for the BFR and FCR groups were 82 and 51% (P=0.03), and the 3-year PFS estimates were 63% and 27% (P=0.001), respectively. The 2-year treatment-related mortality was 8 and 23% and the incidence of grade 3 or 4 GvHD was 4% and 10%, respectively. This study is the first to report that addition of bendamustine to alloSCT conditioning for CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.

Similar and Promising Outcomes in Lymphoma Patients Treated with Myeloablative or Nonmyeloablative Conditioning and Allogeneic Hematopoietic Cell Transplantation

PubMed Central

Tomblyn, Marcie; Brunstein, Claudio; Burns, Linda J.; Miller, Jeffrey S.; MacMillan, Margaret; DeFor, Todd E.; Weisdorf, Daniel J.

2008-01-01

We compared the outcomes of 141 consecutive patients who received allogeneic transplantation with either myeloablative (MA) or nonmyeloablative/reduced intensity (NMA) conditioning for non-Hodgkin and Hodgkin lymphoma at the University of Minnesota. All patients were transplanted between 1997 and 2004. NMA transplant recipients were older and received umbilical cord blood grafts more frequently (MA: 6 [9%]; NMA: 33 [43%], P < .001). NMA patients had more advanced disease and 30 (39%) patients had undergone prior autologous transplantation. The 4-year overall survival (OS) (MA: 46% versus NMA: 49%; p = .34) and the 3-year progression-free survival (PFS) (MA: 44% versus NMA: 31%; P = 0.82) were similar after MA or NMA conditioning. However, MA conditioning resulted in significantly higher 1-year treatment-related mortality (TRM) (MA: 43% versus NMA: 17%; P < .01) but a lower risk of relapse at 3 years (MA: 11% versus NMA: 36%; P < .01). We conclude that similar transplant outcomes are achieved after allogeneic hematopoietic stem cell transplantation using MA conditioning in younger patients and NMA conditioning in older patients or those with prior autologous transplantation not eligible for MA conditioning. Modifications to refine patient assignment to the preferred conditioning intensity and reduce relapse risks with NMA approaches are needed. PMID:18410896

Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia.

PubMed

Cai, Bo; Guo, Mei; Wang, Yao; Zhang, Yajing; Yang, Jun; Guo, Yelei; Dai, Hanren; Yu, Changlin; Sun, Qiyun; Qiao, Jianhui; Hu, Kaixun; Zuo, Hongli; Dong, Zheng; Zhang, Zechuan; Feng, Mingxing; Li, Bingxia; Sun, Yujing; Liu, Tieqiang; Liu, Zhiqing; Wang, Yi; Huang, Yajing; Yao, Bo; Han, Weidong; Ai, Huisheng

2016-11-25

Elderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T) cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined. We treated a 71-year-old female with relapsed and refractory ALL who received co-infusion of haplo-identical donor-derived CD19-directed CAR-T cells and mobilized peripheral blood stem cells (PBSC) following induction chemotherapy. Undetectable minimal residual disease by flow cytometry was achieved, and full donor cell engraftment was established. The transient release of cytokines and mild fever were detected. Significantly elevated serum lactate dehydrogenase, alanine transaminase, bilirubin and glutamic-oxalacetic transaminase were observed from days 14 to 18, all of which were reversible after immunosuppressive therapy. Our preliminary results suggest that co-infusion of haplo-identical donor-derived CAR-T cells and mobilized PBSCs may induce full donor engraftment in relapsed and refractory ALL including elderly patients, but complications related to donor cell infusions should still be cautioned. Allogeneic CART-19 for Elderly Relapsed/Refractory CD19+ ALL. NCT02799550.

A Comprehensive Assessment of Toxicities in Patients with Central Nervous System Lymphoma Undergoing Autologous Stem Cell Transplantation Using Thiotepa, Busulfan, and Cyclophosphamide Conditioning.

PubMed

Scordo, Michael; Bhatt, Valkal; Hsu, Meier; Omuro, Antonio M; Matasar, Matthew J; DeAngelis, Lisa M; Dahi, Parastoo B; Moskowitz, Craig H; Giralt, Sergio A; Sauter, Craig S

2017-01-01

High-dose therapy and autologous stem cell transplantation (ASCT) with thiotepa, busulfan, and cyclophosphamide (TBC) conditioning has emerged as an effective postinduction treatment strategy for patients with primary central nervous system lymphoma (PCNSL) or secondary central nervous system lymphoma (SCNSL), but it is associated with considerable toxicity and transplantation-related mortality (TRM) in the modern era. Forty-three adult patients with chemosensitive PCNSL or SCNSL underwent TBC-conditioned ASCT between 2006 and 2015. Twenty-eight of these patients received pharmacokinetically (PK)-targeted busulfan dosing. The median number of clinically relevant individual grade ≥3 nonhematologic toxicities per patient was 5. We found no association between pretransplantation patient characteristics and the presence of more than 5 grade ≥3 nonhematologic toxicities. Patients with elevated first-dose busulfan area under the curve values did not experience more toxicity. Paradoxically, patients treated with more than 2 regimens before undergoing ASCT had lower first-dose busulfan AUC values. With a median follow-up among survivors of 20 months, 1-year progression-free survival (PFS) and overall survival (OS) from the time of ASCT were 83% and 87%, respectively. Although this study reaffirms the favorable PFS and OS associated with TBC-conditioned ASCT for PCNSL or SCNSL, this treatment strategy carries a large toxicity burden. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Long-term outcomes of fludarabine, melphalan and antithymocyte globulin as reduced-intensity conditioning regimen for allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiency disorders: a prospective single center study.

PubMed

Hamidieh, A A; Behfar, M; Pourpak, Z; Faghihi-Kashani, S; Fazlollahi, M R; Hosseini, A S; Movahedi, M; Mozafari, M; Moin, M; Ghavamzadeh, A

2016-02-01

Reduced-intensity conditioning (RIC) has offered many primary immunodeficiency disorder (PID) patients who are ineligible for myeloablative regimens a chance of cure. However, the beneficial role of RIC was questioned following reports suggesting higher chance of rejection and lower symptom resolution rate in mixed chimerism settings. Forty-five children affected by PIDs with a median age of 21 months underwent allogeneic hematopoietic stem cell transplantation in our institute from 2007 to 2013. All patients received an identical RIC regimen. Forty-one patients had successful primary engraftment (91%). Of the successful engraftments, 80% (n=33) had stable full donor chimerism at last contact. Overall, eleven transplant-related mortalities were reported including five patients due to sepsis, three children due to grade IV acute GvHD, two due to chronic GvHD and one patient due to sepsis after primary graft failure. The median post-transplantation follow-up of deceased patients was 55 days. Five-year overall survival and disease-free survival was 75.6% and 68.89%, respectively. All surviving patients with successful engraftment became disease free, regardless of having full or mixed chimerism. Our study suggests that RIC regimen provides satisfactory rates of successful engraftment and full chimerism. Furthermore, patients with mixed chimerism were stable in long-term follow-up and this chimerism status offered the potential to resolve symptoms of immunodeficiency.

Does quality of life impact the decision to pursue stem cell transplantation for elderly patients with advanced MDS?

PubMed

El-Jawahri, A; Kim, H T; Steensma, D P; Cronin, A M; Stone, R M; Watts, C D; Chen, Y-B; Cutler, C S; Soiffer, R J; Abel, G A

2016-08-01

The factors that influence utilization of reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HCT) among medically fit older patients with advanced myelodysplastic syndromes (MDS) are largely unknown. The MDS Transplant-Associated Outcomes (MDS-TAO) study is an ongoing prospective observational study at the Dana-Farber Cancer Institute and Massachusetts General Hospital that enrolls transplant-eligible fit patients aged 60-75 years with advanced MDS and follows them through RIC HCT vs non-HCT treatment. In this analysis of 127 patients enrolled from May 2011 to June 2014, we examined the influence of age, gender, cytogenetics, International Prognostic Scoring System (IPSS) category, performance status, distance from HCT center and baseline patient-reported quality of life (QOL) from the EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) on the likelihood of receiving RIC HCT using competing risk regression modeling. With a median follow-up of 16 months, 44 patients (35%) had undergone RIC HCT. In multivariable analyses, age (hazard ratio (HR) 0.87 per year, 95% confidence interval (CI): 0.81-0.92, P<0.001) and higher IPSS (intermediate-2/high; HR 2.29, 95% CI: 1.25-4.19, P=0.007) were significantly predictive of receipt of RIC HCT; neither global QOL score nor any QOL subscales scores were predictive. These data suggest that baseline patient-reported QOL has little influence on the decision to undergo RIC HCT for older patients with advanced MDS.

Immune Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation and Association With Occurrence and Outcome of Invasive Aspergillosis.

