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Sample records for autologous stem cells

  1. Cryptococcal meningitis post autologous stem cell transplantation.

    PubMed

    Chaaban, S; Wheat, L J; Assi, M

    2014-06-01

    Disseminated Cryptococcus disease occurs in patients with defective T-cell immunity. Cryptococcal meningitis following autologous stem cell transplant (SCT) has been described previously in only 1 patient, 4 months post SCT and while off antifungal prophylaxis. We present a unique case of Cryptococcus meningitis pre-engraftment after autologous SCT, while the patient was receiving fluconazole prophylaxis. A 41-year-old man with non-Hodgkin's lymphoma underwent autologous SCT. Post-transplant prophylaxis consisted of fluconazole 400 mg daily, levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post transplant, he developed fever and headache. Peripheral white blood cell count (WBC) was 700/μL. Magnetic resonance imaging of the brain showed lesions consistent with meningoencephalitis. Cerebrospinal fluid (CSF) analysis revealed a WBC of 39 with 77% lymphocytes, protein 63, glucose 38, CSF pressure 20.5 cmH2 O, and a positive cryptococcal antigen. CSF culture confirmed Cryptococcus neoformans. The patient was treated with liposomal amphotericin B 5 mg/kg intravenously daily, and flucytosine 37.5 mg/kg orally every 6 h. He was switched to fluconazole 400 mg daily after 3 weeks of amphotericin therapy, with sterilization of the CSF with negative CSFCryptococcus antigen and negative CSF culture. Review of the literature revealed 9 cases of cryptococcal disease in recipients of SCT. Median time of onset was 64 days post transplant. Only 3 meningitis cases were described; 2 of them after allogeneic SCT. Fungal prophylaxis with fluconazole post autologous SCT is recommended at least through engraftment, and for up to 100 days in high-risk patients. A high index of suspicion is needed to diagnose and treat opportunistic infections, especially in the face of immunosuppression and despite adequate prophylaxis. Infection is usually fatal without treatment, thus prompt diagnosis and therapy might be life saving.

  2. Autologous stem cell transplantation for systemic sclerosis.

    PubMed

    Farge, Dominique; Nash, Richard; Laar, Jacob M

    2008-12-01

    Systemic sclerosis (SSc) is a generalised autoimmune disease, of yet unknown origin, with two major clinical subsets: the limited (lcSSc) and the diffuse cutaneous (dcSSc) forms, which can be distinguished by the extent of skin involvement, the autoantibody profile and the pattern of organ involvement. With an incidence of 1/10(5), SSc affects around 250,000 people in Europe and is responsible for significant morbidity with a 5-year mortality rate of at least 30% of all patients. In patients with rapidly progressive dcSSc, the 5-year mortality is estimated to be 40-50%. Hematopoietic stem cell transplantation (HSCT), mostly autologous but also allogeneic in some specific cases, has been employed worldwide since 1996 as a new therapeutic strategy in patients with a poor prognosis. In 2007, 150 HSCT procedures have been reported in the EBMT data base. We review herein both the short and the long-term reports from the various European and North American phase I-II studies, which have shown that autologous HSCT in selected patients with severe dcSSc results in sustained improvement of skin thickening and stabilisation of organ function up to seven years after transplantation. Based on these promising results, ongoing phase III trials have been designed in parallel, both in Europe (ASTIS) and in North America (SCOTT) aiming to analyse the respective benefits from autologous HSCT respectively without or with high dose irradiation. This review reports the current data concerning the effects of HSCT on survival, skin, and major organ function in patients with severe dcSSc.

  3. Autologous hematopoietic stem cell transplantation in progressive severe multiple sclerosis.

    PubMed

    Pandit, Awadh Kishor; Prasad, Kameshwar; Seth, Tulika

    2015-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system (CNS), which is disabling and majorly involves younger population. Various available treatments in forms of immunomodulation are not very effective; however, stem cell transplantation seems to be promising in recent literature. The current case report is a novel evidence for autologous hematopoietic stem cell transplantation (HSCT) in progressive MS. A 33 year old male with secondary progressive MS (SPMS), after being failed and/or intolerance to standard approved interferon (IFN) and mitoxantrone therapy, autologous HSCT was administered. At 2years of post-stem cell transplantation follow-up, he has remained stable with some improvement in functional status (Expanded Disability Status Scale (EDSS) reduced by 1.5), with no relapse, no treatment related complications, and no fresh magnetic resonance imaging (MRI) lesions. Autologous stem cell transplantation may be beneficial in progressive forms of MS, but needs to be tested in well-designed randomized trial.

  4. [Treatment of relapsed Hodgkin lymphoma after autologous stem cell transplantation].

    PubMed

    Illés, Árpád; Simon, Zsófia; Udvardy, Miklós; Magyari, Ferenc; Jóna, Ádám; Miltényi, Zsófia

    2017-08-01

    Approximately 10-30% of Hodgkin lymphoma patients relapses or experience refractory disease after first line treatment. Nowadays, autologous stem cell transplantation can successfully salvage half of these patients, median overall survival is only 2-2.5 years. Several prognostic factors determine success of autologous stem cell transplantation. Result of transplantation can be improved considering these factors and using consolidation treatment, if necessary. Patients who relapse after autologous transplantation had worse prognosis, treatment of this patient population is unmet clinical need. Several new treatment options became available in the recent years (brentuximab vedotin and immuncheckpoint inhibitors). These new treatment options offer more chance for cure in relapsed/refractory Hodgkin patients. Outcome of allogenic stem cell transplantation can be improved by using haploidentical donors. New therapeutic options will be discussed in this review. Orv Hetil. 2017; 158(34): 1338-1345.

  5. Necrobiotic xanthogranuloma successfully treated with autologous stem cell transplantation.

    PubMed

    Goede, Jeroen S; Misselwitz, Benjamin; Taverna, Christian; Schanz, Urs; Dispenzieri, Angela; Hummel, Yvonne; Trüeb, Ralph M; Fehr, Jörg

    2007-04-01

    Paraproteinemia can be complicated by necrobiotic xanthogranuloma. Therapeutic options for this progressive disease are limited, and there is no agreement on a single best strategy. We report the case of a patient with a massive periorbital infiltration narrowing the palpebral fissure and blinding the patient. Conventional myeloma therapy had only limited benefit in our patient. However, he was successfully treated with high-dose chemotherapy followed by autologous stem cell transplantation, rendering the patient free of symptoms. This is the first report of autologous stem cell transplantation in a patient with necrobiotic xanthogranuloma.

  6. Therapeutic potential of autologous stem cell transplantation for cerebral palsy.

    PubMed

    Purandare, Chaitanya; Shitole, D G; Belle, Vaijayantee; Kedari, Aarti; Bora, Neeta; Joshi, Meghnad

    2012-01-01

    Background. Cerebral palsy (CP) is a severe disabling disease with worldwide incidence being 2 to 3 per 1000 live births. CP was considered as a noncurable, nonreparative disorder, but stem cell therapy offers a potential treatment for CP. Objective. The present study evaluates the safety and efficacy of autologous bone-marrow-derived mononuclear cell (BMMNCs) transplantation in CP patient. Material and Methods. In the present study, five infusions of autologous stem cells were injected intrathecally. Changes in neurological deficits and improvements in function were assessed using Gross Motor Function Classification System (GMFCS-E&R) scale. Results. Significant motor, sensory, cognitive, and speech improvements were observed. Bowel and bladder control has been achieved. On the GMFCS-E&R level, the patient was promoted from grade III to I. Conclusion. In this study, we report that intrathecal infusion of autologous BMMNCs seems to be feasible, effective, and safe with encouraging functional outcome improvements in CP patient.

  7. Sustained telomere erosion due to increased stem cell turnover during triple autologous hematopoietic stem cell transplantation.

    PubMed

    Widmann, Thomas; Kneer, Harald; König, Jochem; Herrmann, Markus; Pfreundschuh, Michael

    2008-01-01

    Telomeres cap chromosomal ends and are shortened throughout a lifetime. Additional telomere erosion has been documented during conventional chemotherapy or hematopoietic stem cell transplantation. Previous studies of stem cell transplantation reported variable amounts of telomere shortening with inconsistent results regarding the persistence of telomere shortening. Here we have prospectively studied telomere length and proliferation kinetics of hematopoietic cells in aggressive non-Hodgkin lymphoma patients who underwent a four-course high-dose chemotherapy protocol combined with triple autologous stem cell transplantation. We observed sustained telomere shortening in hematopoietic cells after triple stem cell transplantation with prolonged stem cell replication during the first year after stem cell transplantation.

  8. Autologous stem cell transplant with gene therapy for Friedreich ataxia.

    PubMed

    Tajiri, Naoki; Staples, Meaghan; Kaneko, Yuji; Kim, Seung U; Zesiewicz, Theresa A; Borlongan, Cesar V

    2014-09-01

    We advance the overarching hypothesis that stem cell therapy is a potent treatment for Friedreich's ataxia (FRDA). Here, we discuss the feasibility of autologous transplantation in FRDA, highlighting the need for the successful isolation of the FRDA patient's bone marrow-derived mesenchymal stem cells, followed by characterization that these cells maintain the GAA repeat expansion and the reduced FXN mRNA expression, both hallmark features of FRDA. Next, we discuss the need for assessment of the proliferative capability and pluripotency of FRDA patient's bone marrow-derived mesenchymal stem cells. In particular, we view the need for characterizing the in vitro differentiation of bone marrow-derived mesenchymal stem cells into the two cell types primarily affected in FRDA, peripheral neurons and cardiomyocytes. Finally, we discuss the need to test the application of bone marrow-derived mesenchymal stem cells as potent autologous donor cells for FRDA. The demonstration of the functional correction of the mutated gene in these cells will be a critical endpoint of determining the potential of stem cell therapy in FRDA. We envision a gene-based cell transplant strategy as a likely therapeutic approach for FRDA, involving stable insertion of functional human bacterial artificial chromosomes or BACs containing the intact FXN gene into stem cells, thereafter leading to the expression of frataxin protein in differentiated neurons/cardiomyocytes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Autologous hematopoietic stem cell transplantation for systemic sclerosis.

    PubMed

    Milanetti, Francesca; Bucha, Jurate; Testori, Alessandro; Burt, Richard K

    2011-03-01

    Systemic sclerosis is a rare disorder manifesting as skin and internal organ fibrosis, a diffuse vasculopathy, inflammation, and features of autoimmunity. Patients with diffuse cutaneous disease or internal organ involvement have a poor prognosis with high mortality. To date no therapy has been shown to reverse the natural course of the disease. Immune suppressive drugs are commonly utilized to treat patients, but randomized trials have generally failed to demonstrate any long-term benefit. In phase I/II trials, autologous hematopoietic stem cell transplantation (HSCT) has demonstrated impressive reversal of skin fibrosis, improved functionality and quality of life, and stabilization of internal organ function, but initial studies were complicated by significant treatment-related mortality. Treatment-related mortality was reduced by better pre-transplant evaluation to exclude patients with compromised cardiac function and by treating patients earlier in disease, allowing selected patients the option of autologous HSCT treatment. There are currently three ongoing randomized trials of autologous HSCT for systemic sclerosis: ASSIST (American Systemic Sclerosis Immune Suppression versus Transplant), SCOT (scleroderma cyclophosphamide versus Transplant), and ASTIS (Autologous Stem cell Transplantation International Scleroderma). The results from these trials should clarify the role of autologous HSCT in the currently limited therapeutic arsenal of severe systemic sclerosis.

  10. [Therapeutic intensification and autologous stem cell transplantation in autoimmune diseases].

    PubMed

    Marjanovic, Z; Gerber, I; Toledano, C; Hen-Solal, J; Damade, R; de Saint-Cyr, I; Sarrot-Reynauld, F; Ilié, D; Daneshpouy, M; Mounier, N; Ruivard, M; Tyndall, C; Vidal, E; Quere, I; Durand, J-M; Constans, J; Farge, D

    2005-02-26

    THE PATHOPHYSIOLOGY of most autoimmune diseases is often poorly understood. EXPERIMENTAL CONSIDERATIONS and clinical experience suggest that high doses immunoablation followed by stem cell transplantation is a therapeutic option to consider for certain severe autoimmune disorders. THE CONCEPT OF RESTORING NORMAL IMMUNE REACTIVITY must in part br true since current results of 466 transplants (445 autologous, 21 allogeneic) patients suffering from various autoimmune diseases show a beneficial outcome in approximately 2/3 of the patients. TO IMPROVE THE EFFICACY AND SAFETY OF SUCH AN AGGRESSIVE PROCEDURE in patients with potentially affected vital organs by the underlying autoimmune disease, it is especially important to follow international consensus guidelines and to centrally collect clinical data for in depth analysis in the EBMT International Stem Cell Project for Autoimmune Disease in Basel, Switzerland. PHASE III STUDIES ARE RUNNING FOR SYSTEMIC SCLEROSIS (Astis, Autologous Stem cell Transplantation International Rheumatoid Arthritis Trial) started in 2003. A STUDY PROJECT IS PLANNED FOR MULTIPLE SCLEROSIS (Astims, Autologous Stem cell Transplantation International Multiple Sclerosis).

  11. Outpatient Autologous Stem Cell Transplantation for Patients With Myeloma.

    PubMed

    Paul, Thomas M; Liu, Stephen V; Chong, Elise A; Luger, Selina M; Porter, David L; Schuster, Stephen J; Tsai, Donald E; Nasta, Sunita D; Loren, Alison; Frey, Noelle; Perl, Alexander; Cohen, Adam D; Weiss, Brendan M; Stadtmauer, Edward A; Vogl, Dan T

    2015-09-01

    High-dose melphalan with autologous stem cell support improves survival for patients with myeloma. For selected patients, we have been using a protocol of short hospitalization, discharging patients to home with careful outpatient monitoring in the office, which we hypothesized would reduce complications and utilization of inpatient beds. We reviewed 301 initial autologous transplants for myeloma, categorized as brief stay (≤ 4 days, 82 patients) or prolonged stay (≥ 5 days, 219 patients). Selection for a brief stay was determined by clinical characteristics, availability of caregivers at home, distance from our medical center, and patient preference. Within the brief stay population, 67% required readmission before day + 100, but this group still had fewer cumulative hospital days (9 vs. 18, P < .0001). There were fewer documented infections among brief stay patients (22% vs. 46% P < .001) and fewer admissions to intensive care units (0% vs. 5.9%, P = .02). The groups had similar rates of bleeding (1.2% vs. 1.4% P = 1.0) and thrombosis (3.7% vs. 4.6% P = 1.0). No patients in the brief stay group died within 100 days, compared with mortality of 1.8% (P = .6) in the prolonged stay group. Carefully selected patients receiving an autologous stem cell transplant for treatment of myeloma can be managed with a brief initial hospitalization and outpatient follow-up, with low morbidity and mortality. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. [Cell-based therapy options for osteochondral defects. Autologous mesenchymal stem cells compared to autologous chondrocytes].

    PubMed

    Grässel, S; Anders, S

    2012-05-01

    Cartilage defects are multifactorial and site-specific and therefore need a clear analysis of the underlying pathology as well as an individualized therapy so that cartilage repair lacks a one-for-all therapy. The results of comparative clinical studies using cultured chondrocytes in autologous chondrocyte implantation (ACI) have shown some superiority over conventional microfracturing under defined conditions, especially for medium or large defects and in long-term durability. Adult mesenchymal stem cells can be isolated from bone marrow, have the potency to proliferate in culture and are capable of differentiating into the chondrogenic pathway. They represent a promising versatile cell source for cartilage repair but the ideal conditions for cultivation and application in cartilage repair are not yet known or have not yet been characterized. Adding a scaffold offers mechanical stability and advances chondrogenic differentiation for both possible cell sources.

  13. Autologous stem cell transplantation for adult acute leukemia.

    PubMed

    Gorin, Norbert-Claude

    2002-03-01

    Autologous stem cell transplantation using marrow or peripheral blood is routinely used to consolidate patients with acute myelocytic leukemia in complete remission. The situation is less clear for adult acute lymphocytic leukemia in which results achieved with all strategies are disappointing. In acute myelocytic leukemia, autografts should be done in patients with good and standard risk factors. Patients with high-risk acute myelocytic leukemia defined by poor cytogenetics or failure to achieve remission with the first induction course, should proceed to allogeneic stem cell transplantation with the best available human leukocyte antigen-identical donor (family or unrelated), and the nature of the conditioning regimen (myelo-ablative or non-myelo-ablative) should be decided in relation to age, and the patient's clinical condition. Results of autografting in acute myelocytic leukemia rely strongly on the quality of the graft. Higher doses of infused stem cells translate into lower relapse rates. Marrow purging with cyclophosphamide derivatives also diminishes the relapse incidence. Autologous stem cell transplantations using peripheral blood are presently preferred to marrow as the source of stem cells, but an aggressive prior in vivo purge (high-dose consolidation course(s) before cytaphereses) is then mandatory. In good-risk acute myelocytic leukemia, autografting is superior to high-dose ARA-C; in standard-risk acute myelocytic leukemia, both are supposedly equivalent. There is no prospective randomized study testing the two approaches in the good-standard-risk population. We presently test the combination of marrow and blood both purged by mafosfamide. In adult acute lymphocytic leukemia, good-risk patients get the best benefit from autografting over conventional chemotherapy. Maintenance chemotherapy after transplant is likely to bring benefit. Research in progress aims at facilitating access of the largest number of patients to autografting and at

  14. Mesenchymal stem cell therapy in treatment of erectile dysfunction: autologous or allogeneic cell sources?

    PubMed

    Mangir, Naside; Akbal, Cem; Tarcan, Tufan; Simsek, Ferruh; Turkeri, Levent

    2014-12-01

    To compare the efficacy of intracavernosal injection of autologous and allogeneic mesenchymal stem cells as potential treatment of erectile dysfunction in an experimental rat model. Mesenchymal stem cells were isolated from rat paratesticular fat tissue. Bilateral cavernous nerve injury was carried out followed by immediate intracavernosal injection of either autologous or allogeneic mesenchymal stem cells or mesenchymal stem cell lysates. One month after injection, erectile function was evaluated by means of intracavernosal pressure measurement. All rats were eventually killed, and penile tissues were taken for immunhistochemical and molecular investigation. A total of 36 Sprague-Dawley rats were used. The mean maximum intracavernosal pressure in the sham-operated, autologous and allogeneic mesenchymal stem cell injection groups were significantly better compared with the vehicle injection group (80.5 [3.56], 71.1 [2.9] and 69.2 [3.2] vs 40.33 [4.4], respectively). Mean maximum intracavernosal pressure to mean arterial pressure ratios in the autologous and allogeneic mesenchymal stem cell and mesenchymal stem cell lysate injection groups were not significantly different. Intracavernosal injection of both autologous or allogeneic mesenchymal stem cells improve erectile functions in a rat model of cavernous nerve injury. Allogeneic mesenchymal stem cells might provide clinicians with ready to use, standardized and, in certain cases, more effective products. More studies focusing on long-term immunological aspects of allogeneic mesenchymal stem cells are required. © 2014 The Japanese Urological Association.

  15. Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

    PubMed Central

    Cortez, Afonso José Pereira; Dulley, Frederico Luiz; Saboya, Rosaura; Mendrone Júnior, Alfredo; Amigo Filho, Ulisses; Coracin, Fabio Luiz; Buccheri, Valéria; Linardi, Camila da Cruz Gouveia; Ruiz, Milton Artur; Chamone, Dalton de Alencar Fischer

    2011-01-01

    Background Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. Objectives To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. Methods A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. Results The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. Conclusion Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not been previously reported

  16. Autologous hematopoietic stem cells for refractory Crohn's disease.

    PubMed

    DiNicola, C A; Zand, A; Hommes, D W

    2017-05-01

    Autologous hematopoietic stem cells are gaining ground as an effective and safe treatment for treating severe refractory Crohn's disease (CD). Autologous hematopoietic stem cell therapy (AHSCT) induces resetting of the immune system by de novo regeneration of T-cell repertoire and repopulation of epithelial cells by bone-marrow derived cells to help patients achieve clinical and endoscopic remission. Areas covered: Herein, the authors discuss the use of AHSCT in treating patients with CD. Improvements in disease activity have been seen in patients with severe autoimmune disease and patients with severe CD who underwent AHSCT for a concomitant malignant hematological disease. Clinical and endoscopic remission has been achieved in patients treated with AHSCT for CD. The only randomized trial published to date, the ASTIC Trial, did not support further use of AHSCT to treat CD. Yet, critics of this trial have deemed AHSCT as a promising treatment for severe refractory CD. Expert opinion: Even with the promising evidence presented for HSCT for refractory CD, protocols need to be refined through the collaboration of GI and hemato-oncology professionals. The goal is to incorporate safe AHSCT and restore tolerance by delivering an effective immune 'cease fire' as a treatment option for severe refractory CD.

  17. [Sarcoidosis flare after autologous stem cell transplantation: An immune paradox?

    PubMed

    Marchal, A; Charlotte, F; Maksud, P; Haroche, J; Lifferman, F; Miyara, M; Choquet, S; Amoura, Z; Cohen Aubart, F

    2017-09-01

    Sarcoidosis is a systemic granulomatous disorder of unknown cause. Apparition or flare of previously diagnosed sarcoidosis following hematopoietic stem cell transplantation (HSCT) has rarely been reported. We report a 62-year-old woman who presented a radiological flare of sarcoidosis post-autologous stem cell transplantation for a POEMS syndrome. Imaging findings and lymph node histology, which revealed non-caseating granuloma, were consistent with the sarcoidosis diagnosis. The patient was asymptomatic and was kept free of treatment. Sarcoidosis must be considered ahead of compatible clinicoradiological presentation occurring after HSCT. Sarcoidosis can mimic metastatic cancer or lymphatic relapse. Tissue biopsies and exclusion of differential diagnosis of granuloma diseases are warranted to confirm sarcoidosis diagnosis. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  18. Autologous Stem Cell Mobilization in the Age of Plerixafor.

    PubMed

    Cooper, Dennis L; Medoff, Erin; Patel, Natalie; Baker, Julie; Pratt, Kathryn; Foss, Francine; Seropian, Stuart E; Perreault, Sarah; Wu, Yanyun

    2016-07-01

    Autologous stem cell transplantation remains important in the treatment of myeloma and relapsed lymphoma. Plerixafor has been shown to significantly enhance stem cell mobilization but is very expensive. We evaluated plerixafor use in the 3-year period after its approval in December 2008. A total of 277 patients with myeloma and lymphoma had stem cell mobilization; 97.5% were successfully mobilized, including 41.5% who received plerixafor. Plerixafor was generally used for rescue after suboptimal granulocyte-colony stimulating factor (G-CSF) mobilization ("just in time") or for remobilization after an unsuccessful attempt with chemotherapy plus G-CSF. In addition, 10% of patients received planned G-CSF plus plerixafor because of high risk factors for inadequate collection. Rescue plerixafor was more effective in patients with myeloma than lymphoma as after 1 dose of plerixafor; 85% versus 55% collected a minimum number of stem cells (2 × 10E6 CD34 cells/kg) for 1 transplant and 51% versus 15% collected > 5 × 10E6 CD34 cells/kg. After transplantation, there were no significant differences in engraftment as a consequence of plerixafor use. Among all patients, there were less platelet transfusions in patients provided ≥ 3.5 × 10E6 CD34(+) cells/kg. With the judicious use of plerixafor, nearly all patients can collect enough stem cells to proceed to transplantation. Further studies, including hematologic tolerance to posttransplantation therapy, are required to determine the cost-effectiveness of using plerixafor to convert adequate to more optimal mobilizers. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. T-cell subsets in autologous and allogeneic peripheral blood stem cell concentrates.

    PubMed

    Strobel, J; Moellmer, I; Zingsem, J; Hauck-Dlimi, B; Eckstein, R; Strasser, E

    2015-11-01

    Regulatory T cells (Tregs) and other T-cell subsets are of importance in the setting of autologous and allogeneic stem cell transplantations. We conducted a study to assess the content of peripheral blood stem cell concentrates and related apheresis parameters in the autologous and allogeneic setting. We characterized 53 donors, patients and peripheral blood stem cell concentrates (PBSC) regarding the content of CD45(+) cells, lymphocytes, CD3(+) cells, CD3(+) CD4(+) T cells, CD3(+) CD4(+) CD25(+) T cells, CD3(+) CD4(+) CD25(+) CD127(low/negative) Tregs and CD34(+) cells and calculated cell yields, recruitment factors and collection efficiency for all cell types. We compared allogeneic data with autologous data. Autologous PBSC show significantly lower concentrations of T-cell subsets compared to allogeneic PBSC (17,112/μl CD4(+), 14,858/μl CD4(+) CD25(+) and 1579/μl CD3(+) CD4(+) CD25(+) CD127(low/negative) Tregs in autologous compared to 65,539/μl CD4(+), 44,208(+) /μl CD4(+) CD25(+) and 5040/μl CD3(+) CD4(+) CD25(+) CD127(low/negative) Tregs in allogeneic PBSC, respectively), in contrast to CD34(+) concentrations (5342/μl CD34(+) in autologous compared to 2367/μl CD34(+) in allogeneic PBSC, respectively). Accordantly, all T-cell yields are lower in the autologous setting compared to allogeneic PBSC. However, recruitment factor and collection efficiency of all cell types are higher in autologous compared to allogeneic PBSC, but not all parameters differ significantly when groups are compared. T-cell subsets and especially Tregs are a substantial part of PBSC transplantation, as considerable recruitment during apheresis occurs. In large volume apheresis, the collection efficiency of Treg is comparable to that of CD34(+) cells, while recruitment factors are even higher. © 2015 International Society of Blood Transfusion.

  20. Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis.

    PubMed

    Muraro, Paolo A; Martin, Roland; Mancardi, Giovanni Luigi; Nicholas, Richard; Sormani, Maria Pia; Saccardi, Riccardo

    2017-07-01

    Autologous haematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from haematopoietic stem cells. Originally developed for the treatment of haematological malignancies, the procedure has been adapted for the treatment of severe immune-mediated disorders. Results from ∼20 years of research make a compelling case for selective use of AHSCT in patients with highly active multiple sclerosis (MS), and for controlled trials. Immunological studies support the notion that AHSCT causes qualitative immune resetting, and have provided insight into the mechanisms that might underlie the powerful treatment effects that last well beyond recovery of immune cell numbers. Indeed, studies have demonstrated that AHSCT can entirely suppress MS disease activity for 4-5 years in 70-80% of patients, a rate that is higher than those achieved with any other therapies for MS. Treatment-related mortality, which was 3.6% in studies before 2005, has decreased to 0.3% in studies since 2005. Current evidence indicates that the patients who are most likely to benefit from and tolerate AHSCT are young, ambulatory and have inflammatory MS activity. Clinical trials are required to rigorously test the efficacy, safety and cost-effectiveness of AHSCT against highly active MS drugs.

  1. Autologous haemopoietic stem cell transplantation for autoimmune diseases.

    PubMed

    Zeher, Margit; Papp, Gabor; Szodoray, Peter

    2011-09-01

    Autoimmune diseases are signified by complex errors of immune-regulation, and the development of autoreactive T and B cells targeting self-antigens, which eventually can lead to permanent organ damage. Despite novel therapeutic protocols, the disease course is chronic, debilitating and in some instances the outcome is lethal. Previously, stem cell transplantation has been reported to be beneficial in autoimmune animal models, as well as in autoimmune diseases related to hematological abnormalities, which opened potential new avenues in the treatment of human autoimmune diseases. In this review, the authors describe the compound cellular regulatory effects of autologous hemopoietic stem cell transplantation (ASCT) and also clinical observations, related to the therapy in a variety of organ-specific and systemic autoimmune diseases. ASCT has a broad effect on the re-populated immune system, complex regulatory potentials and long term beneficial effect via down-regulating immune-reactivity, yet its widespread use in autoimmune diseases is limited, mostly due to the serious side-effects of the conditioning treatments. However, in certain autoimmune diseases with severe debilitating, or even life-threatening course, including systemic lupus erythematosus, systemic sclerosis or multiple sclerosis, ASCT can be a reasonable choice when conventional therapy has failed.

  2. Optimizing autologous cell grafts to improve stem cell gene therapy.

    PubMed

    Psatha, Nikoletta; Karponi, Garyfalia; Yannaki, Evangelia

    2016-07-01

    Over the past decade, stem cell gene therapy has achieved unprecedented curative outcomes for several genetic disorders. Despite the unequivocal success, clinical gene therapy still faces challenges. Genetically engineered hematopoietic stem cells are particularly vulnerable to attenuation of their repopulating capacity once exposed to culture conditions, ultimately leading to low engraftment levels posttransplant. This becomes of particular importance when transduction rates are low or/and competitive transplant conditions are generated by reduced-intensity conditioning in the absence of a selective advantage of the transduced over the unmodified cells. These limitations could partially be overcome by introducing megadoses of genetically modified CD34(+) cells into conditioned patients or by transplanting hematopoietic stem cells hematopoietic stem cells with high engrafting and repopulating potential. On the basis of the lessons gained from cord blood transplantation, we summarize the most promising approaches to date of increasing either the numbers of hematopoietic stem cells for transplantation or/and their engraftability, as a platform toward the optimization of engineered stem cell grafts. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  3. Autologous and allogeneic hematopoietic stem cell transplantation in follicular lymphoma.

    PubMed

    Bhatt, V R; Armitage, J O

    2016-01-01

    High-dose chemotherapy and autologous stem cell transplantation (ASCT) improve survival in follicular lymphoma; however, relapse remains the most common cause of death. The lower risk of relapse with allogeneic SCT (alloSCT) is offset by a high transplant-related mortality (TRM). English articles indexed in the MEDLINE database were reviewed to discuss the role of graft purging, rituximab maintenance after ASCT, reduced-intensity conditioning (RIC) alloSCT, T-cell depletion, donor lymphocyte infusion (DLI) and alternate donor sources. Optimal salvage consolidation strategy may utilize ASCT following non-total body irradiation-based conditioning regimen in second remission. Rituximab maintenance after ASCT may improve molecular remission but is not yet shown to improve overall survival. RIC alloSCT permits its use in older and less-fit patients. Studies with T-cell depleted graft failed to reduce TRM despite a decline in graft-versus-host disease; however, these studies did demonstrate a therapeutic role of DLI in post-transplant relapses. In recent years, haploidentical and umbilical cord blood donors have emerged as alternative donor sources, with outcomes comparable to matched unrelated donor SCT. In the future, incorporation of novel therapeutic agents, improved risk-adapted treatment strategies, and advancement of transplant techniques may provide a better chance of survival.

  4. Persistent seropositivity for yellow fever in a previously vaccinated autologous hematopoietic stem cell transplantation recipient.

    PubMed

    Hayakawa, Kayoko; Takasaki, Tomohiko; Tsunemine, Hiroko; Kanagawa, Shuzo; Kutsuna, Satoshi; Takeshita, Nozomi; Mawatari, Momoko; Fujiya, Yoshihiro; Yamamoto, Kei; Ohmagari, Norio; Kato, Yasuyuki

    2015-08-01

    The duration of a protective level of yellow fever antibodies after autologous hematopoietic stem cell transplantation in a previously vaccinated person is unclear. The case of a patient who had previously been vaccinated for yellow fever and who remained seropositive for 22 months after autologous peripheral blood stem cell transplantation for malignant lymphoma is described herein. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Angiogenesis in rat uterine cicatrix after injection of autologous bone marrow mesenchymal stem cells.

    PubMed

    Maiborodin, I V; Yakimova, N V; Matveyeva, V A; Pekarev, O G; Maiborodina, E I; Pekareva, E O

    2011-04-01

    Results of injection of autologous bone marrow mesenchymal stem cells with transfected GFP gene into the rat uterine horn cicatrix were studied by light microscopy. Large groups of blood vessels with blood cells inside were seen after injection of autologous bone marrow cells into the cicatrix on the right horn, formed 2 months after its ligation; no groups of vessels of this kind were found in the cicatrix in the contralateral horn. Examination of unstained sections in reflected UV light showed sufficiently bright fluorescence in the endothelium and outer vascular membrane in the uterine horn cicatrix only on the side of injection. Hence, autologous mesenchymal stem cells injected into the cicatrix formed the blood vessels due to differentiation into endotheliocytes and pericytes. The expression of GFP gene not only in the vascular endothelium, but also in vascular outer membranes indicated that autologous mesenchymal stem cells differentiated in the endothelial and pericytic directions.

  6. Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells

    PubMed Central

    Muscogiuri, Giovanna; Palomba, Stefano; Serio, Bianca; Sessa, Mariarosaria; Giudice, Valentina; Ferrara, Idalucia; Tauchmanovà, Libuse; Colao, Annamaria; Selleri, Carmine

    2014-01-01

    Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT. PMID:24883377

  7. Effectiveness of autologous serum as an alternative to fetal bovine serum in adipose-derived stem cell engineering.

    PubMed

    Choi, Jaehoon; Chung, Jee-Hyeok; Kwon, Geun-Yong; Kim, Ki-Wan; Kim, Sukwha; Chang, Hak

    2013-09-01

    In cell culture, medium supplemented with fetal bovine serum is commonly used, and it is widely known that fetal bovine serum supplies an adequate environment for culture and differentiation of stem cells. Nevertheless, the use of xenogeneic serum can cause several problems. We compared the effects of four different concentrations of autologous serum (1, 2, 5, and 10%) on expansion and adipogenic differentiation of adipose-derived stem cells using 10% fetal bovine serum as a control. The stem cells were grafted on nude mice and the in vivo differentiation capacity was evaluated. The isolation of adipose-derived stem cells was successful irrespective of the culture medium. The proliferation potential was statistically significant at passage 2, as follows: 10% autologous serum > 10% fetal bovine serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. The differentiation capacity appeared statistically significant at passage 4, as follows: 10% fetal bovine serum > 10% autologous serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. Ten percent autologous serum and 10% fetal bovine serum had greater differentiation capacity than 1 and 2% autologous serum in vivo, and no significant difference was observed between the groups at ≥ 5% concentration at 14 weeks. In conclusion, 10% autologous serum was at least as effective as 10% fetal bovine serum with respect to the number of adipose-derived stem cells at the end of both isolation and expansion, whereas 1 and 2% autologous serum was inferior.

  8. The potential role of autologous stem cell transplantation in patients with systemic lupus erythematosus.

    PubMed

    Hahn, B H

    1997-05-01

    Transfer of disease by bone marrow cells has been described in experimental models of systemic lupus erythematosus (SLE). In one experiment, marrow ablation followed by transfer of T depleted allogeneic marrow resulted in prolonged survival of animals with SLE. Some experimental studies suggest a rationale for autologous stem cell transplantation indicating this intervention might "reset the thermostat" so that normal immunoregulation can control disease, while others indicate it might not be beneficial. The pros and cons of offering patients with SLE autologous hematopoietic stem cell transplantation are considered. A profile of the patient with SLE who might be considered as a candidate for autologous stem cell transplantation can be constructed by evaluating causes of death and factors that increase mortality. This profile includes life threatening disease, inadequate response to aggressive immunosuppressive therapy, and adequate function of all major organs so that risks associated with stem cell transplantation can be minimized.

  9. Rapid deterioration of preexisting renal insufficiency after autologous mesenchymal stem cell therapy.

    PubMed

    Kim, Jun-Seop; Lee, Jong-Hak; Kwon, Owen; Cho, Jang-Hee; Choi, Ji-Young; Park, Sun-Hee; Kim, Chan-Duck; Kim, Yong-Jin; Kim, Yong-Lim

    2017-06-01

    Administration of autologous mesenchymal stem cells (MSCs) has been shown to improve renal function and histological findings in acute kidney injury (AKI) models. However, its effects in chronic kidney disease (CKD) are unclear, particularly in the clinical setting. Here, we report our experience with a CKD patient who was treated by intravenous infusion of autologous MSCs derived from adipose tissue in an unknown clinic outside of Korea. The renal function of the patient had been stable for several years before MSC administration. One week after the autologous MSC infusion, the preexisting renal insufficiency was rapidly aggravated without any other evidence of AKI. Hemodialysis was started 3 months after MSC administration. Renal biopsy findings at dialysis showed severe interstitial fibrosis and inflammatory cell infiltration, with a few cells expressing CD34 and CD117, 2 surface markers of stem cells. This case highlights the potential nephrotoxicity of autologous MSC therapy in CKD patients.

  10. The Use of Autologous Mesenchymal Stem Cells for Cell Therapy of Patients with Amyotrophic Lateral Sclerosis in Belarus.

    PubMed

    Rushkevich, Yu N; Kosmacheva, S M; Zabrodets, G V; Ignatenko, S I; Goncharova, N V; Severin, I N; Likhachev, S A; Potapnev, M P

    2015-08-01

    We studied a new method of treatment of amyotrophic lateral sclerosis with autologous mesenchymal stem cells. Autologous mesenchymal stem cells were injected intravenously (intact cells) or via lumbar puncture (cells committed to neuronal differentiation). Evaluation of the results of cell therapy after 12-month follow-up revealed slowing down of the disease progression in 10 patients in comparison with the control group consisting of 15 patients. The cell therapy was safe for the patients.

  11. SECOND AUTOLOGOUS STEM CELL TRANSPLANTATION FOR RELAPSED LYMPHOMA AFTER A PRIOR AUTOLOGOUS TRANSPLANT

    PubMed Central

    Smith, Sonali M.; van Besien, Koen; Carreras, Jeanette; Bashey, Asad; Cairo, Mitchell S.; Freytes, Cesar O.; Gale, Robert Peter; Hale, Gregory A.; Hayes-Lattin, Brandon; Holmberg, Leona A.; Keating, Armand; Maziarz, Richard T.; McCarthy, Philip L.; Navarro, Willis H.; Pavlovsky, Santiago; Schouten, Harry C.; Seftel, Matthew; Wiernik, Peter H.; Vose, Julie M.; Lazarus, Hillard M.; Hari, Parameswaran

    2012-01-01

    We determined treatment-related mortality (TRM), progression free survival (PFS), and overall survival (OS) after a second autologous HCT (HCT2) for patients with lymphoma relapse after a prior HCT (HCT1). Outcomes for patients with either Hodgkin lymphoma (HL, n=21) or non-Hodgkin lymphoma (NHL, n=19) receiving HCT2 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) were analyzed. The median age at HCT2 was 38 years (range, 16–61) and 22 (58%) patients had a Karnofsky performance score less than 90. HCT2 was performed >1 year after HCT1 in 82%. The probability of TRM at day 100 was 15% (95% CI, 3–22%). The 1, 3 and 5 yr probabilities of PFS were 50% (95% CI, 34–66%), 36% (95% CI, 21–52%) and 30% (95% CI, 16–46%), respectively. Corresponding probabilities of survival were 65% (95% CI, 50–79%), 36% (95% CI, 22–52%) and 30% (95% CI, 17–46%), respectively. At a median follow up of 72 months (range, 12–124 months) after HCT2, 29 patients (73%) have died, 18 (62%) secondary to relapsed lymphoma. The outcomes of patients with HL and NHL were similar. In summary, this series represents the largest reported group of patients with relapsed lymphomas undergoing SCT2 following failed SCT1, and with long-term follow-up. Our series suggests that SCT2 is feasible in patients relapsing after prior HCT1, with a lower TRM than that reported for allogeneic transplant in this setting. HCT2 should be considered for patients with relapsed HL or NHL after HCT1 without alternative allogeneic stem cell transplant options. PMID:18640574

  12. Untested, unproven, and unethical: the promotion and provision of autologous stem cell therapies in Australia.

    PubMed

    McLean, Alison K; Stewart, Cameron; Kerridge, Ian

    2015-02-09

    An increasing number of private clinics in Australia are marketing and providing autologous stem cell therapies to patients. Although advocates point to the importance of medical innovation and the primacy of patient choice, these arguments are unconvincing. First, it is a stark truth that these clinics are flourishing while the efficacy and safety of autologous stem cell therapies, outside of established indications for hematopioetic stem cell transplantation, are yet to be shown. Second, few of these therapies are offered within clinical trials. Third, patients with chronic and debilitating illnesses, who are often the ones who take up these therapies, incur significant financial burdens in the expectation of benefiting from these treatments. Finally, the provision of these stem cell therapies does not follow the established pathways for legitimate medical advancement. We argue that greater regulatory oversight and professional action are necessary to protect vulnerable patients and that at this time the provision of unproven stem cell therapies outside of clinical trials is unethical.

  13. Allogeneic and autologous mode of stem cell transplantation in regenerative medicine: which way to go?

    PubMed

    Mamidi, Murali Krishna; Dutta, Susmita; Bhonde, Ramesh; Das, Anjan Kumar; Pal, Rajarshi

    2014-12-01

    Stem cell transplantation is a generic term covering different techniques. However there is argument over the pros and cons of autologous and allogeneic transplants of mesenchymal stem cells (MSCs) for regenerative therapy. Given that the MSCs have already been proven to be safe in patients, we hypothesize that allogeneic transplantation could be more effective and cost-effective as compared to autologous transplantation specifically in older subjects who are the likely victims of degenerative diseases. This analysis is based on the scientific logic that allogeneic stem cells extracted in large numbers from young and healthy donors could be physiologically, metabolically and genetically more stable. Therefore stem cells from young donors may be expected to exhibit higher vigor in secreting trophic factors leading to activation of host tissue-specific stem cells and also be more efficient in remodeling the micro-environmental niche of damaged tissue. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Debrided Skin as a Source of Autologous Stem Cells for Wound Repair

    DTIC Science & Technology

    2011-08-01

    surgical debridement of necrotic tissue associated with eschar, fol- lowed by the application of skin grafts or tissue-engineered skin substitutes ...REGENERATIVE MEDICINE Debrided Skin as a Source of Autologous Stem Cells for Wound Repair SHANMUGASUNDARAM NATESAN, NICOLE L. WRICE, DAVID G. BAER...wounds • Perivascular niche ABSTRACT Major traumatic injuries to the body, such as large sur- face area burns, limit the availability of autologous

  15. Gastrocnemius tendon strain in a dog treated with autologous mesenchymal stem cells and a custom orthosis.

    PubMed

    Case, J Brad; Palmer, Ross; Valdes-Martinez, Alex; Egger, Erick L; Haussler, Kevin K

    2013-05-01

    To report clinical findings and outcome in a dog with gastrocnemius tendon strain treated with autologous mesenchymal stem cells and a custom orthosis. Clinical report. A 4-year-old spayed female Border Collie. Bone-marrow derived, autologous mesenchymal stem cells were transplanted into the tendon core lesion. A custom, progressive, dynamic orthosis was fit to the tarsus. Serial orthopedic examinations and ultrasonography as well as long-term force-plate gait analysis were utilized for follow up. Lameness subjectively resolved and peak vertical force increased from 43% to 92% of the contralateral pelvic limb. Serial ultrasonographic examinations revealed improved but incomplete restoration of normal linear fiber pattern of the gastrocnemius tendon. Findings suggest that autologous mesenchymal stem cell transplantation with custom, progressive, dynamic orthosis may be a viable, minimally invasive technique for treatment of calcaneal tendon injuries in dogs. © Copyright 2013 by The American College of Veterinary Surgeons.

  16. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

    SciTech Connect

    Puente, Pilar de la

    2013-02-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.

  17. [Autologous transplantation of peripheral blood stem cells in malignant lymphomas].

    PubMed

    Sánchez Luceros, A; Koziner, B

    1995-01-01

    The administration of high dose chemotherapy and or radiotherapy with autologous hematopoietic rescue has become a treatment modality with increasing number of indications in a variety of malignant conditions. Improvements in the conditioning regimens and supportive measures used, as well as a more refined patient selection based on prognostic factors, have resulted in progressively better results. The availability of precursor cells from peripheral blood has allowed a faster restoration of hematopoiesis, decreasing the period and intensity of myelosuppression. The following revision gives an updated image of the accumulated experience with this mode of support in malignant lymphomas.

  18. Autologous stem cell transplantation as first line treatment after incomplete excision of pancreatoblastoma.

    PubMed

    Meneses, Clarice Franco; Osório, Carolina Dame; de Castro Junior, Claudio Galvão; Brunetto, Algemir Lunardi

    2013-01-01

    Pancreatoblastoma is a rare tumor and surgery with complete resection is the main treatment approach. Prognosis for patients with residual disease after surgery is usually dismal. A 14-year-old girl with pancreatoblastoma in the pancreatic body and tail was submitted to preoperative chemotherapy. She underwent surgery and the tumor was resected with microscopic margins. Postoperative chemotherapy was followed by high dose chemotherapy and autologous hematopoietic stem cell transplantation. After four years she remains very well with no evidence of disease. This is the first case reported of pancreatoblastoma that was treated with autologous hematopoietic stem cell transplantation as first line treatment without radiotherapy at the site of the microscopic disease.

  19. Autologous and Allogeneic Equine Mesenchymal Stem Cells Exhibit Equivalent Immunomodulatory Properties In Vitro.

    PubMed

    Colbath, Aimée C; Dow, Steven W; Phillips, Jennifer N; McIlwraith, C Wayne; Goodrich, Laurie R

    2017-04-01

    The use of allogeneic bone marrow-derived mesenchymal stem cells (BMDMSCs) may provide an effective alternative to autologous BMDMSCs for treatment of equine musculoskeletal injuries. However, concerns have been raised regarding the potential safety and effectiveness of allogeneic BMDMSCs. We conducted studies to assess the immunological properties of equine allogeneic BMDMSCs compared with those of autologous BMDMSCs. For assessment of inherent immunogenicity, the relative ability of allogeneic and autologous BMDMSCs to stimulate spontaneous proliferation of equine lymphocytes was compared. The immunosuppressive activity of the two cell types was evaluated by adding autologous or allogeneic BMDMSCs to activated lymphocytes and assessing suppression of lymphocyte proliferation and IFNγ production. Fifty-six allogeneic and 12 autologous combinations were evaluated. Studies were also done to elucidate mechanisms by which equine mesenchymal stem cells (MSCs) suppress lymphocyte function. Potential mechanisms evaluated included production of prostaglandin E2 (PGE2), nitric oxide, transforming growth factor-beta, and indoleamine 2,3-dioxygenase. We found that autologous and allogeneic BMDMSCs both induced mild but equivalent levels of spontaneous lymphocyte activation in vitro. In in vitro assays assessing the ability of BMDMSCs to suppress activated lymphocytes, both allogeneic and autologous BMDMSCs suppressed T cell proliferation and IFNγ production to an equal degree. The primary mechanism of equine BMDMSC suppression of T cells was mediated by PGE2. We concluded that allogeneic and autologous BMDMSCs are equivalent in terms of their immunomodulatory properties, and stimulated peripheral blood mononuclear cells appear to trigger the immunosuppressive properties of MSCs. Therefore, both cell types appear to have equal potency in modulating inflammatory processes related to acute or chronic musculoskeletal injuries in the horse.

  20. Regulatory considerations for the development of autologous induced pluripotent stem cell therapies.

    PubMed

    Carpenter, Melissa K; Couture, Larry A

    2010-07-01

    Induced pluripotent stem (iPS) cells offer tremendous opportunity for the creation of autologous cellular therapies, in which gene correction or the avoidance of immune response issues are desirable. In addition, iPS cells avoid the ethical concerns raised by the sourcing of human embryonic stem cells (hESCs) from embryos. iPS cells share many characteristics with hESCs and it is anticipated that existing experience with hESCs will translate to rapid progress in moving iPS cell-derived products toward clinical trials. While the potential clinical value for these products is considerable, the nature of current manufacturing paradigms for autologous iPS cell products raises considerable regulatory concerns. Here, the regulatory challenges posed by autologous iPS cell-derived products are examined. We conclude that there will be considerable regulatory concerns primarily relating to reproducibility of the manufacturing process and safety testing within clinically limited time constraints. Demonstrating safety of the final cell product in an autologous setting will be the single greatest obstacle to progressing autologous iPS cell-based therapies into the clinic.

  1. Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke.