PubMed

Stuehler, Claudia; Kuenzli, Esther; Jaeger, Veronika K; Baettig, Veronika; Ferracin, Fabrizia; Rajacic, Zarko; Kaiser, Deborah; Bernardini, Claudia; Forrer, Pascal; Weisser, Maja; Elzi, Luigia; Battegay, Manuel; Halter, Joerg; Passweg, Jakob; Khanna, Nina

2015-09-15

Invasive aspergillosis (IA) remains a leading cause of morbidity and mortality in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). To date, no reliable immunological biomarkers for management and outcome of IA exist. Here, we investigated reconstitution of antifungal immunity in patients during the first 12 months after HSCT and correlated it with IA. Fifty-one patients were included, 9 with probable/proven IA. We determined quantitative and qualitative reconstitution of polymorphonuclear (PMN), CD4, CD8, and natural killer (NK) cells against Aspergillus fumigatus over 5 time points and compared the values to healthy donors. Absolute CD4 and CD8 cell counts, antigen-specific T-cell responses, and killing capacity of PMN against A. fumigatus were significantly decreased in all patients over 12 months. In patients with probable/proven IA, reactive oxygen species (ROS) production tended to be lower compared to patients without IA, and absolute NK-cell counts remained below 200 cells/µL. Patients with well-controlled IA showed significantly higher ROS production and NK-cell counts compared to patients with poor outcome. This study highlights the importance of functional PMN, T-cell, and NK-cell immunity for the outcome of IA. Larger multicenter studies should address the potential use of NK-cell counts for the management of antifungal therapy. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Improved targeting and enhanced retention of the human, autologous, fibroblast-derived, induced, pluripotent stem cells to the sarcomeres of the infarcted myocardium with the aid of the bioengineered, heterospecific, tetravalent antibodies**

PubMed Central

Malecki, Marek

2013-01-01

Clinical trials, to regenerate the human heart injured by myocardial infarction, involve the delivery of stem cells to the site of the injury. However, only a small fraction of the introduced stem cells are detected at the site of the injury, merely two weeks after this therapeutic intervention. This significantly hampers the effectiveness of the stem cell therapy. To resolve the aforementioned problem, we genetically and molecularly bioengineered heterospecific, tetravalent antibodies (htAbs), which have both exquisite specificity and high affinity towards human, pluripotent, stem cells through the htAbs’ domains binding SSEA-4, SSEA-3, TRA-1-60, and TRA-1-81, as well as towards the injured cardiac muscle through the htAbs’ domains binding human cardiac myosin, α-actinin, actin, and titin. The cardiac tissue was acquired from the patients, who were receiving heart transplants. The autologous, human, induced, pluripotent stem cells (hiPSCs) were generated from the patients’ fibroblasts by non-viral delivery and transient expression of the DNA constructs for: Oct4, Nanog, Sox2, Lin28, Klf4, c-Myc. In the trials involving the htAbs, the human, induced, pluripotent stem cells anchored to the myocardial sarcomeres with the efficiency, statistically, significantly higher, than in the trials with non-specific or without antibodies (p < 0.0003). Moreover, application of the htAbs resulted in cross-linking of the sarcomeric proteins to create the stable scaffolds for anchoring of the stem cells. Thereafter, these human, induced pluripotent stem cells differentiated into cardiomyocytes at their anchorage sites. By bioengineering of these novel heterospecific, tetravalent antibodies and using them to guide and to anchor the stem cells specifically to the stabilized sarcomeric scaffolds, we demonstrated the proof of concept in vitro for improving effectiveness of regenerative therapy of myocardial infarction and created the foundations for the trials in vivo. PMID:23956947

Stem cells in pharmaceutical biotechnology.

PubMed

Zuba-Surma, Ewa K; Józkowicz, Alicja; Dulak, Józef

2011-11-01

Multiple populations of stem cells have been indicated to potentially participate in regeneration of injured organs. Especially, embryonic stem cells (ESC) and recently inducible pluripotent stem cells (iPS) receive a marked attention from scientists and clinicians for regenerative medicine because of their high proliferative and differentiation capacities. Despite that ESC and iPS cells are expected to give rise into multiple regenerative applications when their side effects are overcame during appropriate preparation procedures, in fact their most recent application of human ESC may, however, reside in their use as a tool in drug development and disease modeling. This review focuses on the applications of stem cells in pharmaceutical biotechnology. We discuss possible relevance of pluripotent cell stem populations in developing physiological models for any human tissue cell type useful for pharmacological, metabolic and toxicity evaluation necessary in the earliest steps of drug development. The present models applied for preclinical drug testing consist of primary cells or immortalized cell lines that show limitations in terms of accessibility or relevance to their in vivo counterparts. The availability of renewable human cells with functional similarities to their in vivo counterparts is the first landmark for a new generation of cell-based assays. We discuss the approaches for using stem cells as valuable physiological targets of drug activity which may increase the strength of target validation and efficacy potentially resulting in introducing new safer remedies into clinical trials and the marketplace. Moreover, we discuss the possible applications of stem cells for elucidating mechanisms of disease pathogenesis. The knowledge about the mechanisms governing the development and progression of multitude disorders which would come from the cellular models established based on stem cells, may give rise to new therapeutical strategies for such diseases. All together, the applications of various cell types derived from patient specific pluripotent stem cells may lead to targeted drug and cellular therapies for certain individuals.

Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis

PubMed Central

Abrahamsson, Sofia V.; Angelini, Daniela F.; Dubinsky, Amy N.; Morel, Esther; Oh, Unsong; Jones, Joanne L.; Carassiti, Daniele; Reynolds, Richard; Salvetti, Marco; Calabresi, Peter A.; Coles, Alasdair J.; Battistini, Luca; Martin, Roland; Burt, Richard K.

2013-01-01

Autologous haematopoietic stem cell transplantation has been tried as one experimental strategy for the treatment of patients with aggressive multiple sclerosis refractory to other immunotherapies. The procedure is aimed at ablating and repopulating the immune repertoire by sequentially mobilizing and harvesting haematopoietic stem cells, administering an immunosuppressive conditioning regimen, and re-infusing the autologous haematopoietic cell product. ‘Non-myeloablative’ conditioning regimens to achieve lymphocytic ablation without marrow suppression have been proposed to improve safety and tolerability. One trial with non-myeloablative autologous haematopoietic stem cell transplantation reported clinical improvement and inflammatory stabilization in treated patients with highly active multiple sclerosis. The aim of the present study was to understand the changes in the reconstituted immune repertoire bearing potential relevance to its mode of action. Peripheral blood was obtained from 12 patients with multiple sclerosis participating in the aforementioned trial and longitudinally followed for 2 years. We examined the phenotype and function of peripheral blood lymphocytes by cell surface or intracellular staining and multi-colour fluorescence activated cell sorting alone or in combination with proliferation assays. During immune reconstitution post-transplantation we observed significant though transient increases in the proportion of CD4+FoxP3+ T cells and CD56high natural killer cell subsets, which are cell subsets associated with immunoregulatory function. CD8+CD57+ cytotoxic T cells were persistently increased after therapy and were able to suppress CD4+ T cell proliferation with variable potency. In contrast, a CD161high proinflammatory CD8+ T cell subset was depleted at all time-points post-transplantation. Phenotypic characterization revealed that the CD161highCD8+ T cells were mucosal-associated invariant T cells, a novel cell population originating in the gut mucosa but expressing the central nervous system-homing receptor CCR6. Detection of mucosal-associated invariant T cells in post-mortem multiple sclerosis brain white matter active lesions confirmed their involvement in the disease pathology. Intracellular cytokine staining demonstrated interferon γ and interleukin 17 production and lack of interleukin 10 production, a pro-inflammatory profile. Mucosal-associated invariant T cell frequency did not change in patients treated with interferon β; and was more depleted after autologous haematopoietic stem cell transplantation than in patients who had received high-dose cyclophosphamide (n = 7) or alemtuzumab (n = 21) treatment alone, suggesting an additive or synergistic effect of the conditioning regime components. We propose that a favourably modified balance of regulatory and pro-inflammatory lymphocytes underlies the suppression of central nervous system inflammation in patients with multiple sclerosis following non-myeloablative autologous haematopoietic stem cell transplantation with a conditioning regimen consisting of cyclophosphamide and alemtuzumab. PMID:23864273

10-year results of a new low-monomer cement: follow-up of a randomized RSA study.