    PubMed

    Honmou, Osamu; Houkin, Kiyohiro; Matsunaga, Takuya; Niitsu, Yoshiro; Ishiai, Sumio; Onodera, Rie; Waxman, Stephen G; Kocsis, Jeffery D

    2011-06-01

    Transplantation of human mesenchymal stem cells has been shown to reduce infarct size and improve functional outcome in animal models of stroke. Here, we report a study designed to assess feasibility and safety of transplantation of autologous human mesenchymal stem cells expanded in autologous human serum in stroke patients. We report an unblinded study on 12 patients with ischaemic grey matter, white matter and mixed lesions, in contrast to a prior study on autologous mesenchymal stem cells expanded in foetal calf serum that focused on grey matter lesions. Cells cultured in human serum expanded more rapidly than in foetal calf serum, reducing cell preparation time and risk of transmissible disorders such as bovine spongiform encephalomyelitis. Autologous mesenchymal stem cells were delivered intravenously 36-133 days post-stroke. All patients had magnetic resonance angiography to identify vascular lesions, and magnetic resonance imaging prior to cell infusion and at intervals up to 1 year after. Magnetic resonance perfusion-imaging and 3D-tractography were carried out in some patients. Neurological status was scored using the National Institutes of Health Stroke Scale and modified Rankin scores. We did not observe any central nervous system tumours, abnormal cell growths or neurological deterioration, and there was no evidence for venous thromboembolism, systemic malignancy or systemic infection in any of the patients following stem cell infusion. The median daily rate of National Institutes of Health Stroke Scale change was 0.36 during the first week post-infusion, compared with a median daily rate of change of 0.04 from the first day of testing to immediately before infusion. Daily rates of change in National Institutes of Health Stroke Scale scores during longer post-infusion intervals that more closely matched the interval between initial scoring and cell infusion also showed an increase following cell infusion. Mean lesion volume as assessed by magnetic

  2. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype.

    PubMed

    de la Puente, Pilar; Ludeña, Dolores; López, Marta; Ramos, Jennifer; Iglesias, Javier

    2013-02-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering.

  3. C3 glomerulopathy associated to multiple myeloma successfully treated by autologous stem cell transplant

    PubMed Central

    Hamzi, M. A.; Zniber, A.; Badaoui, G. E.; Mahtat, E.; Alhamany, Z.; Bayahia, R.; Ouzeddoun, N.

    2017-01-01

    A 32-year-old male presented with advanced renal failure and nephrotic proteinuria due to lambda light chain multiple myeloma. Renal biopsy showed a proliferative glomerulonephritis with isolated C3 deposits. Renal recovery was obtained after chemotherapy and autologous stem cell transplant. We review previously described cases of C3 glomerulopathy associated with monoclonal gammopathy. PMID:28356669

  4. How to manage poor mobilizers for high dose chemotherapy and autologous stem cell transplantation?

    PubMed

    Ataca Atilla, Pinar; Bakanay Ozturk, Sule Mine; Demirer, Taner

    2016-12-26

    Today, peripheral blood stem cells are the preferred source of stem cells over bone marrow. Therefore, mobilization plays a crutial role in successful autologous stem cell transplantation. Poor mobilization is generally defined as failure to achieve the target level of at least 2×10(6) CD34(+) cells/kg body weight. There are several strategies to overcome poor mobilization: 1) Larger volume Leukapheresis (LVL) 2) Re-mobilization 3) Plerixafor 4) CM+Plerixafor (P)+G-CSF and 5) Bone Marrow Harvest. In this review, the definitions of successful and poor mobilization are discussed. Management strategies for poor mobilization are defined. The recent research on new agents are included.

  5. Autologous stem cell transplantation improves quality of life in economically challenged, Brazilian multiple myeloma patients

    PubMed Central

    Etto, Leina Y.; Morelli, Vânia Maris; Silva, Vanderleia C.; Hungria, Vania T. M.; Ciconelli, Rozana M.; Almeida, Manuella S. S.; de Oliveira, José Salvador R.; Barros, José Carlos; Durie, Brian G.; Colleoni, Gisele W. B.

    2011-01-01

    OBJECTIVES: 1) To characterize the impact of multiple myeloma on the quality of life of patients treated in two public institutions in São Paulo State, Brazil, using a generic Short Form 36 Health Survey and a questionnaire specific for oncologic patients (QLQ-C30) upon diagnosis, after the clinical treatment, and at day +100 after autologous stem cell transplantation; 2) to evaluate whether autologous stem cell transplantation can improve the quality of life of our economically challenged population aside from providing a clinical benefit and disease control. METHODS: We evaluated 49 patients with multiple myeloma (a total of 70 interviews) using the two questionnaires. The scores upon diagnosis, post-treatment/pre-autologous stem cell transplantation, and at D+100 were compared using ANOVA (a comparison of the three groups), post hoc tests (two-by-two comparisons of the three groups), and paired t-tests (the same case at two different times). RESULTS : Of the included patients, 87.8% had a family budget under US $600 (economic class C, D, or E) per month. The generic Short Form 36 Health Survey questionnaire demonstrated that physical function, role-physical, and bodily pain indices were statistically different across all three groups, favoring the D+100 autologous stem cell transplantation group (ANOVA). The questionnaire specific for oncologic patients, the QLQ-C30 questionnaire, confirmed what had been demonstrated by the Short Form 36 Health Survey with respect to physical function and bodily pain, with improvements in role functioning, fatigue, and lack of appetite and constipation, favoring the D+100 autologous stem cell transplant group (ANOVA). The post hoc tests and paired t-tests confirmed a better outcome after autologous stem cell transplantation. CONCLUSION: The questionnaire specific for cancer patients seems to be more informative than the generic Short Form 36 Health Survey questionnaire and reflects the real benefit of autologous stem cell

  6. Targeted Drugs as Maintenance Therapy after Autologous Stem Cell Transplantation in Patients with Mantle Cell Lymphoma

    PubMed Central

    Yan, Fengting; Gopal, Ajay K.; Graf, Solomon A.

    2017-01-01

    The treatment landscape for mantle cell lymphoma (MCL) is rapidly evolving toward the incorporation of novel and biologically targeted pharmaceuticals with improved disease activity and gentler toxicity profiles compared with conventional chemotherapeutics. Upfront intensive treatment of MCL includes autologous stem cell transplantation (SCT) consolidation aimed at deepening and lengthening disease remission, but subsequent relapse occurs. Maintenance therapy after autologous SCT in patients with MCL in remission features lower-intensity treatments given over extended periods to improve disease outcomes. Targeted drugs are a natural fit for this space, and are the focus of considerable clinical investigation. This review summarizes recent advances in the field and their potential impact on treatment practices for MCL. PMID:28287430

  7. Autologous Pluripotent Stem Cell-Derived β-Like Cells for Diabetes Cellular Therapy.

    PubMed

    Millman, Jeffrey R; Pagliuca, Felicia W

    2017-05-01

    Development of stem cell technologies for cell replacement therapy has progressed rapidly in recent years. Diabetes has long been seen as one of the first applications for stem cell-derived cells because of the loss of only a single cell type-the insulin-producing β-cell. Recent reports have detailed strategies that overcome prior hurdles to generate functional β-like cells from human pluripotent stem cells in vitro, including from human induced pluripotent stem cells (hiPSCs). Even with this accomplishment, addressing immunological barriers to transplantation remains a major challenge for the field. The development of clinically relevant hiPSC derivation methods from patients and demonstration that these cells can be differentiated into β-like cells presents a new opportunity to treat diabetes without immunosuppression or immunoprotective encapsulation or with only targeted protection from autoimmunity. This review focuses on the current status in generating and transplanting autologous β-cells for diabetes cell therapy, highlighting the unique advantages and challenges of this approach. © 2017 by the American Diabetes Association.

  8. Regeneration of Cartilage in Human Knee Osteoarthritis with Autologous Adipose Tissue-Derived Stem Cells and Autologous Extracellular Matrix

    PubMed Central

    Pak, Jaewoo; Lee, Jung Hun; Park, Kwang Seung; Jeong, Byeong Chul; Lee, Sang Hee

    2016-01-01

    Abstract This clinical case series demonstrates that percutaneous injections of autologous adipose tissue-derived stem cells (ADSCs) and homogenized extracellular matrix (ECM) in the form of adipose stromal vascular fraction (SVF), along with hyaluronic acid (HA) and platelet-rich plasma (PRP) activated by calcium chloride, could regenerate cartilage-like tissue in human knee osteoarthritis (OA) patients. Autologous lipoaspirates were obtained from adipose tissue of the abdominal origin. Afterward, the lipoaspirates were minced to homogenize the ECM. These homogenized lipoaspirates were then mixed with collagenase and incubated. The resulting mixture of ADSCs and ECM in the form of SVF was injected, along with HA and PRP activated by calcium chloride, into knees of three Korean patients with OA. The same affected knees were reinjected weekly with additional PRP activated by calcium chloride for 3 weeks. Pretreatment and post-treatment magnetic resonance imaging (MRI) data, functional rating index, range of motion (ROM), and pain score data were then analyzed. All patients' MRI data showed cartilage-like tissue regeneration. Along with MRI evidence, the measured physical therapy outcomes in terms of ROM, subjective pain, and functional status were all improved. This study demonstrates that percutaneous injection of ADSCs with ECM contained in autologous adipose SVF, in conjunction with HA and PRP activated by calcium chloride, is a safe and potentially effective minimally invasive therapy for OA of human knees. PMID:27588219

  9. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    PubMed

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL).

  10. Allogeneic cellular and autologous stem cell therapy for sickle cell disease: 'whom, when and how'.

    PubMed

    Freed, J; Talano, J; Small, T; Ricci, A; Cairo, M S

    2012-12-01

    Sickle cell disease (SCD) is an autosomal recessive inherited hematological disorder characterized by chronic hemolysis and vaso-occlusion, resulting in multiorgan dysfunction and premature death. The only known curative therapy for patients with severe SCD is myeloablative conditioning and allo-SCT from HLA-matched sibling donors. In this state of the art review, we discuss current and future considerations including patient selection/eligibility, intensity of conditioning regimens, allogeneic graft sources, graft manipulation, mixed donor chimerism, organ function and stability and autologous gene correction stem cell strategies. Recent novel approaches to promote mixed donor chimerism have included the use of matched unrelated adult donors, umbilical cord blood donors, haploidentical familial donors and the utilization of nonmyeloablative, such as reduced intensity and reduced toxicity conditioning regimens. Future strategies will include gene therapy and autologous gene correction stem cell designs. Prospects are bright for novel stem and cellular approaches for patients with severe SCD, and we are currently at the end of the beginning for utilizing cellular therapeutics for the curative treatment of this chronic and debilitating condition.

  11. Successful autologous hematopoietic stem cell transplantation for a patient with rapidly progressive localized scleroderma.

    PubMed

    Nair, Velu; Sharma, Ajay; Sharma, Sanjeevan; Das, Satyaranjan; Bhakuni, Darshan S; Narayanan, Krishnan; Nair, Vivek; Shankar, Subramanian

    2015-03-01

    Autologous hematopoietic stem cell transplant (HSCT) for rapidly progressive disease has not been reported in localized scleroderma. Our patient, a 16-year-old girl had an aggressive variant of localized scleroderma, mixed subtype (linear-generalized) with Parry Romberg syndrome, with no internal organ involvement, that was unresponsive to immunosuppressive therapy and was causing rapid disfigurement. She was administered autologous HSCT in June 2011 and has maintained drug-free remission with excellent functional status at almost 3.5 years of follow-up. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  12. Regulatory T cells enhance mesenchymal stem cell survival and proliferation following autologous cotransplantation in ischemic myocardium.

    PubMed

    Zhou, Yifu; Singh, Avneesh K; Hoyt, Robert F; Wang, Suna; Yu, Zuxi; Hunt, Timothy; Kindzelski, Bogdan; Corcoran, Philip C; Mohiuddin, Muhammad M; Horvath, Keith A

    2014-09-01

    We sought to investigate if autologous freshly isolated regulatory T cells (Tregs) provide a protective and supportive role when cotransplanted with mesenchymal stem cells (MSCs). In a porcine model of chronic ischemia, autologous MSCs were isolated and expanded ex vivo for 4 weeks. Autologous Treg cells were freshly isolated from 100 mL peripheral blood and purified by fluorescence-activated cell sorting. MSCs and Treg cells were then cotransplanted into the chronic ischemic myocardium of Yorkshire pigs by direct intramyocardial injection (1.2 × 10(8) MSCs plus an average of 1.5 million Treg cells in 25 injection sites). Animals were killed 6 weeks postinjection to study the fate of the cells and compare the effect of combined MSCs + Treg cells transplantation versus MSCs alone. The coinjection of MSCs along with Tregs was safe and no deleterious side effects were observed. Six weeks after injection of the cell combination, spherical MSCs clusters with thin layer capsules were found in the injected areas. In animals treated with MSCs only, the MSC clusters were less organized and not encapsulated. Immunofluorescent staining showed CD25+ cells among the CD90+ (MSC marker) cells, suggesting that the injected Treg cells remained present locally, and survived. Factor VIII+ cells were also prevalent suggesting new angiogenesis. We found no evidence that coinjections were associated with the generation of cardiac myocytes. The cotransplantation of Treg cells with MSCs dramatically increased the MSC survival rate, proliferation, and augmented their role in angiogenesis, which suggests a new way for future clinical application of cell-based therapy. Published by Mosby, Inc.

  13. Human transgene-free amniotic-fluid-derived induced pluripotent stem cells for autologous cell therapy.

    PubMed

    Jiang, Guihua; Di Bernardo, Julie; Maiden, Michael M; Villa-Diaz, Luis G; Mabrouk, Omar S; Krebsbach, Paul H; O'Shea, K Sue; Kunisaki, Shaun M

    2014-11-01

    The establishment of a reliable prenatal source of autologous, transgene-free progenitor cells has enormous potential in the development of regenerative-medicine-based therapies for infants born with devastating birth defects. Here, we show that a largely CD117-negative population of human amniotic fluid mesenchymal stromal cells (AF-MSCs) obtained from fetuses with or without prenatally diagnosed anomalies are readily abundant and have limited baseline differentiation potential when compared with bone-marrow-derived MSCs and other somatic cell types. Nonetheless, the AF-MSCs could be easily reprogrammed into induced pluripotent stem cells (iPSCs) using nonintegrating Sendai viral vectors encoding for OCT4, SOX2, KLF4, and cMYC. The iPSCs were virtually indistinguishable from human embryonic stem cells in multiple assays and could be used to generate a relatively homogeneous population of neural progenitors, expressing PAX6, SOX2, SOX3, Musashi-1, and PSA-NCAM, for potential use in neurologic diseases. Further, these neural progenitors showed engraftment potential in vivo and were capable of differentiating into mature neurons and astrocytes in vitro. This study demonstrates the usefulness of AF-MSCs as an excellent source for the generation of human transgene-free iPSCs ideally suited for autologous perinatal regenerative medicine applications.

  14. Autologous transplantation of amniotic fluid-derived mesenchymal stem cells into sheep fetuses.

    PubMed

    Shaw, S W Steven; Bollini, Sveva; Nader, Khalil Abi; Gastaldello, Annalisa; Gastadello, Annalisa; Mehta, Vedanta; Filppi, Elisa; Cananzi, Mara; Gaspar, H Bobby; Qasim, Waseem; De Coppi, Paolo; David, Anna L

    2011-01-01

    Long-term engraftment and phenotype correction has been difficult to achieve in humans after in utero stem cell transplantation mainly because of allogeneic rejection. Autologous cells could be obtained during gestation from the amniotic fluid with minimal risk for the fetus and the mother. Using a sheep model, we explored the possibility of using amniotic fluid mesenchymal stem cells (AFMSCs) for autologous in utero stem cell/gene therapy. We collected amniotic fluid (AF) under ultrasound-guided amniocentesis in early gestation pregnant sheep (n = 9, 58 days of gestation, term = 145 days). AFMSCs were isolated and expanded in all sampled fetal sheep. Those cells were transduced using an HIV vector encoding enhanced green fluorescent protein (GFP) with 63.2% (range 38.3-96.2%) transduction efficiency rate. After expansion, transduced AFMSCs were injected into the peritoneal cavity of each donor fetal sheep at 76 days under ultrasound guidance. One ewe miscarried twin fetuses after amniocentesis. Intraperitoneal injection was successful in the remaining 7 fetal sheep giving a 78% survival for the full procedure. Tissues were sampled at postmortem examination 2 weeks later. PCR analysis detected GFP-positive cells in fetal tissues including liver, heart, placenta, membrane, umbilical cord, adrenal gland, and muscle. GFP protein was detected in these tissues by Western blotting and further confirmed by cytofluorimetric and immunofluorescence analyses. This is the first demonstration of autologous stem cell transplantation in the fetus using AFMSCs. Autologous cells derived from AF showed widespread organ migration and could offer an alternative way to ameliorate prenatal congenital disease.

  15. Autologous Transplantation of Amniotic Fluid-Derived Mesenchymal Stem Cells into Sheep Fetuses.

    PubMed

    Shaw, S W Steven; Bollini, Sveva; Nader, Khalil Abi; Gastaldello, Annalisa; Mehta, Vedanta; Filppi, Elisa; Cananzi, Mara; Gaspar, H Bobby; Qasim, Waseem; De Coppi, Paolo; David, Anna L

    2016-03-01

    Long-term engraftment and phenotype correction has been difficult to achieve in humans after in utero stem cell transplantation mainly because of allogeneic rejection. Autologous cells could be obtained during gestation from the amniotic fluid with minimal risk for the fetus and the mother. Using a sheep model, we explored the possibility of using amniotic fluid mesenchymal stem cells (AFMSCs) for autologous in utero stem cell/gene therapy. We collected amniotic fluid (AF) under ultrasound-guided amniocentesis in early gestation pregnant sheep ( n = 9, 58 days of gestation, term = 145 days). AFMSCs were isolated and expanded in all sampled fetal sheep. Those cells were transduced using an HIV vector encoding enhanced green fluorescent protein (GFP) with 63.2% (range 38.3-96.2%) transduction efficiency rate. After expansion, transduced AFMSCs were injected into the peritoneal cavity of each donor fetal sheep at 76 days under ultrasound guidance. One ewe miscarried twin fetuses after amniocentesis. Intraperitoneal injection was successful in the remaining 7 fetal sheep giving a 78% survival for the full procedure. Tissues were sampled at postmortem examination 2 weeks later. PCR analysis detected GFP-positive cells in fetal tissues including liver, heart, placenta, membrane, umbilical cord, adrenal gland, and muscle. GFP protein was detected in these tissues by Western blotting and further confirmed by cytofluorimetric and immunofluorescence analyses. This is the first demonstration of autologous stem cell transplantation in the fetus using AFMSCs. Autologous cells derived from AF showed widespread organ migration and could offer an alternative way to ameliorate prenatal congenital disease.

  16. Autologous Hematopoietic Stem Cell Transplantation-10 Years of Data From a Developing Country.

    PubMed

    Ali, Natasha; Adil, Salman Naseem; Shaikh, Mohammad Usman

    2015-08-01

    Intensive chemotherapy followed by autologous stem cell transplantation is the treatment of choice for patients with hematological malignancies. The objective of the present study was to evaluate the outcomes of patients with mainly lymphoma and multiple myeloma after autologous stem cell transplant. The pretransplant workup consisted of the complete blood count, an evaluation of the liver, kidney, lung, and infectious profile, chest radiographs, and a dental review. For lymphoma, all patients who achieved at least a 25% reduction in the disease after salvage therapy were included in the study. Mobilization was done with cyclophosphamide, followed by granulocyte colony-stimulating factor, 300 µg twice daily. The conditioning regimens included BEAM (carmustine, etoposide, cytarabine, melphalan) and high-dose melphalan. A total of 206 transplants were performed from April 2004 to December 2014. Of these, 137 were allogeneic transplants and 69 were autologous. Of the patients receiving an autologous transplant, 49 were male and 20 were female. Of the 69 patients, 26 underwent transplantation for Hodgkin's lymphoma, 23 for non-Hodgkin's lymphoma, and 15 for multiple myeloma and 4 and 1 for Ewing's sarcoma and neuroblastoma, respectively. The median age ± SD was 34 ± 13.1 years (range, 4-64). A mean of 4.7 × 10⁸ ± 1.7 mononuclear cells per kilogram were infused. The median time to white blood cell recovery was 18.2 ± 5.34 days. Transplant-related mortality occurred in 10 patients. After a median follow-up period of 104 months, the overall survival rate was 86%. High-dose chemotherapy, followed by autologous stem cell transplant, is an effective treatment option for patients with hematological malignancies, allowing further consolidation of response.

  17. [Autologous stem cell transplantation for autoimmune diseases: recommendations from the SFGM-TC].

    PubMed

    Farge, D; Terriou, L; Badoglio, M; Cras, A; Desreumaux, P; Hadj-Khelifa, S; Marjanovic, Z; Moisan, A; Dulery, R; Faucher, C; Hij, A; Martin, T; Vermersch, P; Yakoub-Agha, I

    2014-08-01

    Autologous hematopoietic stem cell transplantation is a valid alternative to immunosuppressive treatment in patients with auto-immune disease; however, the role of this approach remains subject to debate. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. In this article we give an overview regarding the indications of autologous stem cell transplantation in auto-immune diseases as well as recommendations regarding post-transplant follow-up of patients.

  18. Autologous Bone Marrow Derived Stem Cells for the Treatment of Multiple Sclerosis.

    PubMed

    Abi Chahine, Nassim; Wehbe, Tarek; Rashed, Johny; Hilal, Ramzi; Elias, Nada

    2016-11-30

    Stem cell therapy, an evolving, progressive field of therapeutics has shown several successes in areas where classic treatments failed to prevent or stop disability. Starting in 2009, twenty two sequential patients with progressive Multiple Sclerosis (MS) courses were treated with Autologous Bone Marrow Mononuclear stem cells (BM-MNSCs). The cells were given both intravenously and intrathecally. Using the Expanded Disability Status Scale (EDSS) score for evaluation, our data indicates that the majority of the patients benefited on the average one point on the scale. This paper adds to the body of evidence suggesting the safety and efficacy of autologous BM-MNSCs in the treatment of MS and awaits validation through larger, randomized studies.

  19. Autologous Bone Marrow Derived Stem Cells for the Treatment of Multiple Sclerosis

    PubMed Central

    Chahine, Nassim Abi; Wehbe, Tarek; Rashed, Johny; Hilal, Ramzi; Elias, Nada

    2016-01-01

    Stem cell therapy, an evolving, progressive field of therapeutics has shown several successes in areas where classic treatments failed to prevent or stop disability. Starting in 2009, twenty two sequential patients with progressive Multiple Sclerosis (MS) courses were treated with Autologous Bone Marrow Mononuclear stem cells (BM-MNSCs). The cells were given both intravenously and intrathecally. Using the Expanded Disability Status Scale (EDSS) score for evaluation, our data indicates that the majority of the patients benefited on the average one point on the scale. This paper adds to the body of evidence suggesting the safety and efficacy of autologous BM-MNSCs in the treatment of MS and awaits validation through larger, randomized studies. PMID:27788571

  20. [Phase III clinical trial using autologous mesenchymal stem cells for stroke patients].

    PubMed

    Honmou, Osamu

    2016-04-01

    We conduct a double-blind randomized placebo-controlled clinical trial (Phase III: confirmatory trial) of intravenous infusion of autologous mesenchymal stem cells for cerebral infarction patients. The objectives of this study were to examine feasibility, safety, and efficacy of cell therapy using auto serum-expanded autologous mesenchymal stem cells derived from bone marrow in the stroke patients. Inclusion criteria is (1) Cerebral infarction onset within 40 days, (2) Supra-tentorial cerebral infarction(NINDS-III 1990) diagnosed by MRI(or CT), MRA (3D-CTA or DSA), ECG, chest X-ray etc., (3) Classified under grade 4 or 5 of mRS (modified Rankin scale), (4) Age between 20 to 80, (5) The written informed consent from subjects and legal representative is provided.

  1. Biosimilar G-CSF based mobilization of peripheral blood hematopoietic stem cells for autologous and allogeneic stem cell transplantation.

    PubMed

    Schmitt, Michael; Publicover, Amy; Orchard, Kim H; Görlach, Matthias; Wang, Lei; Schmitt, Anita; Mani, Jiju; Tsirigotis, Panagiotis; Kuriakose, Reeba; Nagler, Arnon

    2014-01-01

    The use of granulocyte colony stimulating factor (G-CSF) biosimilars for peripheral blood hematopoietic stem cell (PBSC) mobilization has stimulated an ongoing debate regarding their efficacy and safety. However, the use of biosimilar G-CSF was approved by the European Medicines Agency (EMA) for all the registered indications of the originator G-CSF (Neupogen (®) ) including mobilization of stem cells. Here, we performed a comprehensive review of published reports on the use of biosimilar G-CSF covering patients with hematological malignancies as well as healthy donors that underwent stem cell mobilization at multiple centers using site-specific non-randomized regimens with a biosimilar G-CSF in the autologous and allogeneic setting. A total of 904 patients mostly with hematological malignancies as well as healthy donors underwent successful autologous or allogeneic stem cell mobilization, respectively, using a biosimilar G-CSF (520 with Ratiograstim®/Tevagrastim, 384 with Zarzio®). The indication for stem cell mobilization in hematology patients included 326 patients with multiple myeloma, 273 with Non-Hodgkin's lymphoma (NHL), 79 with Hodgkin's lymphoma (HL), and other disease. 156 sibling or volunteer unrelated donors were mobilized using biosimilar G-CSF. Mobilization resulted in good mobilization of CD34+ stem cells with side effects similar to originator G-CSF. Post transplantation engraftment did not significantly differ from results previously documented with the originator G-CSF. The side effects experienced by the patients or donors mobilized by biosimilar G-CSF were minimal and were comparable to those of originator G-CSF. In summary, the efficacy of biosimilar G-CSFs in terms of PBSC yield as well as their toxicity profile are equivalent to historical data with the reference G-CSF.

  2. Multiple Myeloma Relapse Following Autologous Stem Cell Transplant Presenting With Diffuse Pulmonary Nodules

    PubMed Central

    Sumrall, Bradley; Diethelm, Lisa; Brown, Archie

    2013-01-01

    Background Multiple myeloma is a common disease, accounting for about 10% of hematologic malignancies in the United States. For eligible patients, the treatment of choice includes induction therapy (usually involving newer biologic agents) followed by autologous stem cell transplant; however, this treatment is generally not considered curative, and relapses usually occur. However, extramedullary relapse is an uncommon presentation, and relapses that involve the lungs have only rarely been described. Case Report We report the case of a patient who underwent an autologous stem cell transplant for multiple myeloma and subsequently relapsed with diffuse pulmonary nodules. She then had a rapid clinical and serologic response following initiation of salvage therapy. Conclusion This case is remarkable for both the radiographic appearance of the pulmonary involvement, as well as the rapid resolution of these findings after 2 cycles of treatment with bortezomib, dexamethasone, and lenalidomide. PMID:24358007

  3. Fractionated stem cell infusions for patients with plasma cell myeloma undergoing autologous hematopoietic cell transplantation.

    PubMed

    Landau, Heather; Wood, Kevin; Chung, David J; Koehne, Guenther; Lendvai, Nikoletta; Hassoun, Hani; Lesokhin, Alexander; Hoover, Elizabeth; Zheng, Junting; Devlin, Sean M; Giralt, Sergio

    2016-08-01

    We conducted a phase II trial investigating the impact of fractionated hematopoietic cell infusions on engraftment kinetics and symptom burden in patients with plasma cell myeloma (PCM) undergoing autologous hematopoietic cell transplant (AHCT). We hypothesized that multiple hematopoietic cell infusions would reduce duration of neutropenia and enhance immune recovery resulting in a better tolerated procedure. Twenty-six patients received high-dose melphalan followed by multiple cell infusions (Days 0, +2, +4, +6) and were compared to PCM patients (N = 77) who received high-dose melphalan and a single infusion (Day 0) (concurrent control group). The primary endpoint was number of days with ANC <500K/mcL. Symptom burden was assessed using the MSK-modified MD Anderson Symptom Inventory. Median duration of neutropenia was similar in study (4 days, range 3-5) and control patients (4 days, range 3-9) (p = 0.654). There was no significant difference in the number of red cell or platelet transfusions, days of fever, diarrhea, antibiotics, number of documented infections, or length of admission. Symptom burden surveys showed that AHCT was well-tolerated in both study and control patients. We conclude that fractionated stem cell infusions following high-dose melphalan do not enhance engraftment kinetics or significantly alter patients' clinical course following AHCT in PCM.

  4. Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration.

    PubMed

    Mandai, Michiko; Watanabe, Akira; Kurimoto, Yasuo; Hirami, Yasuhiko; Morinaga, Chikako; Daimon, Takashi; Fujihara, Masashi; Akimaru, Hiroshi; Sakai, Noriko; Shibata, Yumiko; Terada, Motoki; Nomiya, Yui; Tanishima, Shigeki; Nakamura, Masahiro; Kamao, Hiroyuki; Sugita, Sunao; Onishi, Akishi; Ito, Tomoko; Fujita, Kanako; Kawamata, Shin; Go, Masahiro J; Shinohara, Chikara; Hata, Ken-Ichiro; Sawada, Masanori; Yamamoto, Midori; Ohta, Sachiko; Ohara, Yasuo; Yoshida, Kenichi; Kuwahara, Junko; Kitano, Yuko; Amano, Naoki; Umekage, Masafumi; Kitaoka, Fumiyo; Tanaka, Azusa; Okada, Chihiro; Takasu, Naoko; Ogawa, Seishi; Yamanaka, Shinya; Takahashi, Masayo

    2017-03-16

    We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929 .).

  5. The positive impact of regular exercise program on stem cell mobilization prior to autologous stem cell transplantation.

    PubMed

    Keser, Ilke; Suyani, Elif; Aki, Sahika Zeynep; Sucak, Ayhan Gulsan Turkoz

    2013-10-01

    The present study was planned to determine the effects of regular exercise program on hematopoietic stem cell (HSC) mobilization prior to autologous stem cell transplantation. Twenty-two consecutive patients were enrolled in the study. A regular 20 min exercise program was administered to the patients. The hematopoietic stem cell mobilization outcome, number of Granulocyte Colony-Stimulating Factor (G-CSF) and aphaeresis application days were compared with 20 case-matched controls who did not receive exercise program during HSC mobilization. The median number of CD34(+) stem cells collected in the exercise and control groups were 8.15 × 10(6)/kg (range: 2.85-33.06 × 10(6)/kg) and 7.3 × 10(6)/kg (range: 1.78-25.9 × 10(6)/kg), respectively (p=0.696). G-CSF was administered for a median of 8 days (range, 5-10) in the exercise group and 8 days (range, 5-12) in the control group (p=0.848). The median apheresis duration was 1 day (range, 1-3) in both exercise and control groups (p=0.226). Exercise seems to have a positive impact on stem cell mobilization though without statistical significance. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Patients with mantle-cell lymphoma relapsing after autologous stem cell transplantation may be rescued by allogeneic transplantation.

    PubMed

    Martínez, C; Carreras, E; Rovira, M; Urbano-Ispizua, A; Esteve, J; Perales, M; Fernández, F; Montserrat, E

    2000-09-01

    Two patients with disseminated mantle-cell lymphoma relapsed 24 and 13 months, respectively, after high-dose chemotherapy and autologous stem cell transplantation (autoSCT). Both patients had an HLA-identical sibling and received an allogeneic stem cell transplant (alloSCT) 32 and 18 months after autologous transplant, after conditioning with fractionated 12 Gy total body irradiation plus cyclophosphamide 120 mg/kg. They are both alive and in complete remission 24 months after transplant. Both patients have developed chronic graft-versus-host disease and their Karnofsky performance status is 90%. AlloSCT may offer a useful approach in a subgroup of patients with mantle-cell lymphoma who have relapsed after autologous transplantation.

  7. Safety Concern between Autologous Fat Graft, Mesenchymal Stem Cell and Osteosarcoma Recurrence

    PubMed Central

    Perrot, Pierre; Rousseau, Julie; Bouffaut, Anne-Laure; Rédini, Françoise; Cassagnau, Elisabeth; Deschaseaux, Frédéric; Heymann, Marie-Françoise; Heymann, Dominique; Duteille, Franck; Trichet, Valérie; Gouin, François

    2010-01-01

    Background Osteosarcoma is the most common malignant primary bone tumour in young adult treated by neo adjuvant chemotherapy, surgical tumor removal and adjuvant multidrug chemotherapy. For correction of soft tissue defect consecutive to surgery and/or tumor treatment, autologous fat graft has been proposed in plastic and reconstructive surgery. Principal Findings We report here a case of a late local recurrence of osteosarcoma which occurred 13 years after the initial pathology and 18 months after a lipofilling procedure. Because such recurrence was highly unexpected, we investigated the possible relationship of tumor growth with fat injections and with mesenchymal stem/stromal cell like cells which are largely found in fatty tissue. Results obtained in osteosarcoma pre-clinical models show that fat grafts or progenitor cells promoted tumor growth. Significance These observations and results raise the question of whether autologous fat grafting is a safe reconstructive procedure in a known post neoplasic context. PMID:20544017

  8. Phase I trial of active specific immunotherapy with autologous dendritic cells pulsed with autologous irradiated tumor stem cells in hepatitis B-positive patients with hepatocellular carcinoma.

    PubMed

    Wang, Xiaojin; Bayer, Michael E; Chen, Xiaosong; Fredrickson, Craig; Cornforth, Andrew N; Liang, Greg; Cannon, Jessica; He, Jia; Fu, Qingchun; Liu, Jia; Nistor, Gabriel I; Cao, Wei; Chen, Chengwei; Dillman, Robert O

    2015-06-01

    Hepatocellular carcinoma (HCC) is often associated with chronic hepatitis due to hepatitis-B or -C viruses. Active specific immunotherapy (ASI) with autologous dendritic cells (DC) presenting antigens from autologous tumor stem cell (TC) lines is associated with promising long-term survival in metastatic cancer, but hepatitis patients were excluded. ASI might benefit high-risk primary HCC patients following surgical resection, but first it is important to show that ASI does not exacerbate hepatitis. Previously untreated HCC patients with a solitary lesion > 5 cm, or three lesions with at least one > 3 cm, or more than three lesions, underwent surgical resection from which autologous TC lines were established. Irradiated TC were incubated with autologous DC to create DC-TC. After one course of trans-arterial chemoembolization therapy (TACE), three weekly subcutaneous injections of DC-TC suspended in granulocyte-macrophage colony stimulating factor were administered. Patients were monitored for eight weeks. HCC cell lines were established within five weeks for 15/15 patients. Eight patients, all with chronic hepatitis B, were treated. There was no increase in hepatic transaminases, hepatitis B antigens, or viral DNA. Autologous DC-TC did not exacerbate HBV in these HCC patients. A phase II efficacy trial is being planned. © 2015 Wiley Periodicals, Inc.

  9. Reconstitution of immune cell populations in multiple sclerosis patients after autologous stem cell transplantation.

    PubMed

    Karnell, F G; Lin, D; Motley, S; Duhen, T; Lim, N; Campbell, D J; Turka, L A; Maecker, H T; Harris, K M

    2017-09-01

    Multiple sclerosis is an inflammatory T cell-mediated autoimmune disease. In a Phase II clinical trial, high-dose immunosuppressive therapy combined with autologous CD34(+) haematopoietic stem cell transplant resulted in 69·2% of subjects remaining disease-free without evidence of relapse, loss of neurological function or new magnetic resonance imaging (MRI) lesions to year 5 post-treatment. A combination of CyTOF mass cytometry and multi-parameter flow cytometry was used to explore the reconstitution kinetics of immune cell subsets in the periphery post-haematopoietic cell transplant (HSCT) and the impact of treatment on the phenotype of circulating T cells in this study population. Repopulation of immune cell subsets progressed similarly for all patients studied 2 years post-therapy, regardless of clinical outcome. At month 2, monocytes and natural killer (NK) cells were proportionally more abundant, while CD4 T cells and B cells were reduced, relative to baseline. In contrast to the changes observed at earlier time-points in the T cell compartment, B cells were proportionally more abundant and expansion in the proportion of naive B cells was observed 1 and 2 years post-therapy. Within the T cell compartment, the proportion of effector memory and late effector subsets of CD4 and CD8 T cells was increased, together with transient increases in proportions of CD45RA-regulatory T cells (Tregs ) and T helper type 1 (Th1 cells) and a decrease in Th17·1 cells. While none of the treatment effects studied correlated with clinical outcome, patients who remained healthy throughout the 5-year study had significantly higher absolute numbers of memory CD4 and CD8 T cells in the periphery prior to stem cell transplantation. © 2017 British Society for Immunology.

  10. NK Cell Subgroups, Phenotype, and Functions After Autologous Stem Cell Transplantation.

    PubMed

    Jacobs, Benedikt; Tognarelli, Sara; Poller, Kerstin; Bader, Peter; Mackensen, Andreas; Ullrich, Evelyn

    2015-01-01

    High-dose chemotherapy with consecutive autologous stem cell transplantation (autoSCT) is a well-established treatment option for patients suffering from malignant lymphoma or multiple myeloma. Natural killer (NK) cells are an important part of the immune surveillance, and their cell number after autoSCT is predictive for progression-free and overall survival. To improve knowledge about the role of NK cells after autoSCT, we investigated different NK cell subgroups, their phenotype, and their functions in patients treated with autoSCT. Directly after leukocyte regeneration (>1000 leukocytes/μl) following autoSCT, CD56(++) NK cells were the major NK cell subset. Surprisingly, these cells showed unusually high surface expression levels of CD57 and killer Ig-like receptors (KIRs) compared to expression levels before or at later time points after autoSCT. Moreover, these NK cells strongly upregulated KIR2DL2/3/S2 and KIR3DL1, whereas KIR2DL1/S1 remained constant, indicating that this cell population arose from more immature NK cells instead of from activated mature ones. Remarkably, NK cells were already able to degranulate and produce IFN-γ and MIP-1β upon tumor interaction early after leukocyte regeneration. In conclusion, we describe an unusual upregulation of CD57 and KIRs on CD56(++) NK cells shortly after autoSCT. Importantly, these NK cells were functionally competent upon tumor interaction at this early time point.

  11. A novel autologous stem cell procedure for the treatment of aplastic anaemia using reprogrammed mature adult cells: a pilot study.

    PubMed

    Abuljadayel, Ilham Saleh; Mohanty, Dipika; Suri, Rajendar K

    2012-06-01

    Aplastic anaemia is a life threatening rare bone marrow failure disorder. The underlying haematopoietic cellular deficit leads to haemorrhage, infection and severe anaemia. The treatment of choice for this haematological condition is allogeneic bone marrow transplantation from fully matched HLA sibling. Though this procedure is curative in the majority of young patients with aplastic anaemia, extending this benefit to older patients or those lacking a family donor remains a major challenge. Herein, the safety and efficacy of infusing autologous retrodifferentiated haematopoietic stem cells (RHSC) into four patients with aplastic anaemia without the use of any pre- or post-conditioning regimen including immunosuppression is described. Un-mobilized, mononuclear cells were harvested from four patients with acquired aplastic anaemia by aphaeresis. Mononuclear cells of patients were cultured with purified monoclonal antibody against the monomorphic regions of the beta chain of MHC class II antigens (Clone CR3/43) for 3 h, to obtain autologous RHSC. Autologous RHSC were washed and infused into the four patients without the use of any pre- or post-conditioning regimen. Thereafter, the efficacy (engraftment) of autologous RHSC was assessed in these patients. Following single infusion of the autologous RHSC, two of the four patients with aplastic anaemia become transfusion independent for more than seven years. Karyotyping and G-banding analysis prior and post-procedure in all patients remained the same. The findings of this pilot study demonstrated the functional utility of reprogrammed fully differentiated adult cells into pluripotent stem cells with extensive repopulation potentials in a human setting and without any pre- or post-conditioning regimen, including immunosuppression. This autologous approach of stem cell creation may broaden the curative potentials of stem cell therapy to a wider population of patients with aplastic anaemia, including many patients suffering

  12. Effective activity of cytokine-induced killer cells against autologous metastatic melanoma including cells with stemness features.

    PubMed

    Gammaitoni, Loretta; Giraudo, Lidia; Leuci, Valeria; Todorovic, Maja; Mesiano, Giulia; Picciotto, Franco; Pisacane, Alberto; Zaccagna, Alessandro; Volpe, Maria Giuseppa; Gallo, Susanna; Caravelli, Daniela; Giacone, Elena; Venesio, Tiziana; Balsamo, Antonella; Pignochino, Ymera; Grignani, Giovanni; Carnevale-Schianca, Fabrizio; Aglietta, Massimo; Sangiolo, Dario

    2013-08-15

    We investigate the unknown tumor-killing activity of cytokine-induced killer (CIK) cells against autologous metastatic melanoma and the elusive subset of putative cancer stem cells (mCSC). We developed a preclinical autologous model using same patient-generated CIK cells and tumor targets to consider the unique biology of each patient/tumor pairing. In primary tumor cell cultures, we visualized and immunophenotypically defined a putative mCSC subset using a novel gene transfer strategy that exploited their exclusive ability to activate the promoter of stemness gene Oct4. The CIK cells from 10 patients with metastatic melanoma were successfully expanded (median, 23-fold; range, 11-117). Primary tumor cell cultures established and characterized from the same patients were used as autologous targets. Patient-derived CIK cells efficiently killed autologous metastatic melanoma [up to 71% specific killing (n = 26)]. CIK cells were active in vivo against autologous melanoma, resulting in delayed tumor growth, increased necrotic areas, and lymphocyte infiltration at tumor sites. The metastatic melanoma cultures presented an average of 11.5% ± 2.5% putative mCSCs, which was assessed by Oct4 promoter activity and stemness marker expression (Oct4, ABCG2, ALDH, MITF). Expression was confirmed on mCSC target molecules recognized by CIK cells (MIC A/B; ULBPs). CIK tumor killing activity against mCSCs was intense (up to 71%, n = 4) and comparable with results reported against differentiated metastatic melanoma cells (P = 0.8). For the first time, the intense killing activity of CIK cells against autologous metastatic melanoma, including mCSCs, has been shown. These findings move clinical investigation of a new immunotherapy for metastatic melanoma, including mCSCs, closer. ©2013 AACR.

  13. Autologous Stem Cells Transplantation in Egyptian Patients with Liver Cirrhosis on Top of Hepatitis C Virus

    PubMed Central

    Al Tayeb, Hoda; El Dorry, Ahmed; Amer, Nehad; Mowafy, Nadia; Zimaity, Maha; Bayoumy, Essam; Saleh, Shereen A.

    2015-01-01

    Background and Objectives Use of pluripotent stem cells is an ideal solution for liver insufficiencies. This work aims is to evaluate the safety and feasibility of autologous stem cells transplantation (SCT) in Egyptian patients of liver cirrhosis on top of hepatitis C virus (HCV). Subjects and Results 20 patients with HCV induced liver cirrhosis were divided into 2 groups. Group I: included 10 patients with liver cirrhosis Child score ≥9, for whom autologous stem cell transplantation was done using granulocyte colony stimulating factor (G-CSF) for stem cells mobilization. Separation and collection of the peripheral blood stem cells was done by leukapheresis. G-CSF mobilized peripheral blood mononuclear cells (G-CSF PB-MNCs) were counted by flow cytometry. Stem cell injection into the hepatic artery was done. Group II: included 10 patients with HCV induced liver cirrhosis as a control group. Follow up and comparison between both groups were done over a follow up period of 6 months. The procedure was well tolerated. Mobilization was successful and the total number of G-CSF PB-MNCs in the harvests ranged from 25×106 to 191×106. There was improvement in the quality of life, serum albumin, total bilirubin, liver enzymes and the Child-Pugh score of group I over the first two-three months after the procedure. Conclusion SCT in HCV induced liver cirrhosis is a safe procedure. It can improve the quality of life and hepatic functions transiently with no effect on the life expectancy or the fate of the liver cirrhosis. PMID:26634069

  14. A question of ethics: selling autologous stem cell therapies flaunts professional standards.

    PubMed

    Munsie, Megan; Hyun, Insoo

    2014-11-01

    The idea that the body's own stem cells could act as a repair kit for many conditions, including cardiac repair, underpins regenerative medicine. While progress is being made, with hundreds of clinical trials underway to evaluate possible autologous cell-based therapies, some patients and physicians are not prepared to wait and are pursuing treatments without evidence that the proposed treatments are effective, or even safe. This article explores the inherent tension between patients, practitioners and the need to regulate the development and commercialization of new cellular therapies--even when the cells come from the patient. Copyright © 2014. Published by Elsevier B.V.

  15. Intraarterial autologous implantation of adult stem cells for patients with Parkinson disease.

    PubMed

    Brazzini, Augusto; Cantella, Raúl; De la Cruz, Antonio; Yupanqui, Jorge; León, Carlos; Jorquiera, Tamara; Brazzini, Mariana; Ortega, Melitón; Saenz, Luis N

    2010-04-01

    To evaluate the feasibility, safety, and effectiveness of intraarterial autologous implantation of adult stem cells for Parkinson disease (PD). From June 2006 to August 2008, 36 men and 14 women (mean age, 62.5 years +/- 10.4; range, 38-81 y) with PD (mean duration, 9.3 years; range, 1-28 y) underwent autologous implantation of stem cells with superselective arterial catheterization. Patients were evaluated with clinical and neurologic examinations; internationally recognized scales for the evaluation of PD, disability, activities of daily living, depression, and quality of life (QOL); as well as videos, magnetic resonance (MR) imaging, and MR spectroscopy. Stem cells were implanted in the posterior region of the circle of Willis. Patients were evaluated according to clinical measures. Comparison was made versus data collected from all scales before treatment, as well as videos and spectroscopy in eight patients. In a mean follow-up of 7.4 months +/- 4.5 (range, 1-18 months), patients showed a median improvement of 51.1% and quartile deviation (QD) of 24.8% on the Unified PD Rating Scale. They showed significant improvement in disability, activities of daily living, depression, and QOL (P < .5). No complications were observed. In eight patients, follow-up MR spectroscopy revealed mean improvements in n-acetylaspartate/creatine ratio from 1.805 to 2.07 (12.8%) and from 1.25 to 1.88 (43.56%) in right and left basal ganglia, respectively, versus preprocedural values (P < .05). Treatment of PD with intraarterial autologous implantation of adult stem cells is feasible and safe and results in improved severity of disease and QOL. Copyright 2010 SIR. Published by Elsevier Inc. All rights reserved.

  16. Early Prognostic Value of Monitoring Serum Free Light Chain in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation.

    PubMed

    Özkurt, Zübeyde Nur; Sucak, Gülsan Türköz; Akı, Şahika Zeynep; Yağcı, Münci; Haznedar, Rauf

    2017-03-16

    We hypothesized the levels of free light chains obtained before and after autologous stem cell transplantation can be useful in predicting transplantation outcome. We analyzed 70 multiple myeloma patients. Abnormal free light chain ratios before stem cell transplantation were found to be associated early progression, although without any impact on overall survival. At day +30, the normalization of levels of involved free light chain related with early progression. According to these results almost one-third reduction of free light chain levels can predict favorable prognosis after autologous stem cell transplantation.

  17. Effect of autologous adipose-derived stem cells in renal cold ischemia and reperfusion injury.

    PubMed

    Wang, Y-L; Li, G; Zou, X-F; Chen, X-B; Liu, T; Shen, Z-Y

    2013-11-01

    The aim of this study was to investigate the effect of autologous adipose-derived stem cells (ADSCs) on renal cold ischemia and reperfusion (I/R) injury via intravenous infusion on rats. A renal cold I/R injury rat model was established. Rats were equally randomized into Sham group, Cold I/R group (cold I/R plus culture medium only), and ADSC-treated group (cold I/R plus immediate intrarenal administration of 2 × 10(6) autologous ADSCs, followed by intravenous autologous ADSCs 6 hours after reperfusion). All rats were killed 24 hours after the I/R procedure. Serum creatinine levels were significantly reduced in the ADSC-treated group compared with the Cold I/R group (P < .01). The renal tissue in the ADSC-treated group had well conserved renal architecture compared with the Cold I/R group. The mRNA expression of tumor necrosis factor α was significantly lower and Bcl-2 was higher in the ADSC-treated group than in the Cold I/R group (P < .05). Autologous ADSC infusions ameliorated renal damage undergoing cold I/R injury and improved the renal function, partly through inhibiting inflammatory reactions and reducing apoptosis. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Autologous hematopoietic stem cell transplantation for autoimmune disease--is it now ready for prime time?

    PubMed

    Atkins, Harold L; Muraro, Paolo A; van Laar, Jacob M; Pavletic, Steven Z

    2012-01-01

    Current systemic therapies are rarely curative for patients with severe life-threatening forms of autoimmune disease (AID). During the past 15 years, autologous hematopoietic stem cell transplantation (HCT) has been demonstrated to cure some patients with severe AID refractory to all other available therapies, and thus AID has become an emerging indication for cell therapy. The sustained clinical effects after autologous HCT are better explained by qualitative change in the reconstituted immune repertoire rather than transient depletion of immune cells. Since 1996, more than 1300 AID patients have been registered by the European Group for Blood and Marrow Transplantation (EBMT) and almost 500 patients by the Center for International Blood and Marrow Transplant Research (CIBMTR). Autologous HCT is most commonly performed for patients with multiple sclerosis (MS) or systemic sclerosis (SSc). Systemic lupus, Crohn's disease, type I diabetes, and juvenile idiopathic arthritis are other common indications. Allogeneic transplants are still considered too toxic for use in AID, except for cases of immune cytopenia. Although biologic therapies have been effective at controlling the manifestations of the disease, they require continuous administration, thus raising questions about their increasing costs, morbidity, and mortality related to prolonged therapy. Perhaps it is a reasonable time to ask, "Is autologous HCT for severe AID now ready for prime time?" Yet, the paucity of controlled studies, the short-term toxicities, and the upcoming availability of second-generation biologic and targeted immunotherapies argues that perhaps HCT for AID should be still limited to clinical trials. In this article, we focus on the results of autologous HCT for MS and SSc because these are the two most commonly transplanted diseases. The promising data that is emerging may establish these diseases as standard indications for HCT.

  19. Autologous stem cell transplantation in a rare multicentric Castleman disease of the plasma cell variant.

    PubMed

    Tal, Yuval; Haber, Guy; Cohen, Matan J; Phillips, Micci; Amir, Gail; Ben-Yehuda, Dina; Ben-Yehuda, Arie

    2011-05-01

    We present a case of a 52-year-old male who was evaluated due to anorexia, persistent diarrhea, weight loss, and liver enzyme elevations, with no hematologic laboratory abnormalities. Imaging modalities revealed several tissue lesions involving the pancreas, the right kidney, and an axillary lymph node. Diagnosis of Castleman disease was reached only due to the tissue obtained from the lymph node. Chemotherapy and immunosuppression led to a short remission. The patient underwent autologous stem cell transplantation, and has since been in remission. This case demonstrates the cryptogenic and chameleon-like nature of Castleman disease. Challenges in treating Castleman disease patients reflect current limitations and the need for a greater understanding of disease pathogenesis.

  20. Fast Cars and No Brakes: Autologous Stem Cell Transplantation as a Platform for Novel Immunotherapies.

    PubMed

    Perales, Miguel-Angel; Sauter, Craig S; Armand, Philippe

    2016-01-01

    Autologous stem cell transplantation (ASCT) is indicated in a number of hematologic malignancies, including multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma. Relapse, however, remains 1 of the main causes of post-ASCT failure, and several strategies are being investigated to decrease the risk of relapse of progression. Recent advances in the treatment of hematological malignancies have included adoptive transfer of genetically modified T cells that express chimeric antigen receptors or T cell receptors, as well the use of checkpoint inhibitors. Early clinical results in nontransplantation patients have been very promising. This review will focus on the use of gene-modified T cells and checkpoint inhibitors in stem cell transplantation.

  1. Fast Cars and No Brakes: Autologous Stem Cell Transplantation as a Platform for Novel Immunotherapies

    PubMed Central

    Perales, Miguel-Angel; Sauter, Craig S.; Armand, Philippe

    2015-01-01

    Autologous stem cell transplantation (ASCT) is indicated in a number of hematologic malignancies, including multiple myeloma, non-Hodgkin lymphoma and Hodgkin lymphoma. Relapse however remains one of the main causes of post-ASCT failures, and several strategies are being investigated to decrease the risk of relapse of progression. Recent advances in the treatment of hematological malignancies have included adoptive transfer of genetically modified T cells that express chimeric antigen receptors or T cell receptors, as well the use of checkpoint inhibitors. Early clinical results in non-transplant patients have been very promising. This review will focus on the use of gene-modified T cells and checkpoint inhibitors in stem cell transplantation. PMID:26485445

  2. Cellular Therapy With Human Autologous Adipose-Derived Adult Stem Cells for Advanced Keratoconus.

    PubMed

    Alió Del Barrio, Jorge L; El Zarif, Mona; de Miguel, María P; Azaar, Albert; Makdissy, Norman; Harb, Walid; El Achkar, Ibrahim; Arnalich-Montiel, Francisco; Alió, Jorge L

    2017-08-01

    The aim of this phase 1 study was to preliminarily evaluate the safety and efficacy of autologous adipose-derived adult stem cell (ADASC) implantation within the corneal stroma of patients with advanced keratoconus. Five consecutive patients were selected. Autologous ADASCs were obtained by elective liposuction. ADASCs (3 × 10) contained in 1 mL saline were injected into the corneal stroma through a femtosecond-assisted 9.5-mm diameter lamellar pocket under topical anesthesia. Patients were reviewed at 1 day, 1 week, 1, 3, and 6 months postoperatively. Visual function, manifest refraction, slit-lamp biomicroscopy, intraocular pressure, endothelial cell density, corneal topography, corneal optical coherence tomography, and corneal confocal biomicroscopy were recorded. No intraoperative or postoperative complications were recorded, with full corneal transparency recovery within 24 hours. Four patients completed the full follow-up. All patients improved their visual function (mean: 1 line of unaided and spectacle-corrected distance vision and 2 lines of rigid contact lens distance vision). Manifest refraction and topographic keratometry remained stable. Corneal optical coherence tomography showed a mean improvement of 16.5 μm in the central corneal thickness, and new collagen production was observed as patchy hyperreflective areas at the level of the stromal pocket. Confocal biomicroscopy confirmed the survival of the implanted stem cells at the surgical plane. Intraocular pressure and endothelial cell density remained stable. Cellular therapy of the human corneal stroma in vivo with autologous ADASCs appears to be safe. Stem cells survive in vivo with intrastromal new collagen production. Future studies with larger samples are required to confirm these preliminary results.

  3. Harvesting autologous stem cells from a patient with red blood cell abnormalities of β-thalassemia intermedia.

    PubMed

    Sanford, Kimberly; Roseff, Susan D; Anderson, Jennifer; Chung, Harold M; McPherson, Richard A

    2014-07-01

    Autologous stem cell transplants in patients with hemoglobinopathies are limited. Previous reports used granulocyte-colony-stimulating factor (G-CSF) for mobilization of stem cells; there are no reported cases undergoing plerixafor mobilization. We report such a patient, providing guidance for peripheral blood stem cells collection when aberrant red blood cells (RBCs) disrupt normal separation. A patient with β-thalassemia intermedia and hereditary persistence of fetal hemoglobin presented for peripheral blood stem cell collection for autologous transplant for myeloma. He underwent splenectomy for anemia secondary to hemoglobinopathy and chemotherapy, ceasing RBC transfusions. The patient was mobilized using plerixafor after collection with G-CSF failed. Collections were performed using an apheresis system, processing 24 L daily. Peripheral blood and apheresis product CD34 determinations were performed daily. On Day 1, the product yield was 0.04 × 10(6) CD34 cells/kg, less than expected based on white blood cell count and CD34-positive cells. Peripheral blood smear showed nucleated RBCs and RBC morphologic abnormalities. Changes in instrument variables were made after consultation with Terumo BCT to adjust for variable distribution of mononuclear and stem cells during centrifugation. Collecting stem cells at a deeper location and centrifuging faster improved collection, and a cumulative total of 4.40 × 10(6) CD34 cells/kg was achieved after four collections. The patient underwent tandem autologous transplantation and engrafted within 12 to 13 days of each transplant. Adjustments in apheresis variables allowed successful collection of peripheral blood stem cells from a patient with RBC anomalies of β-thalassemia that interfered with standard stem cell harvesting. © 2014 AABB.

  4. Biosimilar Filgrastim in Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization and Post-Transplant Hematologic Recovery.

    PubMed

    Marchesi, Francesco; Mengarelli, Andrea

    2016-01-01

    To date, two kinds of Granulocyte Colony-Stimulating Factors (G-CSF) have been approved for autologous peripheral blood hematopoietic stem cell (PBSCs) mobilization and posttransplant hematologic recovery after high-dose chemotherapy: filgrastim (originator and biosimilar) and lenograstim. Biosimilar filgrastim has been approved on the basis of comparable efficacy and safety in clinical studies where it has been used as chemotherapy-induced febrile neutropenia prophylaxis, but no specific pre-registration studies have been published in the transplant setting. Hence, there is still general skepticism about the role of biosimilar G-CSFs in this setting of patients. This review of biochemical, pre-clinical and clinical data suggests significant comparability of biosimilar filgrastim with both originator filgrastim and lenograstim in autologous PBSCs mobilization and post-autograft hematologic recovery.

  5. Optimal treatment strategies in myeloma: An argument against maintenance therapy after autologous stem cell transplantation.

    PubMed

    Richter, Joshua; Biran, Noa; Vesole, David; Siegel, David

    2016-12-01

    Despite continuing advancements in novel therapeutics for multiple myeloma (MM), high-dose therapy with autologous stem cell rescue continues to represent the standard approach to treat transplant-eligible, newly diagnosed patients. As the disease remains essentially incurable, and median progression-free survival (PFS) times after autologous transplant are measured in years and not decades, attempts to improve outcomes in the post-transplant setting have been extensive and commonly focused on a "maintenance" approach. Although multiple trials have demonstrated PFS advantages for a variety of maintenance strategies, it is our position that the potential risks outweigh the benefits of this approach and this should not be the standard of care outside of clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Evaluation of autologous bone marrow in wound healing in animal model: a possible application of autologous stem cells.

    PubMed

    Akela, Ashok; Nandi, Samit Kumar; Banerjee, Dibyajyoti; Das, Partha; Roy, Subhasis; Joardar, Siddhartha Narayan; Mandal, Mohan; Das, Pradip Kumar; Pradhan, Nisith Ranjan

    2012-10-01

    A study was conducted to evaluate the potential of autologous bone marrow-derived cells in comparison with buffy coat of autologous blood for rapid cutaneous wound healing in rabbit model. Three square full-thickness skin excisional wounds were created in 15 selected experimental animals (rabbit) divided randomly into three groups. The wound was treated with autologous bone marrow cells in plasma (group 1), buffy coat of blood in plasma (group 2) and autologous plasma as control (group 3). Wounds were observed for 30 days for granulation tissue formation, biochemical, histomorphological and histochemical evaluation. In this study, granulation tissue appeared significantly lesser in wounds of group 3 animals followed by group 2 and 1 animals. Neovascularisation, granulation tissue formation, denser, thicker and better arranged collagen fibres, reticulin fibres and elastin fibres formation was more in group 1 as compared with other groups. It was concluded that the application of bone marrow-derived nucleated cells into the wound margins resulted in early and significantly faster rate of complete healing as compared with buffy coat of autologous blood and autologous plasma (control). This approach may be beneficial in various surface wounds that heal at a slower rate and recommended for healing of various complicated wound in future.

  7. T cell repertoire following autologous stem cell transplantation for multiple sclerosis.

    PubMed

    Muraro, Paolo A; Robins, Harlan; Malhotra, Sachin; Howell, Michael; Phippard, Deborah; Desmarais, Cindy; de Paula Alves Sousa, Alessandra; Griffith, Linda M; Lim, Noha; Nash, Richard A; Turka, Laurence A

    2014-03-01

    Autologous hematopoietic stem cell transplantation (HSCT) is commonly employed for hematologic and non-hematologic malignancies. In clinical trials, HSCT has been evaluated for severe autoimmunity as a method to "reset" the immune system and produce a new, non-autoimmune repertoire. While the feasibility of eliminating the vast majority of mature T cells is well established, accurate and quantitative determination of the relationship of regenerated T cells to the baseline repertoire has been difficult to assess. Here, in a phase II study of HSCT for poor-prognosis multiple sclerosis, we used high-throughput deep TCRβ chain sequencing to assess millions of individual TCRs per patient sample. We found that HSCT has distinctive effects on CD4+ and CD8+ T cell repertoires. In CD4+ T cells, dominant TCR clones present before treatment were undetectable following reconstitution, and patients largely developed a new repertoire. In contrast, dominant CD8+ clones were not effectively removed, and the reconstituted CD8+ T cell repertoire was created by clonal expansion of cells present before treatment. Importantly, patients who failed to respond to treatment had less diversity in their T cell repertoire early during the reconstitution process. These results demonstrate that TCR characterization during immunomodulatory treatment is both feasible and informative, and may enable monitoring of pathogenic or protective T cell clones following HSCT and cellular therapies.

  8. Reengineering autologous bone grafts with the stem cell activator WNT3A.

    PubMed

    Jing, Wei; Smith, Andrew A; Liu, Bo; Li, Jingtao; Hunter, Daniel J; Dhamdhere, Girija; Salmon, Benjamin; Jiang, Jie; Cheng, Du; Johnson, Chelsey A; Chen, Serafine; Lee, Katherine; Singh, Gurpreet; Helms, Jill A

    2015-04-01

    Autologous bone grafting represents the standard of care for treating bone defects but this biomaterial is unreliable in older patients. The efficacy of an autograft can be traced back to multipotent stem cells residing within the bone graft. Aging attenuates the viability and function of these stem cells, leading to inconsistent rates of bony union. We show that age-related changes in autograft efficacy are caused by a loss in endogenous Wnt signaling. Blocking this endogenous Wnt signal using Dkk1 abrogates autograft efficacy whereas providing a Wnt signal in the form of liposome-reconstituted WNT3A protein (L-WNT3A) restores bone forming potential to autografts from aged animals. The bioengineered autograft exhibits significantly better survival in the hosting site. Mesenchymal and skeletal stem cell populations in the autograft are activated by L-WNT3A and mitotic activity and osteogenic differentiation are significantly enhanced. In a spinal fusion model, aged autografts treated with L-WNT3A demonstrate superior bone forming capacity compared to the standard of care. Thus, a brief incubation in L-WNT3A reliably improves autologous bone grafting efficacy, which has the potential to significantly improve patient care in the elderly. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium.

    PubMed

    Tang, Yao Liang; Zhao, Qiang; Zhang, Y Clare; Cheng, Leilei; Liu, Mingya; Shi, Jianhui; Yang, Yin Zeng; Pan, Chuizhen; Ge, Junbo; Phillips, M Ian

    2004-01-15

    Neovascularization induced by vascular endothelial growth factor (VEGF) represents an appealing approach for treating ischemic heart disease. However, VEGF therapy has been associated with transient therapeutic effects and potential risk for hemangioma growth. Adult mesenchymal stem cells (MSCs) derived from bone marrow are a promising source for tissue regeneration and repair. In order to achieve a safe and persistent angiogenic effect, we have explored the potential of autologous MSCs transplantation to enhance angiogenesis and cardiac function of ischemic hearts. One week after myocardial infarction induced by occlusion of left anterior descending artery, autologous MSCs expanded in vitro was administrated intramyocardially into the infarct area of the same donor rats. By 2 months, MSCs implantation significantly elevated VEGF expression levels, accompanied by increased vascular density and regional blood flow in the infarct zone. The neovascularization resulted in a decreased apoptosis of hypertrophied myocytes and markedly improved the left ventricular contractility (ejection fraction: 79.9+/-7.6% vs. 37.2+/-6.9% in control animals). Therefore, mechanisms underlying MSCs improvement of cardiac functions may involve neovascularization induced by differentiation of MSCs to endothelial cells and para-secretion of growth factors, in addition to the apoptosis reduction and previously reported cardiomyocytes regeneration. Two months after cell transplantation, there are significant improvement of left ventricular function. Hence, autologous MSCs transplantation may represent a promising therapeutic strategy free of ethical concerns and immune rejection, for neovascularization in ischemic heart diseases.

  10. Nephrotoxicity of high-dose ifosfamide/carboplatin/etoposide in adults undergoing autologous stem cell transplantation.

    PubMed

    Agaliotis, D P; Ballester, O F; Mattox, T; Hiemenz, J W; Fields, K K; Zorsky, P E; Goldstein, S C; Perkins, J B; Rosen, R M; Elfenbein, G J

    1997-11-01

    The objective of this study was to evaluate nephrotoxicity in adult patients treated with high-dose ifosfamide, carboplatin, and etoposide followed by autologous stem cell transplantation. We conducted a retrospective analysis of clinical and laboratory data from 131 patients with various malignancies who received treatment with escalating doses of ifosfamide, carboplatin, and etoposide followed by autologous stem cell transplantation as part of a phase I/II therapeutic trial. Abnormalities in glomerular filtration were evaluated by measuring peak creatinine levels and tubular dysfunction by the lowest recorded serum levels of potassium, magnesium, and bicarbonate, at different time periods after administration of ifosfamide, carboplatin, and etoposide, and after autologous stem cell transplantation. For the entire group of 131 patients, peak creatinine levels were > 1.5 mg/dL but < 3.0 mg/dL in 37% and levels were > 3.0 mg/dL in 11% at some time during their hospital stay. At the time of discharge, creatinine levels were 1.6 mg/dL to 3.0 mg/dL in 25% of patients and were > 3 mg/dL in 5%. Immediately after high-dose therapy, peak creatinine levels were significantly higher in patients receiving higher doses of ifosfamide compared to those receiving lower doses (P < 0.00001) and those receiving intermediate doses (P < 0.005). There was a dramatic decrease in serum bicarbonate, potassium, and magnesium levels immediately after chemotherapy, and they remained significantly decreased throughout the patient's hospital stay, despite massive replacement efforts (P ranging between < 0.008 and < 0.001). This is the largest adult population study documenting the incidence and severity of ifosfamide/carboplatin/etoposide-associated acute nephrotoxicity. Renal dysfunction was dose related and reversible in the majority of patients.

  11. Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Stem Cells in Subacute Ischemic Stroke Patients.

    PubMed

    Ghali, Azza Abass; Yousef, Mohamed Khalil; Ragab, Osama AbdAllah; ElZamarany, Enas Arafa

    2016-01-01

    Based on many preclinical and small clinical trials, stem cells can help stroke patient with the possibility of replacing the cells and supporting the remaining cells. The aim of this study was to evaluate the safety and feasibility of bone marrow mononuclear (BMMN) stem cell transplantation in subacute ischemic stroke patients. Thirty-nine (n = 39) patients with subacute ischemic cerebral infarct due to large artery occlusion in the middle cerebral artery (MCA) territory were recruited. They were distributed into two groups: first group (n = 21) served as an experimental group, which received intra-arterial (IA) mononuclear stem cells (bone marrow-derived mononuclear cell), while the other group (n = 18) served as a control group. All the patients were evaluated clinically by National Institutes of Health Stroke Scale, modified Rankin Scale, Barthel Index, modified and standardized Arabic version of the Comprehensive Aphasia Test, and radiological for 12 months. The stem cell-treated group showed better improvement, but it was not significant when compared with the non-treated group. The volume of infarction changes at the end of the study was non-significant between both the groups. There was no, or minimal, adverse reactions in stem cell-treated group. The study results suggest that autologous BMMN stem cell IA transplantation in subacute MCA ischemic stroke patients is safe with very minimal hazards, but no significant improvement of motor, language disturbance, or infarction volume was detected in stem cell-treated group compared with the non-treated group.

  12. Engraftment Syndrome after Autologous Stem Cell Transplantation: An Update Unifying the Definition and Management Approach.

    PubMed

    Cornell, Robert Frank; Hari, Parameswaran; Drobyski, William R

    2015-12-01

    Engraftment syndrome (ES) encompasses a continuum of periengraftment complications after autologous hematopoietic stem cell transplantation. ES may include noninfectious fever, skin rash, diarrhea, hepatic dysfunction, renal dysfunction, transient encephalopathy, and capillary leak features, such as noncardiogenic pulmonary infiltrates, hypoxia, and weight gain with no alternative etiologic basis other than engraftment. Given its pleiotropic clinical presentation, the transplant field has struggled to clearly define ES and related syndromes. Here, we present a comprehensive review of ES in all documented disease settings. Furthermore, we discuss the proposed risk factors, etiology, and clinical relevance of ES. Finally, our current approach to ES is included along with a proposed treatment algorithm for the management of this complication.

  13. Brain pathology of a patient 7years after autologous hematopoietic stem cell transplantation for multiple sclerosis.

    PubMed

    Wundes, Annette; Bowen, James D; Kraft, George H; Maravilla, Kenneth R; McLaughlin, Bernadette; von Geldern, Gloria; Georges, George; Nash, Richard A; Lu, Jian-Qiang

    2017-02-15

    Aggressive immunosuppression followed by autologous hematopoietic stem cell transplantation (aHSCT) can be an effective treatment for severe multiple sclerosis (MS), but not all stages of disease may benefit equally. The case of a 49-year-old woman with advanced secondary-progressive MS whose clinical course was not improved by aHSCT and who seven years after transplantation succumbed to complications of severe MS disease-related disability is presented. Autopsy findings of ongoing neurodegeneration despite only rare infiltrating T-lymphocytes illustrate that late MS disease may not represent a suitable disease stage for aHSCT. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. High-Dose Chemotherapy and Autologous Stem Cell Transplant in Older Patients with Lymphoma

    PubMed Central

    Lahoud, Oscar B.; Sauter, Craig S.; Hamlin, Paul A.

    2017-01-01

    High-dose chemotherapy followed by autologous hematopoietic stem cell transplant (HDT/ASCT) can improve survival in patients with lymphoma. Limited experience is available on the safety and efficacy of HDT/ASCT in elderly patients. In this article, we review the published data on the role of HDT/ASCT in management of lymphoma in older patients. Based on available data, evaluation of comorbidities, functional status, and comprehensive geriatric assessment (CGA) will help identify those who can benefit most from this intervention. Prospective clinical trials focusing on HDT/ASCT in older patients with lymphoma are needed to establish optimal management protocols in this select population. PMID:26201264

  15. Neck Rhabdoid Tumors: Clinical Features and Consideration of Autologous Stem Cell Transplant.

    PubMed

    Wolfe, Adam D; Capitini, Christian M; Salamat, Shahriar M; DeSantes, Kenneth; Bradley, Kristin A; Kennedy, Tabassum; Dehner, Louis P; Patel, Neha J

    2017-04-03

    Extrarenal malignant rhabdoid tumors (MRT) have a poor prognosis despite aggressive therapy. Adding high-dose chemotherapy with autologous stem cell rescue (HDC-ASCR) as consolidative therapy for MRT is controversial. We describe 2 patients, age 13 years and 19 months, with unresectable neck MRT. After chemotherapy and radiotherapy, both underwent HDC-ASCR and remain in remission over 4 years later. We reviewed all published cases of neck MRT, and found poorer outcomes and more variable age of presentation and time to progression than MRT at other sites. Neck MRT may represent a higher-risk subset of MRT, and addition of HDC-ASCR merits consideration.

  16. High-dose treatment with autologous stem cell transplantation versus sequential chemotherapy: the GELA experience.

    PubMed

    Bosly, A; Haioun, C; Gisselbrecht, C; Reyes, F; Coiffier, B

    2001-07-01

    Autologous stem-cell transplantation (ASCT) has permitted to deliver high-dose therapy (HDT). In aggressive lymphomas, the GELA group conducted prospective and retrospective studies comparing HDT + ASCT to conventional sequential chemotherapy. In relapsing patients and in partial remission, retrospective studies showed a survival advantage for HDT + ASCT over sequential chemotherapy. In complete response, advantage for HDT + ASCT was demonstrated in a prospective trial only for patients with high intermediate or high risk in the IPI score. The attainment of a maximal reduction of the tumoral mass before going HDT is very important either in first line or in relapsing patients.

  17. T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis

    PubMed Central

    Gorin, Norbert-Claude; Labopin, Myriam; Piemontese, Simona; Arcese, William; Santarone, Stella; Huang, He; Meloni, Giovanna; Ferrara, Felicetto; Beelen, Dietrich; Sanz, Miguel; Bacigalupo, Andrea; Ciceri, Fabio; Mailhol, Audrey; Nagler, Arnon; Mohty, Mohamad

    2015-01-01

    Adult patients with acute leukemia in need of a transplant but without a genoidentical donor are usually considered upfront for transplantation with stem cells from any other allogeneic source, rather than autologous stem cell transplantation. We used data from the European Society for Blood and Marrow Transplantation and performed a matched pair analysis on 188 T-cell-replete haploidentical and 356 autologous transplants done from January 2007 to December 2012, using age, diagnosis, disease status, cytogenetics, and interval from diagnosis to transplant as matching factors. “Haploidentical expert” centers were defined as having reported more than five haploidentical transplants for acute leukemia (median value for the study period). The median follow-up was 28 months. Multivariate analyses, including type of transplant categorized into three classes (“haploidentical regular”, “haploidentical expert” and autologous), conditioning intensity (reduced intensity versus myeloablative conditioning) and the random effect taking into account associations related to matching, showed that non-relapse mortality was higher following haploidentical transplants in expert (HR: 4.7; P=0.00004) and regular (HR: 8.98; P<10−5) centers. Relapse incidence for haploidentical transplants was lower in expert centers (HR:0.39; P=0.0003) but in regular centers was similar to that for autologous transplants. Leukemia-free survival and overall survival rates were higher following autologous transplantation than haploidentical transplants in regular centers (HR: 1.63; P=0.008 and HR: 2.31; P=0.0002 respectively) but similar to those following haploidentical transplants in expert centers. We conclude that autologous stem cell transplantation should presently be considered as a possible alternative to haploidentical transplantation in regular centers that have not developed a specific expert program. PMID:25637051

  18. T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis.

    PubMed

    Gorin, Norbert-Claude; Labopin, Myriam; Piemontese, Simona; Arcese, William; Santarone, Stella; Huang, He; Meloni, Giovanna; Ferrara, Felicetto; Beelen, Dietrich; Sanz, Miguel; Bacigalupo, Andrea; Ciceri, Fabio; Mailhol, Audrey; Nagler, Arnon; Mohty, Mohamad

    2015-04-01

    Adult patients with acute leukemia in need of a transplant but without a genoidentical donor are usually considered upfront for transplantation with stem cells from any other allogeneic source, rather than autologous stem cell transplantation. We used data from the European Society for Blood and Marrow Transplantation and performed a matched pair analysis on 188 T-cell-replete haploidentical and 356 autologous transplants done from January 2007 to December 2012, using age, diagnosis, disease status, cytogenetics, and interval from diagnosis to transplant as matching factors. "Haploidentical expert" centers were defined as having reported more than five haploidentical transplants for acute leukemia (median value for the study period). The median follow-up was 28 months. Multivariate analyses, including type of transplant categorized into three classes ("haploidentical regular", "haploidentical expert" and autologous), conditioning intensity (reduced intensity versus myeloablative conditioning) and the random effect taking into account associations related to matching, showed that non-relapse mortality was higher following haploidentical transplants in expert (HR: 4.7; P=0.00004) and regular (HR: 8.98; P<10(-5)) centers. Relapse incidence for haploidentical transplants was lower in expert centers (HR:0.39; P=0.0003) but in regular centers was similar to that for autologous transplants. Leukemia-free survival and overall survival rates were higher following autologous transplantation than haploidentical transplants in regular centers (HR: 1.63; P=0.008 and HR: 2.31; P=0.0002 respectively) but similar to those following haploidentical transplants in expert centers. We conclude that autologous stem cell transplantation should presently be considered as a possible alternative to haploidentical transplantation in regular centers that have not developed a specific expert program.

  19. Aging of bone marrow mesenchymal stromal/stem cells: Implications on autologous regenerative medicine.

    PubMed

    Charif, N; Li, Y Y; Targa, L; Zhang, L; Ye, J S; Li, Y P; Stoltz, J F; Han, H Z; de Isla, N

    2017-01-01

    With their proliferation, differentiation into specific cell types, and secretion properties, mesenchymal stromal/stem cells (MSC) are very interesting tools to be used in regenerative medicine. Bone marrow (BM) was the first MSC source characterized. In the frame of autologous MSC therapy, it is important to detect donor's parameters affecting MSC potency. Age of the donors appears as one parameter that could greatly affect MSC properties. Moreover, in vitro cell expansion is needed to obtain the number of cells necessary for clinical developments. It will lead to in vitro cell aging that could modify cell properties. This review recapitulates several studies evaluating the effect of in vitro and in vivo MSC aging on cell properties.

  20. Residual β-Cell Function Predicts Clinical Response After Autologous Hematopoietic Stem Cell Transplantation.

    PubMed

    Xiang, Hang; Yang, Chao; Xiang, Tianyuan; Wang, Zheng; Ge, Xin; Li, Fan; Su, Yuehan; Chen, Haixu; Huang, Xianyong; Zeng, Qiang

    2016-05-01

    New strategies of autologous hematopoietic stem cell transplantation (auto-HSCT) have gained much interest for the treatment of type 1 diabetes mellitus. However, assessing the clinical response and residual β-cell function still has limitations. The aim of the study was to select the optimal quantitative index to assess pre-existing β-cell function and to explore its predictive function for clinical response after auto-HSCT therapy. In this study, all of the patients who had undergone auto-HSCT were clustered into a responder group (Δβ-score > 0) and a nonresponder group (Δβ-score ≤ 0). We compared their quantitative metabolic indexes at baseline and performed receiver-operating characteristic (ROC) analysis to analyze the correlations between the indexes and clinical response. Kaplan-Meier analysis was conducted to compare the cumulative response durations in each quartile of the selected indexes. In an average of 15.13 ± 6.15 months of follow-up, 44 of 112 patients achieved a clinical response. The responder group had lower levels of fasting plasma glucose and quantitative insulin sensitivity check index (QUICKI) but higher levels of fasting C-peptide, fasting insulin, and homeostasis model assessments for insulin resistance (HOMA-IR). ROC analysis showed that HOMA-IR had the largest area under the curve (0.756), which was similar to that of QUICKI. Kaplan-Meier analysis further confirmed that the third quartile (1.3371-1.7018) of HOMA-IR or the second quartile (0.3523-0.3657) of QUICKI was preferential for a prolonged response. In conclusion, HOMA-IR and QUICKI could be optimal measurements for β-cell reserves, and they were predictive for the clinical response after auto-HSCT. The β-score was comprehensive and reliable in evaluating clinical response after autologous hematopoietic stem cell transplantation (HSCT). The homeostasis model assessments for insulin resistance and the quantitative insulin sensitivity check index could serve as precise

  1. [Complete autologous bone marrow recovery after allogeneic stem cell transplantation in a child with acute monoblastic leukemia].

    PubMed

    Balwierz, Walentyna; Chełmecka-Hanusiewic, Liliana; Klekawka, Tomasz; Wójcik, Beata; Kowalczyk, Jerzy R; Ksiazek, Teofila

    2010-01-01

    We present a case of autologous bone marrow recovery after allogeneic hematopoietic stem cell transplantation (HSCT) in a 7-year old girl who was treated due to acute myelocytic leukemia. First complete remission is lasting for 81 months after the allo-HSCT. Presented case constitutes an exceptional clinical situation and it indicates that diagnosis of leukemia relapse should be cautiously considered once the autologous bone marrow recovery is observed after allogeneic HSCT.

  2. The Role of Autologous and Allogeneic Hematopoietic Stem Cell Transplantation for Hodgkin Lymphoma

    PubMed Central

    Holmberg, Leona; Maloney, David G.

    2011-01-01

    Patients with Hodgkin lymphoma are usually cured by primary therapy using chemotherapy alone or combined modality therapy with external beam radiation. Patients who do not experience a complete remission or those who experience relapse may by salvaged by high-dose therapy and autologous hematopoietic stem cell transplantation (ASCT). Success of this approach is largely dependent on the tumor being sensitive to salvage chemotherapy before transplant. More studies are showing the predictive value of functional imaging in this setting. Allogeneic hematopoietic stem cell transplantation has greater risk of nonrelapse mortality and is generally reserved for patients who experience relapse post-ASCT, but may provide long-term survival for some patients through graft-versus-tumor immune effects. PMID:21917627

  3. Autologous Transplantation of Bone Marrow Adult Stem Cells for the Treatment of Idiopathic Dilated Cardiomyopathy

    PubMed Central

    Westphal, Ricardo João; Bueno, Ronaldo Rocha Loures; Galvão, Paulo Bezerra de Araújo; Zanis Neto, José; Souza, Juliano Mendes; Guérios, Ênio Eduardo; Senegaglia, Alexandra Cristina; Brofman, Paulo Roberto; Pasquini, Ricardo; da Cunha, Claudio Leinig Pereira

    2014-01-01

    Background Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients. Objective Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Methods We administered 4,54 x 108 ± 0,89 x 108 bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year. Results During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years. Conclusion Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation. PMID:25590932

  4. Pharmacoeconomic analysis of palifermin to prevent mucositis among patients undergoing autologous hematopoietic stem cell transplantation

    PubMed Central

    Kaufman, Jonathan L.; Flowers, Christopher R.; Langston, Amelia; Steuer, Conor; Graiser, Michael; Ali, Zahir; Shah, Nishi N.; Rangaraju, Sravanti; Nickleach, Dana; Gao, Jingjing; Lonial, Sagar; Waller, Edmund K.

    2014-01-01

    Prior trials have shown benefits ofpalifermin in reducing the incidence and severity of oral mucositis in patients with hematological malignancies undergoing autologous hematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI)-based conditioning regimens. Similar outcomes data are lacking for patients receiving non-TBI-based regimens. We performed a retrospective evaluation on the pharmacoeconomic benefit of palifermin in the setting of non-TBI-based conditioning and autologous HSCT. 524 patients that underwent autologous HSCT for myeloma (melphalan 200 mg/m2) and lymphoma (high-dose busulfan, cyclophosphamide, and etoposide)as preparative regimen between January 2002 and December 2010 were analyzed. Usage of patient controlled analgesia (PCA) was significantly lower in the palifermin-treated groups (myeloma: 13% vs. 53%; p<0.001; lymphoma: 46% vs. 68%; p<0.001).Median total transplant charges were significantly higher in the palifermin-treated group, after controlling for inflation (myeloma: $167,820 vs. $143,200, p<0.001; lymphoma: $168,570 vs. $148,590, p<0.001). Palifermin treatment was not associated with a difference in days to neutrophil engraftment, length of stay and overall survival; and was associated with an additional cost of $5.5K (myeloma) and $14K (lymphoma) per day of PCA avoided. Future studies are suggested to evaluate the cost-effectiveness of palifermin compared with other symptomatic treatments to reduce transplant toxicity using validated measures for pain and quality of life. PMID:24607557

  5. Pharmacoeconomic analysis of palifermin to prevent mucositis among patients undergoing autologous hematopoietic stem cell transplantation.

    PubMed

    Nooka, Ajay K; Johnson, Heather R; Kaufman, Jonathan L; Flowers, Christopher R; Langston, Amelia; Steuer, Conor; Graiser, Michael; Ali, Zahir; Shah, Nishi N; Rangaraju, Sravanti; Nickleach, Dana; Gao, Jingjing; Lonial, Sagar; Waller, Edmund K

    2014-06-01

    Trials have shown benefits of palifermin in reducing the incidence and severity of oral mucositis in patients with hematological malignancies undergoing autologous hematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI)-based conditioning regimens. Similar outcome data are lacking for patients receiving non-TBI-based regimens. We performed a retrospective evaluation on the pharmacoeconomic benefit of palifermin in the setting of non-TBI-based conditioning and autologous HSCT. Between January 2002 and December 2010, 524 patients undergoing autologous HSCT for myeloma (melphalan 200 mg/m²) and lymphoma (high-dose busulfan, cyclophosphamide, and etoposide) as preparative regimen were analyzed. Use of patient-controlled analgesia (PCA) was significantly lower in the palifermin-treated groups (myeloma: 13% versus 53%, P < .001; lymphoma: 46% versus 68%, P < .001). Median total transplant charges were significantly higher in the palifermin-treated group, after controlling for inflation (myeloma: $167,820 versus $143,200, P < .001; lymphoma: $168,570 versus $148,590, P < .001). Palifermin treatment was not associated with a difference in days to neutrophil engraftment, length of stay, and overall survival and was associated with an additional cost of $5.5K (myeloma) and $14K (lymphoma) per day of PCA avoided. Future studies are suggested to evaluate the cost-effectiveness of palifermin compared with other symptomatic treatments to reduce transplant toxicity using validated measures for pain and quality of life.

  6. Interferon-gamma modification of mesenchymal stem cells: implications of autologous and allogeneic mesenchymal stem cell therapy in allotransplantation.

    PubMed

    Sivanathan, Kisha Nandini; Gronthos, Stan; Rojas-Canales, Darling; Thierry, Benjamin; Coates, P Toby

    2014-06-01

    Bone marrow-derived mesenchymal stem cells (MSC) have unique immunomodulatory and reparative properties beneficial for allotransplantation cellular therapy. The clinical administration of autologous or allogeneic MSC with immunosuppressive drugs is able to prevent and treat allograft rejection in kidney transplant recipients, thus supporting the immunomodulatory role of MSC. Interferon-gamma (IFN-γ) is known to enhance the immunosuppressive properties of MSC. IFN-γ preactivated MSC (MSC-γ) directly or indirectly modulates T cell responses by enhancing or inducing MSC inhibitory factors. These factors are known to downregulate T cell activation, enhance T cell negative signalling, alter T cells from a proinflammatory to an anti-inflammatory phenotype, interact with antigen-presenting cells and increase or induce regulatory cells. Highly immunosuppressive MSC-γ with increased migratory and reparative capacities may aid tissue repair, prolong allograft survival and induce allotransplant tolerance in experimental models. Nevertheless, there are contradictory in vivo observations related to allogeneic MSC-γ therapy. Many studies report that allogeneic MSC are immunogenic due to their inherent expression of major histocompatibility (MHC) molecules. Enhanced expression of MHC in allogeneic MSC-γ may increase their immunogenicity and this can negatively impact allograft survival. Therefore, strategies to reduce MSC-γ immunogenicity would facilitate "off-the-shelf" MSC therapy to efficiently inhibit alloimmune rejection and promote tissue repair in allotransplantation. In this review, we examine the potential benefits of MSC therapy in the context of allotransplantation. We also discuss the use of autologous and allogeneic MSC and the issues associated with their immunogenicity in vivo, with particular focus on the use of enhanced MSC-γ cellular therapy.

  7. How we manage autologous stem cell transplantation for patients with multiple myeloma

    PubMed Central

    Dingli, David

    2014-01-01

    An estimated 22 350 patients had multiple myeloma diagnosed in 2013, representing 1.3% of all new cancers; 10 710 deaths are projected, representing 1.8% of cancer deaths. Approximately 0.7% of US men and women will have a myeloma diagnosis in their lifetime, and with advances in therapy, 77 600 US patients are living with myeloma. The 5-year survival rate was 25.6% in 1989 and was 44.9% in 2005. The median age at diagnosis is 69 years, with 62.4% of patients aged 65 or older at diagnosis. Median age at death is 75 years. The rate of new myeloma cases has been rising 0.7% per year during the past decade. The most common indication for autologous stem cell transplantation in the United States is multiple myeloma, and this article is designed to provide the specifics of organizing a transplant program for multiple myeloma. We review the data justifying use of stem cell transplantation as initial management in myeloma patients. We provide selection criteria that minimize the risks of transplantation. Specific guidelines on mobilization and supportive care through the transplant course, as done at Mayo Clinic, are given. A review of the data on tandem vs sequential autologous transplants is provided. PMID:24973360

  8. Human autologous mesenchymal stem cells with extracorporeal shock wave therapy for nonunion of long bones

    PubMed Central

    Zhai, Lei; Ma, Xin-Long; Jiang, Chuan; Zhang, Bo; Liu, Shui-Tao; Xing, Geng-Yan

    2016-01-01

    Background: Currently, the available treatments for long bone nonunion (LBN) are removing of focus of infection, bone marrow transplantation as well as Ilizarov methods etc. Due to a high percentage of failures, the treatments are complex and debated. To develop an effective method for the treatment of LBN, we explored the use of human autologous bone mesenchymal stems cells (hBMSCs) along with extracorporeal shock wave therapy (ESWT). Materials and Methods: Sixty three patients of LBN were subjected to ESWT treatment and were divided into hBMSCs transplantation group (Group A, 32 cases) and simple ESWT treatment group (Group B, 31 cases). Results: The patients were evaluated for 12 months after treatment. In Group A, 14 patients were healed and 13 showed an improvement, with fracture healing rate 84.4%. In Group B, eight patients were healed and 13 showed an improvement, with fracture healing rate 67.7%. The healing rates of the two groups exhibited a significant difference (P < 0.05). There was no significant difference for the callus formation after 3 months treatment (P > 0.05). However, the callus formation in Group A was significantly higher than that in the Group B after treatment for 6, 9, and 12 months (P < 0.05). Conclusion: Autologous bone mesenchymal stems cell transplantation with ESWT can effectively promote the healing of long bone nonunions. PMID:27746499

  9. Being in protective isolation following autologous haematopoietic stem cell transplantation: A phenomenological study.

    PubMed

    Biagioli, Valentina; Piredda, Michela; Annibali, Ombretta; Iacorossi, Laura; D'Angelo, Daniela; Matarese, Maria; Alvaro, Rosaria; De Marinis, Maria Grazia

    2017-02-23

    To explore the lived experiences of patients with haematological malignancies who had been in protective isolation during their hospital stay for autologous haematopoietic stem cell transplantation. Although protective isolation aims to benefit patients' health by preventing infection, it could also imply harmful psycho-social implications for patients, such as loneliness. A descriptive phenomenological study was conducted in an Italian university hospital. Nine patients with haematological malignancies who had been in protective isolation for autologous haematopoietic stem cell transplantation were enrolled. They were interviewed during their weekly ambulatory visits, which are usually carried out up to 100 days post-transplant, and asked about their stay in isolation. Giorgi's method of analysis was used to describe the experience of protective isolation from the patient' perspective. Eight themes emerged: isolation is a defence, threats from which patients have to defend themselves, rules for defence, the burden of the defence, external strategies for defence, inner strengths for defence, defending loved ones and outcomes of the defence. The general structure was expressed as a defence from suffering. While fighting a hard battle against cancer, informants largely accepted the strict isolation measure and represented it as a shield for an effective defence. Nurses should provide emotional and social support to help patients feel like active fighters and strengthen their strategies for an effective defence from suffering. © 2017 John Wiley & Sons Ltd.

  10. Clonal Hematopoiesis Associated With Adverse Outcomes After Autologous Stem-Cell Transplantation for Lymphoma.

    PubMed

    Gibson, Christopher J; Lindsley, R Coleman; Tchekmedyian, Vatche; Mar, Brenton G; Shi, Jiantao; Jaiswal, Siddhartha; Bosworth, Alysia; Francisco, Liton; He, Jianbo; Bansal, Anita; Morgan, Elizabeth A; Lacasce, Ann S; Freedman, Arnold S; Fisher, David C; Jacobsen, Eric; Armand, Philippe; Alyea, Edwin P; Koreth, John; Ho, Vincent; Soiffer, Robert J; Antin, Joseph H; Ritz, Jerome; Nikiforow, Sarah; Forman, Stephen J; Michor, Franziska; Neuberg, Donna; Bhatia, Ravi; Bhatia, Smita; Ebert, Benjamin L

    2017-01-09

    Purpose Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition characterized by somatic mutations in the blood of otherwise healthy adults. We hypothesized that in patients undergoing autologous stem-cell transplantation (ASCT) for lymphoma, CHIP at the time of ASCT would be associated with an increased risk of myelodysplastic syndrome and acute myeloid leukemia, collectively termed therapy-related myeloid neoplasm (TMN), and other adverse outcomes. Methods We performed whole-exome sequencing on pre- and post-ASCT samples from 12 patients who developed TMN after autologous transplantation for Hodgkin lymphoma or non-Hodgkin lymphoma and targeted sequencing on cryopreserved aliquots of autologous stem-cell products from 401 patients who underwent ASCT for non-Hodgkin lymphoma between 2003 and 2010. We assessed the effect of CHIP at the time of ASCT on subsequent outcomes, including TMN, cause-specific mortality, and overall survival. Results For six of 12 patients in the exome sequencing cohort, mutations found in the TMN specimen were also detectable in the pre-ASCT specimen. In the targeted sequencing cohort, 120 patients (29.9%) had CHIP at the time of ASCT, which was associated with an increased rate of TMN (10-year cumulative incidence, 14.1% v 4.3% for those with and without CHIP, respectively; P = .002). Patients with CHIP had significantly inferior overall survival compared with those without CHIP (10-year overall survival, 30.4% v 60.9%, respectively; P < .001), including increased risk of death from TMN and cardiovascular disease. Conclusion In patients undergoing ASCT for lymphoma, CHIP at the time of transplantation is associated with inferior survival and increased risk of TMN.

  11. Derivation of Neural Stem Cells from Human Adult Peripheral CD34+ Cells for an Autologous Model of Neuroinflammation

    PubMed Central

    Wang, Tongguang; Choi, Elliot; Monaco, Maria Chiara G.; Campanac, Emilie; Medynets, Marie; Do, Thao; Rao, Prashant; Johnson, Kory R.; Elkahloun, Abdel G.; Von Geldern, Gloria; Johnson, Tory; Subramaniam, Sriram; Hoffman, Dax; Major, Eugene; Nath, Avindra

    2013-01-01

    Proinflammatory factors from activated T cells inhibit neurogenesis in adult animal brain and cultured human fetal neural stem cells (NSC). However, the role of inhibition of neurogenesis in human neuroinflammatory diseases is still uncertain because of the difficulty in obtaining adult NSC from patients. Recent developments in cell reprogramming suggest that NSC may be derived directly from adult fibroblasts. We generated NSC from adult human peripheral CD34+ cells by transfecting the cells with Sendai virus constructs containing Sox2, Oct3/4, c-Myc and Klf4. The derived NSC could be differentiated to glial cells and action potential firing neurons. Co-culturing NSC with activated autologous T cells or treatment with recombinant granzyme B caused inhibition of neurogenesis as indicated by decreased NSC proliferation and neuronal differentiation. Thus, we have established a unique autologous in vitro model to study the pathophysiology of neuroinflammatory diseases that has potential for usage in personalized medicine. PMID:24303066

  12. Bone Marrow Very Small Embryonic-Like Stem Cells: New Generation of Autologous Cell Therapy Soon Ready for Prime Time?

    PubMed

    Smadja, David M

    2017-04-01

    Very small embryonic-like stem cells (VSELs) are major pluripotent stem cells described in human and mouse. In this issue of Stem Cell Reviews and Reports, Shaikh and colleagues show in a valuable work that mouse bone marrow collected after 5FU treatment contains VSELs able to undergo in vitro multi-lineage differentiation into cells from all three germ layers and also in germ and hematopoietic cells. These findings are robust since no confounding factor such as feeder cell fusion with VSELs can occur here. This paper allows one to better appreciate bone marrow-VSELs differentiation potential and opens new perspectives for autologous cell therapy. Furthermore, it might help explaining lots of contradictive data from the past 20 years, in particular related to ability of bone marrow cells to differentiate into cardiomyocytes.