PubMed

Söderlund, Per; Dahl, Jon; Röhrl, Stephan; Nivbrant, Bo; Nilsson, Kjell G

2012-12-01

The properties and performance of a new low-monomer cement were examined in this prospective randomized, controlled RSA study. 5-year data have already been published, showing no statistically significant differences compared to controls. In the present paper we present the 10-year results. 44 patients were originally randomized to receive total hip replacement with a Lubinus SPII titanium-aluminum-vanadium stem cemented either with the new Cemex Rx bone cement or with control bone cement, Palacos R. Patients were examined using RSA, Harris hip score, and conventional radiographs. At 10 years, 33 hips could be evaluated clinically and 30 hips could be evaluated with RSA (16 Cemex and 14 Palacos). 9 patients had died and 4 patients were too old or infirm to be investigated. Except for 1 hip that was revised for infection after less than 5 years, no further hips were revised before the 10-year follow-up. There were no statistically significant clinical differences between the groups. The Cemex cement had magnitudes of migration similar to or sometimes lower than those of Palacos cement. In both groups, most hips showed extensive radiolucent lines, probably due to the use of titanium alloy stems. At 10 years, the Cemex bone cement tested performed just as well as the control (Palacos bone cement).

Low-dose cidofovir treatment of BK virus-associated hemorrhagic cystitis in recipients of hematopoietic stem cell transplant.

PubMed

Savona, M R; Newton, D; Frame, D; Levine, J E; Mineishi, S; Kaul, D R

2007-06-01

In recipients of hematopoietic stem cell transplants (HSCTs), BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC). In our institution, HSCT recipients with BKV-associated HC are treated with 1 mg/kg of cidofovir weekly. We identified HSCT recipients with BKV-associated HC, treated with weekly cidofovir. Microbiological response was defined as at least a one log reduction in urinary BKV viral load; clinical response was defined as improvement in symptoms and stability or reduction in the grade of cystitis. Nineteen allogeneic HSCT patients received a mean of 4.5 weekly doses of cidofovir. HC occurred at a mean of 68.7 days after transplant. A clinical response was detected in 16/19 (84%) patients, and 9/19 (47%) had a measurable microbiological response (8/10 nonresponders had a BKV viral load above the upper limit of the assay before treatment). Fourteen out of nineteen (74%) patients had no significant increase in serum creatinine. Five patients with renal dysfunction resolved after completion of the therapy and removal of other nephrotoxic agents. We conclude that weekly low-dose cidofovir appears to be a safe treatment option for BKV-associated HC. Although the efficacy of low-dose cidofovir is not proven, a prospective trial is warranted.

The effect of N-acetyl-l-cysteine (NAC) on liver toxicity and clinical outcome after hematopoietic stem cell transplantation.

PubMed

El-Serafi, Ibrahim; Remberger, Mats; El-Serafi, Ahmed; Benkessou, Fadwa; Zheng, Wenyi; Martell, Eva; Ljungman, Per; Mattsson, Jonas; Hassan, Moustapha

2018-05-29

Busulphan (Bu) is a myeloablative drug used for conditioning prior to hematopoietic stem cell transplantation. Bu is predominantly metabolized through glutathione conjugation, a reaction that consumes the hepatic glutathione. N-acetyl-l-cysteine (NAC) is a glutathione precursor used in the treatment of acetaminophen hepatotoxicity. NAC does not interfere with the busulphan myeloablative effect. We investigated the effect of NAC concomitant treatment during busulphan conditioning on the liver enzymes as well as the clinical outcome. Prophylactic NAC treatment was given to 54 patients upon the start of busulphan conditioning. These patients were compared with 54 historical matched controls who did not receive NAC treatment. In patients treated with NAC, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were significantly (P < 0.05) decreased after conditioning compared to their start values. Within the NAC-group, liver enzymes were normalized in those patients (30%) who had significantly high start values. No significant decrease in enzyme levels was observed in the control group. Furthermore, NAC affected neither Bu kinetics nor clinical outcome (sinusoidal obstruction syndrome incidence, graft-versus-host disease and/or graft failure). NAC is a potential prophylactic treatment for hepatotoxicity during busulphan conditioning. NAC therapy did not alter busulphan kinetics or affect clinical outcome.

Clinical trials update from the American Heart Association: REPAIR-AMI, ASTAMI, JELIS, MEGA, REVIVE-II, SURVIVE, and PROACTIVE.

PubMed

Cleland, John G F; Freemantle, Nick; Coletta, Alison P; Clark, Andrew L

2006-01-01

This article provides information and a commentary on trials presented at the American Heart Association meeting held in November 2005, relevant to the pathophysiology, prevention and treatment of heart failure. All reports should be considered as preliminary data, as analyses may change in the final publication. In REPAIR-AMI an improvement in ejection fraction was observed in post-MI patients following infusion of bone marrow stem cells. However, the ASTAMI study showed no benefit of stem cell implantation in a similar patient cohort. The JELIS study reported a reduction in major coronary events in patients receiving statins plus fish oil compared to statins alone. MEGA showed that low dose statins in a low risk population reduce the incidence of major cardiovascular events. Two studies of levosimendan in acute heart failure gave conflicting results, in the REVIVE-II study levosimendan was reported to have a superior effect on the composite primary outcome compared to placebo, however, in SURVIVE despite a trend to early benefit with levosimendan, there was no difference in effect on long-term outcome versus dobutamine. The PROACTIVE study showed encouraging results for the use of pioglitazone in post-myocardial infarction patients with concomitant type 2 diabetes.

Graft-versus-host disease

MedlinePlus

GVHD; Bone marrow transplant - graft-versus-host disease; Stem cell transplant - graft-versus-host disease; Allogeneic transplant - ... GVHD may occur after a bone marrow, or stem cell, transplant in which someone receives bone marrow ...

Dose-escalation study for the targeting of CD44v+ cancer stem cells by sulfasalazine in patients with advanced gastric cancer (EPOC1205).

PubMed

Shitara, Kohei; Doi, Toshihiko; Nagano, Osamu; Imamura, Chiyo K; Ozeki, Takeshi; Ishii, Yuya; Tsuchihashi, Kenji; Takahashi, Shunji; Nakajima, Takako E; Hironaka, Shuichi; Fukutani, Miki; Hasegawa, Hiromi; Nomura, Shogo; Sato, Akihiro; Einaga, Yasuaki; Kuwata, Takeshi; Saya, Hideyuki; Ohtsu, Atsushi

2017-03-01

Cancer stem cells (CSCs) have enhanced mechanisms of protection from oxidative stress. A variant form of CD44 (CD44v), a major CSC marker, was shown to interact with xCT, a subunit of cystine-glutamate transporter, which maintains high levels of intracellular reduced glutathione (GSH) which defend the cell against oxidative stress. Sulfasalazine (SSZ) is an inhibitor of xCT and was shown to suppress the survival of CD44v-positive stem-like cancer cells both in vitro and in vivo. To find the dose of SSZ which can safely reduce the population of CD44v-positive cells in tumors, a dose-escalation study in patients with advanced gastric cancer was conducted. SSZ was given four times daily by oral administration with 2 weeks as one cycle. Tumor biopsies were obtained before and after 14 days of administration of SSZ to evaluate expression of CD44v and the intratumoral level of GSH. Eleven patients were enrolled and received a dosage from 8 to 12 g/day. Safety was confirmed up to a dosage of 12 g/day, which was considered the maximum tolerated dose. Among the eight patients with CD44v-positive cells in their pretreatment biopsy samples, the CD44v-positive cancer cell population appeared to be reduced in the posttreatment biopsy tissues of four patients. Intratumoral GSH levels were also decreased in two patients, suggesting biological effectiveness of SSZ at 8 g/day or greater. This is the first study of SSZ as an xCT inhibitor for targeting CSCs. Reduction of the levels of CD44v-positive cells and GSH was observed in some patients, consistent with the mode of action of SSZ in CSCs.

Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study.

PubMed

Biondi, Andrea; Schrappe, Martin; De Lorenzo, Paola; Castor, Anders; Lucchini, Giovanna; Gandemer, Virginie; Pieters, Rob; Stary, Jan; Escherich, Gabriele; Campbell, Myriam; Li, Chi-Kong; Vora, Ajay; Aricò, Maurizio; Röttgers, Silja; Saha, Vaskar; Valsecchi, Maria Grazia