  13. Effectiveness of Autologous Stem Cell Therapy for the Treatment of Lower Extremity Ulcers: A Systematic Review and Meta-Analysis.

    PubMed

    Jiang, Xupin; Zhang, Hengshu; Teng, Miao

    2016-03-01

    Primary studies in animal models and humans have suggested the therapeutic potential of autologous stem cell for treating chronic lower extremity ulcers. However, the results of pilot randomized controlled trials (RCTs) in humans have been inconsistent. A meta-analysis of RCTs was performed to evaluate the role of autologous stem cell-based therapy for lower extremity ulcers.Studies were identified during a systematic search of Medline, Embase, Cochrane's library, and references cited in related reviews and studies. Studies were included if they were RCTs published in English, recruited patients with lower extremity ulcers who were assigned to either a group for the topical therapy with autologous stem cells, and reported data regarding the healing of the ulcers.Relative risks (RRs) for healing rate and standardized mean differences (SMDs) for the changes in the mean sizes of ulcers were evaluated with a random-effects model. Overall, autologous stem cell-based therapy was associated with better healing of lower extremity ulcers (12 comparisons, 290 patients, RR for partial healing = 3.07, 95% confidence interval [CI] = 1.14-8.24, P = 0.03; RR for complete healing = 2.26, 95% CI = 1.48-3.16, P < 0.001) with little heterogeneity (I = 0%). Moreover, autologous stem cell-based therapy was associated with a greater reduction in mean ulcer size (SMD = -0.63, 95% CI = -1.03 to -0.22, P = 0.002). Subgroup analyses indicated that stem cells from peripheral blood and bone marrow seemed to exert similar beneficial effects on the healing of ulcers. Stem cell therapy was not associated with any increased risks for adverse events. The optimized sources, amounts, and delivery methods of stem cell -based therapy for patients with chronic lower extremity ulcers need to be determined, and the long-term effects of stem cell-based therapy on clinical outcomes need further exploration.Autologous stem cell-based therapy is effective and safe for

  14. Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma.

    PubMed

    Tuchman, Sascha A; Bacon, Wendi A; Huang, Li-Wen; Long, Gwynn; Rizzieri, David; Horwitz, Mitchell; Chute, John P; Sullivan, Keith; Morris Engemann, Ashley; Yopp, Amanda; Li, Zhiguo; Corbet, Kelly; Chao, Nelson; Gasparetto, Cristina

    2015-06-01

    High-dose cyclophosphamide (Cy) is frequently employed for peripheral blood mobilization of hematopoietic stem cells before high-dose chemotherapy with autologous stem cell transplantation (ASCT) in multiple myeloma (MM). The benefit of mobilization with Cy over filgrastim (granulocyte colony-stimulating factor; G-CSF) alone is unclear. Between 2000 and 2008, 167 patients with newly diagnosed MM underwent single ASCT after melphalan conditioning at our institution. Seventy-three patients were mobilized with G-CSF alone, and 94 patients with Cy plus G-CSF (Cy+G-CSF). We retrospectively analyzed Cy's impact on both toxicity and efficacy. Mobilization efficiency was augmented by Cy; a mean total of 12 versus 5.8 × 10(6) CD34+ cells/kg were collected from patients mobilized with Cy+G-CSF versus G-CSF, respectively, (P < 0.01), over a mean of 1.6 versus 2.2 days of peripheral blood apheresis (p = 0.001). Mobilization-related toxicity was also, however, augmented by Cy; 14% of Cy+G-CSF patients were hospitalized because of complications versus none receiving G-CSF (P < 0.0001). Toxicity, including death, related to ASCT was similar between cohorts. Regarding long-term outcomes, multivariate analysis revealed no difference for Cy+G-CSF versus G-CSF (hazard ratio 0.8 for event-free survival [95% confidence interval {CI} 0.57-1.25] and 0.96 for overall survival [95% CI 0.61-1.54]). In summary, we show that mobilization with Cy increases toxicity without positively impacting long-term outcomes in MM. Our findings place into question Cy's benefit as a routine component of stem cell mobilization regimens in MM. Randomized trials are needed to elucidate the risks and benefits of Cy more definitively.

  15. Therapeutic Efficacy of Fresh, Autologous Mesenchymal Stem Cells for Severe Refractory Gingivostomatitis in Cats

    PubMed Central

    Mills-Ko, Emily; Verstraete, Frank J.M.; Kol, Amir; Walker, Naomi J.; Badgley, Megan R.; Fazel, Nasim; Murphy, William J.; Vapniarsky, Natalia; Borjesson, Dori L.

    2016-01-01

    Mesenchymal stem cells (MSCs) are a promising therapy for immune-mediated and inflammatory disorders, because of their potent immunomodulatory properties. In this study, we investigated the use of fresh, autologous, adipose-derived MSCs (ASCs) for feline chronic gingivostomatitis (FCGS), a chronic, debilitating, idiopathic, oral mucosal inflammatory disease. Nine cats with refractory FCGS were enrolled in this pilot study. Each cat received 2 intravenous injections of 20 million autologous ASCs, 1 month apart. Oral biopsies were taken before and at 6 months after the first ASC injection. Blood immune cell subsets, serum protein, and cytokine levels were measured at 0, 1, 3, and 6 months after treatment to assess immunomodulatory effects. Seven of the 9 cats completed the study. Five cats responded to treatment by either complete clinical remission (n = 3) or substantial clinical improvement (n = 2). Two cats were nonresponders. Cats that responded to treatment also exhibited systemic immunomodulation demonstrated by decreased numbers of circulating CD8+ T cells, a normalization of the CD4/CD8 ratio, decreased neutrophil counts, and interferon-γ and interleukin (IL)-1β concentration, and a temporary increase in serum IL-6 and tumor necrosis factor-α concentration. No clinical recurrence has occurred following complete clinical remission (follow-up of 6–24 months). In this study, cats with <15% cytotoxic CD8 T cells with low expression of CD8 (CD8lo) cells were 100% responsive to ASC therapy, whereas cats with >15% CD8lo cells were nonresponders. The relative absence of CD8lo cells may be a biomarker to predict response to ASC therapy, and may shed light on pathogenesis of FCGS and mechanisms by which ASCs decrease oral inflammation and affect T-cell phenotype. Significance This study is the first to demonstrate the safety and efficacy of fresh, autologous, adipose-derived stem cell systemic therapy for a naturally occurring, chronic inflammatory disease in cats

  16. Therapeutic Efficacy of Fresh, Autologous Mesenchymal Stem Cells for Severe Refractory Gingivostomatitis in Cats.

    PubMed

    Arzi, Boaz; Mills-Ko, Emily; Verstraete, Frank J M; Kol, Amir; Walker, Naomi J; Badgley, Megan R; Fazel, Nasim; Murphy, William J; Vapniarsky, Natalia; Borjesson, Dori L

    2016-01-01

    Mesenchymal stem cells (MSCs) are a promising therapy for immune-mediated and inflammatory disorders, because of their potent immunomodulatory properties. In this study, we investigated the use of fresh, autologous, adipose-derived MSCs (ASCs) for feline chronic gingivostomatitis (FCGS), a chronic, debilitating, idiopathic, oral mucosal inflammatory disease. Nine cats with refractory FCGS were enrolled in this pilot study. Each cat received 2 intravenous injections of 20 million autologous ASCs, 1 month apart. Oral biopsies were taken before and at 6 months after the first ASC injection. Blood immune cell subsets, serum protein, and cytokine levels were measured at 0, 1, 3, and 6 months after treatment to assess immunomodulatory effects. Seven of the 9 cats completed the study. Five cats responded to treatment by either complete clinical remission (n=3) or substantial clinical improvement (n=2). Two cats were nonresponders. Cats that responded to treatment also exhibited systemic immunomodulation demonstrated by decreased numbers of circulating CD8+ T cells, a normalization of the CD4/CD8 ratio, decreased neutrophil counts, and interferon-γ and interleukin (IL)-1β concentration, and a temporary increase in serum IL-6 and tumor necrosis factor-α concentration. No clinical recurrence has occurred following complete clinical remission (follow-up of 6-24 months). In this study, cats with <15% cytotoxic CD8 T cells with low expression of CD8 (CD8lo) cells were 100% responsive to ASC therapy, whereas cats with >15% CD8lo cells were nonresponders. The relative absence of CD8lo cells may be a biomarker to predict response to ASC therapy, and may shed light on pathogenesis of FCGS and mechanisms by which ASCs decrease oral inflammation and affect T-cell phenotype. This study is the first to demonstrate the safety and efficacy of fresh, autologous, adipose-derived stem cell systemic therapy for a naturally occurring, chronic inflammatory disease in cats. The findings

  17. Bilayer Hydrogel with Autologous Stem Cells Derived from Debrided Human Burn Skin for Improved Skin Regeneration

    DTIC Science & Technology

    2013-02-01

    grafting surgeries using autologous skin. Unfortunately, large surface burn wounds lack autologous viable unin- jured tissue for grafting , making...1 Natesan et al 19 skin or tissue-engineered substitutes containing allogeneic and/or autologous cells. These tissue- engineered wound dressings...dsASC-bilayer hydrogels contribute significantly to wound healing and provide support for their use as a vascularized dermal substitute for skin

  18. Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis.

    PubMed

    Cohen, Jeffrey A; Imrey, Peter B; Planchon, Sarah M; Bermel, Robert A; Fisher, Elizabeth; Fox, Robert J; Bar-Or, Amit; Sharp, Susan L; Skaramagas, Thomai T; Jagodnik, Patricia; Karafa, Matt; Morrison, Shannon; Reese Koc, Jane; Gerson, Stanton L; Lazarus, Hillard M

    2017-04-01

    Mesenchymal stem cells (MSCs) exhibit immunomodulatory, tissue-protective, and repair-promoting properties in vitro and in animals. Clinical trials in several human conditions support the safety and efficacy of MSC transplantation. Published experience in multiple sclerosis (MS) is modest. To assess feasibility, safety, and tolerability and explore efficacy of autologous MSC transplantation in MS. Participants with relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS), Expanded Disability Status Scale score 3.0-6.5, disease activity or progression in the prior 2 years, and optic nerve involvement were enrolled. Bone-marrow-derived MSCs were culture-expanded and then cryopreserved. After confirming fulfillment of release criteria, 1-2 × 10(6) MSCs/kg were thawed and administered IV. In all, 24 of 26 screened patients were infused: 16 women and 8 men, 10 RRMS and 14 SPMS, mean age 46.5, mean Expanded Disability Status Scale score 5.2, 25% with gadolinium-enhancing magnetic resonance imaging (MRI) lesions. Mean cell dosage (requiring 1-3 passages) was 1.9 × 10(6) MSCs/kg (range, 1.5-2.0) with post-thaw viability uniformly ⩾95%. Cell infusion was tolerated well without treatment-related severe or serious adverse events, or evidence of disease activation. Autologous MSC transplantation in MS appears feasible, safe, and well tolerated. Future trials to assess efficacy more definitively are warranted.

  19. Autologous Transplantation of Adult Mice Spermatogonial Stem Cells into Gamma Irradiated Testes

    PubMed Central

    Koruji, Morteza; Movahedin, Mansoureh; Mowla, Seyed Javad; Gourabi, Hamid; Pour-Beiranvand, Shahram; Jabbari Arfaee, Ali

    2012-01-01

    Objective: We evaluated structural and functional changes of fresh and frozen-thawed adult mouse spermatogonial stem cells following auto-transplantation into gamma-irradiated testes. Materials and Methods: In this experimental research, the right testes from adult mice (n=25) were collected, then Sertoli and spermatogonial cells were isolated using two-step enzymatic digestion, lectin immobilization and differential plating. Three weeks after cultivation, the Bromodeoxyuridine (BrdU)-labeled spermatogonial cells were transplanted, via rete testis, into the other testis of the same mouse, which had been irradiated with 14Gy. The mice were transplanted with: fresh cells (control 1), fresh cells co-cultured with Sertoli cells (control 2), the frozen-thawed cells (experimental 1) and frozen-thawed cells co-cultured with Sertoli cells (experimental 2). The morphological changes between different transplanted testes groups were compared in 8 weeks after transplantation. The statistical significance between mean values was determined by Kruskal Wallis and one-way analysis of variance in efficiency of transplantation. Results: The statistical analysis revealed significant increases in the mean percentage of testis weight and normal seminiferous tubules following spermatogonial stem cells transplantation in the recipient'fs testes. The normal seminiferous tubules percentage in the co-culture system with fresh cells and frozen-thawed groups were more than those in non-transplanted and fresh cell transplanted groups (p≤0.001). Conclusion: Our results demonstrated that spermatogonial stem cells in the colonies could result sperm production in the recipient’s testes after autologous transplantation. PMID:23507977

  20. Unilateral partial limbal stem cell deficiency: contralateral versus ipsilateral autologous cultivated limbal epithelial transplantation.

    PubMed

    Vazirani, Jayesh; Basu, Sayan; Kenia, Hemal; Ali, Md Hasnat; Kacham, Santhosh; Mariappan, Indumathi; Sangwan, Virender

    2014-03-01

    To report the outcomes of autologous cultivated limbal epithelial transplantation using the healthy part of the affected eye or the fellow eye as a source of limbal stem cells in patients with unilateral, partial limbal stem cell deficiency (LSCD). Retrospective, nonrandomized, interventional case series. setting: L. V. Prasad Eye Institute, Hyderabad, India. study population: Patients with unilateral, partial LSCD who underwent autologous cultivated limbal epithelial transplantation between 2001 and 2011. intervention: The limbal biopsy was taken either from the healthy part of the limbus of the same eye (ipsilateral group) or from the healthy fellow eye (contralateral group). Cells were cultivated using a xeno-free explant culture technique, and cultivated cells were transplanted onto the affected surface. primary outcome measure: Success of cultivated limbal epithelial transplantation, defined as a completely epithelialized, avascular, and clinically stable corneal surface. Seventy eyes of 70 patients were studied. The mean follow up was 17.5 ± 7 months. In 34 eyes the limbal biopsy was taken from the ipsilateral eye and in the remaining 36 eyes from the contralateral eye. Clinical success was achieved in 70.59% of eyes in the ipsilateral group and 75% of eyes in the contralateral group (P = .79). Limbal transplant survival rates at the final follow-up visit were 65.1% ± 0.09% in the ipsilateral group and 53.6% ± 0.12% in the contralateral group (P = .74). Ocular surface restoration in partial LSCD is possible with cell-based therapy. Outcomes are similar irrespective of whether the limbal biopsy is taken from the healthy part of the ipsilateral eye or the contralateral eye. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Genome Therapy of Myotonic Dystrophy Type 1 iPS Cells for Development of Autologous Stem Cell Therapy.

    PubMed

    Gao, Yuanzheng; Guo, Xiuming; Santostefano, Katherine; Wang, Yanlin; Reid, Tammy; Zeng, Desmond; Terada, Naohiro; Ashizawa, Tetsuo; Xia, Guangbin

    2016-08-01

    Myotonic dystrophy type 1 (DM1) is caused by expanded Cytosine-Thymine-Guanine (CTG) repeats in the 3'-untranslated region (3' UTR) of the Dystrophia myotonica protein kinase (DMPK) gene, for which there is no effective therapy. The objective of this study is to develop genome therapy in human DM1 induced pluripotent stem (iPS) cells to eliminate mutant transcripts and reverse the phenotypes for developing autologous stem cell therapy. The general approach involves targeted insertion of polyA signals (PASs) upstream of DMPK CTG repeats, which will lead to premature termination of transcription and elimination of toxic mutant transcripts. Insertion of PASs was mediated by homologous recombination triggered by site-specific transcription activator-like effector nuclease (TALEN)-induced double-strand break. We found genome-treated DM1 iPS cells continue to maintain pluripotency. The insertion of PASs led to elimination of mutant transcripts and complete disappearance of nuclear RNA foci and reversal of aberrant splicing in linear-differentiated neural stem cells, cardiomyocytes, and teratoma tissues. In conclusion, genome therapy by insertion of PASs upstream of the expanded DMPK CTG repeats prevented the production of toxic mutant transcripts and reversal of phenotypes in DM1 iPS cells and their progeny. These genetically-treated iPS cells will have broad clinical application in developing autologous stem cell therapy for DM1.

  2. Acute graft-versus-host disease and bronchiolitis obliterans after autologous stem cell transplantation in a patient with multiple myeloma

    PubMed Central

    Alonso, Sara; Cabrero, Mónica; Caballero, Juan C; Dávila, Julio; de la Calle, Veronica Gonzalez; López-Godino, Oriana; López-Corral, Lucia; Pérez, Estefanía; Vázquez, Lourdes; Corral, Rocío; Caballero, Dolores; del Cañizo, Consuelo; Mateos, María Victoria

    2015-01-01

    Key Clinical Message Sixty-seven-year-old patient, diagnosed with multiple myeloma who had received autologous stem cell transplantation, following bortezomib, dexamethasone and thalidomide conventional regimen, achieving complete response, developed rash, diarrhea, and severe respiratory failure, 80 days after the transplantation procedure. He was diagnosed with graft-versus-host disease and bronchiolitis obliterans syndrome. PMID:26185631

  3. Autologous stem-cell transplantation can be performed safely without the use of blood-product support.

    PubMed

    Ballen, Karen K; Becker, Pamela S; Yeap, Beow Yong; Matthews, Barbara; Henry, David H; Ford, Patricia A

    2004-10-15

    Autologous stem-cell transplantation has been shown to be a curative procedure for a variety of leukemias and lymphomas. Most transplants require RBC and platelet support. We report the ability to perform autologous transplantation without blood-product support. In this study, we treated 26 patients with religious objection to blood products with autologous stem-cell support without the use of any blood products. Patients received a combination of granulocyte colony-stimulating factor (G-CSF), erythropoietin, and interleukin-11 or G-CSF alone to mobilize stem cells. Post-transplant patients received intravenous iron, erythropoietin, G-CSF, and epsilon aminocaproic acid. There were two major bleeding complications (8%), with two treatment-related deaths (8%). There were three minor bleeding complications (12%). The median fall in hemoglobin level was 4.7 g/dL; the median hemoglobin level 30 days after transplantation was 9.2 g/dL. The median total number of days with platelet count less than 10 x 10(9)/L was 4 days; the median days to platelet recovery greater than 20 x 10(9)/L was 12 days. Autologous stem-cell transplantation can be performed safely without the use of any blood products.

  4. Intravitreal Implantation of Genetically Modified Autologous Bone Marrow-Derived Stem Cells for Treating Retinal Disorders.

    PubMed

    Tracy, Christopher J; Sanders, Douglas N; Bryan, Jeffrey N; Jensen, Cheryl A; Castaner, Leilani J; Kirk, Mark D; Katz, Martin L

    2016-01-01

    A number of retinal degenerative diseases may be amenable to treatment with continuous intraocular delivery of therapeutic agents that cannot be delivered effectively to the retina via systemic or topical administration. Among these disorders are lysosomal storage diseases resulting from deficiencies in soluble lysosomal enzymes. Most cells, including those of the retina, are able to take up these enzymes and incorporate them in active form into their lysosomes. In theory, therefore, continuous intraocular administration of a normal form of a soluble lysosomal enzyme should be able to cure the molecular defect in the retinas of subjects lacking this enzyme. Experiments were conducted to determine whether genetically modified bone marrow-derived stem cells implanted into the vitreous could be used as -vehicles for continuous delivery of such enzymes to the retina. Bone marrow-derived mesenchymal stem cells (MSCs) from normal mice were implanted into the vitreous of mice undergoing retinal degeneration as a result of a mutation in the PPT1 gene. The implanted cells appeared to survive indefinitely in the vitreous without proliferating or invading the retina. This indicates that intravitreal implantation of MSCs is likely a safe means of long-term delivery of proteins synthesized by the implanted cells. Experiments have been initiated to test the efficacy of using genetically modified autologous MSCs to inhibit retinal degeneration in a canine model of neuronal ceroid lipofuscinosis.

  5. Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure.

    PubMed

    Worel, Nina; Fritsch, Gerhard; Agis, Hermine; Böhm, Alexandra; Engelich, Georg; Leitner, Gerda C; Geissler, Klaus; Gleixner, Karoline; Kalhs, Peter; Buxhofer-Ausch, Veronika; Keil, Felix; Kopetzky, Gerhard; Mayr, Viktor; Rabitsch, Werner; Reisner, Regina; Rosskopf, Konrad; Ruckser, Reinhard; Zoghlami, Claudia; Zojer, Niklas; Greinix, Hildegard T

    2016-08-31

    Plerixafor in combination with granulocyte-colony stimulating factor (G-CSF) is approved for autologous stem cell mobilization in poor mobilizing patients with multiple myeloma or malignant lymphoma. The purpose of this study was to evaluate efficacy and safety of plerixafor in an immediate rescue approach, administrated subsequently to G-CSF alone or chemotherapy and G-CSF in patients at risk for mobilization failure. Eighty-five patients mobilized with G-CSF alone or chemotherapy were included. Primary endpoint was the efficacy of the immediate rescue approach of plerixafor to achieve ≥2.0 × 10(6) CD34(+) cells/kg for a single or ≥5 × 10(6) CD34(+) cells/kg for a double transplantation and potential differences between G-CSF and chemotherapy-based mobilization. Secondary objectives included comparison of stem cell graft composition including CD34(+) cell and lymphocyte subsets with regard to the mobilization regimen applied. No significant adverse events were recorded. A median 3.9-fold increase in CD34(+) cells following plerixafor was observed, resulting in 97% patients achieving at least ≥2 × 10(6) CD34+ cells/kg. Significantly more differentiated granulocyte and monocyte forming myeloid progenitors were collected after chemomobilization whereas more CD19(+) and natural killer cells were collected after G-CSF. Fifty-two patients underwent transplantation showing rapid and durable engraftment, irrespectively of the stem cell mobilization regimen used. The addition of plerixafor in an immediate rescue model is efficient and safe after both, G-CSF and chemomobilization and results in extremely high success rates. Whether the differences in graft composition have a clinical impact on engraftment kinetics, immunologic recovery, and graft durability have to be analysed in larger prospective studies.

  6. Current status of haematopoietic autologous stem cell transplantation in lymphoid malignancies: a European perspective.

    PubMed

    Hübel, Kai; de la Rubia, Javier; Azar, Nabih; Corradini, Paolo

    2015-01-01

    The use of autologous haematopoietic stem cell transplantation (ASCT) has increased considerably in lymphoid malignancies in the last decade, and it is now considered as the standard of care in particular circumstances. This review aims to present an overview of the current situation with ASCT in lymphoid malignancies in Europe, in terms of both current use and issues. It will also look briefly at ASCT in rarer haematological malignancies and at the future. It is intended as a reflection of opinion from selected centres in Europe and as an aid to understanding for those who are new to the area. The review is based on a series of four preceptorship meetings held in Europe in 2013. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Engraftment Syndrome following Autologous Stem Cell Transplantation – an Update Unifying the Definition and Management Approach

    PubMed Central

    Cornell, Robert Frank; Hari, Parameswaran; Drobyski, William R.

    2015-01-01

    Engraftment syndrome encompasses a continuum of peri-engraftment complications after autologous hematopoietic stem cell transplantation. ES may include non-infectious fever; skin rash; diarrhea; hepatic dysfunction; renal dysfunction; transient encephalopathy; and capillary leak features, such as non-cardiogenic pulmonary infiltrates, hypoxia, and weight gain with no alternative etiologic basis other than engraftment. Given its pleiotropic clinical presentation, the transplant field has struggled to clearly define ES and related syndromes. Here, we present a comprehensive review of ES in all documented disease settings. Furthermore, we discuss the proposed risk factors, etiology, and clinical relevance of ES. Finally, our current approach to ES is included along with a proposed treatment algorithm for the management of this complication. PMID:26327628

  8. Update on the Role of Autologous Hematopoietic Stem Cell Transplantation in Follicular Lymphoma

    PubMed Central

    Cabrero, Mónica; Redondo, Alba; Martin, Alejandro; Caballero, Dolores

    2012-01-01

    Follicular lymphoma (FL) remains incurable despite advances in new strategies of treatment, including monoclonal antibodies (MoAb). Except for early stages, FL is characterized by responses to treatments and systematic relapses. The main objective in this disease is to achieve a better progression free survival (PFS) and to increase overall survival (OS), mainly in young patients. In order to improve the results of conventional chemotherapy, autologous stem cell transplant (ASCT) is a feasible treatment in these patients. In this moment, ASCT is not recommended as first line treatment, except for transformed FL, but is a good strategy as salvage therapy with an improved PFS and OS. New drugs have been introduced to enhance responses of ASCT, but nowadays they are not part of conventional conditioning regimen. PMID:23205262

  9. Update on the role of autologous hematopoietic stem cell transplantation in follicular lymphoma.

    PubMed

    Cabrero, Mónica; Redondo, Alba; Martin, Alejandro; Caballero, Dolores

    2012-01-01

    Follicular lymphoma (FL) remains incurable despite advances in new strategies of treatment, including monoclonal antibodies (MoAb). Except for early stages, FL is characterized by responses to treatments and systematic relapses. The main objective in this disease is to achieve a better progression free survival (PFS) and to increase overall survival (OS), mainly in young patients. In order to improve the results of conventional chemotherapy, autologous stem cell transplant (ASCT) is a feasible treatment in these patients. In this moment, ASCT is not recommended as first line treatment, except for transformed FL, but is a good strategy as salvage therapy with an improved PFS and OS. New drugs have been introduced to enhance responses of ASCT, but nowadays they are not part of conventional conditioning regimen.

  10. The effect of erythropoietin on autologous stem cell-mediated bone regeneration.

    PubMed

    Nair, Ashwin M; Tsai, Yi-Ting; Shah, Krishna M; Shen, Jinhui; Weng, Hong; Zhou, Jun; Sun, Xiankai; Saxena, Ramesh; Borrelli, Joseph; Tang, Liping

    2013-10-01

    Mesenchymal stem cells (MSCs) although used for bone tissue engineering are limited by the requirement of isolation and culture prior to transplantation. Our recent studies have shown that biomaterial implants can be engineered to facilitate the recruitment of MSCs. In this study, we explore the ability of these implants to direct the recruitment and the differentiation of MSCs in the setting of a bone defect. We initially determined that both stromal derived factor-1alpha (SDF-1α) and erythropoietin (Epo) prompted different degrees of MSC recruitment. Additionally, we found that Epo and bone morphogenetic protein-2 (BMP-2), but not SDF-1α, triggered the osteogenic differentiation of MSCs in vitro. We then investigated the possibility of directing autologous MSC-mediated bone regeneration using a murine calvaria model. Consistent with our in vitro observations, Epo-releasing scaffolds were found to be more potent in bridging the defect than BMP-2 loaded scaffolds, as determined by computed tomography (CT) scanning, fluorescent imaging and histological analyses. These results demonstrate the tremendous potential, directing the recruitment and differentiation of autologous MSCs has in the field of tissue regeneration.

  11. Maintenance rituximab after autologous stem cell transplantation in patients with mantle cell lymphoma.

    PubMed

    Graf, S A; Stevenson, P A; Holmberg, L A; Till, B G; Press, O W; Chauncey, T R; Smith, S D; Philip, M; Orozco, J J; Shustov, A R; Green, D J; Libby, E N; Bensinger, W I; Pagel, J M; Maloney, D G; Zhou, Y; Cassaday, R D; Gopal, A K

    2015-11-01

    High-dose therapy and autologous stem cell transplantation (ASCT) improves outcomes for patients with mantle cell lymphoma (MCL), but relapse ultimately occurs in most patients. Recently presented interim results from a phase III prospective trial suggest maintenance rituximab (MR) after ASCT for MCL improves progression-free survival (PFS). The maturation of these data and any benefit of MR on overall survival (OS) remain to be defined. In this retrospective study, we examined a cohort of consecutive patients with MCL that underwent ASCT for MCL at our center and evaluated their outcomes according to whether they received MR after ASCT (n = 50) or did not (n = 107). MR was treated as a time-dependent covariate to account for variation in timing of its initiation. MR was associated with an improved PFS [hazard ratio (HR) 0.44; confidence interval (CI) (0.24-0.80), P = 0.007] and overall survival (OS; HR 0.46; CI 0.23-0.93, P = 0.03) following a multivariate adjustment for confounding factors with a median follow-up of ∼5 years. Grade 4 neutropenia was increased (34% versus 18%, P = 0.04) in the MR group, but no effect on the rate of mortality unrelated to relapse was observed. These data support that MR after ASCT for MCL confers a benefit in PFS and additionally suggest it may improve OS. General application of this strategy will require confirmation of benefit in prospective randomized trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  12. Thalidomide maintenance following high-dose melphalan with autologous stem cell support in myeloma

    PubMed Central

    Chang, Julie E.; Juckett, Mark B.; Callander, Natalie S.; Kahl, Brad S.; Gangnon, Ronald E.; Mitchell, Teri L.; Longo, Walter L.

    2010-01-01

    Background Recent experience with thalidomide maintenance after high-dose chemotherapy with autologous stem cell support has demonstrated improvement in progression-free and overall survival. We further explored the tolerability and efficacy of lower doses of maintenance thalidomide in this single institution study. Patients and Methods Thirty-eight myeloma patients were enrolled and treated with melphalan 200 mg/m2 followed by autologous stem cell transplant. Thalidomide 50 mg/day was started on day ≥60 after recovery of blood counts and escalated to a maximum dose of 200 mg/day. Responses were assessed at 2 months, 1 year, and 2 years post-transplant. Results Of the 38 enrolled patients, 7 patients never received thalidomide. Among 31 patients receiving thalidomide, complete or very good partial responses were observed in 65% and 42% of patients at 1 and 2 years, respectively. Tolerability was a major issue, with only 17 patients completing 1 year of thalidomide. The goal dosing of 200 mg/day was achieved in just 17/31 patients, and the median tolerated thalidomide dose was 100 mg/day. Sensory neuropathy was the primary reason for dose modification and discontinuation. No thromboembolic events were observed. Median progression-free survival was 20.8 months and the median overall survival was more than 60 months. Conclusion Thalidomide maintenance at a goal dose of 200 mg/day was not feasible in this population, with our data suggesting that 100 mg/day is a more reasonable maintenance dose. PMID:18650178

  13. The financial requirements and time commitments of caregivers for autologous stem cell transplant recipients.

    PubMed

    Meehan, Kenneth R; Fitzmaurice, Thomas; Root, Lynn; Kimtis, Elizabeth; Patchett, Linda; Hill, John

    2006-04-01

    This study is a prospective evaluation of the time commitment and financial requirements of caregivers of autologous stem cell recipients during the period of inpatient hospitalization. Eligible patients identified one caregiver, and a one-page survey addressing the necessary time commitment and out-of-pocket expenses was completed by the caregiver at each visit. The caregivers of 40 patients participated (non-Hodgkin's lymphoma [n = 19], multiple myeloma [n = 18], Hodgkin's lymphoma [n = 2], or acute myelogenous leukemia [n = 1]). Caregivers included spouses (n = 35), partners/friends (n = 2), or family members (n = 3). Results were summarized for the patient's total length of stay. Each caregiver traveled a median of 829 miles over 17.8 hours. Out-of-pocket expenses varied greatly depending on whether a caregiver stayed in local accommodations (cohort 1; n = 11) or in the patient's hospital room (cohort 2; n = 29). Total expenses (median) for each caregiver in cohort 1 were dollar 849.35, including accommodations (dollar 560), gasoline (dollar 87.35), and food (dollar 202). Total expenses (median) for each caregiver in cohort 2 were dollar 181.15, including gasoline (dollar 70) and food (dollar 111.15). Each caregiver in cohort 1 lost a median of 43.5 hours of work compared with 8 hours for each caregiver in cohort 2. The results from this prospective study demonstrate that there is a significant financial and time requirement on the part of the caregiver when a family member or significant other is hospitalized for an autologous stem cell transplant.

  14. Autologous stem cell transplantation for the treatment of neuroblastoma in Korea.

    PubMed Central

    Ryu, Kyung Ha; Ahn, Hyo Seop; Koo, Hong Hoe; Kook, Hoon; Kim, Moon Kyu; Kim, Hack Ki; Ghim, Thad; Moon, Hyung Nam; Seo, Jong Jin; Sung, Ki Woong; Shin, Hee Young; Yoo, Eun Sun; Lyu, Chuhl Joo; Lee, Young Ho; Lee, Hahng; Cho, Bin; Cho, Hyun Sang; Choi, Hyung Soo; Hah, Jeong Ok; Hwang, Tai Ju

    2003-01-01

    Autologous stem cell transplantation (ASCT) for the treatment of high-risk neuroblastoma (NBL) is an accepted method for restoring bone marrow depression after high dose chemotherapy. We retrospectively analyzed eighty eight cases of NBL that underwent ASCT following marrow ablative therapy at 12 transplant centers of the Korean Society of Pediatric Hematology-Oncology between January 1996 and September 2000. Seventy nine children were of stage IV NBL and 9 were of stage III with N-myc amplification. Various cytoreductive regimens were used. However, the main regimen was 'CEM' consisting of carboplatin, etoposide and melphalan, and this was used in 66 patients. Total body irradiation was also added in 36 patients for myeloablation. To reduce tumor cell contamination, stem cell infusions after CD34+ cell selection were performed in 16 patients. Post-transplantation therapies included the second transplantation in 18 patients, interleukin2 therapy in 45, 13-cis retinoic acid in 40, 131-meta-iodobenzylguanidine in 4, conventional chemotherapy in 11, and local radiotherapy in 8. Twenty two patients died, sixty six patients are surviving 1 to 46 months after ASCT (median followup duration, 14.5 months). Although the follow-up period was short and the number of patients small, we believe that ASCT might improve the survival rate in high-risk NBL. PMID:12692423

  15. Poor peripheral blood stem cell mobilization affects long-term outcomes in multiple myeloma patients undergoing autologous stem cell transplantation.

    PubMed

    Moreb, Jan S; Byrne, Michael; Shugarman, Ilicia; Zou, Fei; Xiong, Sican; May, William S; Norkin, Maxim; Hiemenz, John; Brown, Randall; Cogle, Christopher; Wingard, John R; Hsu, Jack W

    2017-05-29

    Peripheral blood stem cell (PBSC) mobilization is routinely undertaken prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). A number of studies have identified risk factors for poor PBSC mobilization, however, little data exists to correlate mobilization with disease-specific outcomes in this patient population. Prospective work in MM has demonstrated similar outcomes in a homogenous patient population. In this single institution analysis, we retrospectively studied the impact of poor PBSC mobilization on progression free survival (PFS) and OS in MM patients undergoing PBSC mobilization. Poor mobilizers are defined as patients that collected < 4 × 10(6) CD34(+) cells/kg over maximum of 5 apheresis days, or those that required ≥2 mobilization cycles to achieve this target. We confirm that poor PBSC mobilization is significantly associated with a shortened PFS (P = .0012) and OS (P = .0005) compared with good mobilizers. Our univariate analysis also shows that independent risk factors for poor mobilization include male gender, higher ideal body weight, and a greater median number of lines of chemotherapy prior to PBSC mobilization. However, by multivariate analysis, only number of prior lines of chemotherapy remains significantly predictive of poor mobilization (Odds ratio 1.857, P = .0095). The use of high-dose G-CSF (> 10 mcg/kg/day) and/or plerixafor can significantly improve mobilization and ASCT chances in this population. These data indicate that poor mobilization can be predictable and is associated with more aggressive disease biology and worse outcomes, warranting intensive post-ASCT management. © 2017 Wiley Periodicals, Inc.

  16. High-dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with multiple myeloma and renal insufficiency.

    PubMed

    Ballester, O F; Tummala, R; Janssen, W E; Fields, K K; Hiemenz, J W; Goldstein, S C; Perkins, J B; Sullivan, D M; Rosen, R; Sackstein, R; Zorsky, P; Saez, R; Elfenbein, G J

    1997-10-01

    Six patients with multiple myeloma and chronic renal insufficiency (serum creatinine >3.0 mg/dl), including four on dialysis, received high-dose busulfan and cyclophosphamide (BUCY) followed by autologous peripheral stem cell transplantation. Peripheral blood stem cells were collected after priming with cyclophosphamide, etoposide and G-CSF. Patterns of engraftment and toxicities were not apparently different from those seen in myeloma patients with normal renal function. There was one toxicity-related death, resulting from a massive spontaneous subdural hematoma. One patient died of disease progression 6 months after transplant, while the remaining four patients are alive and free of myeloma progression 6 to 39 months after high-dose therapy. Two of these patients have remained in complete remission for 28 and 39 months. Our experience suggests that high-dose therapy with BUCY and autologous peripheral blood stem cell rescue is feasible in patients with multiple myeloma and renal failure.

  17. Autologous stem cell transplantation for a monoclonal gammopathy of undetermined significance mimicking amyotrophic lateral sclerosis: A case report

    PubMed Central

    XIE, LINNA; ZHOU, FANG

    2014-01-01

    It is rare for patients with monoclonal gammopathy of undetermined significance (MGUS) to present with clinical features of fatal motor neuron disease, for example amyotrophic lateral sclerosis (ALS). There is no standard and effective therapy for either MGUS or ALS. In addition, stem cell transplantation appears to be ineffective for the treatment of this disease. In the present study, a 47-year old female with MGUS that mimicked ALS is presented. The M-protein levels of the patient were normalized following two cycles of chemotherapy and autologous stem cell transplantation treatment. MGUS was found to be alleviated and the symptoms of ALS did not deteriorate. The results showed a positive therapeutic effect of autologous stem cell transplantation for MGUS. PMID:25120635

  18. Combined transplantation of autologous hematopoietic stem cells and allogenic mesenchymal stem cells increases T regulatory cells in systemic lupus erythematosus with refractory lupus nephritis and leukopenia.

    PubMed

    Wang, Q; Qian, S; Li, J; Che, N; Gu, L; Wang, Q; Liu, Y; Mei, H

    2015-10-01

    Autologous hematopoietic stem cell (HSC) and mesenchymal stem cell (MSC) transplantation is currently being evaluated as a novel treatment for autoimmune diseases, such as systemic lupus erythematosus (SLE). Here we report a case of autologous HSC transplantation combined with MSCs in a 25-year-old severe SLE patient with multiple life-threatening complications and refractory to conventional cyclophosphamide (CYC) therapy. After being pretreated with CYC, fludarabine and antithymocyte globulin, the patient was transplanted with autologous CD34+HSCs and MSCs by intravenous infusion. Hematopoietic regeneration was observed on day 12 thereafter. After HSC and MSC transplantation, the patient's clinical symptoms caused by SLE were remitted, and the SLEDAI score decreased. Moreover, CD4+CD25+FoxP3+Treg cells increased in peripheral blood mononuclear cells (PBMCs) after transplantation. This result suggests that the combined transplantation of HSCs and MSCs may reset the adaptive immune system to re-establish self-tolerance in SLE. A 36-month follow-up showed that the clinical symptoms remained in remission. Although a longer follow-up is required for assessing the long-term efficacy, our present results suggest that the combined transplantation of HSCs and MSCs may be a novel and effective therapy for refractory SLE. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  19. Beneficial Effects of Autologous Bone Marrow-Derived Mesenchymal Stem Cells in Naturally Occurring Tendinopathy

    PubMed Central

    Smith, Roger Kenneth Whealands; Werling, Natalie Jayne; Dakin, Stephanie Georgina; Alam, Rafiqul; Goodship, Allen E.; Dudhia, Jayesh

    2013-01-01

    Tendon injuries are a common age-related degenerative condition where current treatment strategies fail to restore functionality and normal quality of life. This disease also occurs naturally in horses, with many similarities to human tendinopathy making it an ideal large animal model for human disease. Regenerative approaches are increasingly used to improve outcome involving mesenchymal stem cells (MSCs), supported by clinical data where injection of autologous bone marrow derived MSCs (BM-MSCs) suspended in marrow supernatant into injured tendons has halved the re-injury rate in racehorses. We hypothesized that stem cell therapy induces a matrix more closely resembling normal tendon than the fibrous scar tissue formed by natural repair. Twelve horses with career-ending naturally-occurring superficial digital flexor tendon injury were allocated randomly to treatment and control groups. 1X107 autologous BM-MSCs suspended in 2 ml of marrow supernatant were implanted into the damaged tendon of the treated group. The control group received the same volume of saline. Following a 6 month exercise programme horses were euthanized and tendons assessed for structural stiffness by non-destructive mechanical testing and for morphological and molecular composition. BM-MSC treated tendons exhibited statistically significant improvements in key parameters compared to saline-injected control tendons towards that of normal tendons and those in the contralateral limbs. Specifically, treated tendons had lower structural stiffness (p<0.05) although no significant difference in calculated modulus of elasticity, lower (improved) histological scoring of organisation (p<0.003) and crimp pattern (p<0.05), lower cellularity (p<0.007), DNA content (p<0.05), vascularity (p<0.03), water content (p<0.05), GAG content (p<0.05), and MMP-13 activity (p<0.02). Treatment with autologous MSCs in marrow supernatant therefore provides significant benefits compared to untreated tendon repair in

  20. Selective purging of human multiple myeloma cells from autologous stem cell transplant grafts using oncolytic myxoma virus

    PubMed Central

    Bartee, Eric; Chan, Winnie S.; Moreb, Jan S.; Cogle, Christopher R.; McFadden, Grant

    2012-01-01

    Autologous stem cell transplantation (ASCT) and novel therapies have improved overall survival of patients with multiple myeloma; however, most patients relapse and eventually succumb to their disease. Evidence indicates that residual cancer cells contaminate autologous grafts and may contribute to early relapses after ASCT. Here, we demonstrate that ex vivo treatment with an oncolytic poxvirus called myxoma virus results in specific elimination of human myeloma cells by inducing rapid cellular apoptosis while fully sparing normal hematopoietic stem and progenitor cells (HSPCs). The specificity of this elimination is based on strong binding of the virus to myeloma cells coupled with an inability of the virus to bind or infect CD34+ HSPCs. These two features allow myxoma to readily identify and distinguish even low levels of myeloma cells in complex mixtures. This ex vivo MYXV treatment also effectively inhibits systemic in vivo engraftment of human myeloma cells into immunodeficient mice and results in efficient elimination of primary CD138+ myeloma cells contaminating patient hematopoietic cell products. We conclude that ex vivo myxoma treatment represents a safe and effective method to selectively eliminate myeloma cells from hematopoietic autografts prior to reinfusion. PMID:22516053

  1. Autologous peripheral blood stem cell harvest: Collection efficiency and factors affecting it

    PubMed Central

    Tiwari, Aseem K.; Pandey, Prashant; Subbaraman, Harini; Bhargava, Rahul; Rawat, Ganesh; Madiraju, Shivani; Raina, Vimarsh; Bhargava, Richa

    2016-01-01

    Background: Harvest of hematopoietic progenitor cells via leukapheresis is being used increasingly for transplants in India. Adequate yield of cells per kilogram body weight of recipient is required for successful engraftment. Collection efficiency (CE) is an objective quality parameter used to assess the quality of leukapheresis program. In this study, we calculated the CE of the ComTec cell separator (Fresenius Kabi, Germany) using two different formulae (CE1 and CE2) and analyzed various patient and procedural factors, which may affect it. Materials and Methods: One hundred and one consecutive procedures in 77 autologous donors carried out over 3 years period were retrospectively reviewed. Various characteristics like gender, age, weight, disease status, hematocrit, preprocedure total leukocyte count, preprocedure CD34 positive (CD34+) cells count, preprocedure absolute CD34+ cell count and processed apheresis volume effect on CE were compared. CE for each procedure was calculated using two different formulae, and results were compared using statistical correlation and regression analysis. Results: The mean CE1 and CE2 was 41.2 and 49.1, respectively. CE2 appeared to be more accurate indicator of overall CE as it considered the impact of continued mobilization of stem cells during apheresis procedure, itself. Of all the factors affecting CE, preprocedure absolute CD34+ was the only independent factor affecting CE. Conclusion: The only factor affecting CE was preprocedure absolute CD34+ cells. Though the mean CE2 was higher than CE1, it was not statistically significant. PMID:27011680

  2. Stem/precursor cell-based CNS therapy: the importance of circumventing immune suppression by transplanting autologous cells.

    PubMed

    Kulbatski, Iris

    2010-09-01

    Stem/precursor cell (SPC) therapy for neurodegeneration and neurotrauma has enormous therapeutic potential, but despite ongoing research efforts the success of clinical trials remains limited. Therapies that utilize immune suppression in combination with SPC transplantation have thus far failed to consider the beneficial role of the immune system in central nervous system (CNS) recovery. Systemic immune suppression may prevent neural repair, and in some cases exacerbate the underlying disorder. Until about a decade ago, immunosuppression for CNS disorders was viewed as a therapeutic target, based on the perception that all immune activity in the CNS was destructive. However, recent studies show that the infiltration of blood-borne immune cells into the CNS following neurotrauma and during chronic neurodegeneration promote CNS protection and regeneration. In the context of SPC therapies, although immune suppression prevents rejection of non-autologous cell grafts, it also prevents the restorative immune response by eliminating the immune mediated guidance cues that are required for SPCs to migrate to the location they are needed, and preventing SPC-mediated immunomodulation. This article argues in favor of transplanting autologous SPCs, particularly bone marrow derived cells. The therapeutic use of autologous SPCs for neural repair circumvents the need for concomitant immune suppression, exploits the immunomodulatory capacity of these cells, and maintains the immune niche that supports neural repair and is required to guide these cells to their appropriate locations. Overall, such an approach accommodates the requirements for translational therapeutics, and provides a standardized platform for reconciling the inherent controversies in the science.

  3. Total Marrow Irradiation as Part of Autologous Stem Cell Transplantation for Asian Patients with Multiple Myeloma

    PubMed Central

    Lin, Shih-Chiang; Hsieh, Pei-Ying; Shueng, Pei-Wei; Tien, Hui-Ju; Wang, Li-Ying

    2013-01-01

    To compare the outcomes of melphalan 200 mg/m2 (HDM200) and 8 Gy total marrow irradiation (TMI) delivered by helical tomotherapy plus melphalan 140 mg/m2 (HDM140 + TMI 8 Gy) in newly diagnosed symptomatic multiple myeloma (MM) Asian patients. Between 2007 and 2010, nine consecutive myeloma patients who were scheduled to undergo autologous stem cell transplantation (ASCT) were studied. The patients received three cycles of vincristine-adriamycin-dexamethasone (VAD) regimen as induction chemotherapy, and if they had a partial response, peripheral blood stem cells were collected by dexamethasone-etoposide-cyclophosphamide-cisplatin (DECP). In arm A, six patients received the HDM200. In arm B, three patients received HDM140 + TMI 8 Gy. In arm B, the neutropenic duration was slightly longer than in arm A (P = 0.048). However, hematologic recovery (except for neutrophils), transfusion requirement, median duration of hospitalization, and the dose of G-CSF were similar in both arms. The median duration of overall survival and event-free survival was similar in the two arms (P = 0.387). As a conditioning regiment, HDM140 + TMI 8 Gy provide another chance for MM Asian patients who were not feasible for HDM200. PMID:24089671

  4. 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.

  5. Importance of mesenchymal stem cells in autologous fat grafting: a systematic review of existing studies.

    PubMed

    Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter Viktor; Elberg, Jens Jørgen; Fischer-Nielsen, Anne; Drzewiecki, Krzysztof Tadeusz

    2012-04-01

    Autologous fat grafting (lipofilling) enables repair and augmentation of soft tissues and is increasingly used both in aesthetic and reconstructive surgery. Autologous fat has several advantages, including biocompatibility, versatility, natural appearance, and low donor site morbidity. The main limitation is unpredictable graft resorption, which ranges from 25%-80%, probably as a result of ischaemia and lack of neoangiogenesis. To obviate these disadvantages, several studies have searched for new ways of increasing the viability of the transplanted tissue. One promising approach has been to enrich the fat graft with adipose tissue-derived mesenchymal stem cells (ASC) before transplantation. We have reviewed original studies published on fat transplantation enriched with ASC. We found four murine and three human studies that investigated the subject after a sensitive search of publications. In the human studies, so-called cell assisted lipotransfer (CAL) increased the ASC concentration 2-5 times compared with non-manipulated fat grafts, which caused a questionable improvement in survival of fat grafts, compared with that of traditional lipofilling. In contrast, in two of the murine studies ASC-concentrations were increased 1250 and 6250 times, respectively, by ASC ex vivo expansion, which resulted in considerably improved fat transplant survival as well as quality. This effect of high-level enrichment with ASC is thought to have been caused by paracrine signalling, cellular differentiation, or both. The surgical and tissue handling techniques used in lipofilling are well proved, but the added effect of high-level enrichment with ex vivo expanded ASC still needs to be investigated properly in human lipofilling studies, combined with a thorough follow up and matched control groups. In conclusion, ASC-enriched lipofilling theoretically has the potential for transforming lipofilling from a relatively unpredictable intervention into one in which the resorption rate

  6. Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia.

    PubMed

    Reeves, Daniel B; Peterson, Christopher W; Kiem, Hans-Peter; Schiffer, Joshua T

    2017-07-01

    Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient.IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the "Berlin patient" remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact

  7. Autologous, allogeneic, induced pluripotent stem cell or a combination stem cell therapy? Where are we headed in cartilage repair and why: a concise review.

    PubMed

    Vonk, Lucienne A; de Windt, Tommy S; Slaper-Cortenbach, Ineke C M; Saris, Daniël B F

    2015-05-15

    The evolution of articular cartilage repair procedures has resulted in a variety of cell-based therapies that use both autologous and allogeneic mesenchymal stromal cells (MSCs). As these cells are increasingly available and show promising results both in vitro and in vivo, cell-based strategies, which aim to improve ease of use and cost-effectiveness, are progressively explored. The use of MSCs in cartilage repair makes it possible to develop single-stage cell-based therapies. However, true single-stage procedures rely on one intervention, which will limit cell sources to fraction concentrates containing autologous MSCs or culture-expanded allogeneic MSCs. So far, it seems both autologous and allogeneic cells can safely be applied, but clinical studies are still ongoing and little information on clinical outcome is available. Further development of cell-based therapies may lead to clinical-grade, standardized, off-the-shelf products with easy handling for orthopedic surgeons. Although as of yet no preclinical or clinical studies are ongoing which explore the use of induced pluripotent stem cells for cartilage repair, a good manufacturing practice-grade induced pluripotent stem cell line might become the basis for such a product in the future, providing that cell fate can be controlled. The use of stem cells in clinical trials brings along new ethical issues, such as proper controls and selecting primary outcome measures. More clinical trials are needed to estimate detailed risk-benefit ratios and trials must be carefully designed to minimize risks and burdens for patients while choosing outcome measures that allow for adequate comparison with results from similar trials. In this review, we discuss the different aspects of new stem cell-based treatments, including safety and ethical issues, as well as provide an overview of current clinical trials exploring these approaches and future perspectives.

  8. The Mutual Interactions between Mesenchymal Stem Cells and Myoblasts in an Autologous Co-Culture Model

    PubMed Central

    Szczepanska, Izabela; Zarychta-Wisniewska, Weronika; Pajak, Beata; Bojarczuk, Kamil; Dybowski, Bartosz; Paczek, Leszek

    2016-01-01

    Both myoblasts and mesenchymal stem cells (MSC) take part in the muscle tissue regeneration and have been used as experimental cellular therapy in muscular disorders treatment. It is possible that co-transplantation approach could improve the efficacy of this treatment. However, the relations between those two cell types are not clearly defined. The aim of this study was to determine the reciprocal interactions between myoblasts and MSC in vitro in terms of the features important for the muscle regeneration process. Primary caprine muscle-derived cells (MDC) and bone marrow-derived MSC were analysed in autologous settings. We found that MSC contribute to myotubes formation by fusion with MDC when co-cultured directly, but do not acquire myogenic phenotype if exposed to MDC-derived soluble factors only. Experiments with exposure to hydrogen peroxide showed that MSC are significantly more resistant to oxidative stress than MDC, but a direct co-culture with MSC does not diminish the cytotoxic effect of H2O2 on MDC. Cell migration assay demonstrated that MSC possess significantly greater migration ability than MDC which is further enhanced by MDC-derived soluble factors, whereas the opposite effect was not found. MSC-derived soluble factors significantly enhanced the proliferation of MDC, whereas MDC inhibited the division rate of MSC. To conclude, presented results suggest that myogenic precursors and MSC support each other during muscle regeneration and therefore myoblasts-MSC co-transplantation could be an attractive approach in the treatment of muscular disorders. PMID:27551730

  9. Plerixafor for mobilization of blood stem cells in autologous transplantation: an update.

    PubMed

    Jantunen, Esa; Varmavuo, Ville

    2014-06-01

    About 99% of all autologous transplants are now performed with blood stem cells. G-CSF alone or combined with chemotherapy have been used to mobilize CD34(+) cells. Plerixafor is a novel drug used for mobilization purposes. We have evaluated recent data in regard to plerixafor use in predicted or proven poor mobilizers. In addition, we have looked for preemptive strategies to optimize the use of this expensive drug. Also cost-efficacy issues and effects of plerixafor on graft composition and post-transplant outcomes will be discussed. Plerixafor added to G-CSF is superior than G-CSF alone for mobilization of CD34(+) cells. This combination is also efficient in patients who have failed a previous mobilization attempt with other methods or in patients with risk factors for poor mobilization. Addition of plerixafor to G-CSF or chemotherapy plus G-CSF mobilization in patients who appear to mobilize poorly is under active investigation and algorithms for a preemptive use of this expensive agent have been proposed. Grafts collected after plerixafor appear to contain more lymphoid cells than the grafts collected without it. Whether this affects post-transplant outcomes such as immune reconstitution and risk of relapse needs to be evaluated.

  10. Administration of Autologous Bone Marrow-Derived Stem Cells for Treatment of Cerebral Palsy Patients: A Proof of Concept.

    PubMed

    Bansal, Himanshu; Singh, Lipi; Verma, Poonam; Agrawal, Anupama; Leon, Jerry; Sundell, I Birgitta; Koka, Prasad S

    Stem cell therapy is a promising treatment for cerebral palsy, which refers to a category of brain diseases that are associated with chronic motor disability in children. Autologous bone marrow stem cells may be a better cell source and have been studied for the treatment of cerebral palsy because of their functions in tissue repair and the regulation of immunological processes. To assess autologous marrow stem cells as a novel treatment for patients with moderate-to-severe cerebral palsy, a total of 10 cerebral palsy patients were enrolled in this clinical study with 24 months follow-up. A total of 10 cerebral palsy patients received autologous bone marrow cells transplantation (4.5 × 10(8) mononuclear cells; 90% viability) into the subarachnoid cavity and rehabilitation. We recorded the gross motor function measurement scores, manual ability function measurement score, and adverse events up to 24 months post-treatment. The gross motor function measurement scores were significantly higher at month 6 post-treatment compared with the baseline scores and were stable up to 24 months follow-up. The increase in manual ability and communication function measurement scores at 6 months were not significant when compared to the baseline score. All the 10 patients survived and none of the patients experienced any serious adverse events or complications. Our results indicated that bone marrow derived MNCs are safe and effective for the treatment of motor deficits related to cerebral palsy. Further randomized clinical trials are necessary to establish the efficacy of this procedure.

  11. Stem cell mobilization and autologous stem cell transplantation after pretreatment with bendamustine, prednisone and bortezomib (BPV) in newly diagnosed multiple myeloma.

    PubMed

    Poenisch, Wolfram; Plötze, Madlen; Holzvogt, Bruno; Andrea, Marc; Schliwa, Thomas; Zehrfeld, Thomas; Hammerschmidt, Doreen; Schwarz, Maik; Edelmann, Thomas; Becker, Cornelia; Hoffmann, Franz Albert; Schwarzer, Andreas; Kreibich, Ute; Gutsche, Kerstin; Reifenrath, Kolja; Schwarzbach, Heidrun; Heyn, Simone; Franke, Georg-Nikolaus; Jentzsch, Madlen; Leiblein, Sabine; Schwind, Sebastian; Lange, Thoralf; Vucinic, Vladan; AlAli, Haifa-Katrin; Niederwieser, Dietger

    2015-11-01

    Reliable information on stem cell toxicity and mobilization of stem cells for autologous stem cell transplantation (SCT) after induction treatment with a combination of bendamustine, prednisone and bortezomib (BPV) is missing. A retrospective analysis of peripheral blood stem cell mobilization and autologous SCT was performed in 35 patients with MM who had received at least one cycle of a BPV-induction therapy consisting of bendamustine 60 mg/m(2) on days 1 and 2, bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11 and prednisone 100 mg on days 1, 2, 4, 8 and 11 between October 2008 and May 2014. The mobilization regimen consisted of cyclophosphamide 4 g/m(2) and G-CSF (2 × 5 μg/kg). Apheresis was started as soon as peripheral CD34(+) counts exceeded 20 × 10(6)/L with a harvest target of 8 × 10(6) CD34(+)/kg. The minimal accepted target was 2 × 10(6) CD34(+)/kg. The transplantation conditioning therapy consisted of melphalan 200 mg/m(2). A median number of two (range 1-5) BPV cycles were given. The majority of patients (n = 31, 89 %) responded with two sCR, five nCR, 11 VGPR and 13 PR after BPV induction. Three patients had MR, and one SD. Stem cell mobilization and harvest were successful in all patients. In 19 of 35 patients (54 %), a single apheresis was sufficient to reach the target. The median number of aphereses was one (range 1-4), and the median CD34(+) cell-count/kg was 13.5 (range 3.2-33.1)  × 106. All patients received an autologous SCT. Engraftment was successful in 34 of 35 patients. The median time to a leukocyte count >l × 10(9)/L was 11 days, and the time to untransfused platelet count of >50 × 10(9)/L was 13 days. Thirty-four patients (97 %) responded after the autologous SCT with 11 sCR, two CR, seven nCR, seven VGPR and seven PR. The progression-free survival at 18 months was 87 %, and overall survival was 92 %. Stem cell mobilization and autologous SCT are feasible in MM patients who have received BPV

  12. Autologous stem cell transplantation aids autoimmune patients by functional renewal and TCR diversification of regulatory T cells.

    PubMed

    Delemarre, Eveline M; van den Broek, Theo; Mijnheer, Gerdien; Meerding, Jenny; Wehrens, Ellen J; Olek, Sven; Boes, Marianne; van Herwijnen, Martijn J C; Broere, Femke; van Royen, Annet; Wulffraat, Nico M; Prakken, Berent J; Spierings, Eric; van Wijk, Femke

    2016-01-07

    Autologous hematopoietic stem cell transplantation (HSCT) is increasingly considered for patients with severe autoimmune diseases whose prognosis is poor with standard treatments. Regulatory T cells (Tregs) are thought to be important for disease remission after HSCT. However, eliciting the role of donor and host Tregs in autologous HSCT is not possible in humans due to the autologous nature of the intervention. Therefore, we investigated their role during immune reconstitution and re-establishment of immune tolerance and their therapeutic potential following congenic bone marrow transplantation (BMT) in a proteoglycan-induced arthritis (PGIA) mouse model. In addition, we determined Treg T-cell receptor (TCR) CDR3 diversity before and after HSCT in patients with juvenile idiopathic arthritis and juvenile dermatomyositis. In the PGIA BMT model, after an initial predominance of host Tregs, graft-derived Tregs started dominating and displayed a more stable phenotype with better suppressive capacity. Patient samples revealed a striking lack of diversity of the Treg repertoire before HSCT. This ameliorated after HSCT, confirming reset of the Treg compartment following HSCT. In the mouse model, a therapeutic approach was initiated by infusing extra Foxp3(GFP+) Tregs during BMT. Infusion of Foxp3(GFP+) Tregs did not elicit additional clinical improvement but conversely delayed reconstitution of the graft-derived T-cell compartment. These data indicate that HSCT-mediated amelioration of autoimmune disease involves renewal of the Treg pool. In addition, infusion of extra Tregs during BMT results in a delayed reconstitution of T-cell compartments. Therefore, Treg therapy may hamper development of long-term tolerance and should be approached with caution in the clinical autologous setting. © 2016 by The American Society of Hematology.

  13. Current Role of Autologous and Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma

    PubMed Central

    Castagna, Luca; Carlo-Stella, Carmelo; Mazza, Rita; Santoro, Armando

    2015-01-01

    Classical Hodgkin lymphoma (cHL) is a relatively rare disease, with approximately 9,200 estimated new cases and 1,200 estimated deaths per year in the United States. First-line chemo-radiotherapy leads to cure rates approaching 80% in patients with advanced-stage disease. However, 25 to 30% of these patients are not cured with chemotherapy alone (i.e., the ABVD regimen) and show either primary refractoriness to chemotherapy, early disease relapse or late disease relapse. Second-line salvage high-dose chemotherapy (HDC) and autologous stem cell transplantation (SCT) have an established role in the management of refractory/relapsed cHL, leading to durable responses in approximately 50% of relapsed patients and a minority of refractory patients. However, due to the poor responses to second-line salvage chemotherapy and dismal long-term disease control of primary refractory and early relapsed patients, their treatment represents an unmet medical need. Allogeneic SCT represents, by far, the only strategy with a curative potential for these patients; however, as discussed in this review, it’s role in cHL remains controversial. Despite a general consensus that early relapsed and primary refractory patients represent a clinical challenge requiring effective treatments to achieve long-term disease control, there has been no consensus on the optimal therapy that should be offered to these patients. This review will briefly discuss the clinical results and the main issues regarding autologous SCT as well as the current role of allogeneic SCT. PMID:25745542

  14. Intravenous autologous bone marrow mononuclear stem cell therapy for ischemic stroke: a multicentric, randomized trial.

    PubMed

    Prasad, Kameshwar; Sharma, Alka; Garg, Ajay; Mohanty, Sujata; Bhatnagar, Shinjini; Johri, Sharat; Singh, Kunwar Karni; Nair, Velu; Sarkar, Ravi Shankar; Gorthi, Sankar Prasad; Hassan, Kaukab Maqbool; Prabhakar, Sudesh; Marwaha, Neelam; Khandelwal, Niranjan; Misra, Usha Kant; Kalita, Jayantee; Nityanand, Soniya

    2014-12-01

    Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells (BMSCs) in stroke. We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke. This was a phase II, multicenter, parallel group, randomized trial with blinded outcome assessment that included 120 patients. Patients with subacute ischemic stroke were randomly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm. Coprimary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180. Secondary outcomes were change in infarct volume, National Institute of Health Stroke Scale (NIHSS) at day 90 and 180. Main safety outcomes were adverse events, any new area of (18)fluorodeoxyglucose positron emission tomography uptake in any body part over 365 days. Fifty-eight patients received a mean of 280.75 million BMSCs at median of 18.5 days after stroke onset. There was no significant difference between BMSCs arm and control arm in the Barthel Index score (63.1 versus 63.6; P=0.92), modified Rankin scale shift analysis (P=0.53) or score >3 (47.5% versus 49.2%; P=0.85), NIHSS score (6.3 versus 7.0; P=0.53), change in infarct volume (-11.1 versus -7.36; P=0.63) at day 180. Adverse events were also similar in the 2 arms, and no patient showed any new area of (18)fluorodeoxyglucose uptake. With the methods used, results of this hitherto first randomized controlled trial indicate that intravenous infusion of BMSCs is safe, but there is no beneficial effect of treatment on stroke outcome. URLs: http://ctri.nic.in/Clinicaltrials and http://www.clinicaltrials.gov. Unique identifiers: CTRI-ROVCTRI/2008/091/0004 and NCT0150177. © 2014 American Heart Association, Inc.

  15. Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells into the Testes of Infertile Male Rats and New Germ Cell Formation

    PubMed Central

    Ghasemzadeh-Hasankolaei, Mohammad; Batavani, Roozali; Eslaminejad, Mohamadreza Baghaban; Sayahpour, Foroughazam

    2016-01-01

    Background Mesenchymal stem cells (MSCs), have been suggested as a potential choice for treatment of male infertility. Yet, the effects of MSCs on regeneration of germinal epithelium of seminiferous tubules and recovery of spermatogenesis have remained controversial. In this research, we have evaluated and compared the fate of autologous bone marrow (BM)-MSCs during three different periods of time- 4, 6 and 8 weeks after transplantation into the testes of busulfan-induced infertile male rats. Methods Rats BM samples were collected from tibia bone under anesthesia. The samples were directly cultured in culture medium. Isolated, characterized and purified BM-MSCs were labeled with PKH26, and transplanted into the testes of infertile rats. After 4, 6 and 8 weeks, the testes were removed and underwent histological evaluations. Results Immunohistochemical analysis showed that transplanted BM-MSCs survived in all three groups. Some of the cells homed at the germinal epithelium and expressed spermatogonia markers (Dazl and Stella). The number of homed spermatogonia-like cells in 4-week testes, was more than the 6-week testes. The 8-week testes had the least numbers of homed cells (p<0.05). Immunostaining for vimentin showed that BM-MSCs did not differentiate into the sertoli cells in the testes. Conclusions From our results, it could be concluded that, autologous BM-MSCs could survive in the testis, migrate onto the seminiferous tubules basement membrane and differentiate into spermatogonia. Although, no more differentiation was observed in the produced spermatogonia, generation of such endogenous GCs would be a really promising achievement for treatment of male infertility using autologous stem cells. PMID:27430978

  16. Treatment of Recurrent Posttransplant Lymphoproliferative Disorder with Autologous Blood Stem Cell Transplant

    PubMed Central

    Malhotra, Bharat; Rahal, Ahmad K.; Farhoud, Hussam; Moore, Dennis F.; Kallail, K. James

    2015-01-01

    Background. Posttransplant lymphoproliferative disorders (PTLDs) occur after solid organ transplantation. Treatment guidelines include reduction in immunosuppression (RIS), radiation, rituximab, chemotherapy, and immunological agents. We present a rare case of recurrent diffuse large B-cell lymphoma presenting as a PTLD in a heart transplant patient treated with autologous blood stem cell transplant (ASCT) after failure of conventional therapy. Case Presentation. A 66-year-old male presented with a neck mass. He has a history of Hodgkin's disease status after staging laparotomy with splenectomy and heart transplantation due to dilated nonischemic cardiomyopathy 8 years prior to the development of PTLD. His examination was remarkable for right submandibular swelling. An excisional biopsy confirmed the diagnosis of diffuse large B-cell NHL. Patient received RIS, rituximab, chemotherapy, and radiation therapy with a complete remission. His lymphoma relapsed and he subsequently was treated with RICE salvage chemotherapy and consolidative high-dose chemotherapy with BEAC regimen followed by ASCT resulting in a complete remission. Conclusion. Patients with PTLD present a difficult therapeutic challenge. In this case, the patient's prior history of Hodgkin's disease, splenectomy, and a heart transplant appear to be unique features, the significance of which is unclear. ASCT might be a promising therapy for patients with relapsed or refractory PTLD. PMID:26688773

  17. Outcome of autologous hematopoietic stem cell transplantation in refractory multiple myeloma.

    PubMed

    Veltri, Lauren W; Milton, Denái R; Delgado, Ruby; Shah, Nina; Patel, Krina; Nieto, Yago; Kebriaei, Partow; Popat, Uday R; Parmar, Simrit; Oran, Betul; Ciurea, Stefan; Hosing, Chitra; Lee, Hans C; Manasanch, Elisabet; Orlowski, Robert Z; Shpall, Elizabeth J; Champlin, Richard E; Qazilbash, Muzaffar H; Bashir, Qaiser

    2017-09-15

    Despite the introduction of effective, novel agents, the outcome of patients with refractory multiple myeloma remains poor, particularly those who are refractory to both proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). Limited data are available on the role of autologous hematopoietic stem cell transplantation in this population. Patients with refractory myeloma who underwent first autologous hematopoietic stem cell transplantation (auto-HCT) between March 2000 and October 2015 were retrospectively analyzed. Those who had primary refractory disease and those with relapsed and refractory disease were included. Disease that was refractory to at least 1 PI and at least 1 IMiD was classified as double-refractory multiple myeloma (DR-MM). In total, 233 patients were identified, including 105 (45%) classified with DR-MM and 128 (55%) classified with nondouble-refractory myeloma (NDR-MM). At a median follow-up of 42 months for surviving patients, at least a partial response was observed in 188 patients (81%; 83 patients in the DR-MM group [79%] and 105 patients in the NDR-MM [82%]; P = .77). A near complete response or better was observed in 52 patients (22%; 25 patients in the DR-MM group [24%] and 27 patients in the NDR-MM group [21%]; P = .77). The median progression-free survival was 17.6 months (14.4 months in the DR-MM group and 18.2 months in the NDR-MM group), and the 2-year progression-free survival rate was 38% (35% in the DR-MM group and 40% in the NDR-MM group; P = .40). The median overall survival was 48 months (38.9 months in the DR-MM group and 56.6 months in the NDR-MM group), and the 2-year overall survival rate was 74% (71% in the DR-MM group and 76% in the NDR-MM group; P = .27). The current findings indicate that auto-HCT is an effective and safe therapy in patients with refractory multiple myeloma, including those who are refractory to IMiDs and PIs. Cancer 2017;123:3568-75. © 2017 American Cancer Society. © 2017

  18. Autologous haematopoietic stem cell transplantation reduces abnormalities in the expression of immune genes in multiple sclerosis.

    PubMed

    de Paula A Sousa, Alessandra; Malmegrim, Kelen C R; Panepucci, Rodrigo A; Brum, Doralina S; Barreira, Amilton A; Carlos Dos Santos, Antonio; Araújo, Amélia G; Covas, Dimas Tadeu; Oliveira, Maria C; Moraes, Daniela A; Pieroni, Fabiano; Barros, George M; Simões, Belinda P; Nicholas, Richard; Burt, Richard K; Voltarelli, Júlio C; Muraro, Paolo A

    2015-01-01

    Autologous haematopoietic stem-cell transplantation (AHSCT) has been experimented as a treatment in patients affected by severe forms of multiple sclerosis (MS) who failed to respond to standard immunotherapy. The rationale of AHSCT is to 'reboot' the immune system and reconstitute a new adaptive immunity. The aim of our study was to identify, through a robust and unbiased transcriptomic analysis, any changes of gene expression in T-cells potentially underlying the treatment effect in patients who underwent non-myeloablative AHSCT for treatment of MS. We evaluated by microarray DNA-chip technology the gene expression of peripheral CD4+ and CD8+ T-cell subsets sorted from patients with MS patients before AHSCT, at 6 months, 1 year and 2 years after AHSCT and from healthy control subjects. Hierarchical clustering analysis revealed that reconstituted CD8+ T-cells of MS patients at 2 years post-transplantation, aggregated together with healthy controls, suggesting a normalization of gene expression in CD8+ cells post-therapy. When we compared the gene expression in MS patients before and after therapy, we detected a large number of differentially expressed genes (DEG) in both CD8+ and CD4+ T-cell subsets at all time points after transplantation. We catalogued the biological function of DEG and we selected 27 genes known to be involved in immune function for accurate quantification of gene expression by real-time PCR. The analysis confirmed and extended with quantitative data, a number of significant changes in both the CD4+ and CD8+ T-cells subsets from MS post-transplant. Notably, CD8+ T-cells revealed more extensive changes in the expression of genes involved in effector immune responses.

  19. Phase 1 Trial of Autologous Bone Marrow Stem Cell Transplantation in Patients with Spinal Cord Injury.

    PubMed

    Kakabadze, Zurab; Kipshidze, Nickolas; Mardaleishvili, Konstantine; Chutkerashvili, Gocha; Chelishvili, Irakli; Harders, Albrecht; Loladze, George; Shatirishvili, Gocha; Kipshidze, Nodar; Chakhunashvili, David; Chutkerashvili, Konstantine

    2016-01-01

    Introduction. A total of 18 patients, with complete motor deficits and paraplegia caused by thoracic and lumbar spine trauma without muscle atrophy or psychiatric problems, were included into this study. Materials and Methods. The bone marrow was aspirated from the anterior iliac crest under local anesthesia and the mononuclear fraction was isolated by density gradient method. At least 750 million mononuclear-enriched cells, suspended in 2 mL of saline, were infused intrathecally. Results and Discussion. The study reports demonstrated improvement of motor and sensory functions of various degrees observed in 9 of the 18 (50%) cases after bone marrow stem cell transplantation. Measured by the American Spinal Injury Association (ASIA) scale, 7 (78%) out of the 9 patients observed an improvement by one grade, while two cases (22%) saw an improvement by two grades. However, there were no cases in which the condition was improved by three grades. Conclusions. Analysis of subsequent treatment results indicated that the transplantation of mononuclear-enriched autologous BMSCs is a feasible and safe technique. However, successful application of the BMSCs in the clinical practice is associated with the necessity of executing more detailed examinations to evaluate the effect of BMSCs on the patients with spinal cord injury.

  20. Ethical and Regulatory Challenges with Autologous Adult Stem Cells: A Comparative Review of International Regulations.

    PubMed

    Lysaght, Tamra; Kerridge, Ian H; Sipp, Douglas; Porter, Gerard; Capps, Benjamin J

    2017-02-28

    Cell and tissue-based products, such as autologous adult stem cells, are being prescribed by physicians across the world for diseases and illnesses that they have neither been approved for or been demonstrated as safe and effective in formal clinical trials. These doctors often form part of informal transnational networks that exploit differences and similarities in the regulatory systems across geographical contexts. In this paper, we examine the regulatory infrastructure of five geographically diverse but socio-economically comparable countries with the aim of identifying similarities and differences in how these products are regulated and governed within clinical contexts. We find that while there are many subtle technical differences in how these regulations are implemented, they are sufficiently similar that it is difficult to explain why these practices appear more prevalent in some countries and not in others. We conclude with suggestions for how international governance frameworks might be improved to discourage the exploitation of vulnerable patient populations while enabling innovation in the clinical application of cellular therapies.

  1. Steroids prevent engraftment syndrome after autologous hematopoietic stem cell transplantation without increasing the risk of infection.

    PubMed

    Mossad, S; Kalaycio, M; Sobecks, R; Pohlman, B; Andresen, S; Avery, R; Rybicki, L; Jarvis, J; Bolwell, B

    2005-02-01

    Engraftment syndrome (ES) following autologous hematopoietic stem cell transplantation (AHSCT) is characterized by fever and rash. In January 2002, we instituted steroid prophylaxis for ES from day +4 to +14. This study was conducted to assess whether this practice increased the risk of infection. In total, 194 consecutive patients were reviewed, 111 did not receive steroid prophylaxis (group A), and 83 did (group B). Initial antimicrobial prophylaxis was the same in both groups. There were no significant differences between groups in age, gender, race, prior radiation therapy, number of prior chemotherapy regimens, disease status at transplant, mobilization regimen, days of leukopheresis, CD34(+) cell dose, and days to platelet and neutrophil engraftment. Group B had significantly fewer patients with non-Hodgkin's lymphoma and multiple myeloma, shorter median duration from diagnosis to transplant, lower risk of ES, and shorter mean length of hospital stay. The incidence of early and late microbiologically confirmed infections was not significantly different between groups. Types of infections and types of organisms identified were similar in both groups. Hospital readmission rates were similar in both groups. Steroid prophylaxis significantly decreases the risk of ES following AHSCT, and is associated with shortened hospitalization, without increasing risk of infection.

  2. High-dose ifosfamide/carboplatin/etoposide: maximum tolerable doses, toxicities, and hematopoietic recovery after autologous stem cell reinfusion.

    PubMed

    Fields, K K; Elfenbein, G J; Perkins, J B; Janssen, W E; Ballester, O F; Hiemenz, J W; Zorsky, P E; Kronish, L E; Foody, M C

    1994-10-01

    We treated 115 patients in a phase I/II dose-escalation study of ifosfamide/carboplatin/etoposide (ICE) followed by autologous stem cell rescue. Patients treated had a variety of diagnoses, including breast cancer (high-risk stage II disease with eight or more positive nodes, stage III disease, and responsive metastatic disease), non-Hodgkin's lymphoma, Hodgkin's disease, acute leukemia in first remission, and various solid tumors that were responsive to induction therapy. Patients received autologous bone marrow stem cells or peripheral blood stem cells primed by one of several methods. The maximum tolerated dose of ICE was determined to be ifosfamide 20,100 mg/m2, carboplatin 1,800 mg/m2, and etoposide 3,000 mg/m2 when administered as a 6-day regimen. The dose-limiting toxicities included acute renal failure, severe central nervous system toxicity, and "leaky capillary syndrome" with hypoalbuminemia, profound fluid overload, and pulmonary insufficiency. Analysis of hematologic recovery based on stem cell source and influence of hematopoietic growth factor administration was undertaken. Hematopoietic growth factor use significantly reduced neutrophil engraftment time for patients receiving bone marrow stem cells, with evidence of earlier recovery times for patients receiving granulocyte colony-stimulating factor compared with granulocyte-macrophage colony-stimulating factor. Neutrophil recovery times varied based on the source of stem cells used, with the earliest engraftment times seen for patients receiving peripheral blood stem cells primed with cyclophosphamide and granulocyte colony-stimulating factor. Platelet recovery times were not statistically different for any of the subsets. In conclusion, the maximum tolerated dose of ICE has been defined, and the source of stem cells and the use of hematopoietic growth factors influence hematopoietic recovery.

  3. Cryopreserved amniotic fluid-derived cells: a lifelong autologous fetal stem cell source for heart valve tissue engineering.

    PubMed

    Schmidt, Dörthe; Achermann, Josef; Odermatt, Bernhard; Genoni, Michele; Zund, Gregor; Hoerstrup, Simon P

    2008-07-01

    Fetal stem cells represent a promising cell source for heart valve tissue engineering. In particular, amniotic fluid-derived cells (AFDC) have been shown to lead to autologous fetal-like heart valve tissues in vitro for pediatric application. In order to expand the versatility of these cells also for adult application, cryopreserved AFDC were investigated as a potential life-long available cell source for heart valve tissue engineering. Human AFDC were isolated using CD133 magnetic beads, and then differentiated and analyzed. After expansion of CD133- as well as CD133+ cells up to passage 7, a part of the cells was cryopreserved. After four months, the cells were re-cultured and phenotyped by flow cytometry and immunohistochemistry, including expression of CD44, CD105, CD90, CD34, CD31, CD141, eNOS and vWF, and compared to their non-cryopreserved counterparts. The stem cell potential was investigated in differentiation assays. The viability of cryopreserved AFDC for heart valve tissue engineering was assessed by creating heart valve leaflets in vitro. After cryopreservation, amniotic fluid-derived CD133- and CD133+ cells retained their stem cell-like phenotype, expressing mainly CD44, CD90 and CD105. This staining pattern was comparable to that of their non-cryopreserved counterparts. Moreover, CD133- cells demonstrated differentiation potential into osteoblast-like and adipocyte-like cells. CD133+ cells showed characteristics of endothelial-like cells by eNOS, CD141 and beginning vWF expression. When used for the fabrication of heart valve leaflets, cryopreserved CD133- cells produced extracellular matrix elements comparable to their non-cryopreserved counterparts. Moreover, the resulting tissues showed a cellular layered tissue formation covered by functional endothelia. The mechanical properties were similar to those of tissues fabricated from non-cryopreserved cells. The study results suggest that the use of cell bank technology fetal amniotic fluid

  4. Consolidation treatment for high risk solid tumors in children with myeloablative chemotherapy and autologous hematopoietic progenitor stem cell transplantation

    PubMed Central

    Vargas, Alberto Olaya; Luna, Roberto Rivera; Garcia, Martin Perez; Cardos, Rocio Cárdenas; Hidalgo, Liliana Velasco; Jácome, Doris LordMéndez; Gutiérrez, Mariana Campos

    2013-01-01

    Background In childhood cancer, consolidation treatment with chemotherapy followed by autologous hematopoietic progenitor stem cell transplantation is currently an accepted treatment modality in patients with high-risk solid tumors or in patients who have relapsed after conventional treatment. Objectives The objective of this study was to describe the results of transplantation of a group of children who had high-risk solid tumors or relapsed after conventional chemotherapy regimens. Methods A retrospective analysis was conducted from January 1998 to October 2004 of all children with pathologic diagnoses of high-risk solid tumors or children that had previously relapsed after conventional chemotherapy and that were subsequently submitted to autologous hematopoietic progenitor stem cell transplantation. The analysis included overall survival rates, event-free survival rates, mortality rates and chemotherapy complications. Results Nineteen patients were submitted to this approach. The age range was from 27 to 196 months with a median age of 52 months. The overall survival rate at 100 days was observed in 79%, the three-year event-free survival rate was 63%. The mortality rate secondary to the myeloablative chemotherapy regimen was 21% (n = 4). Only three patients (15.8%) relapsed with tumor progression after transplant. Conclusion Autologous hematopoietic progenitor stem cell transplantation is still a successful procedure in patients with solid tumors refractory to conventional chemotherapy. PMID:24255618

  5. Cytomegalovirus infection in autologous stem cell transplant recipients in the era of rituximab.

    PubMed

    Jain, Tania; John, Jisha; Kotecha, Aditya; Deol, Abhinav; Saliminia, Tanaz; Revankar, Sanjay; Chandrasekar, Pranatharthi

    2016-08-01

    The incidence of cytomegalovirus (CMV) reactivation/disease after autologous stem cell transplant (ASCT) is much lower than that after allogeneic stem cell transplantation. With the recent use of rituximab during cancer chemotherapy or conditioning regimens prior to transplantation, there has been an increasing concern of opportunistic infections including CMV. In the present study, we reviewed the patients undergoing ASCT from December 2007 to December 2013 to identify those developing CMV reactivation/disease. Out of the 978 patients who underwent ASCT at the Karmanos Cancer Institute, 239 patients were tested for symptomatic CMV reactivation based on clinical suspicion. Of the tested patients, 7/239 (2.9 %) were documented to have CMV reactivation within 90 days of ASCT. The median time to develop CMV viremia was 32 days from transplantation. Of the 239 patients tested, CMV viremia was detected in 3 out of 72 patients who received rituximab as compared to 4 out of 167 patients who did not. Three of these seven viremic patients were treated with anti-viral drugs; viremia resolved in all patients at a median of 24 days. Three patients were found to develop other bacterial and/or fungal infections following CMV viremia. Two of the seven patients died during 1-year follow-up, due to primary disease progression or Candida sepsis. None of the patients developed proven tissue-invasive CMV disease. The study did not evaluate the incidence of asymptomatic CMV infection/reactivation. Despite prior publications based on limited data, rituximab does not appear to contribute to an increased frequency of symptomatic CMV reactivation following ASCT.

  6. High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis

    PubMed Central

    Nash, Richard A.; Bowen, James D.; McSweeney, Peter A.; Pavletic, Steven Z.; Maravilla, Kenneth R.; Park, Man-soo; Storek, Jan; Sullivan, Keith M.; Al-Omaishi, Jinan; Corboy, John R.; DiPersio, John; Georges, George E.; Gooley, Theodore A.; Holmberg, Leona A.; LeMaistre, C. Fred; Ryan, Kate; Openshaw, Harry; Sunderhaus, Julie; Storb, Rainer; Zunt, Joseph; Kraft, George H.

    2010-01-01

    There were 26 patients enrolled in a pilot study of high-dose immunosuppressive therapy (HDIT) for severe multiple sclerosis (MS). Median baseline expanded disability status scale (EDSS) was 7.0 (range, 5.0–8.0). HDIT consisted of total body irradiation, cyclophosphamide, and antithymocyte globulin (ATG) and was followed by transplantation of autologous, granulocyte colony-stimulating factor (G-CSF)-mobilized CD34-selected stem cells. Regimen-related toxicities were mild. Because of bladder dysfunction, there were 8 infectious events of the lower urinary tract. One patient died from Epstein-Barr virus (ESV)-related posttransplantation lymphoproliferative disorder (PTLD) associated with a change from horse-derived to rabbit-derived ATG in the HDIT regimen. An engraftment syndrome characterized by noninfectious fever with or without rash developed in 13 of the first 18 patients and was associated in some cases with transient worsening of neurologic symptoms. There were 2 significant adverse neurologic events that occurred, including a flare of MS during mobilization and an episode of irreversible neurologic deterioration after HDIT associated with fever. With a median follow-up of 24 (range, 3–36) months, the Kaplan-Meier estimate of progression (≥ 1.0 point EDSS) at 3 years was 27%. Of 12 patients who had oligoclonal bands in the cerebrospinal fluid at baseline, 9 had persistence after HDIT. After HDIT, 4 patients developed new enhancing lesions on magnetic resonance imaging of the brain. The estimate of survival at 3 years was 91%. Important clinical issues in the use of HDIT and stem cell transplantation for MS were identified; however, modifications of the initial approaches appear to reduce treatment risks. This was a heterogeneous high-risk group, and a phase 3 study is planned to fully assess efficacy. PMID:12763935

  7. High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis.

    PubMed

    Nash, Richard A; Bowen, James D; McSweeney, Peter A; Pavletic, Steven Z; Maravilla, Kenneth R; Park, Man-soo; Storek, Jan; Sullivan, Keith M; Al-Omaishi, Jinan; Corboy, John R; DiPersio, John; Georges, George E; Gooley, Theodore A; Holmberg, Leona A; LeMaistre, C Fred; Ryan, Kate; Openshaw, Harry; Sunderhaus, Julie; Storb, Rainer; Zunt, Joseph; Kraft, George H

    2003-10-01

    There were 26 patients enrolled in a pilot study of high-dose immunosuppressive therapy (HDIT) for severe multiple sclerosis (MS). Median baseline expanded disability status scale (EDSS) was 7.0 (range, 5.0-8.0). HDIT consisted of total body irradiation, cyclophosphamide, and antithymocyte globulin (ATG) and was followed by transplantation of autologous, granulocyte colony-stimulating factor (G-CSF)-mobilized CD34-selected stem cells. Regimen-related toxicities were mild. Because of bladder dysfunction, there were 8 infectious events of the lower urinary tract. One patient died from Epstein-Barr virus (EBV)-related posttransplantation lymphoproliferative disorder (PTLD) associated with a change from horse-derived to rabbit-derived ATG in the HDIT regimen. An engraftment syndrome characterized by noninfectious fever with or without rash developed in 13 of the first 18 patients and was associated in some cases with transient worsening of neurologic symptoms. There were 2 significant adverse neurologic events that occurred, including a flare of MS during mobilization and an episode of irreversible neurologic deterioration after HDIT associated with fever. With a median follow-up of 24 (range, 3-36) months, the Kaplan-Meier estimate of progression (>/= 1.0 point EDSS) at 3 years was 27%. Of 12 patients who had oligoclonal bands in the cerebrospinal fluid at baseline, 9 had persistence after HDIT. After HDIT, 4 patients developed new enhancing lesions on magnetic resonance imaging of the brain. The estimate of survival at 3 years was 91%. Important clinical issues in the use of HDIT and stem cell transplantation for MS were identified; however, modifications of the initial approaches appear to reduce treatment risks. This was a heterogeneous high-risk group, and a phase 3 study is planned to fully assess efficacy.

  8. Treatment of progressive supranuclear palsy with autologous adipose tissue-derived mesenchymal stem cells: a case report.

    PubMed

    Choi, Soo Won; Park, Kwon Byong; Woo, Sang Kyu; Kang, Sung Keun; Ra, Jeong Chan

    2014-03-04

    Progressive supranuclear palsy is a relentlessly progressive neurodegenerative disorder and is clinically characterized by parkinsonism. Adipose tissue-derived mesenchymal stem cells have recently demonstrated the possibility of treating neurological disorders. Therefore, autologous adipose tissue-derived mesenchymal stem cells transplantation can be an alternative method for treating progressive supranuclear palsy. This study was approved by the Korea Food and Drug Administration through the Emergency Use Investigational New Drug Application. A 71-year-old Asian man from South Korea with progressive supranuclear palsy was treated with five intravenous infusions (each time 2×108 cells) and four intrathecal infusions (each time 5×107 cells) with autologous adipose tissue-derived mesenchymal stem cells expanded under good manufacturing practice conditions. Clinical examinations were performed immediately before treatment and throughout the six months of follow-up. The tests included: 1) Progressive Supranuclear Palsy Rating Scale; 2) Berg Balance Scale; 3) Korean Mini Mental State Examination; 4) Modified Barthel Index; 5) grip strength; 6) Box and Block Test; and 7) Nine-Hole Peg Test.The Progressive Supranuclear Palsy Rating Scale results gradually decreased, and the clinical rating scale scores of the Berg Balance Scale, Korean Mini Mental State Examination, and Modified Barthel Index gradually increased. Grip strength was maintained. Performance in the Box and Block Test and Nine-Hole Peg Test improved after adipose tissue-derived mesenchymal stem cells treatment compared to baseline throughout the six months of follow-up. Except for the intermittent mild fever and transient elevated blood pressure, the treatment of our patient with progressive supranuclear palsy with autologous adipose tissue-derived mesenchymal stem cells showed no significant adverse events, and delayed the progression of neurological deficits by achieving functional improvement in the

  9. Tbo-Filgrastim versus Filgrastim during Mobilization and Neutrophil Engraftment for Autologous Stem Cell Transplantation.

    PubMed

    Elayan, Mohammed M; Horowitz, Justin G; Magraner, Jose M; Shaughnessy, Paul J; Bachier, Carlos

    2015-11-01

    There are limited data available supporting the use of the recombinant granulocyte colony-stimulating factor (G-CSF), tbo-filgrastim, rather than traditionally used filgrastim to mobilize peripheral blood stem cells (PBSC) or to accelerate engraftment after autologous stem cell transplantation (ASCT). We sought to compare the efficacy and cost of tbo-filgrastim to filgrastim in these settings. Patients diagnosed with lymphoma or plasma cell disorders undergoing G-CSF mobilization, with or without plerixafor, were included in this retrospective analysis. The primary outcome was total collected CD34(+) cells/kg. Secondary mobilization endpoints included peripheral CD34(+) cells/μL on days 4 and 5 of mobilization, adjunctive use of plerixafor, CD34(+) cells/kg collected on day 5, number of collection days and volumes processed, number of collections reaching 5 million CD34(+) cells/kg, and percent reaching target collection goal in 1 day. Secondary engraftment endpoints included time to neutrophil and platelet engraftment, number of blood product transfusions required before engraftment, events of febrile neutropenia, and length of stay. A total of 185 patients were included in the final analysis. Patients receiving filgrastim (n = 86) collected a median of 5.56 × 10(6) CD34(+) cells/kg, compared with a median of 5.85 × 10(6) CD34(+) cells/kg in the tbo-filgrastim group (n = 99; P = .58). There were no statistically significant differences in all secondary endpoints with the exception of apheresis volumes processed (tbo-filgrastim, 17.0 liters versus filgrastim, 19.7 liters; P < .01) and mean platelet transfusions (tbo-filgrastim, 1.7 units versus filgrastim, 1.4 units; P = .04). In conclusion, tbo-filgrastim demonstrated similar CD34(+) yield compared with filgrastim in mobilization and post-transplantation settings, with no clinically meaningful differences in secondary efficacy and safety endpoints. Furthermore, tbo-filgrastim utilization was associated

  10. Advances in delivery of ambulatory autologous stem cell transplantation for multiple myeloma.

    PubMed

    Khouri, Jack; Majhail, Navneet S

    2017-09-15

    Autologous stem cell transplantation (ASCT) is generally performed in the inpatient setting in its entirety. Several centers have demonstrated the feasibility of performing ASCT for myeloma in the ambulatory setting. We review the safety, cost-effectiveness, complications and outcomes of outpatient ASCT for myeloma. Published studies are heterogeneous but suggest that outpatient ASCT for myeloma is cost-effective and associated with a shorter or no initial hospitalization, albeit there is a high rate of readmission for complications. The transplant-related mortality rate is less than 1%. Stringent patient selection criteria that include emphasis on functional status, caregiving support and psychosocial aspects for each patient are critical for identifying patients most appropriate for ASCT in the ambulatory setting. There exists considerable variability in outpatient transplant models and supportive care guidelines and data do not support preference for one delivery model over another. Survival and other transplant-related outcomes have not been reported widely and whether patients fare better with outpatient transplantation remains to be explored. Outpatient ASCT for multiple myeloma is feasible and well tolerated in selected patients. Several care models for outpatient ASCT exist and can be implemented based on transplant resources and preference.

  11. Early versus delayed autologous stem cell transplantation in patients receiving novel therapies for Multiple Myeloma

    PubMed Central

    Dunavin, Neil C.; Wei, Lai; Elder, Patrick; Phillips, Gary S; Benson, Don M; Hofmeister, Craig C.; Penza, Sam; Greenfield, Carli; Rose, Karen S.; Rieser, Gisele; Merritt, Lisa; Ketcham, Jill; Heerema, Nyla; Byrd, John C.; Devine, Steven M.; Efebera, Yvonne A.

    2013-01-01

    Autologous stem cell transplant (ASCT) is an effective treatment for multiple myeloma (MM). However the timing of ASCT in the era of novel agents (lenalidomide, thalidomide, bortezomib) is unknown. We retrospectively reviewed the outcome of MM patients who received novel agent based induction treatment and received first ASCT within 12 months of diagnosis (early ASCT, N = 102), or at a later date (late ASCT, N = 65). Median time to ASCT was 7.9 months vs. 17.7 months in the early vs. late ASCT. The 3 and 5 yr overall Survival (OS) from diagnosis was 90 and 63% versus 82 and 63% in early and late ASCT respectively (P=0.45). Forty-one and 36 patients in the early and late ASCT have relapsed or progressed with median time to relapse of 28 and 23 mos (p=0.055). On multivariable analysis, factors predictive of increased risk for progression were ISS stage III (p=0.007), and < VGPR post-ASCT (p<0.001). Factor predictive of worst outcomes for OS was being on hemodialysis (p=0.037). No superiority of one agent was seen. In summary, early or late ASCT is a viable option for MM patients receiving induction treatment with novel targeted therapies. PMID:23194056

  12. Autologous adipose stem cells and polylactide discs in the replacement of the rabbit temporomandibular joint disc

    PubMed Central

    Ahtiainen, Katja; Mauno, Jari; Ellä, Ville; Hagström, Jaana; Lindqvist, Christian; Miettinen, Susanna; Ylikomi, Timo; Kellomäki, Minna; Seppänen, Riitta

    2013-01-01

    The temporomandibular joint (TMJ) disc lacks functional replacement after discectomy. We investigated tissue-engineered bilayer polylactide (PLA) discs and autologous adipose stem cells (ASCs) as a potential replacement for the TMJ disc. These ASC discs were pre-cultured either in control or in differentiation medium, including transforming growth factor (TGF)-β1 for one week. Prior to implantation, expression of fibrocartilaginous genes was measured by qRT-PCR. The control and differentiated ASC discs were implanted, respectively, in the right and left TMJs of rabbits for six (n = 5) and 12 months (n = 5). Thereafter, the excised TMJ areas were examined with cone beam computed tomography (CBCT) and histology. No signs of infection, inflammation or foreign body reactions were detected at histology, whereas chronic arthrosis and considerable condylar hypertrophy were observed in all operated joints at CBCT. The left condyle treated with the differentiated ASC discs appeared consistently smoother and more sclerotic than the right condyle. The ASC disc replacement resulted in dislocation and morphological changes in the rabbit TMJ. The ASC discs pre-treated with TGF-β1 enhanced the condylar integrity. While adverse tissue reactions were not shown, the authors suggest that with improved attachment and design, the PLA disc and biomaterial itself would hold potential for TMJ disc replacement. PMID:23720535

  13. Autologous adipose stem cells and polylactide discs in the replacement of the rabbit temporomandibular joint disc.

    PubMed

    Ahtiainen, Katja; Mauno, Jari; Ellä, Ville; Hagström, Jaana; Lindqvist, Christian; Miettinen, Susanna; Ylikomi, Timo; Kellomäki, Minna; Seppänen, Riitta

    2013-08-06

    The temporomandibular joint (TMJ) disc lacks functional replacement after discectomy. We investigated tissue-engineered bilayer polylactide (PLA) discs and autologous adipose stem cells (ASCs) as a potential replacement for the TMJ disc. These ASC discs were pre-cultured either in control or in differentiation medium, including transforming growth factor (TGF)-β1 for one week. Prior to implantation, expression of fibrocartilaginous genes was measured by qRT-PCR. The control and differentiated ASC discs were implanted, respectively, in the right and left TMJs of rabbits for six (n = 5) and 12 months (n = 5). Thereafter, the excised TMJ areas were examined with cone beam computed tomography (CBCT) and histology. No signs of infection, inflammation or foreign body reactions were detected at histology, whereas chronic arthrosis and considerable condylar hypertrophy were observed in all operated joints at CBCT. The left condyle treated with the differentiated ASC discs appeared consistently smoother and more sclerotic than the right condyle. The ASC disc replacement resulted in dislocation and morphological changes in the rabbit TMJ. The ASC discs pre-treated with TGF-β1 enhanced the condylar integrity. While adverse tissue reactions were not shown, the authors suggest that with improved attachment and design, the PLA disc and biomaterial itself would hold potential for TMJ disc replacement.