2012-09-01

Trials of imatinib have provided evidence of activity in adults with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (ALL), but the drug's role when given with multidrug chemotherapy to children is unknown. This study assesses the safety and efficacy of oral imatinib in association with a Berlin-Frankfurt-Munster intensive chemotherapy regimen and allogeneic stem-cell transplantation for paediatric patients with Philadelphia-chromosome-positive ALL. Patients aged 1-18 years recruited to national trials of front-line treatment for ALL were eligible if they had t(9;22)(q34;q11). Patients with abnormal renal or hepatic function, or an active systemic infection, were ineligible. Patients were enrolled by ten study groups between 2004 and 2009, and were classified as good risk or poor risk according to early response to induction treatment. Good-risk patients were randomly assigned by a web-based system with permuted blocks (size four) to receive post-induction imatinib with chemotherapy or chemotherapy only in a 1:1 ratio, while all poor-risk patients received post-induction imatinib with chemotherapy. Patients were stratified by study group. The chemotherapy regimen was modelled on a Berlin-Frankfurt-Munster high-risk backbone; all received four post-induction blocks of chemotherapy after which they became eligible for stem-cell transplantation. The primary endpoints were disease-free survival at 4 years in the good-risk group and event-free survival at 4 years in the poor-risk group, analysed by intention to treat and a secondary analysis of patients as treated. The trial is registered with EudraCT (2004-001647-30) and ClinicalTrials.gov, number NCT00287105. Between Jan 1, 2004, and Dec 31, 2009, we screened 229 patients and enrolled 178: 108 were good risk and 70 poor risk. 46 good-risk patients were assigned to receive imatinib and 44 to receive no imatinib. Median follow-up was 3·1 years (IQR 2·0-4·6). 4-year disease-free survival was 72·9% (95% CI 56·1-84·1) in the good-risk, imatinib group versus 61·7% (45·0-74·7) in the good-risk, no imatinib group (p=0·24). The hazard ratio (HR) for failure, adjusted for minimal residual disease, was 0·63 (0·28-1·41; p=0·26). The as-treated analysis showed 4-year disease-free survival was 75·2% (61·0-84·9) for good-risk patients receiving imatinib and 55·9% (36·1-71·7) for those who did not receive imatinib (p=0·06). 4-year event-free survival for poor-risk patients was 53·5% (40·4-65·0). Serious adverse events were much the same in the good-risk groups, with infections caused by myelosuppression the most common. 16 patients in the good-risk imatinib group versus ten in the good-risk, no imatinib group (p=0·64), and 24 in the poor-risk group, had a serious adverse event. Our results suggests that imatinib in conjunction with intensive chemotherapy is well tolerated and might be beneficial for treatment of children with Philadelphia-chromosome-positive ALL. Projet Hospitalier de Recherche Clinique-Cancer (France), Fondazione Tettamanti-De Marchi and Associazione Italiana per la Ricerca sul Cancro (Italy), Novartis Germany, Cancer Research UK, Leukaemia Lymphoma Research, and Central Manchester University Hospitals Foundation Trust. Copyright © 2012 Elsevier Ltd. All rights reserved.

Development of a Web-Based Intervention for Addressing Distress in Caregivers of Patients Receiving Stem Cell Transplants: Formative Evaluation With Qualitative Interviews and Focus Groups

PubMed

Pensak, Nicole Amoyal; Joshi, Tanisha; Simoneau, Teresa; Kilbourn, Kristin; Carr, Alaina; Kutner, Jean; Laudenslager, Mark L

2017-06-22

Caregivers of cancer patients experience significant burden and distress including depression and anxiety. We previously demonstrated the efficacy of an eight session, in-person, one-on-one stress management intervention to reduce distress in caregivers of patients receiving allogeneic hematopoietic stem cell transplants (allo-HSCT). The objective of this study was to adapt and enhance the in-person caregiver stress management intervention to a mobilized website (eg, tablet, smartphone, or computer-based) for self-delivery in order to enhance dissemination to caregiver populations most in need. We used an established approach for development of a mhealth intervention, completing the first two research and evaluation steps: Step One: Formative Research (eg, expert and stakeholder review from patients, caregivers, and palliative care experts) and Step Two: Pretesting (eg, Focus Groups and Individual Interviews with caregivers of patients with autologous HSCT (auto-HSCT). Step one included feedback elicited for a mock-up version of Pep-Pal session one from caregiver, patients and clinician stakeholders from a multidisciplinary palliative care team (N=9 caregivers and patient stakeholders and N=20 palliative care experts). Step two included two focus groups (N=6 caregivers) and individual interviews (N=9 caregivers) regarding Pep-Pal's look and feel, content, acceptability, and potential usability/feasibility. Focus groups and individual interviews were audio-recorded. In addition, individual interviews were transcribed, and applied thematic analysis was conducted in order to gain an in-depth understanding to inform the development and refinement of the mobilized caregiver stress management intervention, Pep-Pal (PsychoEducation and skills for Patient caregivers). Overall, results were favorable. Pep-Pal was deemed acceptable for caregivers of patients receiving an auto-HSCT. The refined Pep-Pal program consisted of 9 sessions (Introduction to Stress, Stress and the Mind Body Connection, How Thoughts Can Lead to Stress, Coping with Stress, Strategies for Maintaining Energy and Stamina, Coping with Uncertainty, Managing Changing Relationships and Communicating Needs, Getting the Support You Need, and Improving Intimacy) delivered via video instruction through a mobilized website. Feedback from stakeholder groups, focus groups, and individual interviews provided valuable feedback in key areas that was integrated into the development of Pep-Pal with the goal of enhancing dissemination, engagement, acceptability, and usability. ©Nicole Amoyal Pensak, Tanisha Joshi, Teresa Simoneau, Kristin Kilbourn, Alaina Carr, Jean Kutner, Mark L. Laudenslager. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 22.06.2017.

Survival after stem-cell transplant in pediatric and young-adult patients with relapsed and refractory B-cell acute lymphoblastic leukemia.

PubMed

Crotta, Alessandro; Zhang, Jie; Keir, Christopher

2018-03-01

Allogeneic stem-cell transplant (allo-SCT) is the standard of care for pediatric patients with acute lymphoblastic leukemia (ALL) who relapse after frontline chemotherapy; however, for patients who relapse after allo-SCT, outcomes are very poor. Few studies have examined overall survival in this patient population, particularly in patients who received a second allo-SCT. This was a retrospective analysis using data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. The study population included patients aged 3 to 21 years who were diagnosed with B-ALL and underwent their first allo-SCT between 2009 and 2013. The primary endpoint was the time from the date of posttransplant relapse to the date of death due to any reason. Outcomes in 1349 pediatric and young-adult patients were included in this analysis. The Kaplan-Meier estimated probability of survival at 3 years after first allo-SCT was 63.1% (95% CI, 60.2%-65.8%). Overall, 29.2% of patients relapsed after first allo-SCT and had a median survival of 7.4 months (95% CI, 6.0-9.6 months). Twenty-five patients in the analysis developed secondary malignancies, most of which were lymphoproliferative disorders. Survival rates are low in pediatric and young-adult patients who relapse after first and second allo-SCT, and new therapies are needed to improve outcomes in this population. This data can be used as a historical comparison for single-arm trials of novel therapies for this patient population, including chimeric antigen receptor T-cell therapy.

Hematopoietic Stem Cell Transplant in Adolescent and Young Adults With Fanconi Anemia Is Feasible With Acceptable Toxicity, With Those Surviving 100 Days Posttransplant Having Excellent Outcomes.

PubMed

Alhuraiji, Ahmad; Alzahrani, Hazza; Al Mohareb, Fahad; Chaudhri, Naeem; Alsharif, Fahad; Mohamed, Said; Rasheed, Walid; Aldawsari, Ghuzayel; Ahmed, Syed Osman; Aljurf, Mahmoud

2016-12-01

Fanconi anemia is a congenital bone marrow failure syndrome that is associated with congenital anomalies and increased risk of cancer. Hematopoietic stem cell transplant is a potentially curative modality for bone marrow failure in Fanconi anemia patients. Here, we report our center's experience regarding adolescent and young adult patients with Fanconi anemia and hematopoietic stem cell transplant. We conducted a retrospective patient record analyses of patients who presented at our center from 1988 to 2014. We included patients greater than 14 years old with confirmed Fanconi anemia based on positive chromosome breakage study and who underwent hematopoietic stem cell transplant at our institution. Our study group comprised 12 patients with Fanconi anemia who underwent hematopoietic stem cell transplant at our institution. The median age was 20 years (range, 14-31 y) with a female predominance of 83%. Low-dose cyclophosphamide (20-80 mg/kg)-based conditioning regimens were used with different combinations that included fludarabine, antithymocyte globulin, or total body irradiation. All patients had HLA-matched sibling grafts. In all patients, stem cell source was the bone marrow. All patients showed engraftment. Four patients (33%) developed acute graft-versus-host disease. Three patients (25%) died early before day 100 after hematopoietic stem cell transplant due to infectious complications, with 1 patient having steroid refractory acute graft-versus-host disease. Overall survival was 75% at a median follow-up of 43 months. All patients who survived are well and remained transfusion independent without evidence of secondary malignancy. Our findings support the feasibility of reduced intensity conditioning allogeneic hematopoietic stem cell transplant in older and more heavily pretreated patients with Fanconi anemia, especially for those who are engrafted.

Stem cell transplantation as rescue therapy for refractory Crohn's disease: a sytematic review.

PubMed

Labidi, Asma; Serghini, Meriem; Ben Mustapha, Nadia; Fekih, Monia; Boubaker, Jalel; Filali, Azza

2014-11-01

Crohn's disease is a chronic relapsing- remitting affection. It has a strong immunologic component which represent the target of standard therapies including immunosppressants and biological therapies. However, many patients remain refracory or intolerant to these therapies. The aim of this review is to determine the effects of stem cell transplantation in patients with refractory Crohn's disease. Systematic review of observational studies, clinical trials and case reports that focused on the effectiveness and safety of stem cell transplantation in patients with refractory Crohn's disease. Hematopoietic stem cell transplantation seems to be efficient in maintaining clinical and endoscopic remission in patients with Crohn's disease refractory or intolerant to current therapies. However, it has been associated to high morbidity and mortality due to chemotherapy. Mesenchymal stem cell transplantation could induce remission in patients with fistulising refractory Crohns disease with no severe side effects. Its impact on luminal Crohns disease is still controversial. Stem cell transplantation seems to hold promising in patients with refractory Crohn's disease. However, because of the high morbidity and mortality related to chemotherapy, hematopoietic stem cell transplantation should be used as last resort to control this disease. Effectiveness of mesenchymal stem cell transplantation in luminal Crohn's disease has yet to be proven.

Ethical considerations when counseling patients about stem cell tourism.

PubMed

Tsou, Amy

2015-02-01

Worldwide, many clinics market stem-cell based interventions often touted as effective for many diseases including spinal cord injury, multiple sclerosis (MS), and other neurodegenerative diseases. These clinics and their expensive, unproven treatments continue to fuel the practice of stem cell tourism. Given concerns about patient exploitation and safety, how should the physician engage a patient who wants to pursue such treatments? This article presents the case of a patient with neuromyelitis optica interested in pursuing expensive stem cell injections abroad. This article describes stem cell tourism along with some of the ethical issues physicians should consider, while also providing practical resources that physicians may employ to educate and engage patients in making an informed decision.

DHAP plus filgrastim as an effective peripheral stem cell mobilization regimen for autologous stem-cell transplantation in patients with relapsed/refractory lymphoma: A single center experience.

PubMed

Berber, Ilhami; Erkurt, Mehmet Ali; Kuku, Irfan; Kaya, Emin; Bag, Harika Gozukara; Nizam, Ilknur; Koroglu, Mustafa; Ozgul, Mustafa

2016-02-01

This study aimed to evaluate the efficiency of DHAP regimen plus filgrastim for mobilization of stem cells in patients with recurrent and/or refractory lymphoma. Thirty-four patients who took DHAP as salvage therapy prior to autologous stem cell transplantation were included. After chemotherapies, 2 cycles of DHAP plus filgrastim were administered to the patients. Stem cells from 32 patients (94%) were collected on median 11th day (8-12), and the median collected CD34(+) cell dose was 9.7 × 10(6)/kg (range 3.8-41.6). DHAP plus filgrastim was found to be an effective chemotherapy regimen in mobilizing CD34(+) stem cells into the peripheral. Copyright © 2016 Elsevier Ltd. All rights reserved.

Successful control of Epstein-Barr virus (EBV)-infected cells by allogeneic nonmyeloablative stem cell transplantation in a patient with the lethal form of chronic active EBV infection.

PubMed

Uehara, Taeko; Nakaseko, Chiaki; Hara, Satoru; Harima, Akane; Ejiri, Megumi; Yokota, Akira; Saito, Yasushi; Nishimura, Miki

2004-08-01

Chronic active Epstein-Barr virus infection (CAEBV) is a heterogeneous EBV-related disorder, ranging from mild/moderate forms to rapidly lethal disorders. The lethal form of CAEBV is characterized by multiple organ failure, hemophagocytic syndrome, and development of lymphomas. Allogeneic stem cell transplantation is considered as the only potentially curative treatment for the lethal form of CAEBV, but it is not always desirable because of the high incidence of regimen-related toxicities. A 17-year-old female with CAEBV, who was refractory to conventional therapies and considered to be unable to receive a myeloablative regimen because of multiple organ dysfunction, underwent allogeneic nonmyeloablative stem cell transplantation (allo-NST) before developing a hematological malignancy. She has been well without any signs of CAEBV for 27 months after allo-NST, and we confirmed that specific cytotoxic T lymphocyte activity against EBV was reconstituted. This outcome suggests that allo-NST can control CAEBV by reconstituting the host immunity against EBV. Copyright 2004 Wiley-Liss, Inc.

Future Perspectives: Therapeutic Targeting of Notch Signalling May Become a Strategy in Patients Receiving Stem Cell Transplantation for Hematologic Malignancies

PubMed Central

Ersvaer, Elisabeth; Hatfield, Kimberley J.; Reikvam, Håkon; Bruserud, Øystein

2011-01-01

The human Notch system consists of 5 ligands and 4 membrane receptors with promiscuous ligand binding, and Notch-initiated signalling interacts with a wide range of other intracellular pathways. The receptor signalling seems important for regulation of normal and malignant hematopoiesis, development of the cellular immune system, and regulation of immune responses. Several Notch-targeting agents are now being developed, including natural receptor ligands, agonistic and antagonistic antibodies, and inhibitors of intracellular Notch-initiated signalling. Some of these agents are in clinical trials, and several therapeutic strategies seem possible in stem cell recipients: (i) agonists may be used for stem cell expansion and possibly to enhance posttransplant lymphoid reconstitution; (ii) receptor-specific agonists or antagonists can be used for immunomodulation; (iii) Notch targeting may have direct anticancer effects. Although the effects of therapeutic targeting are difficult to predict due to promiscuous ligand binding, targeting of this system may represent an opportunity to achieve combined effects with earlier posttransplant reconstitution, immunomodulation, or direct anticancer effects. PMID:22046566

Clinical and radiographic outcomes after total shoulder arthroplasty with an anatomic press-fit short stem.

PubMed

Szerlip, Benjamin W; Morris, Brent J; Laughlin, Mitzi S; Kilian, Christopher M; Edwards, T Bradley

2018-01-01

There is limited information assessing outcomes after total shoulder arthroplasty (TSA) with a press-fit short stem. The purpose of this study was to evaluate early clinical and radiographic outcomes and complications after TSA with an anatomic press-fit short stem. We identified 118 TSAs completed with press-fit short stem and minimum 2-year follow-up; 85 of these patients had a grit-blasted (GB) short stem placed, whereas 33 patients had short stems with proximal porous coating (PPC). Shoulder function scores, active mobility measurements, and radiographs were assessed. The average age at surgery was 66.7 years, with average follow-up of 3 years. Significant improvements were noted for all shoulder function scores and active mobility measurements from the preoperative state to final follow-up (P < .001). There was no stem loosening in any patients with minimum 2-year follow-up; however, 3 female patients with GB stems had gross loosening of their humeral components before 1 year, 2 requiring revision. Radiolucent lines around the humeral component were found in 5.9% without evidence of loosening. Osseous resorption at the medial cortex was noted in 9.3%. Of patients with PPC stems, no patients were observed to have radiolucent lines compared with 8.2% in the GB group (P = .09). TSAs with anatomic press-fit short stem showed significant clinical improvements from the preoperative state to final short-term follow-up, with few complications and minimal radiographic changes. Lack of PPC may contribute to early loosening in patients with poor bone quality. The authors now use a short stem with PPC. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Late-onset Epstein-Barr virus-related disease in acute leukemia patients after haploidentical hematopoietic stem cell transplantation is associated with impaired early recovery of T and B lymphocytes.

PubMed

Liu, Jiangying; Yan, Chenhua; Zhang, Chunli; Xu, Lanping; Liu, Yanrong; Huang, Xiaojun

2015-10-01

Epstein-Barr virus-related disease (EBVD) is a serious clinical complication in patients who have undergone haploidentical hematopoietic stem cell transplantation (haploHSCT). Some recipients develop EBVD relatively late after haploHSCT, and most of these patients suffer a poor outcome. This retrospective cohort study characterized the early adaptive immune recovery of patients with acute leukemia presenting with EBVD more than 100 d after haploHSCT. Patients with acute leukemia who received haploHSCT and developed EBVD 100 d later (n = 8) were compared with a matched control group without EBVD (n = 24) with regard to peripheral WBC, lymphocytes, and neutrophils (at 30, 60, and 90 d) and recoveries of B and T lymphocytes (at 30 and 90 d, via immunophenotyping/flow cytometry). Ninety days after haploHSCT, the median values of WBCs and lymphocytes, and the recoveries of CD19(+) B cells and CD4(+) , CD8(+) , and CD4(+) CD45RO(+) T cells, were significantly lower in patients who developed EBVD, relative to the control group. These results suggest a significant association between deficient early recovery of B and T lymphocytes and the development of late-onset EBVD after haploHSCT. Our observation could facilitate clinical intervention and the improvement of overall survival of patients undergoing haploHSCT. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Autologous hematopoietic stem cell transplantation in elderly patients (≥ 70 years) with non-Hodgkin's lymphoma: A French Society of Bone Marrow Transplantation and Cellular Therapy retrospective study.