  14. Stomatitis-related pain in women with breast cancer undergoing autologous hematopoietic stem cell transplant.

    PubMed

    Fall-Dickson, Jane M; Mock, Victoria; Berk, Ronald A; Grimm, Patricia M; Davidson, Nancy; Gaston-Johansson, Fannie

    2008-01-01

    The purpose of this cross-sectional, correlational study was to describe stomatitis-related pain in women with breast cancer undergoing autologous hematopoietic stem cell transplant. The hypotheses that significant, positive relationships would exist between oral pain and stomatitis, state anxiety, depression, and alteration in swallowing were tested. Stomatitis, sensory dimension of oral pain, and state anxiety were hypothesized to most accurately predict oral pain overall intensity. Thirty-two women were recruited at 2 East Coast comprehensive cancer centers. Data were collected on bone marrow transplantation day +7 +/- 24 hours using Painometer, Oral Mucositis Index-20, Oral Assessment Guide, State-Trait Anxiety Inventory, and Beck Depression Inventory. Data analysis included descriptive statistics, correlations, and stepwise multiple regression. All participants had stomatitis; 47% had oral pain, with a subset reporting continuous moderate to severe oral pain despite pain management algorithms. Significant, positive associations were seen between oral pain, stomatitis, and alteration in swallowing and between oral pain with swallowing and alteration in swallowing. Oral pain was not significantly correlated with state anxiety and depression. Oral sensory and affective pain intensity most accurately predicted oral pain overall intensity. Future research needs to explore factors that affect perception and response to stomatitis-related oropharyngeal pain and individual patient response to opioid treatment.

  15. Autologous hematopoietic stem cell transplantation in multiple sclerosis: 20 years of experience.

    PubMed

    Currò, Daniela; Mancardi, Gianluigi

    2016-06-01

    Intense immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) has been widely used in the last 20 years for the treatment of aggressive forms of autoimmune disorders, especially multiple sclerosis (MS). All clinical studies, although small and uncontrolled, demonstrate a great efficacy of this procedure in halting inflammation and disease activity, even in those patients affected by "malignant forms" of MS. The long-term follow-up has also revealed the possible maintenance of positive results in the course of time, and this evidence is supported by immunological data that suggest the possibility of a resetting of the immune system after AHSCT. The safety of AHSCT has improved in the last years, but the transplant related mortality is still nowadays of about 1-2 %, pointing out that a careful selection of patients to submit to AHSCT is mandatory. The long clinical experience allowed to identify the ideal candidate: a young patient, with a short disease duration, with recurring and disabling relapses and the presence of inflammatory activity on brain magnetic resonance scans, unresponsive to approved therapies. A large, randomized clinical study comparing AHSCT with the best approved therapies is still necessary to confirm the role of transplantation in MS treatment.

  16. Clinical Application of Autologous Adipose Stem Cells in Patients with Multiple Sclerosis: Preliminary Results.

    PubMed

    Stepien, Adam; Dabrowska, Natalia L; Maciagowska, Marzena; Macoch, Renata Piusinska; Zolocinska, Aleksandra; Mazur, Slawomir; Siennicka, Katarzyna; Frankowska, Emilia; Kidzinski, Rafał; Chalimoniuk, Małgorzata; Pojda, Zygmunt

    2016-01-01

    The clinical outcome of autologous adipose stem cell (ASC) treatment of patients with multiple sclerosis (MS) was investigated following one year of observation. Methods. The clinical and MRI outcomes of 16 ASC-treated patients with RRMS and SPMS are reported after a one-year follow-up period. Results. At 18 months of follow-up, some patients showed "enticing" improvements on some exploratory efficacy measures, although a significant benefit was not observed for any measure across the entire group. Neither the progression of disability nor relapses were observed in any cases. In four patients, we found new gadolinium+ (Gd+) lesions on MRI. Our results indicate that ASC therapy is safe and does not produce any substantial side effects. Disease progression-free survival (PFS) of 18 months was seen in all patients with RRMS and SPMS. In these patients, EDSS scores did not progress above baseline scores. Gd-enhancing lesions were observed in two cases with RRMS, but these patients did not exhibit changes in EDSS score. Conclusion. Intrathecal treatment with ASCs is an attractive form of therapy for patients with MS but should be reserved for cases with aggressive disease progression, for cases that are still in the inflammatory phase, and for the malignant form.

  17. Juvenile Swine Surgical Alveolar Cleft Model to Test Novel Autologous Stem Cell Therapies.

    PubMed

    Caballero, Montserrat; Morse, Justin C; Halevi, Alexandra E; Emodi, Omri; Pharaon, Michael R; Wood, Jeyhan S; van Aalst, John A

    2015-09-01

    Reconstruction of craniofacial congenital bone defects has historically relied on autologous bone grafts. Engineered bone using mesenchymal stem cells from the umbilical cord on electrospun nanomicrofiber scaffolds offers an alternative to current treatments. This preclinical study presents the development of a juvenile swine model with a surgically created maxillary cleft defect for future testing of tissue-engineered implants for bone generation. Five-week-old pigs (n=6) underwent surgically created maxillary (alveolar) defects to determine critical-sized defect and the quality of treatment outcomes with rib, iliac crest cancellous bone, and tissue-engineered scaffolds. Pigs were sacrificed at 1 month. Computed tomography scans were obtained at days 0 and 30, at the time of euthanasia. Histological evaluation was performed on newly formed bone within the surgical defect. A 1 cm surgically created defect healed with no treatment, the 2 cm defect did not heal. A subsequently created 1.7 cm defect, physiologically similar to a congenitally occurring alveolar cleft in humans, from the central incisor to the canine, similarly did not heal. Rib graft treatment did not incorporate into adjacent normal bone; cancellous bone and the tissue-engineered graft healed the critical-sized defect. This work establishes a juvenile swine alveolar cleft model with critical-sized defect approaching 1.7 cm. Both cancellous bone and tissue engineered graft generated bridging bone formation in the surgically created alveolar cleft defect.

  18. Autologous Adipose Stem Cell Therapy for Autonomic Nervous System Dysfunction in Two Young Patients

    PubMed Central

    Kamdar, Ankur; Young, Jane; Butler, Ian. J.

    2017-01-01

    Postural orthostatic tachycardia syndrome and neurocardiogenic syncope are clinical manifestations of autonomic nervous system dysfunction (dysautonomia) that can lead to impaired daily functions. We report two young patients presenting with dysautonomia and autoimmune disease who both received autologous adipose stem cells (ASCs) infusions. This report is the first description of ASCs therapy for patients with combined dysautonomia and autoimmune disease. Case 1: A 21-year-old female presented at 12 years of age with escalating severe dysautonomia with weight loss and gastrointestinal symptoms. She had elevated autoantibodies and cytokines and received multiple immune modulation therapies. Her dysautonomia was treated by volume expanders, vasoconstrictors, and beta blockers with mild improvement. She received ASCs about 2 years before this report with dramatic improvement in her dysautonomia and autoimmune symptoms with a 10 kg weight gain. Case 2: A 7-year-old boy presented at 2 years of age with polyarthritis. At 5 years of age, he manifested orthostatic intolerance. He received immune modulatory therapies with mild improvement. He received ASCs and showed marked improvement of his dysautonomia and immune symptoms. Dysautonomia symptoms of these two patients improved significantly after modulation of autoimmune components by ASC therapy. Favorable clinical responses of these two cases warrant further case–control studies. PMID:27959743

  19. Current Status of Autologous Stem Cell Transplantation in Relapsed and Refractory Hodgkin's Lymphoma

    PubMed Central

    Colpo, Anna; Hochberg, Ephraim

    2012-01-01

    Despite the relatively high long-term disease-free survival (DFS) rate for patients with Hodgkin lymphoma (HL) with modern combination chemotherapy or combined modality regimens, ∼20% of patients die from progressive or relapsed disease. The standard treatment for relapsed and primary refractory HL is salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), which has shown a 5-year progression-free survival rate of ∼50%–60%. Recent developments in a number of diagnostic and therapeutic modalities have begun to improve these results. Functional imaging, refinement of clinical prognostic factors, and development of novel biomarkers have improved the predictive algorithms, allowing better patient selection and timing for ASCT. In addition, these algorithms have begun to identify a group of patients who are candidates for more aggressive treatment beyond standard ASCT. Novel salvage regimens may potentially improve the rate of complete remission prior to ASCT, and the use of maintenance therapy after ASCT has become a subject of current investigation. We present a summary of developments in each of these areas. PMID:22210089

  20. Bortezomib followed by autologous stem cell transplantation in a patient with rheumatoid arthritis

    PubMed Central

    Liu, Junru; Li, Juan; Chen, Meilan; Kuang, Lifen

    2016-01-01

    Abstract Rationale and Patients concerns: Despite the introduction of varied disease-modifying antirheumatic drugs and biological agents, a substantial proportion of patients remain untreatable. We report a 56-year-old Chinese female patient with a case of refractory rheumatoid arthritis (RA) complicated with multiple myeloma (MM) who was treated successfully with Bortezomib followed by autologous stem cell transplantation (ASCT). Diagnosis and Interventions: We report a 56-year-old Chinese female patient who was diagnosed as RA complicating with MM. She received 4 cycles of Bortezomib-based chemotherapy followed by ASCT. The response of her RA and MM were evaluated after every cycle of Bortezomib-based chemotherapy. Interventions and Outcomes: After the first Bortezomib-based chemotherapy cycle, this patient's symptoms were significantly alleviated and thereafter the RA activity continued to improve. After the 4 courses of Bortezomib-based chemotherapy, the C-reactive protein was <0.5 mg/dL and the disease activity score 28-erythrocyte sedimentation rate was 2.0. No hematological or nonhematological side effects were observed during the treatment of Bortezomib. Lessons: Bortezomib might be a new safe and promising drug for refractory RA patients. PMID:28033292

  1. Absence of spontaneous response improvement beyond day +100 after autologous stem cell transplantation in multiple myeloma.

    PubMed

    Fernández de Larrea, C; Dávila, J; Isola, I; Ocio, E M; Rosiñol, L; García-Sanz, R; Cibeira, M T; Tovar, N; Rovira, M; Mateos, M V; Miguel, J S; Bladé, J

    2017-04-01

    The response evaluation after autologous stem-cell transplantation (ASCT) is usually performed at day +100 in patients with multiple myeloma (MM). A recent report suggests that improvement in the response can be observed beyond day +100. The aim of the present study has been to evaluate the rate of improved response and outcome beyond day +100 after ASCT, with and without maintenance therapy. One hundred and forty-four patients who underwent single ASCT with chemosensitive disease and achieved less than CR at day 100 post ASCT were evaluated. Seventy-four patients (51.4%) did not receive any maintenance with only one of them showing an upgrade in the response. The remaining 70 patients (48.6%) received maintenance therapy; eleven of them (15.7%) improved their response beyond day +100. The outcome of these patients was better than those who did not upgrade their response in both progression-free survival and overall survival (P=0.019 and P=0.031, respectively). In conclusion, the improvement in response beyond day +100 after ASCT in patients not receiving any therapy is exceedingly rare. A minority of patients receiving maintenance therapy after ASCT upgrades their response and this finding is associated with better outcome.

  2. Chemical injury treated with autologous limbal epithelial stem cell transplantation and subconjunctival bevacizumab

    PubMed Central

    Cavallini, Gian Maria; Pellegrini, Graziella; Volante, Veronica; Ducange, Pietro; De Maria, Michele; Torlai, Giulio; Benatti, Caterina; Forlini, Matteo

    2014-01-01

    Background Limbal stem cell (LSC) deficiency leads to corneal opacity due to a conjunctivalization of the corneal surface. LSC transplantation, which can be followed by corneal keratoplasty, is an effective procedure to restore corneal transparency; however, a common cause of failure of this procedure is neovascularization (NV). Methods A 59-year-old man with a 21-year history of a corneal chemical burn caused by phosphoric acid in his left eye was examined. He presented with unilateral total LSC deficiency with severe conjunctivalization and a corrected distance visual acuity that was limited to hand motion. Results We reported the short-term in vivo efficacy of subconjunctival bevacizumab for progressive corneal NV in a patient with LSC deficiency that underwent LSC transplantation. Four months after autologous LSC transplantation and 1 month after the second subconjunctival bevacizumab injection, the patient’s corrected distance visual acuity was 1/10. Conclusion Subconjunctival injection of bevacizumab can reduce the corneal NV, reducing conjunctival inflammation and supporting restoration of a stable ocular surface that is able to counteract graft failure, with no toxicity for the transplanted LSC. PMID:25210437

  3. MYELOABLATIVE THERAPY WITH AUTOLOGOUS STEM CELL RESCUE FOR PATIENTS WITH EWING SARCOMA

    PubMed Central

    Gardner, Sharon L.; Carreras, Jeanette; Boudreau, Christian; Camitta, Bruce M.; Adams, Roberta H.; Chen, Allen R.; Davies, Stella M.; Edwards, John R.; Grovas, Alfred C.; Hale, Gregory A.; Lazarus, Hillard M.; Arora, Mukta; Stiff, Patrick J.; Eapen, Mary

    2011-01-01

    Summary The aim of this study was to identify risk factors associated with progression-free survival in patients with Ewing sarcoma undergoing autologous stem cell transplantation (ASCT); 116 patients underwent ASCT in 1989-2000 and reported to the Center for International Blood and Marrow Transplant Research. Eighty patients (69%) received ASCT as first-line therapy and 36 (31%), for recurrent disease. Risk factors affecting ASCT were analyzed with use of the Cox regression method. Metastatic disease at diagnosis, recurrence prior to ASCT and performance score <90 were associated with higher rates of disease recurrence/progression. Five-year probabilities of progression-free survival in patients with localized and metastatic disease at diagnosis who received ASCT as first-line therapy were 49% (95% CI 30 – 69) and 34% (95% CI 22 – 47) respectively. The 5-year probability of progression-free survival in patients with localized disease at diagnosis, and received ASCT after recurrence was 14% (95% CI 3 – 30). Progression-free survival rates after ASCT are comparable to published rates in patients with similar disease characteristics treated with conventional chemotherapy, surgery and irradiation suggesting a limited role for ASCT in these patients. Therefore, ASCT if considered should be for high-risk patients in the setting of carefully controlled clinical trials. PMID:18246113

  4. Multiple myeloma treatment at relapse after autologous stem cell transplantation: A practical analysis.

    PubMed

    Malard, F; Harousseau, J L; Mohty, M

    2017-01-01

    Over the past decade, significant advances have been made in the field of multiple myeloma. Introduction of the so-called novel agents, proteasome inhibitors (PI) and immunomodulatory drugs (IMiD), and improved supportive care have resulted in significantly better outcome. Standard first line treatment in fit patients include PI and IMiD based induction, high dose melphalan with autologous hematopoietic stem cell transplantation (ASCT) and consolidation/maintenance. However, despite these progresses MM remains incurable for the majority of patients and most patients will relapse. Next generation PI (carfilzomib, ixazomib) and IMiD (pomalidomide) and new therapeutic classes: monoclonal antibody (elotuzumab, daratumumab) and pan-deacetylase inhibitors (panobinostat) have been successfully evaluated in relapse multiple myeloma. Some of these new agents are now approved for multiple myeloma treatment at relapse. However choosing the most appropriate treatment at relapse may be difficult. This review sum up the most important studies and provide evidence to choose the most relevant therapeutic strategy for relapse after ASCT, based on disease, patient and previous treatment related parameters.

  5. Quality control of bacterial contamination in autologous peripheral blood stem cells for transplantation.

    PubMed

    Larrea, Luis; de la Rubia, Javier; Soler, Maria Angeles; Ribas, Paz; Fernández, Josè Maria; Picón, Isabel; García-Boyero, Raimundo; García-Bellés, Carmen; Roig, Roberto

    2004-10-01

    Microbiological follow-up is part of quality control of peripheral blood stem cell (PBSC) manipulation. We prospectively studied microbiological cultures performed in 865 consecutive untreated autologous PBSC harvests from 348 patients. Our aim was to know the rate of microbiological contamination, the optimum moment to evaluate the sample and the clinical significance of the positive findings. Fifty-nine of the 852 samples (6.9%) yielded a positive culture after PBSC collection (sample 1) and 62 samples also yielded positive results before cryopreservation (7.2%) (sample 2). At the time of the analysis, a total of 520 aphereses had been infused and the number of positive cultures after thawing (sample 3) and after washing (sample 4; 82 aphereses) was 5.4% and 2.3%, respectively. Most of the positive cultures were due to coagulase-negative staphylococci (48 isolates). After thawing 15 coagulase-negative staphylococci and 2 enterococci isolates were recovered. Comparison between samples using a marginal homogeneity test showed no differences in the rate of contamination observed at the different sampling points. Positive microbiological findings in collected PBSC are not due to contamination within the laboratory. Cryopreservation using DMSO does not eradicate bacteria and manipulation does not seem to affect results. To simplify the procedure it would be possible to eliminate the microbiological controls performed immediately before cryopreservation.

  6. Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma.

    PubMed

    Shah, Nina; Li, Li; McCarty, Jessica; Kaur, Indreshpal; Yvon, Eric; Shaim, Hila; Muftuoglu, Muharrem; Liu, Enli; Orlowski, Robert Z; Cooper, Laurence; Lee, Dean; Parmar, Simrit; Cao, Kai; Sobieiski, Catherine; Saliba, Rima; Hosing, Chitra; Ahmed, Sairah; Nieto, Yago; Bashir, Qaiser; Patel, Krina; Bollard, Catherine; Qazilbash, Muzaffar; Champlin, Richard; Rezvani, Katy; Shpall, Elizabeth J

    2017-03-14

    Multiple myeloma (MM) is a disease with known immune dysregulation. Natural killer (NK) cells have shown preclinical activity in MM. We conducted a first-in-human study of umbilical cord blood-derived (CB) NK cells for MM patients undergoing high dose chemotherapy and autologous haematopoietic stem cell transplantation (auto-HCT). Patients received lenalidomide (10 mg) on days -8 to -2, melphalan 200 mg/m(2) on day -7, CB-NK cells on day -5 and auto-HCT on day 0. Twelve patients were enrolled, three on each of four CB-NK cell dose levels: 5 × 10(6) , 1 × 10(7) , 5 × 10(7) and 1 × 10(8) CB-NK cells/kg. Ten patients had either high-risk chromosomal changes or a history of relapsed/progressed disease. There were no infusional toxicities and no graft-versus-host disease. One patient failed to engraft due to poor autologous graft quality and was rescued with a back-up autologous graft. Overall, 10 patients achieved at least a very good partial response as their best response, including eight with near complete response or better. With a median follow-up of 21 months, four patients have progressed or relapsed, two of whom have died. CB-NK cells were detected in vivo in six patients, with an activated phenotype (NKG2D(+) /NKp30(+) ). These data warrant further development of this novel cellular therapy.

  7. Recovery of mucosal-associated invariant T cells after myeloablative chemotherapy and autologous peripheral blood stem cell transplantation.

    PubMed

    Novak, Jan; Dobrovolny, Jan; Brozova, Jitka; Novakova, Lucie; Kozak, Tomas

    2016-11-01

    Immune reconstitution after high-dose chemotherapy and stem cell transplantation plays a key role in restoring immunocompetence including defense against infection, immune regulation, and onco-immune surveillance. In this work, we examined the recovery of mucosal-associated invariant T (MAIT) cells, recently discovered innate-like T cells, after various types of myeloablative chemotherapy and autologous peripheral blood stem cell transplantation in 29 patients. We show that MAIT cells are relatively resistant to myeloablative conditioning. The median amount of MAIT cells rises to 43 % around day +30 and is sustained through further measurements on days +60 and +100. Moreover, MAIT cell recovery reaches 100 % of pre-treatment values in 33 % of patients already by day +60. The only factor affecting recovery of MAIT cells is age, younger age being associated with earlier MAIT cell recovery. The pre-treatment quantity of MAIT cells carries a prognostic impact on the early post-transplantation course. Patients with high levels of MAIT cells pre-treatment have significantly lower peak CRP levels (79.45 vs. 150 mg/L) post-treatment, reflecting a clinical trend of less severe infectious complications (less febrile days and less days on intravenous antibiotics). Altogether these data suggest that a high proportion of MAIT cells survive myeloablative chemotherapy and maintain their capacity to fight against infections probably on mucosal surfaces.

  8. Investigation of the immune response to autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses.

    PubMed

    Pigott, John H; Ishihara, Akikazu; Wellman, Maxey L; Russell, Duncan S; Bertone, Alicia L

    2013-11-15

    Mesenchymal stem cells have demonstrated immunomodulatory capabilities as well as modest efficacy in animal models of joint injury, warranting further study as a potential treatment of joint disease. The goal of the study was to investigate the blood and synovial immune and histologic response to intra-articular injection of autologous, allogeneic, and xenogeneic bone marrow-derived mesenchymal stem cells (MSC) in horses. The study group consisted of 6 five-year-old Thoroughbred mares that had been injected previously with 15 million, genetically modified autologous, allogeneic, or xenogeneic MSC into the fetlock joints. One group of autologous cells was genetically modified to permit MSC biolocalization in the synovium. To assess response to the injection, synovial biopsies were obtained via arthroscopy 60 days after MSC injection for gross, histologic and molecular analyses. Peripheral blood mononuclear cells were isolated from each horse 120 days after MSC injection and co-cultured with a monolayer of each MSC group to permit quantification of activated CD4+ lymphocytes and cytokine release (ELISA) upon re-exposure to MSC. Arthroscopic examination revealed normal synovium with no grossly detrimental effect to the synovium or cartilage. Intra-articular MSC produced a persistent mononuclear infiltrate for at least 60 days, mostly perivascular, identified as CD3+ lymphocytes. An immune response (significant increase in CD4+ lymphocytes) was detected upon re-exposure to xenogeneic but not to allogeneic or autologous MSC. An inflammatory cytokine release from peripheral blood mononuclear cell/MSC co-cultures was present in all MSC groups but was significantly greater in the xenogeneic group. In conclusion, intra-articular injection of MSC, regardless of cell origin, incited a persistent mononuclear synovitis demonstrating a sustained biologic influence of these cells. Allogeneic cells did not elicit a detectable immune response upon re-exposure using our methods

  9. Post-5-fluorouracil human marrow: stem cell characteristics and renewal properties after autologous marrow transplantation.

    PubMed

    Stewart, F M; Temeles, D; Lowry, P; Thraves, T; Grosh, W W; Quesenberry, P J

    1993-05-01

    The effect of 5-fluorouracil (5-FU) pretreatment on human bone marrow (BM) progenitor/stem cells and recovery of hematopoiesis after autologous marrow transplant was studied. Twenty-one patients were treated with 5-FU (15 mg/kg to 45 mg/kg) intravenously (IV) for 1 to 3 days administered 6 to 22 days before BM harvest. Post-FU marrow was infused into 15 patients after high-dose cyclophosphamide, carmustine (BCNU), and VP-16 (CBV). Seventeen patients (historical controls) were treated with CBV and autologous BM transplantation but did not receive 5-FU before marrow harvest. The groups were comparable for diagnosis and prior therapy. In the 5-FU-treated group and control group, median recovery times for platelet count to 50,000/mm3 were 20 and 30 days, respectively (P = .007), and for platelet count to 100,000/mm3, 23 and 38 days, respectively (P = .007), while neutrophil recovery was not significantly altered. In vitro cultures with 1 to 7 growth factors (interleukin-1 [IL-1], IL-3, IL-4, IL-6, colony-stimulating factor-1 [CSF-1], granulocyte-macrophage colony-stimulating factor [GM-CSF], and G-CSF) were performed. In 8 of 10 patients whose marrow was studied before and after 5-FU treatment, the numbers of CFU-C responsive to the combination of GM-CSF and IL-3 was increased 6.15-fold by 5-FU pretreatment. In 4 of these patients, thymidine suicide of GM-CSF- and IL-3-stimulated CFU-C ranged from 17% to 42%. High proliferative potential colony-forming cell (HPP-CFC) was observed in low frequency in normal marrow and patient's marrow before 5-FU treatment. In 11 of 16 patients pretreated with 5-FU, increased numbers of HPP-CFC were noted. GM-CSF and IL-3 interacted synergistically to stimulate HPP-CFC. Multifactor combinations, especially GM-CSF + G-CSF + IL-3 + IL-6 + IL-1 + CSF-1 did not increase total colony count or classic HPP-CFC but did result in altered morphology, producing huge, loose colonies. The marrow from patients pretreated with 5-FU is enriched with

  10. sb203580 preconditioning recharges matrix-expanded human adult stem cells for chondrogenesis in an inflammatory environment - A feasible approach for autologous stem cell based osteoarthritic cartilage repair.

    PubMed

    Zhang, Ying; Pizzute, Tyler; Li, Jingting; He, Fan; Pei, Ming

    2015-09-01

    Autologous stem cells are a promising cell source for cartilage regeneration; however, cell replicative senescence and joint posttraumatic inflammation provide challenges in bringing this treatment modality to fruition. In this study, we hypothesized that preconditioning with p38 MAPK inhibitor (sb203580) would recharge decellularized extracellular matrix (dECM) expanded human synovium-derived stem cell (hSDSC) chondrogenesis in an inflammatory environment. We found that preconditioning with sb203580 greatly enhanced dECM expanded hSDSC proliferation and chondrogenic potential while supplementation with sb203580 in an induction medium dramatically retarded hSDSC chondrogenic differentiation, even for dECM expanded cells. We also found that sb203580 preconditioning enhanced matrix-expanded hSDSC chondrogenic capacity even in an interleukin-1 (IL-1) induced inflammatory environment. Non-detectable expression of HLA-DR in the hSDSCs grown on allogeneic dECM indicates the feasibility of commercial preparation of these dECMs from healthy, young donors for patients who need autologous transplantation. Our study indicated that p38 MAPK inhibitor has a distinctive priming effect on dECM mediated stem cell cartilage regeneration. Combined rejuvenation with sb203580 and dECM expansion can precondition hSDSCs' resurfacing capacity for osteoarthritic patients with cartilage defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Cell therapy with autologous mesenchymal stem cells-how the disease process impacts clinical considerations.

    PubMed

    Wang, Jin; Liao, Lianming; Wang, Shuiliang; Tan, Jianming

    2013-08-01

    The prospective clinical use of multipotent mesenchymal stromal cells (MSCs) holds enormous promise for the treatment of a large number of degenerative and age-related diseases. In particular, autologous MSCs isolated from bone marrow (BM) are considered safe and have been extensively evaluated in clinical trials. Nevertheless, different efficacies have been reported, depending on the health status and age of the donor. In addition, the biological functions of BM-MSCs from patients with various diseases may be impaired. Furthermore, medical treatments such as long-term chemotherapy and immunomodulatory therapy may damage the BM microenvironment and affect the therapeutic potential of MSCs. Therefore, a number of practical problems must be addressed before autologous BM-MSCs can be widely applied with higher efficiency in patients. As such, this review focuses on various factors that directly influence the biological properties of BM-MSCs, and we discuss the possible mechanisms of these alterations. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  12. Acupoint Injection of Autologous Stromal Vascular Fraction and Allogeneic Adipose-Derived Stem Cells to Treat Hip Dysplasia in Dogs

    PubMed Central

    Marx, Camila; Silveira, Maiele Dornelles; Selbach, Isabel; da Silva, Ariel Silveira; Braga, Luisa Maria Gomes de Macedo; Camassola, Melissa; Nardi, Nance Beyer

    2014-01-01

    Stem cells isolated from adipose tissue show great therapeutic potential in veterinary medicine, but some points such as the use of fresh or cultured cells and route of administration need better knowledge. This study aimed to evaluate the effect of autologous stromal vascular fraction (SVF, n = 4) or allogeneic cultured adipose-derived stem cells (ASCs, n = 5) injected into acupuncture points in dogs with hip dysplasia and weak response to drug therapy. Canine ASCs have proliferation and differentiation potential similar to ASCs from other species. After the first week of treatment, clinical evaluation showed marked improvement compared with baseline results in all patients treated with autologous SVF and three of the dogs treated with allogeneic ASCs. On days 15 and 30, all dogs showed improvement in range of motion, lameness at trot, and pain on manipulation of the joints, except for one ASC-treated patient. Positive results were more clearly seen in the SVF-treated group. These results show that autologous SVF or allogeneic ASCs can be safely used in acupoint injection for treating hip dysplasia in dogs and represent an important therapeutic alternative for this type of pathology. Further studies are necessary to assess a possible advantage of SVF cells in treating joint diseases. PMID:25180040

  13. In-vitro chondrogenic potential of synovial stem cells and chondrocytes allocated for autologous chondrocyte implantation - a comparison : Synovial stem cells as an alternative cell source for autologous chondrocyte implantation.

    PubMed

    Kubosch, Eva Johanna; Heidt, Emanuel; Niemeyer, Philipp; Bernstein, Anke; Südkamp, Norbert P; Schmal, Hagen

    2017-05-01

    The use of passaged chondrocytes is the current standard for autologous chondrocyte implantation (ACI). De-differentiation due to amplification and donor site morbidity are known drawbacks highlighting the need for alternative cell sources. Via clinically validated flow cytometry analysis, we compared the expression of human stem cell and cartilage markers (collagen type 2 (Col2), aggrecan (ACAN), CD44) of chondrocytes (CHDR), passaged chondrocytes for ACI (CellGenix™), bone marrow derived mesenchymal stem cells (BMSC), and synovial derived stem cells (SDSC). Primary, human BMSC and SDSC revealed similar adipogenic, osteogenic, and chondrogenic differentiation potential and stem cell marker expression. However, the expression of the chondrogenic markers Col2 and ACAN was statistically significant higher in SDSC. CHDR and SDSC expressed ACAN and CD44 equally, but Col2 was expressed more strongly on the SDSC surface. The marker expression of SDSC from osteoarthritic joints (Kellgren-Lawrence score ≥3) versus normal knees (Kellgren-Lawrence score ≤2) did not differ. Similarly, there was no difference between temporarily frozen and fresh SDSC. Col2 and ACAN surface expression declined with further passaging, whereas CD44 remained unchanged. We observed the same effect after reducing the serum content. When comparing CHDR for ACI with SDSC of the same passage (P2/3), both Col2 and ACAN, correlating with clinical outcome, were expressed higher in SDSC. In summary, SDSC demonstrated high differentiation potential and a stable chondrogenic phenotype. They might therefore be better suitable for ACI than BMSC or passaged CHDR.

  14. Utility of comorbidity assessment in predicting transplantation-related toxicity following autologous hematopoietic stem cell transplantation for multiple myeloma.

    PubMed

    Labonté, Laura; Iqbal, Tariq; Zaidi, Mukarram A; McDiarmid, Sheryl A; Huebsch, Lothar B; Tay, Jason; Atkins, Harold; Allan, David S

    2008-09-01

    Patients with coexisting medical problems may suffer increased toxicity and reduced quality of life after autologous hematopoietic stem cell transplantation (HSCT). The benefit of high-dose therapy for some patients with multiple myeloma (MM) is debatable. Decision tools that aid in identifying those patients with MM most suited for autologous HSCT may avoid the risk of excess toxicity. An objective assessment of comorbidities was performed in 126 patients with MM undergoing autologous HSCT using the Charlson comorbidity index (CCI), the hematopoietic cell transplantation comorbidity index (HCT-CI), and a modified pretransplantation assessment of mortality (mPAM) to determine the strength of association with increased transplantation-related toxicity and increased length of hospital stay (LOS). Any comorbidity scored using the CCI or HCT-CI (score > 0) was associated with an increased number of organ systems with serious toxicity (at least grade 2 toxicity using the Seattle criteria), an increased total sum of toxicity grades for all organs, and prolonged LOS. An mPAM score > or = 24 was associated with increased LOS. When considering autologous HSCT for a patient with MM, assessment of comorbidities using the CCI or HCT-CI may assist in predicting the risk of transplantation-related toxicity as an adjunct to physician judgment and patient preference.

  15. Salvage autologous stem cell transplantation for multiple myeloma relapsing or progressing after up-front autologous transplantation.

    PubMed

    Auner, Holger W; Szydlo, Richard; Rone, Alero; Chaidos, Aristeidis; Giles, Chrissy; Kanfer, Ed; Macdonald, Donald H; Marin, David; Milojkovic, Dragana; Pavlu, Jiri; Apperley, Jane F; Rahemtulla, Amin

    2013-10-01

    Progression or relapse occurs in the vast majority of patients with multiple myeloma (MM) who undergo up-front autologous hematopoietic cell transplantation (AHCT1), which remains a cornerstone of treatment in the era of novel agents. Limited data are available regarding the value of salvage therapy with a second AHCT (AHCT2) in patients who relapse/progress after AHCT1. We analyzed the outcome of 83 patients who underwent salvage AHCT2 between 1994 and 2011. Most patients (77%) had received treatment with novel agents between AHCT1 and AHCT2, and 28% of patients were from ethnic minority groups. Median overall survival (OS) from AHCT2 was 31.5 months (95% confidence interval [CI]: 22-41), and median progression-free survival (PFS) was 15.5 months (95% CI: 11-20). In multivariate analysis, only disease status (≥ PR) at AHCT2 was associated with better OS. The 3-year OS rates for patients receiving AHCT2 in > PR and PR were 85.9% (95% CI: 61-96) and 51.3% (95% CI: 34-68), respectively. Disease status at AHCT2 and time to progression/relapse after AHCT1 were associated with PFS in multivariate analysis. In summary, salvage AHCT2 is an effective treatment option in patients with chemosensitive relapse/progression and prolonged remission after a prior autograft.

  16. Neural stem cell-like cells derived from autologous bone mesenchymal stem cells for the treatment of patients with cerebral palsy.

    PubMed

    Chen, Guojun; Wang, Yali; Xu, Zhenyu; Fang, Feng; Xu, Renmei; Wang, Yue; Hu, Xiaoli; Fan, Lixing; Liu, Houqi

    2013-01-26

    Stem cell therapy is a promising treatment for cerebral palsy, which refers to a category of brain diseases that are associated with chronic motor disability in children. Autologous MSCs may be a better cell source and have been studied for the treatment of cerebral palsy because of their functions in tissue repair and the regulation of immunological processes. To assess neural stem cell-like (NSC-like) cells derived from autologous marrow mesenchymal stem cells as a novel treatment for patients with moderate-to-severe cerebral palsy, a total of 60 cerebral palsy patients were enrolled in this open-label, non-randomised, observer-blinded controlled clinical study with a 6-months follow-up. For the transplantation group, a total of 30 cerebral palsy patients received an autologous NSC-like cells transplantation (1-2 × 107 cells into the subarachnoid cavity) and rehabilitation treatments whereas 30 patients in the control group only received rehabilitation treatment. We recorded the gross motor function measurement scores, language quotients, and adverse events up to 6 months post-treatment. The gross motor function measurement scores in the transplantation group were significantly higher at month 3 (the score increase was 42.6, 95% CI: 9.8-75.3, P=.011) and month 6 (the score increase was 58.6, 95% CI: 25.8-91.4, P=.001) post-treatment compared with the baseline scores. The increase in the Gross Motor Function Measurement scores in the control group was not significant. The increases in the language quotients at months 1, 3, and 6 post-treatment were not statistically significant when compared with the baseline quotients in both groups. All the 60 patients survived, and none of the patients experienced serious adverse events or complications. Our results indicated that NSC-like cells are safe and effective for the treatment of motor deficits related to cerebral palsy. Further randomised clinical trials are necessary to establish the efficacy of this procedure.

  17. Reconstruction of damaged cornea by autologous transplantation of epidermal adult stem cells.

    PubMed

    Yang, Xueyi; Moldovan, Nicanor I; Zhao, Qingmei; Mi, Shengli; Zhou, Zhenhui; Chen, Dan; Gao, Zhimin; Tong, Dewen; Dou, Zhongying

    2008-06-05

    It is crucial for the treatment of severe ocular surface diseases such as Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP) to find strategies that avoid the risks of allograft rejection and immunosuppression. Here, we report a new strategy for reconstructing the damaged corneal surface in a goat model of total limbal stem cell deficiency (LSCD) by autologous transplantation of epidermal adult stem cells (EpiASC). EpiASC derived from adult goat ear skin by explant culture were purified by selecting single cell-derived clones. These EpiASC were cultivated on denuded human amniotic membrane (HAM) and transplanted onto goat eyes with total LSCD. The characteristics of both EpiASC and reconstructed corneal epithelium were identified by histology and immunohistochemistry. The clinical characteristic of reconstructed corneal surface was observed by digital camera. Ten LSCD goats (10 eyes) were treated with EpiASC transplantation, leading to the restoration of corneal transparency and improvement of postoperative visual acuity to varying degrees in 80.00% (8/10) of the experimental eyes. The corneal epithelium of control groups either with HAM transplantation only or without any transplantation showed irregular surfaces, diffuse vascularization, and pannus on the entire cornea. The reconstructed corneal epithelium (RCE) expressed CK3, CK12, and PAX-6 and had the function of secreting glycocalyx-like material (AB-PAS positive). During the follow-up period, all corneal surfaces remained transparent and there were no serious complications. We also observed that the REC expressed CK1/10 weakly at six months after operation but not at 12 months after operation, suggesting that the REC was derived from grafted EpiASC. Our results showed that EpiASC repaired the damaged cornea of goats with total LSCD and demonstrated that EpiASC can be induced to differentiate into corneal epithelial cell types in vivo, which at least in part correlated with down

  18. Efficacy and safety of autologous hematopoietic stem cell therapy for refractory Crohn's disease: A systematic review and meta-analysis.

    PubMed

    Qiu, Xiao; Feng, Jue-Rong; Chen, Li-Ping; Liu, Shi; Zhang, Meng; Zhou, Zhou; Liu, Jing; Zhao, Qiu

    2017-06-01

    Autologous hematopoietic stem cell transplantation (HSCT) has been proposed for patients with refractory Crohn's disease (CD), but it is associated with mortality and adverse events; the balance between risks and benefits becomes significantly important in the therapy. The aim of the study was to assess the efficacy and safety of autologous HSCT therapy for refractory CD. We conducted a comprehensive search of PubMed, Embase, the Cochrane library, and Web of Science from inception to February 2017. The pooled estimate rates for efficacy and safety of refractory CD was performed by meta-analysis and reported according to the standard Cochrane guidelines and the PRISMA statement. Four prospective uncontrolled cohort studies, 4 prospective case series, and 1 randomized controlled trial (RCT) were included. Autologous HSCT had a high rate of clinical and endoscopic remission in refractory CD [79.4%, 95% confidence interval (95% CI): 0.550-0.924; 81.9%, 95% CI: 0.603-0.931, respectively]. In the case of safety, it had a relatively high incidence rate of transplant-related mortality (6.4%, 95% CI: 0.028-0.140). A significant association was observed between autologous HSCT and the incidence of febrile neutropenia (83.2%, 95% CI: 0.632-0.934). About 18.5% (95% CI: 0.061-0.442) of patients with refractory CD reached clinical remission at mobilization phase. Besides, 82.1% (95% CI: 0.692-0.903) and 54.1% (95% CI: 0.261-0.797) patients with refractory CD could achieve immunosuppressive-free and steroid-free remission for at least 12 months after the therapy. Autologous HSCT could be a complicated treatment with relatively high mortality and significantly high efficacy for refractory CD, which should be used with caution. However, more RCTs of larger samples using refined and standardized protocols and longer period of follow-up time are needed to further assess the outcomes of autologous HSCT therapy.

  19. Characterization of autologous mesenchymal stem cell-derived neural progenitors as a feasible source of stem cells for central nervous system applications in multiple sclerosis.

    PubMed

    Harris, Violaine K; Faroqui, Raihan; Vyshkina, Tamara; Sadiq, Saud A

    2012-07-01

    Bone marrow mesenchymal stem cell-derived neural progenitors (MSC-NPs) are a potential therapeutic source of cells that have been shown to be efficacious in a preclinical model of multiple sclerosis (MS). To examine the feasibility of using MSC-NPs as an autologous source of cells to promote central nervous system (CNS) repair in MS, this study characterized human MSC-NPs from a panel of both MS and non-MS donors. Expanded MSCs showed similar characteristics in terms of growth and cell surface phenotype, regardless of the donor disease status. MSC-NPs derived from all MSCs showed a consistent pattern of gene expression changes that correlated with neural commitment and increased homogeneity. Furthermore, the reduced expression of mesodermal markers and reduced capacity for adipogenic or osteogenic differentiation in MSC-NPs compared with MSCs suggested that MSC-NPs have reduced potential of unwanted mesodermal differentiation upon CNS transplantation. The immunoregulatory function of MSC-NPs was similar to that of MSCs in their ability to suppress T-cell proliferation and to promote expansion of FoxP3-positive T regulatory cells in vitro. In addition, MSC-NPs promoted oligodendroglial differentiation from brain-derived neural stem cells that correlated with the secretion of bioactive factors. Our results provide a set of identity characteristics for autologous MSC-NPs and suggest that the in vitro immunoregulatory and trophic properties of these cells may have therapeutic value in the treatment of MS.

  20. Concise Review: Human Dermis as an Autologous Source of Stem Cells for Tissue Engineering and Regenerative Medicine

    PubMed Central

    Vapniarsky, Natalia; Arzi, Boaz; Hu, Jerry C.; Nolta, Jan A.

    2015-01-01

    The exciting potential for regenerating organs from autologous stem cells is on the near horizon, and adult dermis stem cells (DSCs) are particularly appealing because of the ease and relative minimal invasiveness of skin collection. A substantial number of reports have described DSCs and their potential for regenerating tissues from mesenchymal, ectodermal, and endodermal lineages; however, the exact niches of these stem cells in various skin types and their antigenic surface makeup are not yet clearly defined. The multilineage potential of DSCs appears to be similar, despite great variability in isolation and in vitro propagation methods. Despite this great potential, only limited amounts of tissues and clinical applications for organ regeneration have been developed from DSCs. This review summarizes the literature on DSCs regarding their niches and the specific markers they express. The concept of the niches and the differentiation capacity of cells residing in them along particular lineages is discussed. Furthermore, the advantages and disadvantages of widely used methods to demonstrate lineage differentiation are considered. In addition, safety considerations and the most recent advancements in the field of tissue engineering and regeneration using DSCs are discussed. This review concludes with thoughts on how to prospectively approach engineering of tissues and organ regeneration using DSCs. Our expectation is that implementation of the major points highlighted in this review will lead to major advancements in the fields of regenerative medicine and tissue engineering. Significance Autologous dermis-derived stem cells are generating great excitement and efforts in the field of regenerative medicine and tissue engineering. The substantial impact of this review lies in its critical coverage of the available literature and in providing insight regarding niches, characteristics, and isolation methods of stem cells derived from the human dermis. Furthermore, it

  1. Concise Review: Human Dermis as an Autologous Source of Stem Cells for Tissue Engineering and Regenerative Medicine.

    PubMed

    Vapniarsky, Natalia; Arzi, Boaz; Hu, Jerry C; Nolta, Jan A; Athanasiou, Kyriacos A

    2015-10-01

    The exciting potential for regenerating organs from autologous stem cells is on the near horizon, and adult dermis stem cells (DSCs) are particularly appealing because of the ease and relative minimal invasiveness of skin collection. A substantial number of reports have described DSCs and their potential for regenerating tissues from mesenchymal, ectodermal, and endodermal lineages; however, the exact niches of these stem cells in various skin types and their antigenic surface makeup are not yet clearly defined. The multilineage potential of DSCs appears to be similar, despite great variability in isolation and in vitro propagation methods. Despite this great potential, only limited amounts of tissues and clinical applications for organ regeneration have been developed from DSCs. This review summarizes the literature on DSCs regarding their niches and the specific markers they express. The concept of the niches and the differentiation capacity of cells residing in them along particular lineages is discussed. Furthermore, the advantages and disadvantages of widely used methods to demonstrate lineage differentiation are considered. In addition, safety considerations and the most recent advancements in the field of tissue engineering and regeneration using DSCs are discussed. This review concludes with thoughts on how to prospectively approach engineering of tissues and organ regeneration using DSCs. Our expectation is that implementation of the major points highlighted in this review will lead to major advancements in the fields of regenerative medicine and tissue engineering. Autologous dermis-derived stem cells are generating great excitement and efforts in the field of regenerative medicine and tissue engineering. The substantial impact of this review lies in its critical coverage of the available literature and in providing insight regarding niches, characteristics, and isolation methods of stem cells derived from the human dermis. Furthermore, it provides

  2. [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

    2017-01-01

    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.

  3. An animal model study for repair of tracheal defects with autologous stem cells and differentiated chondrocytes from adipose-derived stem cells.

    PubMed

    Hashemibeni, Batool; Goharian, Vahid; Esfandiari, Ebrahim; Sadeghi, Farzaneh; Fasihi, Farzaneh; Alipur, Razie; Valiani, Ali; Ghorbani, Masoud; Emami, Zahra Motavali; Shabani, Fatemeh; Goharian, Maryam

    2012-11-01

    Stenosis of trachea with mucosal and cartilage lesions is a challenging problem in tracheal surgery. Owing to ease of harvest and abundance, adipose-derived stem cells (ADSCs) are attractive and increasingly used in tissue engineering. The aim of this study was to evaluate the repair of trachea with autologous stem cells and differentiated chondrocytes from adipose-derived stem cells in an animal model. Six canine ADSCs were isolated and proliferated in monolayer culture and CD44; CD90 markers were investigated by flow cytometry. ADSCs were seeded in alginate beads and were differentiated into chondrocytes by TGF-β3. Cartilage-specific markers with reverse transcriptase polymerase chain reaction were demonstrated in differentiated cells. These differentiated cells and stem cells in alginate scaffold were separately transferred to a defect created in canine's trachea. After 8 weeks, the healing and cartilage formation in the trachea was evaluated by histological methods. We identified formed cartilage pieces and chondrocytes with lacuna and extracellular matrix in defects implanted with differentiated cells, but in other groups, staining of the sections did not show the presence of cartilage in the engineered tracheal wall. We showed that cartilage- engineered from differentiated adipose-derived stem cells in alginate biodegradable scaffold could repair tracheal cartilage defects. Published by Elsevier Inc.