PubMed

Hermet, E; Cabrespine, A; Guièze, R; Garnier, A; Tempescul, A; Lenain, P; Bouabdallah, R; Vilque, J P; Frayfer, J; Bordessoule, D; Sibon, D; Janvier, M; Caillot, D; Biron, P; Legros, L; Choufi, B; Drenou, B; Gorin, N C; Bilger, K; Tamburini, J; Soussain, C; Brechignac, S; Bay, J O

2015-09-01

Limited data is available on the feasibility of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) in elderly patients over 70 years of age with non-Hodgkin's lymphoma (NHL). In the setting of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) group, we retrospectively analyzed 81 consecutive patients with NHL over 70 years of age who received AHSCT. The median age at AHSCT was 72.3 years [70-80]. Patients' were diagnosed with diffuse large B-cell lymphoma (n=40), follicular lymphoma (n=16), mantle cell lymphoma (n=15), T-cell lymphoma (n=5), and other (n=5). Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) was 0 in 73% of patients. Main conditionings were BEAM (Carmustine-Etoposide-Cytarabine-Melphalan, n=61) and melphalan alone (n=14). Median delays to reach 0.5×10⁹/L neutrophils and 20 × 10(9)/L platelets were of 12 [9-76] days and 12 [0-143] days, respectively. One hundred day and one year cumulative incidence of NRM was 5.4% and 8.5%, respectively. The main cause of death remains relapse. In conclusion, this study revealed that AHSCT seemed to be acceptable in patients over 70 years of age with NHL. Patient age is not a limiting factor if clinical condition is adequate. Copyright © 2015 Elsevier Inc. All rights reserved.

Interim Positron Emission Tomography Response-Adapted Therapy in Advanced-Stage Hodgkin Lymphoma: Final Results of the Phase II Part of the HD0801 Study.

PubMed

Zinzani, Pier Luigi; Broccoli, Alessandro; Gioia, Daniela Maria; Castagnoli, Antonio; Ciccone, Giovannino; Evangelista, Andrea; Santoro, Armando; Ricardi, Umberto; Bonfichi, Maurizio; Brusamolino, Ercole; Rossi, Giuseppe; Anastasia, Antonella; Zaja, Francesco; Vitolo, Umberto; Pavone, Vincenzo; Pulsoni, Alessandro; Rigacci, Luigi; Gaidano, Gianluca; Stelitano, Caterina; Salvi, Flavia; Rusconi, Chiara; Tani, Monica; Freilone, Roberto; Pregno, Patrizia; Borsatti, Eugenio; Sacchetti, Gian Mauro; Argnani, Lisa; Levis, Alessandro

2016-04-20

The clinical impact of positron emission tomography (PET) evaluation performed early during first-line therapy in patients with advanced-stage Hodgkin lymphoma, in terms of providing a rationale to shift patients who respond poorly onto a more intensive regimen (PET response-adapted therapy), remains to be confirmed. The phase II part of the multicenter HD0801 study involved 519 patients with advanced-stage de novo Hodgkin lymphoma who received an initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and who underwent an early ifosfamide-containing salvage treatment followed by stem-cell transplantation if they showed a positive PET evaluation after two cycles of chemotherapy (PET2). The primary end point was 2-year progression-free survival calculated for both PET2-negative patients (who completed a full six cycles of ABVD treatment) and PET2-positive patients. Overall survival was a secondary end point. In all, 103 of the 512 evaluable patients were PET2 positive. Among them, 81 received the scheduled salvage regimen with transplantation, 15 remained on ABVD (physician's decision, mostly because of minimally positive PET2), five received an alternative treatment, and two were excluded because of diagnostic error. On intention-to-treat analysis, the 2-year progression-free survival was 76% for PET2-positive patients (regardless of the salvage treatment they received) and 81% for PET2-negative patients. Patients with advanced-stage Hodgkin lymphoma for whom treatment was at high risk of failing appear to benefit from early treatment intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70% of PET2-positive patients through obtaining the same 2-year progression-free survival as the PET2-negative subgroup. © 2016 by American Society of Clinical Oncology.

Atypical presentation of Legionella pneumonia among patients with underlying cancer: A fifteen-year review.

PubMed

del Castillo, Maria; Lucca, Anabella; Plodkowski, Andrew; Huang, Yao-Ting; Kaplan, Janice; Gilhuley, Kathleen; Babady, N Esther; Seo, Susan K; Kamboj, Mini

2016-01-01

Immunocompromised patients, especially those receiving treatment with corticosteroids and cytotoxic chemotherapy are at increased risk for developing Legionella pneumonia. The aim of this study was to determine clinical and radiographic characteristics of pulmonary infection due to Legionella in persons undergoing treatment for cancer and stem cell transplant (SCT) recipients. Retrospective review of Legionella cases at MSKCC over a fifteen-year study period from January 1999 and December 2013. Cases were identified by review of microbiology records. During the study period, 40 cases of Legionella infection were identified; nine among these were due to non-pneumophila species. Most cases occurred during the summer. The majority [8/9, (89%)] of patients with non-pneumophila infection had underlying hematologic malignancy, compared to 18/31 (58%) with Legionella pneumophila infections. Radiographic findings were varied-nodular infiltrates mimicking invasive fungal infection were seen only among patients with hematologic malignancy and hematopoietic stem cell transplant (SCT) recipients and were frequently associated with non-pneumophila infections (50% vs 16%; P = 0.0594). All cases of nodular Legionella pneumonia were found incidentally or had an indolent clinical course. Legionella should be considered in the differential diagnosis of nodular lung lesions in immunocompromised patients, especially those with hematologic malignancy and SCT recipients. Most cases of nodular disease due to Legionella are associated with non-pneumophila infections. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

BK Virus-Associated Hemorrhagic Cystitis After Allogeneic Hematopoietic Stem Cell Transplantation in the Pediatric Population.

PubMed

Pérez-Huertas, Pablo; Cueto-Sola, Margarita; Escobar-Cava, Paloma; Fernández-Navarro, José María; Borrell-García, Carmela; Albert-Marí, Asunción; López-Briz, Eduardo; Poveda-Andrés, José Luis

2016-02-22

To study the incidence, risk factors, and treatment of hemorrhagic cystitis secondary to BK-virus reactivation (HC-BKV) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the pediatric population. Case-control study in which all pediatric patients (0-18 years) who underwent allo-HSCT from September 2009 to January 2014 were followed. Twenty-nine patients underwent an allo-HSCT. The median age was 9 years (range = 6 months to 15 years), 61% male. The primary diagnosis was acute lymphoblastic leukemia (72.4%). Six (20.7%) developed HC-BKV. In a multivariate analysis of risk factors, it was observed that the reactivation of BK virus was associated with age more than 10 years (P = .098) and those with positive serology for Epstein-Barr virus (P = .06). Five of the 6 patients with HC-BKV received cidofovir (CDV) at doses of 3 to 5 mg/kg/week. The treatment lasted a median of 3 cycles (range = 2-5). One of the patients (20%) developed nephrotoxicity. Of the 5 patients treated with CDV, 3 (60%) had a complete response, 1 (20%) partial response, and 1 (20%) no response. We conclude that HC-BKV is a frequent complication after allo-HSCT. CDV therapy can be effective but controlled clinical trials are needed. © 2016 by Association of Pediatric Hematology/Oncology Nurses.

The Activating NKG2C Receptor Is Significantly Reduced in NK Cells after Allogeneic Stem Cell Transplantation in Patients with Severe Graft-versus-Host Disease.

PubMed

Kordelas, Lambros; Steckel, Nina-Kristin; Horn, Peter A; Beelen, Dietrich W; Rebmann, Vera

2016-10-27

Natural killer (NK) cells play a central role in the innate immune system. In allogeneic stem cell transplantation (alloSCT), alloreactive NK cells derived by the graft are discussed to mediate the elimination of leukemic cells and dendritic cells in the patient and thereby to reduce the risk for leukemic relapses and graft-versus-host reactions. The alloreactivity of NK cells is determined by various receptors including the activating CD94/NKG2C and the inhibitory CD94/NKG2A receptors, which both recognize the non-classical human leukocyte antigen E (HLA-E). Here we analyze the contribution of these receptors to NK cell alloreactivity in 26 patients over the course of the first year after alloSCT due to acute myeloid leukemia, myelodysplastic syndrome and T cell Non-Hodgkin-Lymphoma. Our results show that NK cells expressing the activating CD94/NKG2C receptor are significantly reduced in patients after alloSCT with severe acute and chronic graft-versus-host disease (GvHD). Moreover, the ratio of CD94/NKG2C to CD94/NKG2A was reduced in patients with severe acute and chronic GvHD after receiving an HLA-mismatched graft. Collectively, these results provide evidence for the first time that CD94/NKG2C is involved in GvHD prevention.

The Activating NKG2C Receptor Is Significantly Reduced in NK Cells after Allogeneic Stem Cell Transplantation in Patients with Severe Graft-versus-Host Disease

PubMed Central

Kordelas, Lambros; Steckel, Nina-Kristin; Horn, Peter A.; Beelen, Dietrich W.; Rebmann, Vera

2016-01-01

Natural killer (NK) cells play a central role in the innate immune system. In allogeneic stem cell transplantation (alloSCT), alloreactive NK cells derived by the graft are discussed to mediate the elimination of leukemic cells and dendritic cells in the patient and thereby to reduce the risk for leukemic relapses and graft-versus-host reactions. The alloreactivity of NK cells is determined by various receptors including the activating CD94/NKG2C and the inhibitory CD94/NKG2A receptors, which both recognize the non-classical human leukocyte antigen E (HLA-E). Here we analyze the contribution of these receptors to NK cell alloreactivity in 26 patients over the course of the first year after alloSCT due to acute myeloid leukemia, myelodysplastic syndrome and T cell Non-Hodgkin-Lymphoma. Our results show that NK cells expressing the activating CD94/NKG2C receptor are significantly reduced in patients after alloSCT with severe acute and chronic graft-versus-host disease (GvHD). Moreover, the ratio of CD94/NKG2C to CD94/NKG2A was reduced in patients with severe acute and chronic GvHD after receiving an HLA-mismatched graft. Collectively, these results provide evidence for the first time that CD94/NKG2C is involved in GvHD prevention. PMID:27801784

Late Effects in Pediatric High-risk Neuroblastoma Survivors After Intensive Induction Chemotherapy Followed by Myeloablative Consolidation Chemotherapy and Triple Autologous Stem Cell Transplants.

PubMed

Armstrong, Amy E; Danner-Koptik, Karina; Golden, Shannon; Schneiderman, Jennifer; Kletzel, Morris; Reichek, Jennifer; Gosiengfiao, Yasmin

2018-01-01

Multimodal treatment in high-risk neuroblastoma has modestly improved survival; limited data exist on the late effects from these regimens. We report the sequelae of treatment incorporating 3 consecutive cycles of high-dose therapy and autologous stem cell transplants (ASCTs) without the use of total body irradiation (TBI). We reviewed the medical records of 61 patients treated on or following the Chicago Pilot 2 protocol between 1991 and 2008. Of the 25 patients who are alive (41%), 19 had near complete data to report. Specific treatment modalities and therapy-related side effects were collected. Fourteen of these 19 patients (74%) received 3 cycles of high-dose therapy with ASCT; follow-up occurred over a median of 13.9 years (range, 5.8 to 18.8 y). The majority of late effects were endocrine-related, including growth failure, hypothyroidism, and hypogonadism. Patients also developed secondary neoplasms and skeletal deformities. The most frequent sequela was hearing loss, seen in 17/19 patients. We found a high prevalence of various late effects in survivors of high-risk neuroblastoma using a non-TBI-based regimen including 3 cycles of high-dose therapy with ASCTs. As current treatment regimens recommend tandem ASCT without TBI, it is imperative that we understand and monitor for the sequelae from these modalities.

Conduit grinding apparatus

DOEpatents

Nachbar, Henry D.; Korytkowski, Alfred S.

1991-01-01

A grinding apparatus for grinding the interior portion of a valve stem receiving area of a valve. The apparatus comprises a faceplate, a plurality of cams mounted to an interior face of the faceplate, a locking bolt to lock the faceplate at a predetermined position on the valve, a movable grinder and a guide tube for positioning an optical viewer proximate the area to be grinded. The apparatus can either be rotated about the valve for grinding an area of the inner diameter of a valve stem receiving area or locked at a predetermined position to grind a specific point in the receiving area.

3D Printing of Personalized Organs and Tissues

NASA Astrophysics Data System (ADS)

Ye, Kaiming

2015-03-01

Authors: Kaiming Ye and Sha Jin, Department of Biomedical Engineering, Watson School of Engineering and Applied Science, Binghamton University, State University of New York, Binghamton, NY 13902-6000 Abstract: Creation of highly organized multicellular constructs, including tissues and organs or organoids, will revolutionize tissue engineering and regenerative medicine. The development of these technologies will enable the production of individualized organs or tissues for patient-tailored organ transplantation or cell-based therapy. For instance, a patient with damaged myocardial tissues due to an ischemic event can receive a myocardial transplant generated using the patient's own induced pluripotent stem cells (iPSCs). Likewise, a type-1 diabetic patient can be treated with lab-generated islets to restore his or her physiological insulin secretion capability. These lab-produced, high order tissues or organs can also serve as disease models for pathophysiological study and drug screening. The remarkable advances in stem cell biology, tissue engineering, microfabrication, and materials science in the last decade suggest the feasibility of generating these tissues and organoids in the laboratory. Nevertheless, major challenges still exist. One of the critical challenges that we still face today is the difficulty in constructing or fabricating multicellular assemblies that recapitulate in vivo microenvironments essential for controlling cell proliferation, migration, differentiation, maturation and assembly into a biologically functional tissue or organoid structure. These challenges can be addressed through developing 3D organ and tissue printing which enables organizing and assembling cells into desired tissue and organ structures. We have shown that human pluripotent stem cells differentiated in 3D environments are mature and possess high degree of biological function necessary for them to function in vivo.

Associations Between Markers of Colorectal Cancer Stem Cells and Adenomas Among Ethnic Groups

PubMed Central

Leavell, Bonita J.; Van Buren, Eric; Antaki, Fadi; Axelrod, Bradley N.; Rambus, Mary Ann; Majumdar, Adhip P. N.

2013-01-01

Background and Purposes Most colorectal tumors develop from adenomatous polyps, which are detected by colonoscopy. African Americans (AAs) have higher incidence of colorectal cancer (CRC) and greater mortality from this disease than Caucasian Americans (CAs). We investigated whether differences in predisposition to CRC and its surrogate (colonic adenomas) between these ethnic groups were related to numbers of cancer stem or stem-like cells (CSCs) in colonocytes. Methods We analyzed colonic effluent from 11 AA and 14 CA patients who underwent scheduled colonoscopy examinations at the John D. Dingell Veterans Affairs Medical Center. We determined proportions of cells that expressed the CSC markers CD44 and CD166 by flow cytometry. Results The proportion of colonocytes that were CD44+CD166– in effluent from patients with adenomas was significantly greater than from patients without adenomas (P = 0.01); the proportion of CD44+CD166+ colonocytes was also greater (P = 0.07). Effluent from AAs with adenomas had 60 % more CD44+166– colonocytes than from CAs with adenomas. Using cutoff values of 8 % for AAs and 3 % for CAs, the proportion of CD44+166– colonocytes that had positive predictive value for detection of adenomas was 100 % for AAs and CAs, determined by receiver operator characteristic curve analysis. Conclusion The proportion of CD44+166– colonocytes in colonic effluent can be used to identify patients with adenoma. AAs with adenomas have a higher proportion of CD44+166– colonocytes than CA. The increased proportion of CSCs in colonic tissue from AA might be associated with the increased incidence of CRC in this population. PMID:22562538

Monitoring of minimal residual disease after allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia allows for the identification of impending relapse: results of the ALL-BFM-SCT 2003 trial.

PubMed

Bader, Peter; Kreyenberg, Hermann; von Stackelberg, Arend; Eckert, Cornelia; Salzmann-Manrique, Emilia; Meisel, Roland; Poetschger, Ulrike; Stachel, Daniel; Schrappe, Martin; Alten, Julia; Schrauder, Andre; Schulz, Ansgar; Lang, Peter; Müller, Ingo; Albert, Michael H; Willasch, Andre M; Klingebiel, Thomas E; Peters, Christina

2015-04-10

To elucidate the impact of minimal residual disease (MRD) after allogeneic transplantation, the Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster Stem Cell Transplantation Group (ALL-BFM-SCT) conducted a prospective clinical trial. In the ALL-BFM-SCT 2003 trial, MRD was assessed in the bone marrow at days +30, +60, +90, +180, and +365 after transplantation in 113 patients with relapsed disease. Standardized quantification of MRD was performed according to the guidelines of the Euro-MRD Group. All patients showed a 3-year probability of event-free survival (pEFS) of 55%. The cumulative incidence rates of relapse and treatment-related mortality were 32% and 12%, respectively. The pEFS was 60% for patients who received their transplantations in second complete remission, 50% for patients in ≥ third complete remission, and 0% for patients not in remission (P = .015). At all time points, the level of MRD was inversely correlated with event-free survival (EFS; P < .004) and positively correlated with the cumulative incidence of relapse (P < .01). A multivariable Cox model was fitted for each time point, which showed that MRD ≥ 10(-4) leukemic cells was consistently correlated with inferior EFS (P < .003). The accuracy of MRD measurements in predicting relapse was investigated with time-dependent receiver operating curves at days +30, +60, +90, and +180. From day +60 onward, the discriminatory power of MRD detection to predict the probability of relapse after 1, 3, 6, and 9 months was more than 96%, more than 87%, more than 71%, and more than 61%, respectively. MRD after transplantation was a reliable marker for predicting impending relapses and could thus serve as the basis for pre-emptive therapy. © 2015 by American Society of Clinical Oncology.