  4. Neural stem cell-like cells derived from autologous bone mesenchymal stem cells for the treatment of patients with cerebral palsy

    PubMed Central

    2013-01-01

    Background Stem cell therapy is a promising treatment for cerebral palsy, which refers to a category of brain diseases that are associated with chronic motor disability in children. Autologous MSCs may be a better cell source and have been studied for the treatment of cerebral palsy because of their functions in tissue repair and the regulation of immunological processes. Methods To assess neural stem cell–like (NSC-like) cells derived from autologous marrow mesenchymal stem cells as a novel treatment for patients with moderate-to-severe cerebral palsy, a total of 60 cerebral palsy patients were enrolled in this open-label, non-randomised, observer-blinded controlled clinical study with a 6-months follow-up. For the transplantation group, a total of 30 cerebral palsy patients received an autologous NSC-like cells transplantation (1-2 × 107 cells into the subarachnoid cavity) and rehabilitation treatments whereas 30 patients in the control group only received rehabilitation treatment. Results We recorded the gross motor function measurement scores, language quotients, and adverse events up to 6 months post-treatment. The gross motor function measurement scores in the transplantation group were significantly higher at month 3 (the score increase was 42.6, 95% CI: 9.8–75.3, P=.011) and month 6 (the score increase was 58.6, 95% CI: 25.8–91.4, P=.001) post-treatment compared with the baseline scores. The increase in the Gross Motor Function Measurement scores in the control group was not significant. The increases in the language quotients at months 1, 3, and 6 post-treatment were not statistically significant when compared with the baseline quotients in both groups. All the 60 patients survived, and none of the patients experienced serious adverse events or complications. Conclusion Our results indicated that NSC-like cells are safe and effective for the treatment of motor deficits related to cerebral palsy. Further randomised clinical trials are necessary to

  5. Very small embryonic-like stem cells with maximum regenerative potential get discarded during cord blood banking and bone marrow processing for autologous stem cell therapy.

    PubMed

    Bhartiya, Deepa; Shaikh, Ambreen; Nagvenkar, Punam; Kasiviswanathan, Sandhya; Pethe, Prasad; Pawani, Harsha; Mohanty, Sujata; Rao, S G Ananda; Zaveri, Kusum; Hinduja, Indira

    2012-01-01

    Very small embryonic-like stem cells (VSELs) are possibly lost during cord blood banking and bone marrow (BM) processing for autologus stem cell therapy mainly because of their small size. The present study was conducted on human umbilical cord blood (UCB, n=6) and discarded red blood cells (RBC) fraction obtained after separation of mononuclear cells from human BM (n=6), to test this hypothesis. The results show that VSELs, which are pluripotent stem cells with maximum regenerative potential, settle along with the RBCs during Ficoll-Hypaque density separation. These cells are very small in size (3-5 μm), have high nucleo-cytoplasmic ratio, and express nuclear Oct-4, cell surface protein SSEA-4, and other pluripotent markers such as Nanog, Sox-2, Rex-1, and Tert as indicated by immunolocalization and quantitative polymerase chain reaction (Q-PCR) studies. Interestingly, a distinct population of slightly larger, round hematopoietic stem cells (HSCs) with cytoplasmic Oct-4 were detected in the "buffy" coat, which usually gets banked or used during autologus stem cell therapy. Immunohistochemical studies on the umbilical cord tissue (UCT) sections (n=3) showed the presence of nuclear Oct-4-positive VSELs and many fibroblast-like mesenchymal stem cells (MSCs) with cytoplasmic Oct-4. These VSELs with nuclear Oct-4, detected in UCB, UCT, and discarded RBC fraction obtained after BM processing, may persist throughout life, maintain tissue homeostasis, and undergo asymmetric cell division to self-renew as well as produce larger progenitor stem cells, viz. HSCs or MSCs, which follow differentiation trajectories depending on the somatic niche. Hence, it can be concluded that the true stem cells in adult body tissues are the VSELs, whereas the HSCs and MSCs are actually progenitor stem cells that arise by asymmetric cell division of VSELs. The results of the present study may help explain low efficacy reported during adult autologous stem cell trials, wherein unknowingly

  6. Epstein-Barr virus-associated lymphoproliferative disorder developed following autologous peripheral blood stem cell transplantation for relapsing Hodgkin's lymphoma.

    PubMed

    Izumiya, Sakura; Ishida, Mitsuaki; Hodohara, Keiko; Yoshida, Takashi; Okabe, Hidetoshi

    2012-06-01

    Post-transplant lymphoproliferative disorders (PTLDs) are lymphoid or plasmacytic proliferations that develop as a consequence of immunosuppression in a recipient of a solid organ, bone marrow or stem cell allograft. The development of PTLDs is usually associated with Epstein-Barr virus (EBV) and the disorder is also termed EBV-associated lymphoproliferative disorder (LPD). The development of PTLD is a rare complication in autologous bone marrow/peripheral blood stem cell transplantation. In the present study, we report a case of EBV-associated LPD which developed following autologous peripheral blood stem cell transplantation for relapsing Hodgkin's lymphoma. A 51-year-old male presented with swelling of the left cervical lymph nodes. A biopsy revealed nodular sclerosis classical Hodgkin's lymphoma. Following four courses of ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) therapy, the Hodgkin's lymphoma relapsed. CHASE (cyclophosphamide, etoposide, cytarabine, dexamethasone) therapy and autologous peripheral blood stem cell transplantation were performed. In the 128 days following the transplantation, lymph node swelling was noted and a biopsy specimen demonstrated EBV-associated LPD. The serum copy number of EBV-DNA was 2.7×10(3) copies/ml. The occurrence of EBV-associated LPD may be on the rise due to the increased number of patients undergoing immunosuppression therapy. The measurement of the serum EBV-DNA copy number and the detection of EBV-infected atypical lymphocytes using in situ hybridization are significant in establishing an early accurate diagnosis and initiating the correct treatment for EBV-associated LPD in patients with immunosuppression.

  7. Content of endothelial progenitor cells in autologous stem cell grafts predict survival after transplantation for multiple myeloma.

    PubMed

    Blix, Egil S; Kildal, Anders B; Bertelsen, Eirin; Waage, Anders; Myklebust, June H; Kolstad, Arne; Husebekk, Anne

    2015-05-01

    Multiple myeloma (MM) is considered an incurable B cell malignancy, although many patients can benefit from high-dose therapy with autologous stem cell transplantation (ASCT) as a first-line treatment. In non-Hodgkin lymphoma (NHL), ASCT is usually performed after relapse with curative intent. Disease progression is often associated with increased angiogenesis, in which endothelial progenitor cells (EPC) may have a central role. Here, we investigated the clinical impact of EPC levels in peripheral blood stem cell (PBSC) autografts for MM and NHL patients who received ASCT. EPC were identified by flow cytometry as aldehyde dehydrogenase(hi) CD34(+) vascular endothelial growth factor receptor 2(+) CD133(+) cells in both MM and NHL autografts. In MM, there was a positive correlation between EPC percentage and serum (s)-β2-microglobulin levels (r(2) = .371, P = .002). Unlike for NHL patients, MM patients with high numbers of infused EPC (EPC cells per kilogram) during ASCT had significant shorter progression-free survival (PFS) (P = .035), overall survival (P = .044) and time to next treatment (P = .009). In multivariate analysis, EPC cells per kilogram was a significant independent negative prognostic indicator of PFS (P = .03). In conclusion, the presence of high number of EPC in PBSC grafts is associated with adverse prognosis after ASCT in MM. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  8. Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis.

    PubMed

    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; Muraro, Paolo A

    2013-09-01

    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 CD56(high) 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 CD161(high) proinflammatory CD8+ T cell subset was depleted at all time-points post-transplantation. Phenotypic characterization revealed that the CD161(high)CD8+ T cells were mucosal-associated invariant T cells, a novel cell population

  9. Pegfilgrastim vs. filgrastim for supportive care after autologous stem cell transplantation: can we decide?

    PubMed

    Ziakas, Panayiotis D; Kourbeti, Irene S

    2012-01-01

    Granulocyte-colony-stimulating factors are helpful for the support of patients receiving autologous hematopoietic stem cell transplantation, resulting in faster neutrophil recovery and lower incidence of febrile neutropenia (FN). Our aim was to evaluate the use of pegfilgrastim vs. filgrastim with regard to absolute neutrophil count (ANC) recovery, risk, and duration of FN and length of hospital stay. Mean difference was the summary effect for continuous data, and odds ratio for binary data, using random-effects modeling. MEDLINE, EMBASE, and the Cochrane Registry of Randomized Controlled Trials were included in the search. Randomized controlled trials (RCTs), case-control studies, and studies with historical control group for filgrastim were eligible. Of the initial 114 studies screened, 12 studies were analyzed (four were RCTs, including one phase III trial). The use of pegfilgrastim resulted in a one d gain in ANC recovery (mean difference -0.82, 95% CI -1.07 to -0.57, p < 0.001) and duration of FN (-0.67, 95% CI -1.28 to -0.06, p < 0.001) but had no effect on the risk of FN or length of stay. Pegfilgrastim was more expensive (baseline marginal cost €116.97, p < 0.001), which was largely determined by the treatment duration and pegfilgrastim cost. Non-randomized setting attenuated the effect on duration of FN whereas delayed onset of filgrastim injections (to pegfilgrastim) overestimated the protective effect on the risk of FN. Both drugs are at least equally effective, though methodology and disease stratification in published trials warrant further improvement. © 2011 John Wiley & Sons A/S.

  10. Autologous stem cell transplantation in diffuse scleroderma: impact on hand structure and function.

    PubMed

    Englert, H; Kirkham, S; Moore, J; Poon, T S; Katelaris, C; McGill, N; Schrieber, L; Manolios, N

    2008-09-01

    The aim of the study was to assess the structural and functional effects of autologous stem cell transplantation (ASCT) on scleroderma finger clawing. Using photocopies of hands of five scleroderma patients who underwent ASCT using photocopies of hands. Functional assessments used a standardized questionnaire. Pre-ASCT, synovitis and tenosynovitis were present in five and four patients, respectively. Modified Rodnan hand skin scores ranged from 6-12/12. Following pulsed chemotherapy, synovitis resolved. Tenosynovitis often did not. Post-ASCT, skin scores fell in four patients (range 0-6/12). Hand tenosynovitis resolved. With disease remission hand function globally improved. Functional improvement, noted early (+3 months) and continuously (+12 months) in disease remitters, occurred in all areas of function. Greatest hand-functional improvement related to paid employment, followed by self-care and hygiene, home-care activities and least by hobbies/sports. The second to fifth metacarpophalangeal width was reproducible and independent of ASCT therapy. In contrast, hand length and measures of abducted finger span (first to fifth fingertip and second to fifth fingertip distance) improved. Finger abduction (abducted first to fifth fingertips/second to fifth metacarpophalangeal width) was a more sensitive discriminator of finger clawing than hand length or hand length/second to fifth metacarpophalangeal width. ASCT improved hand scleroderma over 12 months and resolved previously refractory tenosynovitis. ASCT was unnecessary to treat scleroderma synovitis. ASCT secondarily improved hand function (paid employment, followed by self-care, home care, then by sport/hobbies). Loss of finger abduction was a more sensitive measure of finger clawing than apparent loss of hand length.

  11. Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience.

    PubMed

    Burman, Joachim; Iacobaeus, Ellen; Svenningsson, Anders; Lycke, Jan; Gunnarsson, Martin; Nilsson, Petra; Vrethem, Magnus; Fredrikson, Sten; Martin, Claes; Sandstedt, Anna; Uggla, Bertil; Lenhoff, Stig; Johansson, Jan-Erik; Isaksson, Cecilia; Hägglund, Hans; Carlson, Kristina; Fagius, Jan

    2014-10-01

    Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS. Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months. At 5 years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%). HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a phase II trial.

    PubMed

    Mancardi, Giovanni L; Sormani, Maria P; Gualandi, Francesca; Saiz, Albert; Carreras, Eric; Merelli, Elisa; Donelli, Amedea; Lugaresi, Alessandra; Di Bartolomeo, Paolo; Rottoli, Maria R; Rambaldi, Alessandro; Amato, Maria P; Massacesi, Luca; Di Gioia, Massimo; Vuolo, Luisa; Currò, Daniela; Roccatagliata, Luca; Filippi, Massimo; Aguglia, Umberto; Iacopino, Pasquale; Farge, Dominique; Saccardi, Riccardo

    2015-03-10

    To assess in multiple sclerosis (MS) the effect of intense immunosuppression followed by autologous hematopoietic stem cells transplantation (AHSCT) vs mitoxantrone (MTX) on disease activity measured by MRI. We conducted a multicenter, phase II, randomized trial including patients with secondary progressive or relapsing-remitting MS, with a documented increase in the last year on the Expanded Disability Status Scale, in spite of conventional therapy, and presence of one or more gadolinium-enhancing (Gd+) areas. Patients were randomized to receive intense immunosuppression (mobilization with cyclophosphamide and filgrastim, conditioning with carmustine, cytosine-arabinoside, etoposide, melphalan, and anti-thymocyte globulin) followed by AHSCT or MTX 20 mg every month for 6 months. The primary endpoint was the cumulative number of new T2 lesions in the 4 years following randomization. Secondary endpoints were the cumulative number of Gd+ lesions, relapse rate, and disability progression. Safety and tolerability were also assessed. Twenty-one patients were randomized and 17 had postbaseline evaluable MRI scans. AHSCT reduced by 79% the number of new T2 lesions as compared to MTX (rate ratio 0.21, p = 0.00016). It also reduced Gd+ lesions as well as the annualized relapse rate. No difference was found in the progression of disability. Intense immunosuppression followed by AHSCT is significantly superior to MTX in reducing MRI activity in severe cases of MS. These results strongly support further phase III studies with primary clinical endpoints. The study was registered as EUDRACT No. 2007-000064-24. © 2015 American Academy of Neurology.

  13. Autologous hematopoietic stem cell transplantation in multiple sclerosis: A meta-analysis.

    PubMed

    Sormani, Maria Pia; Muraro, Paolo A; Schiavetti, Irene; Signori, Alessio; Laroni, Alice; Saccardi, Riccardo; Mancardi, Gian Luigi

    2017-05-30

    To summarize the evidence on immunoablative therapy followed by autologous hematopoietic stem cell transplantation (aHSCT) to manage severe and treatment-refractory multiple sclerosis (MS). We collected all the published studies of aHSCT in any form of MS from 1995 to 2016, carefully excluding reports that were updated in subsequent studies. Endpoints were transplant-related mortality (TRM), rate of disease progression, and no evidence of disease activity (NEDA) status. A weighted metaregression based on a Poisson model was run, assessing whether there were study-specific characteristics with an effect on TRM and progression. Fifteen studies including 764 transplanted patients were pooled in the meta-analysis. The pooled estimate of TRM was 2.1% (95% confidence interval [CI] 1.3%-3.4%). TRM was higher in older studies (p = 0.014) and in studies with a lower proportion of patients with relapsing-remitting MS (RRMS) (p = 0.028). A higher baseline Expanded Disability Status Scale (p = 0.013) was also significantly associated with a higher TRM. Pooled rate of progression was 17.1% at 2 years (95% CI 9.7%-24.5%) and 23.3% (95% CI 16.3%-31.8%) at 5 years. Lower 2-year progression rate was significantly associated with higher proportions of patients with RRMS (p = 0.004). The pooled proportion of NEDA patients at 2 years was 83% (range 70%-92%) and at 5 years was 67% (range 59%-70%). The emerging evidence on this therapeutic approach in MS indicates that the largest benefit/risk profile form this therapeutic approach can be obtained in patients with aggressive MS with a relapsing-remitting course and who have not yet accumulated a high level of disability. © 2017 American Academy of Neurology.

  14. Addition of Mesenchymal Stem Cells to Autologous Platelet-Enhanced Fibrin Scaffolds in Chondral Defects

    PubMed Central

    Goodrich, Laurie R.; Chen, Albert C.; Werpy, Natasha M.; Williams, Ashley A.; Kisiday, John D.; Su, Alvin W.; Cory, Esther; Morley, Paul S.; McIlwraith, C. Wayne; Sah, Robert L.; Chu, Constance R.

    2016-01-01

    Background: The chondrogenic potential of culture-expanded bone-marrow-derived mesenchymal stem cells (BMDMSCs) is well described. Numerous studies have also shown enhanced repair when BMDMSCs, scaffolds, and growth factors are placed into chondral defects. Platelets provide a rich milieu of growth factors and, along with fibrin, are readily available for clinical use. The objective of this study was to determine if the addition of BMDMSCs to an autologous platelet-enriched fibrin (APEF) scaffold enhances chondral repair compared with APEF alone. Methods: A 15-mm-diameter full-thickness chondral defect was created on the lateral trochlear ridge of both stifle joints of twelve adult horses. In each animal, one defect was randomly assigned to receive APEF+BMDMSCs and the contralateral defect received APEF alone. Repair tissues were evaluated one year later with arthroscopy, histological examination, magnetic resonance imaging (MRI), micro-computed tomography (micro-CT), and biomechanical testing. Results: The arthroscopic findings, MRI T2 map, histological scores, structural stiffness, and material stiffness were similar (p > 0.05) between the APEF and APEF+BMDMSC-treated repairs at one year. Ectopic bone was observed within the repair tissue in four of twelve APEF+BMDMSC-treated defects. Defects repaired with APEF alone had less trabecular bone edema (as seen on MRI) compared with defects repaired with APEF+BMDMSCs. Micro-CT analysis showed thinner repair tissue in defects repaired with APEF+BMDMSCs than in those treated with APEF alone (p < 0.05). Conclusions: APEF alone resulted in thicker repair tissue than was seen with APEF+BMDMSCs. The addition of BMDMSCs to APEF did not enhance cartilage repair and stimulated bone formation in some cartilage defects. Clinical Relevance: APEF supported repair of critical-size full-thickness chondral defects in horses, which was not improved by the addition of BMDMSCs. This work supports further investigation to determine

  15. 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.

  16. Autologous stem cell transplantation: an effective salvage therapy in multiple myeloma.

    PubMed

    Lemieux, Emilie; Hulin, Cyrille; Caillot, Denis; Tardy, Stéphanie; Dorvaux, Véronique; Michel, Jessica; Gastinne, Thomas; Rossi, Cédric; Legouge, Caroline; Touzeau, Cyrille; Planche, Lucie; Loirat, Marion; Lafon, Ingrid; Moreau, Philippe

    2013-03-01

    Eighty-one patients treated with high-dose therapy and autologous stem cell transplantation (ASCT) as part of salvage therapy after a frontline ASCT were included in a retrospective analysis. The median time between the first and the salvage ASCT was 47 months. After salvage ASCT, 75 patients (93%) achieved at least a partial response, including 67% very good partial responses, and no toxic death was reported. Sixteen patients (20%) underwent consolidation therapy, whereas 30 patients (37%) underwent some form of maintenance therapy after salvage ASCT. For all patients, the median overall survival (OS) was 10 years from diagnosis and 4 years from salvage ASCT. The median progression-free survival (PFS) from the date of the first ASCT to the date of the first relapse was 40 months, and the median PFS from the date of salvage ASCT to the date of subsequent progression was 18 months. In the multivariate analysis of prognostic factors, three independent factors unfavorably affected PFS: a short duration of response to the first ASCT (cut-off value of 24 months), a response less than a very good partial response after salvage therapy, and no maintenance treatment after salvage ASCT. Age over 60 years and a short duration of response after the first ASCT were the two factors adversely affecting OS from the time of diagnosis and OS from the time of salvage ASCT. Our data show that salvage ASCT is a feasible option that should be routinely considered at the time of relapse for patients with a response duration of more than 2 years to frontline high-dose therapy.

  17. Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Atypical Teratoid/Rhabdoid Tumor

    PubMed Central

    Sung, Ki Woong; Lim, Do Hoon; Yi, Eun Sang; Choi, Young Bae; Lee, Ji Won; Yoo, Keon Hee; Koo, Hong Hoe; Kim, Ji Hye; Suh, Yeon-Lim; Joung, Yoo Sook; Shin, Hyung Jin

    2016-01-01

    Purpose We prospectively evaluated the effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in improving the survival of patients with atypical teratoid/rhabdoid tumors while reducing the risks of late adverse effects from radiotherapy (RT). Materials and Methods For young children (< 3 years old), tandem HDCT/auto-SCT was administered after six cycles of induction chemotherapy. RT was deferred until after 3 years of age unless the tumor showed relapse or progression. For older patients (> 3 years old), RT including reduced-dose craniospinal RT (23.4 or 30.6 Gy) was administered either after two cycles of induction chemotherapy or after surgery, and tandem HDCT/auto-SCT was administered after six cycles of induction chemotherapy. Results A total of 13 patients (five young and eight older) were enrolled from November 2004 to June 2012. Eight patients, including all five young patients, had metastatic disease at diagnosis. Six patients (four young and two older) experienced progression before initiation of RT, and seven were able to proceed to HDCT/auto-SCT without progression during induction treatment. Three of six patients who experienced progression during induction treatment underwent HDCT/auto-SCT as salvage treatment. All five young patients died from disease progression. However, four of the eight older patients remain progression-freewith a median follow-up period of 64 months (range, 39 to 108 months). Treatment-related late toxicities were acceptable. Conclusion The required dose of craniospinal RT might be reduced in older patients if the intensity of chemotherapy is increased. However, early administration of RT should be considered to prevent early progression in young patients. PMID:27034140

  18. Importance of Achieving Stringent Complete Response After Autologous Stem-Cell Transplantation in Multiple Myeloma

    PubMed Central

    Kapoor, Prashant; Kumar, Shaji K.; Dispenzieri, Angela; Lacy, Martha Q.; Buadi, Francis; Dingli, David; Russell, Stephen J.; Hayman, Suzanne R.; Witzig, Thomas E.; Lust, John A.; Leung, Nelson; Lin, Yi; Zeldenrust, Steven R.; McCurdy, Arleigh; Greipp, Philip R.; Kyle, Robert A.; Rajkumar, S. Vincent; Gertz, Morie A.

    2013-01-01

    Purpose To study the impact of achieving stringent complete response (sCR), an increasingly attainable goal, after autologous stem-cell transplantation (ASCT) in patients with multiple myeloma (MM). Patients and Methods Maximal response rates were determined in 445 consecutive patients who underwent ASCT within 12 months of diagnosis of MM. The patients achieving varying degrees of complete response (CR) are the focus of our study. Results One hundred and nine patients (25%) achieved sCR after ASCT. The median overall survival (OS) rate from the time of transplantation for patients attaining sCR was not reached (NR), in contrast to those patients achieving conventional complete response (CR; n = 37; OS, 81 months) or near CR (nCR; n = 91; OS, 60 months; P < .001). Five-year OS rates were 80%, 53%, and 47% for sCR, CR, and nCR, respectively. The median time to progression (TTP) from ASCT of patients achieving sCR was significantly longer (50 months) than TTP of patients achieving CR or nCR (20 months and 19 months, respectively). On multivariable analysis, post-ASCT response of sCR was an independent prognostic factor for survival (hazard ratio, 0.44; 95% CI, 0.25 to 0.80; versus CR; P = .008), in addition to proliferation rate, pre-ASCT cytogenetics, and performance status. OS rates of patients attaining sCR continued to remain superior at 2-year landmark (median, NR v 70 months for conventional CR group; P = .007). Conclusion Improved long-term outcome is seen after ASCT with achievement of sCR when compared with lesser degrees of responses. Myeloma trials reporting the response rates should identify patients achieving sCR and CR separately, owing to markedly disparate outcomes of the two categories. PMID:24248686

  19. Autologous haematopoietic stem cell transplantation: a viable treatment option for CIDP.

    PubMed

    Press, R; Askmark, H; Svenningsson, A; Andersen, O; Axelson, H W; Strömberg, U; Wahlin, A; Isaksson, C; Johansson, J E J; Hägglund, H

    2014-06-01

    Only 70-80% of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) respond satisfactorily to the established first-line immunomodulatory treatments. Autologous haematopoietic stem cell transplantation (AHSCT) has been performed as a last treatment resort in a few therapy-refractory cases with CIDP. We describe the results of AHSCT in 11 consecutive Swedish patients with therapy-refractory CIDP with a median follow-up time of 28 months. Case data were gathered retrospectively for AHSCT treatments in 11 patients with CIDP refractory to the first-line immunomodulatory treatments, intravenous high-dose immunoglobulin, corticosteroids and plasma exchange and to one or more second-line treatments used in 10 of the 11 patients. The median Inflammatory Neuropathy Cause and Treatment (INCAT) score within 1 month prior to AHSCT was 6 and the Rankin score 4. Total INCAT and Rankin scores improved significantly within 2-6 months after AHSCT and continued to do so at last follow-up. The motor action potential amplitudes (CMAP) improved already within 4 months (median) after AHSCT. Three of the 11 patients relapsed during the follow-up period, requiring retransplantation with AHSCT in one. Eight of the 11 patients maintained drug-free remission upon last follow-up. AHSCT was safe but on the short term associated with a risk of cytomegalovirus (CMV) and Epstein-Barr virus reactivation, CMV disease, haemorrhagic cystitis and pancreatitis. Our results though hampered by the limited number of patients and the lack of a control group suggest AHSCT to be efficacious in therapy-refractory CIDP, with a manageable complication profile. Confirmation of these results is necessary through randomised controlled trials.

  20. Autologous preconditioned mesenchymal stem cell sheets improve left ventricular function in a rabbit old myocardial infarction model

    PubMed Central

    Tanaka, Yuya; Shirasawa, Bungo; Takeuchi, Yuriko; Kawamura, Daichi; Nakamura, Tamami; Samura, Makoto; Nishimoto, Arata; Ueno, Koji; Morikage, Noriyasu; Hosoyama, Tohru; Hamano, Kimikazu

    2016-01-01

    Mesenchymal stem cells (MSCs) constitute one of the most powerful tools for therapeutic angiogenesis in infarcted hearts. However, conventional MSC transplantation approaches result in insufficient therapeutic effects due to poor retention of graft cells in severe ischemic diseases. Cell sheet technology has been developed as a new method to prolong graft cell retention even in ischemic tissue. Recently, we demonstrated that hypoxic pretreatment enhances the therapeutic efficacy of cell sheet implantation in infarcted mouse hearts. In this study, we investigated whether hypoxic pretreatment activates the therapeutic functions of bone marrow-derived MSC (BM-MSC) sheets and improves cardiac function in rabbit infarcted hearts following autologous transplantation. Production of vascular endothelial growth factor (VEGF) was increased in BM-MSC monolayer sheets and it peaked at 48 h under hypoxic culture conditions (2% O2). To examine in vivo effects, preconditioned autologous BM-MSC sheets were implanted into a rabbit old myocardial infarction model. Implantation of preconditioned BM-MSC sheets accelerated angiogenesis in the peri-infarcted area and decreased the infarcted area, leading to improvement of the left ventricular function of the infarcted heart. Importantly, the therapeutic efficacy of the preconditioned BM-MSC sheets was higher than that of standardly cultured sheets. Thus, implantation of autologous preconditioned BM-MSC sheets is a feasible approach for enhancing therapeutic angiogenesis in chronically infarcted hearts. PMID:27347329

  1. Scaffold-Based Delivery of Autologous Mesenchymal Stem Cells for Mandibular Distraction Osteogenesis: Preliminary Studies in a Porcine Model

    PubMed Central

    Sun, Zongyang; Tee, Boon Ching; Kennedy, Kelly S.; Kennedy, Patrick M.; Kim, Do-Gyoon; Mallery, Susan R.; Fields, Henry W.

    2013-01-01

    Purpose Bone regeneration through distraction osteogenesis (DO) is promising but remarkably slow. To accelerate it, autologous mesenchymal stem cells have been directly injected to the distraction site in a few recent studies. Compared to direct injection, a scaffold-based method can provide earlier cell delivery with potentially better controlled cell distribution and retention. This pilot project investigated a scaffold-based cell-delivery approach in a porcine mandibular DO model. Materials and Methods Eleven adolescent domestic pigs were used for two major sets of studies. The in-vitro set established methodologies to: aspirate bone marrow from the tibia; isolate, characterize and expand bone marrow-derived mesenchymal stem cells (BM-MSCs); enhance BM-MSC osteogenic differentiation using FGF-2; and confirm cell integration with a gelatin-based Gelfoam scaffold. The in-vivo set transplanted autologous stem cells into the mandibular distraction sites using Gelfoam scaffolds; completed a standard DO-course and assessed bone regeneration by macroscopic, radiographic and histological methods. Repeated-measure ANOVAs and t-tests were used for statistical analyses. Results From aspirated bone marrow, multi-potent, heterogeneous BM-MSCs purified from hematopoietic stem cell contamination were obtained. FGF-2 significantly enhanced pig BM-MSC osteogenic differentiation and proliferation, with 5 ng/ml determined as the optimal dosage. Pig BM-MSCs integrated readily with Gelfoam and maintained viability and proliferative ability. After integration with Gelfoam scaffolds, 2.4–5.8×107 autologous BM-MSCs (undifferentiated or differentiated) were transplanted to each experimental DO site. Among 8 evaluable DO sites included in the final analyses, the experimental DO sites demonstrated less interfragmentary mobility, more advanced gap obliteration, higher mineral content and faster mineral apposition than the control sites, and all transplanted scaffolds were completely

  2. Technologies enabling autologous neural stem cell-based therapies for neurodegenerative disease and injury

    NASA Astrophysics Data System (ADS)

    Bakhru, Sasha H.

    The intrinsic abilities of mammalian neural stem cells (NSCs) to self-renew, migrate over large distances, and give rise to all primary neural cell types of the brain offer unprecedented opportunity for cell-based treatment of neurodegenerative diseases and injuries. This thesis discusses development of technologies in support of autologous NSC-based therapies, encompassing harvest of brain tissue biopsies from living human patients; isolation of NSCs from harvested tissue; efficient culture and expansion of NSCs in 3D polymeric microcapsule culture systems; optimization of microcapsules as carriers for efficient in vivo delivery of NSCs; genetic engineering of NSCs for drug-induced, enzymatic release of transplanted NSCs from microcapsules; genetic engineering for drug-induced differentiation of NSCs into specific therapeutic cell types; and synthesis of chitosan/iron-oxide nanoparticles for labeling of NSCs and in vivo tracking by cellular MRI. Sub-millimeter scale tissue samples were harvested endoscopically from subventricular zone regions of living patient brains, secondary to neurosurgical procedures including endoscopic third ventriculostomy and ventriculoperitoneal shunt placement. On average, 12,000 +/- 3,000 NSCs were isolated per mm 3 of subventricular zone tissue, successfully demonstrated in 26 of 28 patients, ranging in age from one month to 68 years. In order to achieve efficient expansion of isolated NSCs to clinically relevant numbers (e.g. hundreds of thousands of cells in Parkinson's disease and tens of millions of cells in multiple sclerosis), an extracellular matrix-inspired, microcapsule-based culture platform was developed. Initial culture experiments with murine NSCs yielded unprecedented expansion folds of 30x in 5 days, from initially minute NSC populations (154 +/- 15 NSCs per 450 mum diameter capsule). Within 7 days, NSCs expanded as almost perfectly homogenous populations, with 94.9% +/- 4.1% of cultured cells staining positive for

  3. Autologous stem cell-based therapy for sickle cell leg ulcer: a pilot study.

    PubMed

    Meneses, José Válber L; Fortuna, Vitor; de Souza, Eliane Silva; Daltro, Gildasio Cerqueira; Meyer, Roberto; Minniti, Caterina P; Borojevic, Radovan

    2016-12-01

    Recurrent chronic leg ulcers are among the most severe vasculopathic complications of sickle cell disease (SCD). Their treatment remains a challenge. Stem cell therapy with bone marrow mononuclear cells (BMMC) is a promising new therapeutic option for other forms of chronic ulcers. This prospective pilot study was performed to evaluate safety and feasibility of BMMC implantation in patients with SCD and chronic leg ulcers (SCLU). Ulcer closure, recurrence and local pain were evaluated. BMMC were successfully administered to 23 SCLU patients and no serious adverse events occurred. During the 6-month follow-up period, 91·3% of patients had improved ulcer pain compared with baseline and 29·2% of the treated ulcers achieved total healing. The frequency of progenitor stem cells (CD34CD45(low) and fibroblast colony-forming units) in BMMC was found to be significantly reduced in SCLU patients and compared to SCD patients without ulcers (P < 0·004 and P < 0·01, respectively). No relationship was observed between treatment outcome and the number of implanted BM progenitor stem cells. In conclusion, BMMC implantation is a feasible and safe procedure, showing favourable outcomes for the treatment of SCLU, and encouraging further controlled clinical trials.

  4. Prenatally engineered autologous amniotic fluid stem cell-based heart valves in the fetal circulation.

    PubMed

    Weber, Benedikt; Emmert, Maximilian Y; Behr, Luc; Schoenauer, Roman; Brokopp, Chad; Drögemüller, Cord; Modregger, Peter; Stampanoni, Marco; Vats, Divya; Rudin, Markus; Bürzle, Wilfried; Farine, Marc; Mazza, Edoardo; Frauenfelder, Thomas; Zannettino, Andrew C; Zünd, Gregor; Kretschmar, Oliver; Falk, Volkmar; Hoerstrup, Simon P

    2012-06-01

    Prenatal heart valve interventions aiming at the early and systematic correction of congenital cardiac malformations represent a promising treatment option in maternal-fetal care. However, definite fetal valve replacements require growing implants adaptive to fetal and postnatal development. The presented study investigates the fetal implantation of prenatally engineered living autologous cell-based heart valves. Autologous amniotic fluid cells (AFCs) were isolated from pregnant sheep between 122 and 128 days of gestation via transuterine sonographic sampling. Stented trileaflet heart valves were fabricated from biodegradable PGA-P4HB composite matrices (n = 9) and seeded with AFCs in vitro. Within the same intervention, tissue engineered heart valves (TEHVs) and unseeded controls were implanted orthotopically into the pulmonary position using an in-utero closed-heart hybrid approach. The transapical valve deployments were successful in all animals with acute survival of 77.8% of fetuses. TEHV in-vivo functionality was assessed using echocardiography as well as angiography. Fetuses were harvested up to 1 week after implantation representing a birth-relevant gestational age. TEHVs showed in vivo functionality with intact valvular integrity and absence of thrombus formation. The presented approach may serve as an experimental basis for future human prenatal cardiac interventions using fully biodegradable autologous cell-based living materials. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells

    PubMed Central

    2011-01-01

    Prolonged life expectancy, life style and environmental changes have caused a changing disease pattern in developed countries towards an increase of degenerative and autoimmune diseases. Stem cells have become a promising tool for their treatment by promoting tissue repair and protection from immune-attack associated damage. Patient-derived autologous stem cells present a safe option for this treatment since these will not induce immune rejection and thus multiple treatments are possible without any risk for allogenic sensitization, which may arise from allogenic stem cell transplantations. Here we report the outcome of treatments with culture expanded human adipose-derived mesenchymal stem cells (hAdMSCs) of 10 patients with autoimmune associated tissue damage and exhausted therapeutic options, including autoimmune hearing loss, multiple sclerosis, polymyotitis, atopic dermatitis and rheumatoid arthritis. For treatment, we developed a standardized culture-expansion protocol for hAdMSCs from minimal amounts of fat tissue, providing sufficient number of cells for repetitive injections. High expansion efficiencies were routinely achieved from autoimmune patients and from elderly donors without measurable loss in safety profile, genetic stability, vitality and differentiation potency, migration and homing characteristics. Although the conclusions that can be drawn from the compassionate use treatments in terms of therapeutic efficacy are only preliminary, the data provide convincing evidence for safety and therapeutic properties of systemically administered AdMSC in human patients with no other treatment options. The authors believe that ex-vivo-expanded autologous AdMSCs provide a promising alternative for treating autoimmune diseases. Further clinical studies are needed that take into account the results obtained from case studies as those presented here. PMID:22017805

  6. The Use Of Laser Irradiation To Stimulate Adipose Derived Stem Cell Proliferation And Differentiation For Use In Autologous Grafts

    NASA Astrophysics Data System (ADS)

    Abrahamse, Heidi

    2009-09-01

    Stem cells are characterized by the qualities of self-renewal, long term viability, and the ability to differentiate into various cell types. Historically, stem cells have been isolated from the inner cell mass of blastocysts and harvesting these cells resulted in the death of the embryo leading to religious, political and ethical issues. The identification and subsequent isolation of adult stem cells from bone marrow stroma have been welcomed as an alternate source for stem cells. The clinical use of Mesenchymal Stem Cells (MSCs) presented problems such as limited cell number, pain and morbidity upon isolation. Adipose tissue is derived from the mesenchyme, is easily isolated, a reliable source of stem cells and able to differentiate into different cell types including smooth muscle. Over the past few years, the identification and characterization of stem cells has led the potential use of these cells as a promising alternative to cell replacement therapy. Smooth muscle is a major component of human tissues and is essential for the normal functioning of many different organs. Low intensity laser irradiation has been shown to increase viability, protein expression and migration of stem cells in vitro, and to stimulate proliferation of various types of stem cells. In addition, the use of laser irradiation to stimulate differentiation in the absence of growth factors has also been demonstrated in normal human neural progenitor cells (NHNPCs) in vitro where NHNPCs are not only capable of being sustained by light in the absence of growth factors, but that they are also able to differentiate normally as assessed by neurite formation. Our work has focused on the ability of laser irradiation to proliferate adipose derived stem cells (ADSCs), maintain ADSC character and increase the rate and maintenance of differentiation of ADSCs into smooth muscle and skin fibroblast cells. Current studies are also investigating the effect of different irradiation wavelengths and

  7. Reversal of Methanol-Induced Blindness in Adults by Autologous Bone Marrow-Derived Stem Cells: A Case Series.

    PubMed

    Bansal, Himanshu; Chaparia, Yogesh; Agrawal, Anupama; Koka, Prasad S

    2015-01-01

    Methanol ingestion leads to severe damage to visual pathways and permanent loss of vision. Current treatment is aimed at removal of methanol from system and prevention of generation of toxic metabolites along with symptomatic management of patient. Autologous bone marrow mononuclear stem cells (MNC) can be used to rejuvenate the damaged retinal cells and restoration of vision. Five patients suffering from methanol induced complete blindness within three months of insult and no known comorbidities during the past 6 months were enrolled to receive autologous bone marrow derived mononuclear cell fraction on compassionate grounds. The visual acuity and visual evoked responses (VER) were done at the time of enrollment and during follow-up visits. Visual acuity of these patients at the time of enrollment: no perception of light. Improvement in visual acuity was recorded by 7 days which reached maximum at 3 weeks after treatment in three patients and three months in two patients. The patients had acuity of 6/9, finger counting and reading with magnifying glasses with no subsequent improvement till 2 years of follow-up. Visual Evoked Responses demonstrated improvements following treatment. No adverse reactions were noticed during follow-up. Treatment with Autologous Bone marrow derived MNC offers a new line of management in patients with loss of vision following methanol ingestion. The efficacy and safety of this line of management needs to be evaluated in controlled clinical trials.

  8. Conditioning with targeted busulfan for autologous peripheral blood stem cells transplantation for acute myelogenous leukemia in an XYY male.

    PubMed

    Sada, Eriko; Henzan, Hideho; Ohtani, Ryoko; Takase, Ken; Miyamoto, Toshihiro; Fukuda, Takahiro; Nagafuji, Koji; Yamauchi, Keita; Takamatsu, Yasushi; Inaba, Shoichi; Harada, Mine

    2005-01-01

    We report herein a 19-year-old Japanese male with XYY syndrome who developed acute myelogenous leukemia. During three courses of cytotoxic chemotherapy, he suffered repeated hepatic and renal insufficiencies, possibly related to latent dysfunction from the XYY syndrome. The patient was treated with granulocyte colony-stimulating factor combined with etoposide, cytarabine, and busulfan (the latter adjusted to a targeting dose) followed by autologous peripheral blood stem cell transplantation. He had no severe regimen-related toxicities and is now free of leukemia.

  9. High-dose chemotherapy with autologous peripheral blood stem cell support for recurrent primary AFP-producing intracranial germinoma

    PubMed Central

    Ziske, Carsten; Mezger, Jörg; Jiménez, Carlos; Kleinschmidt, Rolf; Pels, Hendrik; Schlegel, Uwe; Schmidt-Wolf, Ingo G.H.

    2003-01-01

    We report of a 34-year old man with second intracranial relapse of a suprasellar germinoma. Despite of extensive pretreatment with radiation and conventional chemotherapy relapse occurred and was treated with sequential high-dose chemotherapy followed by transfusion of autologous peripheral stem cells. The high-dose chemotherapy course was complicated by refractory derailment of pineal gland insufficiency. The patient achieved a complete remission after high dose chemotherapy which lasted for 13 months. Subsequently, he developed a third relapse and died. PMID:19675701

  10. Potential new strategies for the treatment of ovarian infertility and degenerative diseases with autologous ovarian stem cells.

    PubMed

    Bukovsky, Antonin; Copas, Pleas; Virant-Klun, Irma

    2006-04-01

    The 50-year-old and currently prevailing view that all oocytes in adult human ovaries persist from the fetal period of life is controversial as it clashes with Darwinian evolutionary theory. Studies of oogenesis and follicular renewal in adult human ovaries, and of the role of hormonal signals and third-party cells (tissue macrophages and T cells), could all be helpful in providing better understanding of the causes of ovarian infertility, its prevention and potential therapy. In addition, the authors recently reported differentiation of distinct cell types and the production of new eggs in cultures derived from premenopausal and postmenopausal human ovaries. It is possible that fertilisation of such eggs will open up new opportunities for providing genetically related children to infertile women for whom conventional in vitro fertilisation has failed. As ovarian stem cells appear to represent a new type of totipotent adult stem cell, they could also be utilised for autologous stem cell therapy of degenerative diseases, without any involvement of allogeneic embryonic stem cells and somatic cell nuclear transfer.

  11. Application of Autologous Bone Marrow Derived Mesenchymal Stem Cells to an Ovine Model of Growth Plate Cartilage Injury

    PubMed Central

    McCarty, Rosa C; Xian, Cory J; Gronthos, Stan; Zannettino, Andrew C.W; Foster, Bruce K

    2010-01-01

    Injury to growth plate cartilage in children can lead to bone bridge formation and result in bone growth deformities, a significant clinical problem currently lacking biological treatment. Mesenchymal stem/stromal cells (MSC) offer a promising therapeutic option for regeneration of damaged cartilage, due to their self renewing and multi-lineage differentiation attributes. Although some small animal model studies highlight the therapeutic potential of MSC for growth plate repair, translational research in large animal models, which more closely resemble the human condition, are lacking. Our laboratory has recently characterised MSCs derived from ovine bone marrow, and demonstrated these cells form cartilage-like tissue when transplanted within the gelatin sponge, Gelfoam, in vivo. In the current study, autologous bone marrow MSC were seeded into Gelfoam scaffold containing TGF-β1, and transplanted into a surgically created defect of the proximal ovine tibial growth plate. Examination of implants at 5 week post-operatively revealed transplanted autologous MSC failed to form new cartilage structure at the defect site, but contributed to an increase in formation of a dense fibrous tissue. Importantly, the extent of osteogenesis was diminished, and bone bridge formation was not accelerated due to transplantation of MSCs or the gelatin scaffold. The current study represents the first work that has utilised this ovine large animal model to investigate whether autologous bone marrow derived MSC can be used to initiate regeneration at the injured growth plate. PMID:20721323

  12. [Effects of rat allogeneic adipose-derived stem cells on the early neovascularization of autologous fat transplantation].

    PubMed

    Tian, Tian; Jia, Chiyu; Liu, Yi; Liu, Zhen; Hu, Guodong; Wang, Ruichen; Chang, Chunjuan

    2014-12-01

    To investigate the effects of allogeneic adipose-derived stem cells (ADSCs) of rat on the early neovascularization of autologous fat transplantation. (1) Experiment 1. Adipose tissue was collected from both inguinal regions of two SD rats to isolate, culture, and purify ADSCs through collagen enzyme digestion, density gradient centrifugation, and adherence method. The fourth passage of cells were collected for morphologic observation, detection of expressions of surface markers CD34, CD49d, CD106, and CD45 of ADSCs with flow cytometer, identification of adipogenic and osteogenic differentiation, and determination of the cell proliferation ability with thiazolyl blue method. (2) Experiment 2. Another 30 SD rats were divided into allogeneic adipose granule (AG) group (A, n = 6), autologous AG group (B, n = 8), autologous ADSCs+autologous AG group (C, n = 8), and allogeneic ADSCs+autologous AG group (D, n = 8) according to the random number table. The fourth passage of ADSCs were obtained from adipose tissue from one side of inguinal region of SD rats in group C. Adipose tissue obtained from one side of inguinal region of SD rats of the other 3 groups was abandoned. The AG was prepared from another side of inguinal region of SD rats in the 4 groups. The mixture of 0.6 g AG from one rat and 1 mL DMEM/F12 nutrient solution was injected subcutaneously into the back of another rat in group A, and so on. Autologous AG was injected into its own body of the rats in group B. The mixture of 1 mL autologous ADSCs mixture which contains 3.0 × 10⁶ cells per mililitre autologous ADSCs combined with autologous AG was injected into the rats in group C. The mixture of 1 mL allogeneic ADSCs mixture which contains 3.0 × 10⁶ cells per mililitre ADSCs extractived from the former 2 rats in experiment 1 combined with autologous AG was injected into the rats in group D. At 7 days post transplantation, fat transplants were harvested for gross observation, measurement of wet weight

  13. Autologous adipose tissue-derived mesenchymal stem cells are involved in rat liver regeneration following repeat partial hepatectomy

    PubMed Central

    LIU, TAO; MU, HONG; SHEN, ZHONGYANG; SONG, ZHUOLUN; CHEN, XIAOBO; WANG, YULIANG

    2016-01-01

    Adipose tissue-derived mesenchymal stem cells (ADSCs) have been considered to be attractive and readily available adult mesenchymal stem cells, and they are becoming increasingly popular for use in regenerative cell therapy, as they are readily accessible through minimally invasive techniques. The present study investigated whether autologous ADSC transplantation promoted liver regeneration following a repeat partial hepatectomy in rats. The rats were divided into three groups as follows: 70% partial hepatectomy (PH) group; repeat PH (R-PH) group and R-PH/ADSC group, subjected to R-PH and treated with autologous ADSCs via portal vein injection. In each group, the rats were sacrificed at different time points postoperatively in order to evaluate the changes in liver function and to estimate the liver regenerative response. The expression of proliferating cell nuclear antigen (PCNA) labeling index in the liver was measured using immunohistochemistry. The expression levels of hepatocyte growth factor (HGF) mRNA were measured using reverse transcription polymerase chain reaction. The results showed that regeneration of the remaining liver following R-PH was significantly promoted by ADSC transplantation, as shown by a significant increase in liver to body weight ratio and the PCNA labeling index at 24 h post-hepatectomy. Additionally, ADSC transplantation markedly inhibited the elevation of serum levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin, increased HGF content and also attenuated hepatic vacuolar degeneration 24 h postoperatively. Furthermore, the liver was found to almost fully recover from hepatocellular damage due to hepatectomy among the three groups at 168 h postoperatively. These results indicated that autologous ADSC transplantation enhanced the regenerative capacity of the remnant liver tissues in the early phase following R-PH. PMID:26783183

  14. Autologous stem cell transplantation for primary refractory Hodgkin's disease: results and clinical variables affecting outcome.