Mammalian target of rapamycin inhibitor-associated stomatitis in hematopoietic stem cell transplantation patients receiving sirolimus prophylaxis for graft-versus-host disease.

PubMed

Villa, Alessandro; Aboalela, Ali; Luskin, Katharine A; Cutler, Corey S; Sonis, Stephen T; Woo, Sook Bin; Peterson, Douglas E; Treister, Nathaniel S

2015-03-01

The mammalian target of rapamycin (mTOR) inhibitor sirolimus is effective in reducing incidence of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Agents that inhibit the mTOR pathway are known to be associated with significant and potentially dose-limiting toxicities, including stomatitis. The objective of this study was to report the clinical features and management outcomes of sirolimus-associated oral ulcers in the context of post-HSCT prophylaxis of GVHD. Seventeen patients, from a study cohort of 967, who were treated with sirolimus as prophylaxis for GVHD after allogeneic HSCT at the Dana-Farber/Brigham and Women's Cancer Center developed oral ulcers and were referred to the oral medicine clinic for evaluation and treatment over a period of 6 years. Clinical characteristics (appearance, anatomic site, size) and therapeutic outcomes (time to complete resolution) were documented. Median time to onset of oral ulceration was 55 days after allogeneic HSCT (range, 6 to 387 days); 92.9% of ulcers were located on nonkeratinized mucosa, with the ventrolateral tongue the most common site of involvement. Thirteen patients were treated with topical corticosteroid therapy; 12 of these patients also required intralesional corticosteroid injections. Clinical improvement (resolution of the lesions and improvement of symptoms) was noted in all cases, with no reported adverse events. Median time to complete resolution after onset of therapy was 14 days (range, 2 to 70 days). Patients receiving sirolimus for GVHD prophylaxis may develop painful oral ulcerations, which can be effectively managed with topical steroid treatment. Further prospective studies are needed to better elucidate the incidence of this complication, identify risk factors, and evaluate the effectiveness of interventions. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Clinical effectiveness of hyperbaric oxygen therapy for BK-virus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation.

PubMed

Savva-Bordalo, J; Pinho Vaz, C; Sousa, M; Branca, R; Campilho, F; Resende, R; Baldaque, I; Camacho, O; Campos, A

2012-08-01

Late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT) has been associated with BK virus (BKV). Antiviral drugs are of limited efficacy and the optimal treatment for HC has not yet been established. Hyperbaric oxygen (HBO) may benefit these patients. We, therefore, retrospectively evaluated the effectiveness of HBO therapy in 16 patients with HC after allogeneic HSCT. All 16 patients had macroscopic hematuria and BKV infection. Patients received 100% oxygen in a hyperbaric chamber at 2.1 atmospheres for 90 min, 5 days per week, with a median 13 treatments (range, 4-84). Fifteen patients (94%) showed complete resolution of hematuria. Median urinary DNA BKV titers declined after HBO (P<0.05). Patients started on HBO earlier after diagnosis of HC responded sooner (P<0.05). HBO was generally well tolerated and proved to be a reliable option for this difficult to manage condition.

One-year results from a prospective randomized trial comparing phlebotomy with deferasirox for the treatment of iron overload in pediatric patients with thalassemia major following curative stem cell transplantation.

PubMed

Inati, Adlette; Kahale, Mario; Sbeiti, Nada; Cappellini, Maria Domenica; Taher, Ali T; Koussa, Suzanne; Nasr, Therese A; Musallam, Khaled M; Abbas, Hussein A; Porter, John B

2017-01-01

Iron overload is well documented in patients with β-thalassemia major, and patients who have undergone hematopoietic stem cell transplantation (HSCT) remain at risk as a result of pre- and immediate post-HSCT transfusions. This is a prospective, randomized, 1-year clinical trial that compares the efficacy and safety of the once-daily oral iron chelator deferasirox versus phlebotomy for the treatment of iron overload in children with β-thalassemia major following HSCT. Patients (aged 12.4 years) received deferasirox (n = 12, 10 mg/kg/day starting dose) or phlebotomy (n = 14, 6 ml/kg/2 weeks) for 1 year. In two and five patients, deferasirox dose was increased to 15 and 20 mg/kg/day, respectively. Magnetic resonance imaging (MRI)-assessed liver iron concentration (LIC) decreased with deferasirox (mean 12.5 ± 10.1 to 8.5 ± 9.3 mg Fe/g dry weight [dw]; P = 0.0005 vs. baseline) and phlebotomy (10.2 ± 6.8 to 8.3 ± 9.2 mg Fe/g dw; P = 0.05). LIC reductions were greater with deferasirox than with phlebotomy for patients with baseline serum ferritin 1,000 ng/ml or higher (-8.1 ± 1.5 vs. -3.5 ± 5.7 mg Fe/g dw; P = 0.048). Serum ferritin and non-transferrin-bound iron also decreased significantly. In two patients with severe cardiac siderosis, a clinically relevant improvement in myocardial T2* was seen, following phlebotomy and deferasirox therapy (n = 1 each). Adverse effects with deferasirox were skin rash, gastrointestinal upset, and increased liver function tests (all n = 1), while those for phlebotomy were difficulty with venous access (n = 4) and distress during procedure (n = 1). Parents of 13/14 children receiving phlebotomy wished to switch to deferasirox, with 1/14 being satisfied with phlebotomy. Deferasirox treatment or phlebotomy reduces iron burden in pediatric patients with β- thalassemia major post-HSCT, with a manageable safety profile. © 2016 Wiley Periodicals, Inc.

76 FR 13970 - Notice of Request for Extension of Approval of an Information Collection; Black Stem Rust...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-15

...] Notice of Request for Extension of Approval of an Information Collection; Black Stem Rust; Identification Requirements for Addition of Rust-Resistant Varieties AGENCY: Animal and Plant Health Inspection Service, USDA... black stem rust quarantine and regulations. DATES: We will consider all comments that we receive on or...

Hardwiring stem cell communication through tissue structure

PubMed Central

Xin, Tianchi; Greco, Valentina; Myung, Peggy

2016-01-01

Adult stem cells across diverse organs self-renew and differentiate to maintain tissue homeostasis. How stem cells receive input to preserve tissue structure and function largely relies on their communication with surrounding cellular and non-cellular elements. As such, how tissues are organized and patterned not only reflects organ function but also inherently hardwires networks of communication between stem cells and their environment to direct tissue homeostasis and injury repair. This review highlights how different methods of stem cell communication reflect the unique organization and function of diverse tissues. PMID:26967287

Reduced hematopoietic stem cell frequency predicts outcome in acute myeloid leukemia.

PubMed

Wang, Wenwen; Stiehl, Thomas; Raffel, Simon; Hoang, Van T; Hoffmann, Isabel; Poisa-Beiro, Laura; Saeed, Borhan R; Blume, Rachel; Manta, Linda; Eckstein, Volker; Bochtler, Tilmann; Wuchter, Patrick; Essers, Marieke; Jauch, Anna; Trumpp, Andreas; Marciniak-Czochra, Anna; Ho, Anthony D; Lutz, Christoph

2017-09-01

In patients with acute myeloid leukemia and low percentages of aldehyde-dehydrogenase-positive cells, non-leukemic hematopoietic stem cells can be separated from leukemic cells. By relating hematopoietic stem cell frequencies to outcome we detected poor overall- and disease-free survival of patients with low hematopoietic stem cell frequencies. Serial analysis of matched diagnostic and follow-up samples further demonstrated that hematopoietic stem cells increased after chemotherapy in patients who achieved durable remissions. However, in patients who eventually relapsed, hematopoietic stem cell numbers decreased dramatically at the time of molecular relapse demonstrating that hematopoietic stem cell levels represent an indirect marker of minimal residual disease, which heralds leukemic relapse. Upon transplantation in immune-deficient mice cases with low percentages of hematopoietic stem cells of our cohort gave rise to leukemic or no engraftment, whereas cases with normal hematopoietic stem cell levels mostly resulted in multi-lineage engraftment. Based on our experimental data, we propose that leukemic stem cells have increased niche affinity in cases with low percentages of hematopoietic stem cells. To validate this hypothesis, we developed new mathematical models describing the dynamics of healthy and leukemic cells under different regulatory scenarios. These models suggest that the mechanism leading to decreases in hematopoietic stem cell frequencies before leukemic relapse must be based on expansion of leukemic stem cells with high niche affinity and the ability to dislodge hematopoietic stem cells. Thus, our data suggest that decreasing numbers of hematopoietic stem cells indicate leukemic stem cell persistence and the emergence of leukemic relapse. Copyright© 2017 Ferrata Storti Foundation.