    PubMed

    Constans, M; Sureda, A; Terol, M J; Arranz, R; Caballero, M D; Iriondo, A; Jarque, I; Carreras, E; Moraleda, J M; Carrera, D; León, A; López, A; Albó, C; Díaz-Mediavilla, J; Fernández-Abellán, P; García-Ruiz, J C; Hernández-Navarro, F; Mataix, R; Petit, J; Pascual, M J; Rifón, J; García-Conde, J; Fernández-Rañada, J M; Mateos, M V; Sierra, J; Conde, E

    2003-05-01

    Patients with primary refractory Hodgkin's disease (PR-HD) have a dismal prognosis when treated with conventional salvage chemotherapy. We analyzed time to treatment failure (TTF), overall survival (OS) and clinical variables influencing the outcome in patients undergoing autologous stem cell transplantation (ASCT) for PR-HD and reported to the Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL/TAMO). Sixty-two patients, 41 males and 21 females with a median age of 27 years (range 13-55) were analyzed. Forty-two patients (68%) had advanced stage at diagnosis, 47 (76%) presented with B symptoms and 29 (47%) with a bulky mediastinal mass. Seventy-five percent of the patients had received more than one line of therapy before ASCT. Thirty-three patients received bone marrow as a source of hematopoietic progenitors, and 29 peripheral blood. Six patients were conditioned with high-dose chemotherapy plus total-body irradiation and 56 received chemotherapy-based protocols. One-year transplantation-related mortality was 14% [95% confidence interval (CI) 6% to 23%]. Response rate at 3 months after ASCT was 52% [complete remission in 21 patients (34%), partial remission in 11 patients (18%)]. Actuarial 5-year TTF and OS were 15% (95% CI 5% to 24%) and 26% (95% CI 13% to 39%), respectively. The presence of B symptoms at ASCT was the only adverse prognostic factor significantly influencing TTF [relative risk (RR) 1.75, 95% CI 0.92-3.35, P = 0.08]. The presence of B symptoms at diagnosis (RR 2.08, 95% CI 0.90-4.79, P = 0.08), MOPP-like regimens as first-line therapy (RR 3.84, 95% CI 1.69-9.09, P = 0.001), bulky disease at ASCT (RR 2.79, 95% CI 0.29-6.03, P = 0.009) and two or more lines of therapy before ASCT (RR 2.24, 95% CI 0.95-5.27, P = 0.06) adversely influenced OS. In our experience, although overall results of ASCT in PR-HD patients are poor, one-quarter of the patients remain alive at 5 years. Despite this, other therapeutic strategies should be

  15. Long-term results of autologous stem cell transplantation for primary refractory or relapsed Hodgkin's lymphoma.

    PubMed

    Majhail, Navneet S; Weisdorf, Daniel J; Defor, Todd E; Miller, Jeffrey S; McGlave, Philip B; Slungaard, Arne; Arora, Mukta; Ramsay, Norma K C; Orchard, Paul J; MacMillan, Margaret L; Burns, Linda J

    2006-10-01

    Autologous hematopoietic stem cell transplantation (ASCT) has become standard therapy for primary refractory (PR REF) or relapsed (REL) Hodgkin's lymphoma (HL); however, more than half of these patients eventually relapse and die of their disease. We studied long-term outcomes and evaluated factors influencing progression-free survival (PFS) in 141 patients with PR REF or REL HL who underwent ASCT between 1985 and 2003. Median age at ASCT was 30 years (range, 7-60 years); 21 patients had PR REF, and 120 had REL HL. With a median follow-up of 6.3 years (range, 1-20 years), the probability of PFS at 5 and 10 years was 48% (95% confidence interval [CI], 39%-57%) and 45% (95% CI, 36%-54%) and that of overall survival (OS) was 53% (95% CI, 44%-62%) and 47% (95% CI, 37%-57%), respectively. Transplant-related mortality at 100 days was 1.4%. Among 45 5- to 20-year survivors, no late relapses of HL were observed. In multivariate analysis, 3 factors were independently predictive of poor PFS: chemoresistant disease (relative risk [RR], 2.9; 95% CI, 1.7-5.0), B-symptoms at pretransplantation relapse (RR, 2.1; 95% CI, 1.3-3.4), and presence of residual disease at the time of transplantation (RR, 2.3; 95% CI, 1.1-4.8). Patients with 0 or 1 of these 3 adverse factors (low-risk disease) had a 5-year PFS of 67% (95% CI, 55%-79%) compared with 37% (95% CI, 22%-52%) in those with 2 factors (intermediate-risk group) and 9% (95% CI, 0-20%) in those with all 3 factors (high-risk group) (P < .001). The rates of OS at 5 years were 71% (95% CI, 60%-82%), 49% (95% CI, 33%-65%) and 13% (95% CI, 0-27%) in the 3 groups, respectively (P < .001). ASCT is associated with durable PFS in appropriately selected patients with PR REF or REL HL. Using a simple prognostic model, we can identify patients with high-risk disease who have predictably unfavorable outcome after ASCT and require novel therapeutic approaches. A risk-adapted approach should be followed in determining treatment options for

  16. Outcomes in patients with multiple myeloma with TP53 deletion after autologous hematopoietic stem cell transplant.

    PubMed

    Gaballa, Sameh; Saliba, Rima M; Srour, Samer; Lu, Gary; Brammer, Jonathan E; Shah, Nina; Bashir, Qaiser; Patel, Krina; Bock, Fabian; Parmar, Simrit; Hosing, Chitra; Popat, Uday; Delgado, Ruby; Rondon, Gabriela; Shah, Jatin J; Manasanch, Elisabet E; Orlowski, Robert Z; Champlin, Richard; Qazilbash, Muzaffar H

    2016-10-01

    TP53 gene deletion is associated with poor outcomes in multiple myeloma (MM). We report the outcomes of patients with MM with and without TP53 deletion who underwent immunomodulatory drug (IMiD) and/or proteasome inhibitor (PI) induction followed by autologous hematopoietic stem cell transplant (auto-HCT). We identified 34 patients with MM and TP53 deletion who underwent IMiD and/or PI induction followed by auto-HCT at our institution during 2008-2014. We compared their outcomes with those of control patients (n = 111) with MM without TP53 deletion. Median age at auto-HCT was 59 years in the TP53-deletion group and 58 years in the control group (P = 0.4). Twenty-one patients (62%) with TP53 deletion and 69 controls (62%) achieved at least partial remission before auto-HCT (P = 0.97). Twenty-three patients (68%) with TP53 deletion and 47 controls (42%) had relapsed disease at auto-HCT (P = 0.01). Median progression-free survival was 8 months for patients with TP53 deletion and 28 months for controls (P < 0.001). Median overall survival was 21 months for patients with TP53 deletion and 56 months for controls (P < 0.001). On multivariate analysis of both groups, TP53 deletion (hazard ratio 3.4, 95% confidence interval 1.9-5.8, P < 0.001) and relapsed disease at auto-HCT (hazard ratio 2.0, 95% confidence interval 1.2-3.4, P = 0.008) were associated with a higher risk of earlier progression. In MM patients treated with PI and/or IMiD drugs, and auto-HCT, TP53 deletion and relapsed disease at the time of auto-HCT are independent predictors of progression. Novel approaches should be evaluated in this high-risk population. Am. J. Hematol. 91:E442-E447, 2016. © 2016 Wiley Periodicals, Inc.

  17. Outcomes of Maintenance Therapy with Bortezomib after Autologous Stem Cell Transplantation for Patients with Multiple Myeloma.

    PubMed

    Sivaraj, Dharshan; Green, Michael M; Li, Zhiguo; Sung, Anthony D; Sarantopoulos, Stefanie; Kang, Yubin; Long, Gwynn D; Horwitz, Mitchell E; Lopez, Richard D; Sullivan, Keith M; Rizzieri, David A; Chao, Nelson J; Gasparetto, Cristina

    2017-02-01

    Comprehensive recommendations for maintenance therapy after autologous stem cell transplantation (ASCT) for patients with multiple myeloma (MM) have yet to be defined. Bortezomib has been utilized as maintenance therapy after ASCT, but data attesting to the safety and efficacy of this agent compared with lenalidomide in the post-ASCT setting are limited. Therefore, we retrospectively analyzed the outcomes of 102 patients with MM who received maintenance therapy with bortezomib after ASCT at Duke University's adult bone marrow transplant clinic between 2005 and 2015. Maintenance with bortezomib was initiated between 60 and 90 days after ASCT as a single agent 1.3 mg/m(2) once every 2 weeks (n = 92) or in combination with lenalidomide (10 mg/day) (n = 10). The median age at ASCT was 64 (range, 31 to 78). Of the 99 patients with molecular data available, 42% had high-risk cytogenetics (including d17p, t(4;14), +1q, and t(14;16) by fluorescein in situ hybridization). Overall, 46% of patients experienced side effects from maintenance therapy, with 31% of all patients experiencing peripheral neuropathy. In total, 2% of patients required discontinuation of bortezomib maintenance because of adverse events. No secondary malignancies were reported from the therapy. The median progression-free survival (PFS) for patients receiving maintenance therapy with bortezomib after ASCT was 36.5 months (95% confidence interval [CI], 21.3 to not available) and median overall survival was 72.7 months (95% CI, 63.9 to not available). The PFS of patients with high-risk cytogenetics was not statistically significantly different from those with standard-risk cytogenetics, suggesting that maintenance with bortezomib may help overcome the impact of high-risk cytogenetics on early progression. These results indicate that maintenance therapy with bortezomib represents a safe, well-tolerated, and efficacious option for patients with high-risk cytogenetics, renal insufficiency, an

  18. Autologous bone marrow stem cell transplantation for the treatment of postoperative hand infection with a skin defect in diabetes mellitus: A case report.

    PubMed

    Liu, Yihong; Liu, Yuchen; Wang, Pujie; Tian, Haoming; Ai, Jianzhong; Liu, Yangbo; Zhou, Yi; Liu, Zhongwen; Guo, Wenjun; Yang, Shenke

    2014-06-01

    Among stem cells, autologous mesenchymal stem cells (MSCs) are ideal for transplantation by virtue of limited rejection reactions and marked proliferative ability. This study presents a novel method by which MSCs were harvested from the bone marrow of a patient who presented with severe post-traumatic infection and a non-healing skin defect in the hand, secondary to uncontrolled diabetes mellitus (DM). An autologous MSC suspension was injected into the persistent skin defect after stabilizing the blood glucose level and appropriate infection control. During the course of a regular 18-month postoperative follow-up, the patient exhibited immediate recovery with no transplant-associated complications, as well as no evidence of tumorigenicity. Thus, transplantation of autologous MSCs may play a role in the clinical application of stem cells, particularly for treatment of skin defects following surgery in cases of DM and for those caused by various other traumas.

  19. Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis.

    PubMed

    Muraro, Paolo A; Pasquini, Marcelo; Atkins, Harold L; Bowen, James D; Farge, Dominique; Fassas, Athanasios; Freedman, Mark S; Georges, George E; Gualandi, Francesca; Hamerschlak, Nelson; Havrdova, Eva; Kimiskidis, Vassilios K; Kozak, Tomas; Mancardi, Giovanni L; Massacesi, Luca; Moraes, Daniela A; Nash, Richard A; Pavletic, Steven; Ouyang, Jian; Rovira, Montserrat; Saiz, Albert; Simoes, Belinda; Trnený, Marek; Zhu, Lin; Badoglio, Manuela; Zhong, Xiaobo; Sormani, Maria Pia; Saccardi, Riccardo

    2017-04-01

    Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies. To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort. Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; information on the administered conditioning regimen and graft manipulation; and at least 1 follow-up visit or report after transplant. The last patient visit was on July 1, 2012. To avoid bias, all eligible patients were included in the analysis regardless of their duration of follow-up. Data analysis was conducted from September 1, 2014 to April 27, 2015. Demographic, disease-related, and treatment-related exposures were considered variables of interest, including age, disease subtype, baseline EDSS score, number of previous disease-modifying treatments, and intensity of the conditioning regimen. The primary outcomes were MS progression-free survival and overall survival. The probabilities of progression-free survival and overall survival were calculated using Kaplan-Meier survival curves and multivariable Cox proportional hazards regression analysis models. Valid data were obtained from 25 centers in 13 countries for 281 evaluable patients, with median follow-up of 6.6 years (range, 0.2-16 years). Seventy-eight percent (218 of 281) of patients had progressive forms of MS. The median EDSS score before mobilization of peripheral blood stem cells was 6.5 (range, 1.5-9). Eight deaths (2.8%; 95% CI, 1.0%-4.9%) were reported within 100 days of transplant and were considered transplant-related mortality. The 5-year probability of progression

  20. Autologous Hematopoetic Stem Cell Transplantation for Refractory Crohn Disease: A Randomized Clinical Trial.

    PubMed

    Hawkey, Christopher J; Allez, Matthieu; Clark, Miranda M; Labopin, Myriam; Lindsay, James O; Ricart, Elena; Rogler, Gerhard; Rovira, Montserrat; Satsangi, Jack; Danese, Silvio; Russell, Nigel; Gribben, John; Johnson, Peter; Larghero, Jerome; Thieblemont, Catherine; Ardizzone, Sandro; Dierickx, Daan; Ibatici, Adalberto; Littlewood, Timothy; Onida, Francesco; Schanz, Urs; Vermeire, Severine; Colombel, Jean-Frederic; Jouet, Jean-Paul; Clark, Elizabeth; Saccardi, Riccardo; Tyndall, Alan; Travis, Simon; Farge, Dominique

    2015-12-15

    Case reports and series suggest hematopoietic stem cell transplantation (HSCT) may benefit some patients with Crohn disease. To evaluate the effect of autologous HSCT on refractory Crohn disease. Parallel-group randomized clinical trial conducted in 11 European transplant units from July 2007 to September 2011, with follow-up through March 2013. Patients were aged 18 to 50 years with impaired quality of life from refractory Crohn disease not amenable to surgery despite treatment with 3 or more immunosuppressive or biologic agents and corticosteroids. All patients underwent stem cell mobilization before 1:1 randomization to immunoablation and HSCT (n = 23) or control treatment (HSCT deferred for 1 year [n = 22]). All were given standard Crohn disease treatment as needed. Sustained disease remission at 1 year, a composite primary end point comprising clinical remission (Crohn Disease Activity Index (CDAI) <150 [range, 0-600]), no use of corticosteroids or immunosuppressive or biologic drugs for at least the last 3 months, and no endoscopic or radiological evidence of active (erosive) disease anywhere in the gastrointestinal (GI) tract. Secondary outcomes were individual components of the primary composite outcome and other measures of disease activity, laboratory results, quality of life and functional status, and GI tract imaging. Twenty-three patients underwent HSCT and 22 received standard Crohn disease treatment (controls). Sustained disease remission was achieved in 2 patients undergoing HSCT (8.7%) vs 1 control patient (4.5%) (absolute difference, 4.2% [95% CI, -14.2% to 22.6%]; P = .60). Fourteen patients undergoing HSCT (61%) vs 5 control patients (23%) had discontinued immunosuppressive or biologic agents or corticosteroids for at least 3 months (difference, 38.1% [95% CI, 9.3% to 59.3%]; P = .01). Ten vs 2 patients had a CDAI less than 150 (remission) at the final evaluation, 8 (34.8%) vs 2 (9.1%) for 3 or more months (difference, 25.7% [95

  1. Scaffold-free Three-dimensional Graft From Autologous Adipose-derived Stem Cells for Large Bone Defect Reconstruction

    PubMed Central

    Dufrane, Denis; Docquier, Pierre-Louis; Delloye, Christian; Poirel, Hélène A.; André, Wivine; Aouassar, Najima

    2015-01-01

    Abstract Long bone nonunion in the context of congenital pseudarthrosis or carcinologic resection (with intercalary bone allograft implantation) is one of the most challenging pathologies in pediatric orthopedics. Autologous cancellous bone remains the gold standard in this context of long bone nonunion reconstruction, but with several clinical limitations. We then assessed the feasibility and safety of human autologous scaffold-free osteogenic 3-dimensional (3D) graft (derived from autologous adipose-derived stem cells [ASCs]) to cure a bone nonunion in extreme clinical and pathophysiological conditions. Human ASCs (obtained from subcutaneous adipose tissue of 6 patients and expanded up to passage 4) were incubated in osteogenic media and supplemented with demineralized bone matrix to obtain the scaffold-free 3D osteogenic structure as confirmed in vitro by histomorphometry for osteogenesis and mineralization. The 3D “bone-like” structure was finally transplanted for 3 patients with bone tumor and 3 patients with bone pseudarthrosis (2 congenital, 1 acquired) to assess the clinical feasibility, safety, and efficacy. Although minor clones with structural aberrations (aneuploidies, such as tri or tetraploidies or clonal trisomy 7 in 6%–20% of cells) were detected in the undifferentiated ASCs at passage 4, the osteogenic differentiation significantly reduced these clonal anomalies. The final osteogenic product was stable, did not rupture with forceps manipulation, did not induce donor site morbidity, and was easily implanted directly into the bone defect. No acute (<3 mo) side effects, such as impaired wound healing, pain, inflammatory reaction, and infection, or long-term side effects, such as tumor development, were associated with the graft up to 4 years after transplantation. We report for the first time that autologous ASC can be fully differentiated into a 3D osteogenic-like implant without any scaffold. We demonstrated that this engineered tissue can

  2. Impact of pre-transplant depression on outcomes of allogeneic and autologous hematopoietic stem cell transplantation.

    PubMed

    El-Jawahri, Areej; Chen, Yi-Bin; Brazauskas, Ruta; He, Naya; Lee, Stephanie J; Knight, Jennifer M; Majhail, Navneet; Buchbinder, David; Schears, Raquel M; Wirk, Baldeep M; Wood, William A; Ahmed, Ibrahim; Aljurf, Mahmoud; Szer, Jeff; Beattie, Sara M; Battiwalla, Minoo; Dandoy, Christopher; Diaz, Miguel-Angel; D'Souza, Anita; Freytes, Cesar O; Gajewski, James; Gergis, Usama; Hashmi, Shahrukh K; Jakubowski, Ann; Kamble, Rammurti T; Kindwall-Keller, Tamila; Lazarus, Hilard M; Malone, Adriana K; Marks, David I; Meehan, Kenneth; Savani, Bipin N; Olsson, Richard F; Rizzieri, David; Steinberg, Amir; Speckhart, Dawn; Szwajcer, David; Schoemans, Helene; Seo, Sachiko; Ustun, Celalettin; Atsuta, Yoshiko; Dalal, Jignesh; Sales-Bonfim, Carmem; Khera, Nandita; Hahn, Theresa; Saber, Wael

    2017-05-15

    To evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post-transplantation. We analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre-HCT depression requiring treatment versus those without pre-HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post-HCT using Poisson models. We also compared the incidence of grade 2-4 acute and chronic graft-versus-host disease (GVHD) in allogeneic HCT. The study included 1116 (15%) patients with pre-transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre-transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04-1.23; P = 0.004) and a higher incidence of grade 2-4 acute GVHD (HR, 1.25; 95% CI, 1.14-1.37; P < 0.0001), but similar incidence of chronic GVHD. Pre-transplant depression was associated with fewer days-alive-and-out-of-the hospital (means ratio [MR] = 0.97; 95% CI, 0.95-0.99; P = 0.004). There were 512 (13.5%) patients with Pre-transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre-transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98-1.34; P = 0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97-0.99; P = 0.002). Pre-transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre

  3. Autologous mesenchymal stem cell therapy for progressive supranuclear palsy: translation into a phase I controlled, randomized clinical study.

    PubMed

    Giordano, Rosaria; Canesi, Margherita; Isalberti, Maurizio; Isaias, Ioannis Ugo; Montemurro, Tiziana; Viganò, Mariele; Montelatici, Elisa; Boldrin, Valentina; Benti, Riccardo; Cortelezzi, Agostino; Fracchiolla, Nicola; Lazzari, Lorenza; Pezzoli, Gianni

    2014-01-17

    Progressive Supranuclear Palsy (PSP) is a sporadic and progressive neurodegenerative disease which belongs to the family of tauopathies and involves both cortical and subcortical structures. No effective therapy is to date available. Autologous bone marrow (BM) mesenchymal stem cells (MSC) from patients affected by different type of parkinsonisms have shown their ability to improve the dopaminergic function in preclinical and clinical models. It is also possible to isolate and expand MSC from the BM of PSP patients with the same proliferation rate and immuphenotypic profile as MSC from healthy donors. BM MSC can be efficiently delivered to the affected brain regions of PSP patients where they can exert their beneficial effects through different mechanisms including the secretion of neurotrophic factors.Here we propose a randomized, placebo-controlled, double-blind phase I clinical trial in patients affected by PSP with MSC delivered via intra-arterial injection. To our knowledge, this is the first clinical trial to be applied in a no-option parkinsonism that aims to test the safety and to exploit the properties of autologous mesenchymal stem cells in reducing disease progression. The study has been designed to test the safety of this "first-in-man" approach and to preliminarily explore its efficacy by excluding the placebo effect. NCT01824121.

  4. Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms' tumor: a CIBMTR retrospective analysis.

    PubMed

    Malogolowkin, M H; Hemmer, M T; Le-Rademacher, J; Hale, G A; Metha, P A; Smith, A R; Kitko, C; Abraham, A; Abdel-Azim, H; Dandoy, C; Angel Diaz, M; Gale, R P; Guilcher, G; Hayashi, R; Jodele, S; Kasow, K A; MacMillian, M L; Thakar, M; Wirk, B M; Woolfrey, A; Thiel, E L

    2017-09-04

    Despite the marked improvement in the overall survival (OS) for patients diagnosed with Wilms' tumor (WT), the outcomes for those who experience relapse have remained disappointing. We describe the outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and were reported to the Center for International Blood and Marrow Transplantation Research. The 5-year estimates for event-free survival (EFS) and OS were 36% (95% confidence interval (CI); 29-43%) and 45% (95 CI; 38-51%), respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. As attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus HDT followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. As disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy.Bone Marrow Transplantation advance online publication, 4 September 2017; doi:10.1038/bmt.2017.178.

  5. A new population of human adult dental pulp stem cells: a useful source of living autologous fibrous bone tissue (LAB).

    PubMed

    Laino, Gregorio; d'Aquino, Riccardo; Graziano, Antonio; Lanza, Vladimiro; Carinci, Francesco; Naro, Fabio; Pirozzi, Giuseppe; Papaccio, Gianpaolo

    2005-08-01

    Stem cells, derived from human adult dental pulp of healthy subjects 30-45 years of age, were cultured, and cells were selected using a FACSorter. A new c-kit+/CD34+/CD45- cell population of stromal bone producing cells (SBP/DPSCs) was selected, expanded, and cultured. These SBP/DPSCs are highly clonogenic and, in culture, differentiate into osteoblast precursors (CD44+/RUNX-2+), still capable of self-renewing, and then in osteoblasts, producing, in vitro, a living autologous fibrous bone (LAB) tissue, which is markedly positive for several bone antibodies. This tissue constitute an ideal source of osteoblasts and mineralized tissue for bone regeneration. In fact, after in vivo transplantation into immunocompromised rats, LAB formed lamellar bone-containing osteocytes. Recently it has been reported that human dental pulp stem cells (DPSCs) are detectable, in humans, only up to the age of 30 years and that they are able to produce in vitro only sporadic calcified nodules and to form, after transplantation in vivo, a mineralized tissue. Stem cells, derived from human adult dental pulp of healthy subjects 30-45 years of age, were cultured, and cells were selected using a FACSorter. Light microscope, histochemistry, immunofluorescence, and RT-PCR analyses were performed to study both stem and differentiating cells. A new c-kit+/CD34+/CD45- cell population of stromal bone producing cells (SBP/DPSCs) has been selected by FACSorting, expanded, and cultured. These SBP/DPSCs are highly clonogenic and, in culture, differentiate into osteoblast precursors (CD44+/RUNX-2+), still capable of self-renewing, and in osteoblasts, producing, in vitro, a living autologous fibrous bone (LAB) tissue. This new-formed tissue is markedly positive for several antibodies for bone, including osteonectin, bone sialoprotein, osteocalcin, fibronectin, collagen III, and bone alkaline phosphatase (BALP). Cells producing LAB can be stored at -80 degrees C for a long period of time and are an

  6. Combination of guided osteogenesis with autologous platelet-rich fibrin glue and mesenchymal stem cell for mandibular reconstruction.

    PubMed

    Liao, Han-Tsung; Chen, Chien-Tzung; Chen, Chih-Hao; Chen, Jyh-Ping; Tsai, Jui-Che

    2011-01-01

    This study examined whether a combination of autologous platelet-rich fibrin glue (PRFG) with mesenchymal stem cells (MSCs) and MEDPOR as guided tissue regeneration (GTR) could act as an osteogenic substitute and whether this treatment yields faster new bone formation than MEDPOR alone or PRFG plus MSC. MSCs were harvested and isolated from the bone marrow of dog ilium. Full-thickness bony defects (1.5×1.5 cm) were created in the bilateral mandible angles of the dog. Treatments for bone defect in each group were as follows: group I (n=4), MEDPOR sheet as GTR and autologous PRFG/MSCs admixtures; group II (n=4), autologous PRFG/MSCs admixtures; group III (n=4), MEDPOR sheet as GTR; and group IV (n=4), control (empty defect). The percentage of new bone regeneration in computerized tomography at 2 months and 4 months was calculated by Analyze version 7.0 software. The mandibles were harvested from all specimens at 4 months, and the grafted sites were evaluated by gross, histologic, and X-ray examination. By radiographic analysis at 16 weeks posttransplantation, it was shown that an average of 72.8%±8.02% new bone formation in group I, 53.34%±6.87% in group II, 26.58%±6.41% in group III, and 15.14%±2.37% in group IV. Histologic examination revealed that the defect was repaired by typical bone tissue in groups I and II, whereas only minimal bone formation with fibrous connection was observed in the groups III and IV group. Besides, muscle incarceration was found in groups II and IV without MEDPOR as GTR. Autologous PRFG plus osteoinduced MSCs have good potential for bone regeneration. In combination with MEDPOR as GTR, bone regeneration is enhanced by preventing soft tissue ingrowth hindering bone regeneration.

  7. Autologous blood stem-cell transplantation in patients with advanced Hodgkin's disease and prior radiation to the pelvic site

    SciTech Connect

    Koerbling, M.H.; Holle, R.; Haas, R.; Knauf, W.; Doerken, B.H.; Ho, A.D.; Kuse, R.; Pralle, H.; Fliedner, T.M.; Hunstein, W. )

    1990-06-01

    Patients with relapsed Hodgkin's disease who respond to salvage therapy are successfully treated with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologus bone marrow transplantation (ABMT). Because of heavy pretreatment including radiation to the pelvic site, marrow harvest was not feasible in those patients. We therefore used blood-derived hemopoietic precursor cells as an alternative stem-cell source to rescue them after superdose chemotherapy. Hemopoietic precursor cells were mobilized into the peripheral blood either by chemotherapeutic induction of transient myelosuppression followed by an overshooting of blood stem-cell concentration, or by continuous intravenous (IV) granulocyte-macrophage colony-stimulating factor (GM-CSF) administration. The median time to reach 1,000 WBC per microliter, 500 polymorphonuclear cells (PMN) per microliter, or 20,000 platelets per microliter was 10, 20.5, and 38 days, respectively, for 50% of all patients. The platelet counts of two patients never dropped below 20,000/microL following autologous blood stem-cell transplantation (ABSCT), whereas two other patients had to be supported with platelets for 75 and 86 days posttransplant until a stable peripheral platelet count of 20,000/microL was attained. Among the 11 assessable patients, seven are in unmaintained complete remission (CR) at a median follow-up of 318 days. This is a first report on a series of ABSCTs in patients with advanced Hodgkin's disease proving that, despite prior damage to the marrow site, the circulating stem-cell pool is still a sufficient source of hemopoietic precursor cells for stem-cell rescue.

  8. An observational study of autologous bone marrow-derived stem cells transplantation in seven patients with nervous system diseases: a 2-year follow-up.

    PubMed

    Ren, Chao; Geng, Run-lu; Ge, Wei; Liu, Xiao-Yun; Chen, Hao; Wan, Mei-Rong; Geng, De-Qin

    2014-05-01

    Currently, autologous bone marrow-derived stem cell is one of the most innovative areas of stem cells research. Previous studies on animal models of nervous system diseases have shown that these cells have a good effect on nervous system disorders. The alternative treatment with stem cells for the nervous system diseases has also gradually reached to clinical application stage. The prospect is captivating, but the safety and efficacy of this procedure need further research. To observe the clinical efficacy and side effects of the treatment for autologous mesenchymal stem cells and neural stem/progenitor cells which are in differentiated form by inducing with cerebrospinal fluid in the patients with nervous system diseases, thirty patients were selected from our hospital (2009-10 to 2012-07) and were followed at 1 month, 3 months, 6 months, 1 year and 2 years after the treatment with autologous mesenchymal stem cells and neural stem/progenitor cells in differentiated form was introduced. In this paper, we will introduce the process to make cells accessible for the clinical application by the description of the changes observed in 7 cases were followed for 2 years. The time for bone marrow mesenchymal stem cells could be available for clinical needs is as early as 5 days, not later than 10 days, and the median time is 8 days, while neural stem/progenitor cells in differentiated form can be available for clinical needs in as early as 12 days, not later than 15 days, and the median time is 13.5 days (statistical explanation: Case 5 only uses autologous mesenchymal stem cells, and Case 7 has two times bone marrow punctures). The neurological function of the patients was improved in 1-month follow-up, and the patients have a better discontinuous trend (statistical explanation: sometimes the neurological function of the patients between two adjacent follow-ups does not change significantly). After transplantation, four patients appeared to have transient fever, but it was

  9. Stem Cell Ophthalmology Treatment Study (SCOTS): improvement in serpiginous choroidopathy following autologous bone marrow derived stem cell treatment

    PubMed Central

    Weiss, Jeffrey N.; Benes, Susan C.; Levy, Steven

    2016-01-01

    We report results in a 77-year-old male patient with visual loss from long-standing serpiginous choroidopathy treated with bone marrow derived stem cells (BMSC) within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and the largest ophthalmology stem cell study registered at the National Institutes of Health to date (ClinicalTrials.gov Identifier: NCT01920867). Eight months after treatment by a combination of retrobulbar, subtenon, intravitreal and intravenous injection of BMSC, the patient's best corrected Snellen acuity improved from 20/80– to 20/60+1 in the right eye and from 20/50– to 20/20–3 in the left eye. The Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity continued to improve over the succeeding 8 months and the optical coherence tomography macular volume increased. The increases in visual acuity and macular volume are encouraging and suggest that the use of BMSC as provided in SCOTS may be a viable approach to treating serpiginous choroidopathy. PMID:27857759

  10. Persistence of Virus Reservoirs in ART-Treated SHIV-Infected Rhesus Macaques after Autologous Hematopoietic Stem Cell Transplant

    PubMed Central

    Lawson, Benton; Lee, S. Thera; Chahroudi, Ann; Kean, Leslie; Silvestri, Guido

    2014-01-01

    Despite many advances in AIDS research, a cure for HIV infection remains elusive. Here, we performed autologous hematopoietic stem cell transplantation (HSCT) in three Simian/Human Immunodeficiency Virus (SHIV)-infected, antiretroviral therapy (ART)-treated rhesus macaques (RMs) using HSCs collected prior to infection and compared them to three SHIV-infected, ART-treated, untransplanted control animals to assess the effect of conditioning and autologous HSCT on viral persistence. As expected, ART drastically reduced virus replication, below 100 SHIV-RNA copies per ml of plasma in all animals. After several weeks on ART, experimental RMs received myeloablative total body irradiation (1080 cGy), which resulted in the depletion of 94–99% of circulating CD4+ T-cells, and low to undetectable SHIV-DNA levels in peripheral blood mononuclear cells. Following HSC infusion and successful engraftment, ART was interrupted (40–75 days post-transplant). Despite the observed dramatic reduction of the peripheral blood viral reservoir, rapid rebound of plasma viremia was observed in two out of three transplanted RMs. In the third transplanted animal, plasma SHIV-RNA and SHIV DNA in bulk PBMCs remained undetectable at week two post-ART interruption. No further time-points could be assessed as this animal was euthanized for clinical reasons; however, SHIV-DNA could be detected in this animal at necropsy in sorted circulating CD4+ T-cells, spleen and lymph nodes but not in the gastro-intestinal tract or tonsils. Furthermore, SIV DNA levels post-ART interruption were equivalent in several tissues in transplanted and control animals. While persistence of virus reservoir was observed despite myeloablation and HSCT in the setting of short term ART, this experiment demonstrates that autologous HSCT can be successfully performed in SIV-infected ART-treated RMs offering a new experimental in vivo platform to test innovative interventions aimed at curing HIV infection in humans. PMID

  11. Comparative epigenetic influence of autologous versus fetal bovine serum on mesenchymal stem cells through in vitro osteogenic and adipogenic differentiation.

    PubMed

    Fani, Nesa; Ziadlou, Reihane; Shahhoseini, Maryam; Baghaban Eslaminejad, Mohamadreza

    2016-06-10

    Mesenchymal stem cells (MSCs) derived from bone marrow (BM) represents a useful source of adult stem cells for cell therapy and tissue engineering. MSCs are present at a low frequency in the BM; therefore expansion is necessary before performing clinical studies. Fetal bovine serum (FBS) as a nutritional supplement for in vitro culture of MSCs is a suitable additive for human cell culture, but not regarding subsequent use of these cells for clinical treatment of human patients due to the risk of viral and prion transmission as well as xenogeneic immune responses after transplantation. Recently, autologous serum (AS) has been as a supplement to replace FBS in culture medium. We compared the effect of FBS versus AS on the histone modification pattern of MSCs through in vitro osteogenesis and adipogenesis. Differentiation of stem cells under various serum conditions to a committed state involves global changes in epigenetic patterns that are critically determined by chromatin modifications. Chromatin immunoprecipitation (ChIP) coupled with real-time PCR showed significant changes in the acetylation and methylation patterns in lysine 9 (Lys9) of histone H3 on the regulatory regions of stemness (Nanog, Sox2, Rex1), osteogenic (Runx2, Oc, Sp7) and adipogenic (Ppar-γ, Lpl, adiponectin) marker genes in undifferentiated MSCs, FBS and AS. All epigenetic changes occurred in a serum dependent manner which resulted in higher expression level of stemness genes in undifferentiated MSCs compared to differentiated MSCs and increased expression levels of osteogenic genes in AS compared to FBS. Adipogenic genes showed greater expression in FBS compared to AS. These findings have demonstrated the epigenetic influence of serum culture conditions on differentiation potential of MSCs, which suggest that AS is possibly more efficient serum for osteogenic differentiation of MSCs in cell therapy purposes. Copyright © 2016. Published by Elsevier Inc.

  12. Use of autologous mesenchymal stem cells derived from bone marrow for the treatment of naturally injured spinal cord in dogs.

    PubMed

    Penha, Euler Moraes; Meira, Cássio Santana; Guimarães, Elisalva Teixeira; Mendonça, Marcus Vinícius Pinheiro; Gravely, Faye Alice; Pinheiro, Cláudia Maria Bahia; Pinheiro, Taiana Maria Bahia; Barrouin-Melo, Stella Maria; Ribeiro-Dos-Santos, Ricardo; Soares, Milena Botelho Pereira

    2014-01-01

    The use of stem cells in injury repair has been extensively investigated. Here, we examined the therapeutic effects of autologous bone marrow mesenchymal stem cells (MSC) transplantation in four dogs with natural traumatic spinal cord injuries. MSC were cultured in vitro, and proliferation rate and cell viability were evaluated. Cell suspensions were prepared and surgically administered into the spinal cord. The animals were clinically evaluated and examined by nuclear magnetic resonance. Ten days after the surgical procedure and MSC transplantation, we observed a progressive recovery of the panniculus reflex and diminished superficial and deep pain response, although there were still low proprioceptive reflexes in addition to a hyperreflex in the ataxic hind limb movement responses. Each dog demonstrated an improvement in these gains over time. Conscious reflex recovery occurred simultaneously with moderate improvement in intestine and urinary bladder functions in two of the four dogs. By the 18th month of clinical monitoring, we observed a remarkable clinical amelioration accompanied by improved movement, in three of the four dogs. However, no clinical gain was associated with alterations in magnetic resonance imaging. Our results indicate that MSC are potential candidates for the stem cell therapy following spinal cord injury.

  13. Use of Autologous Mesenchymal Stem Cells Derived from Bone Marrow for the Treatment of Naturally Injured Spinal Cord in Dogs

    PubMed Central

    Penha, Euler Moraes; Meira, Cássio Santana; Guimarães, Elisalva Teixeira; Mendonça, Marcus Vinícius Pinheiro; Gravely, Faye Alice; Pinheiro, Cláudia Maria Bahia; Pinheiro, Taiana Maria Bahia; Barrouin-Melo, Stella Maria; Ribeiro-dos-Santos, Ricardo; Soares, Milena Botelho Pereira

    2014-01-01

    The use of stem cells in injury repair has been extensively investigated. Here, we examined the therapeutic effects of autologous bone marrow mesenchymal stem cells (MSC) transplantation in four dogs with natural traumatic spinal cord injuries. MSC were cultured in vitro, and proliferation rate and cell viability were evaluated. Cell suspensions were prepared and surgically administered into the spinal cord. The animals were clinically evaluated and examined by nuclear magnetic resonance. Ten days after the surgical procedure and MSC transplantation, we observed a progressive recovery of the panniculus reflex and diminished superficial and deep pain response, although there were still low proprioceptive reflexes in addition to a hyperreflex in the ataxic hind limb movement responses. Each dog demonstrated an improvement in these gains over time. Conscious reflex recovery occurred simultaneously with moderate improvement in intestine and urinary bladder functions in two of the four dogs. By the 18th month of clinical monitoring, we observed a remarkable clinical amelioration accompanied by improved movement, in three of the four dogs. However, no clinical gain was associated with alterations in magnetic resonance imaging. Our results indicate that MSC are potential candidates for the stem cell therapy following spinal cord injury. PMID:24723956

  14. Development of model for analysing respective collections of intended hematopoietic stem cells and harvests of unintended mature cells in apheresis for autologous hematopoietic stem cell collection.

    PubMed

    Hequet, O; Le, Q H; Rodriguez, J; Dubost, P; Revesz, D; Clerc, A; Rigal, D; Salles, G; Coiffier, B

    2014-04-01

    Hematopoietic stem cells (HSCs) required to perform peripheral hematopoietic autologous stem cell transplantation (APBSCT) can be collected by processing several blood volumes (BVs) in leukapheresis sessions. However, this may cause granulocyte harvest in graft and decrease in patient's platelet blood level. Both consequences may induce disturbances in patient. One apheresis team's current purpose is to improve HSC collection by increasing HSC collection and prevent increase in granulocyte and platelet harvests. Before improving HSC collection it seemed important to know more about the way to harvest these types of cells. The purpose of our study was to develop a simple model for analysing respective collections of intended CD34+ cells among HSC (designated here as HSC) and harvests of unintended platelets or granulocytes among mature cells (designated here as mature cells) considering the number of BVs processed and factors likely to influence cell collection or harvest. For this, we processed 1, 2 and 3 BVs in 59 leukapheresis sessions and analysed corresponding collections and harvests with a referent device (COBE Spectra). First we analysed the amounts of HSC collected and mature cells harvested and second the evolution of the respective shares of HSC and mature cells collected or harvested throughout the BV processes. HSC collections and mature cell harvests increased globally (p<0.0001) and their respective shares remained stable throughout the BV processes (p non-significant). We analysed the role of intrinsic (patient's features) and extrinsic (features before starting leukapheresis sessions) factors in collections and harvests, which showed that only pre-leukapheresis blood levels (CD34+cells and platelets) influenced both cell collections and harvests (CD34+cells and platelets) (p<0.001) and shares of HSC collections and mature unintended cells harvests (p<0.001) throughout the BV processes. Altogether, our results suggested that the main factors likely

  15. Effect of intraarticular injection of autologous adipose-derived mesenchymal stem and regenerative cells on clinical signs of chronic osteoarthritis of the elbow joint in dogs.

    PubMed

    Black, Linda L; Gaynor, James; Adams, Cheryl; Dhupa, Sarit; Sams, Andrew E; Taylor, Robert; Harman, Susan; Gingerich, Daniel A; Harman, Robert

    2008-01-01

    Autologous adipose-derived mesenchymal stem cell (AD-MSC) therapy involves harvesting fat from the patient, isolating the stem and regenerative cells, and administering the cells back to the patient. Autologous AD-MSC therapy in veterinary regenerative medicine has been commercially available since 2003. Previously reported results from a blinded, controlled trial in dogs with chronic osteoarthritis of the coxofemoral (hip) joint demonstrated efficacy of a single intraarticular injection of autologous AD-MSC therapy. The primary objective of the current study was to evaluate the effectiveness of this therapy in dogs with chronic osteoarthritis of the humeroradial (elbow) joints and to determine the duration of effect. Fourteen dogs were recruited. Veterinarians assessed each dog for lameness, pain on manipulation, range of motion, and functional disability using a numeric rating scale at baseline and specified intervals up to 180 days after treatment. Statistically significant improvement in outcome measures was demonstrated.

  16. Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission.

    PubMed

    Cowan, Andrew J; Stevenson, Philip A; Cassaday, Ryan D; Graf, Solomon A; Fromm, Jonathan R; Wu, David; Holmberg, Leona A; Till, Brian G; Chauncey, Thomas R; Smith, Stephen D; Philip, Mary; Orozco, Johnnie J; Shustov, Andrei R; Green, Damian J; Libby, Edward N; Bensinger, William I; Shadman, Mazyar; Maloney, David G; Press, Oliver W; Gopal, Ajay K

    2016-02-01

    Autologous stem cell transplantation (ASCT) is standard therapy for mantle cell lymphoma (MCL) in remission after induction chemotherapy, with the best results for patients in complete remission (CR). We hypothesized that evaluation of minimal residual disease (MRD) before ASCT could further stratify outcomes for these patients. Patients with MCL who underwent ASCT in clinical CR between 1996 and 2011 with pretransplantation MRD testing were eligible. Presence of a clonal IgH rearrangement, t(11; 14) by PCR or positive flow cytometry from blood or bone marrow, was considered positive. An adjusted proportional hazards model for associations with progression-free (PFS) and overall survival (OS) was performed. Of 75 MCL patients in CR, 8 (11%) were MRD positive. MRD positivity was associated with shorter OS and PFS. The median OS for MRD-negative patients was not reached, with 82% survival at 5 years, whereas for the MRD-positive patients, median OS was 3.01 years (hazard ratio [HR], 4.04; P = .009), with a median follow-up of 5.1 years. The median PFS for MRD-negative patients was not reached with 75% PFS at 5 years, whereas for MRD-positive patients, it was 2.38 years (HR, 3.69; P = .002). MRD positivity is independently associated with poor outcomes after ASCT for MCL patients in CR. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  17. Analysis of Factors that Influence Hematopoietic Recovery in Autologous Transplanted Patients with Hematopoietic Stem Cells from Peripheral Blood

    PubMed Central

    Grubovic, Rada M.; Georgievski, Borce; Cevreska, Lidija; Genadieva-Stavric, Sonja; Grubovic, Milos R.

    2017-01-01

    BACKGROUND: Successful hematopoietic stem cell transplantation (HSCT) requires a rapid and durable hematopoietic recovery. AIM: The aim of our study was to analyse factors that influence hematopoietic recovery after autologous HSCT. MATERIALS AND METHODS: Multiple regression analysis was used to analyse factors affecting neutrophil and platelet engraftment in 90 autologous transplanted patients – 30 with acute myeloid leukaemia (AML), 30 with lymphoma and 30 with multiple myeloma (MM) from 2008 till 2016. RESULTS: The neutrophil recovery in AML patients was significantly influenced by transfusion support with random-donor platelets, sex and number of transplanted mononuclear cells (MNC) and CD34+ cells; and in lymphoma patients, it was influenced by sex, age, mobilisation strategy and some transplanted MNC. The influence of investigated factors on neutrophil engraftment in MM patients was not statistically significant. The platelet recovery in AML patients was influenced by transfusion support with random-donor platelets; in lymphoma patients, it was influenced by sex, age, time from diagnosis to harvesting and time from diagnosis to HSCT; and in MM patients it was influenced by transfusion support with random-donor platelets. CONCLUSION: Additional studies are necessary to better understanding of engraftment kinetic to improve the safety of HSCT and to minimise potential complications and expenses related to HSCT. PMID:28698751

  18. POEMS Syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy and Skin Changes) Treated with Autologous Hematopoietic Stem Cell Transplantation: A Case Report and Literature Review

    PubMed Central

    Arana, Carlos; Pérez de León, José Antonio; Gómez-Moreno, Gerardo; Pérez-Cano, Ramón; Hernández, Tomás Martín

    2015-01-01

    Patient: Male, 62 Final Diagnosis: POEMS syndrome Symptoms: General malaise • pretibial edemas • weight loss Medication: — Clinical Procedure: Autologous hematopoietic stem cell transplantation Specialty: Hematology Objective: Rare disease Background: POEMS syndrome is a rare systemic pathology of paraneoplastic origin that is associated with plasma cell dyscrasia. It is characterized by the presence of sensorimotor polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes, and other systemic manifestations. The pathogenesis of the syndrome is unknown but over-production of vascular endothelial growth factor is probably responsible for most of the more characteristic symptoms. There is no standard treatment for POEMS syndrome and no randomized controlled clinical trials of treatment exist in the available literature. High-dose melphalan with autologous hematopoietic stem cell transplantation should be considered for younger patients with widespread osteosclerotic lesions, and for patients with rapidly progressive neuropathy. Case Report: This is the case of a 62-year-old Caucasian man who was admitted to our center presenting pretibial edema accompanied by significant weight loss and difficulty walking. POEMS criteria were present and an immunofixation test confirmed the presence of a monoclonal plasmaproliferative disorder. After autologous hematopoietic stem cell transplantation, the monoclonal component disappeared and the patient’s clinical status improved markedly. Conclusions: Autologous hematopoietic stem cell transplantation following high-dose melphalan is an effective therapy for younger patients with widespread osteosclerotic lesions in POEMS syndrome. PMID:25726020

  19. Mexican Biosimilar Filgrastim for Autologous Hematopoietic Stem Cell Mobilization and Transplantation.

    PubMed

    León-González, Mónica; León-Peña, Andrés A; Vallejo-VIllalobos, María Fernanda; Núñez-Cortés, Ana Karen; Ruiz-Argüelles, Alejandro; Ruiz-Argüelles, Guillermo J

    2016-01-01

    Following the release of the initial presentation of filgrastim (granulocyte colony-stimulating factor), several biosimilars have been developed worldwide. To study the efficacy of a Mexican biosimilar granulocyte colony-stimulating factor in a single transplant center. In a group of 19 consecutive patients with multiple sclerosis given autografts, we employed granulocyte colony-stimulating factors to mobilize stem cells from the bone marrow to the peripheral blood, either the original granulocyte colony-stimulating factor (n = 10) or a Mexican granulocyte colony-stimulating factor biosimilar (n = 9). The efficacy of both agents was similar in mobilization capacity, white blood cell count rise, stem cell collection, and kinetics of auto-engraftment. We conclude that both granulocyte colony-stimulating factor agents were similar in their efficacy to mobilize stem cells and usefulness in autografts.

  20. Successful Treatment of Gastric Relapse in Multiple Myeloma with Bortezomib after Autologous Hematopoietic Stem Cell Transplantation (autoHSCT)

    PubMed Central

    Sivgin, Serdar; Baldane, Suleyman; Kaynar, Leylagul; Kurnaz, Fatih; Baskol, Mevlut; Kula, Mustafa; Eroglu, Celalettin; Deniz, Kemal; Eser, Bulent; Unal, Ali; Cetin, Mustafa

    2013-01-01

    We report a case of 59-year-old Turkish man with history of mitral valve replacement (MVR) and chronic obstructive pulmonary disease (COPD) who was diagnosed with stage IIIA IgG lambda multiple myeloma (MM) in 1997. He underwent autologous hematopoietic stem cell transplantation after a conditioning regimen with melphalan 200mg per body area (m2) in February 2006. On February 2011, he was admitted to the emergency service of university hospital with complaints of hematemesis and melena. Pathological evaluation of gastric biopsy, obtained from a lesion of small gastric curvature, showed the gastric mucosa infiltrated by neoplastic plasma cells, monoclonal lambda light chain positive. The patient was considered as having local gastric relapsed disease and was treated with 2 cycles of bortezomib. He achieved an excellent local response after 2 cycles of bortezomib, cyclophosphamide and prednisone (BEP) regimen, with healing of gastric ulcer and no recurrence of the hematemesis or melena. PMID:23350019

  1. High-dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: the GEL-TAMO experience.

    PubMed

    Rodríguez, J; Caballero, M D; Gutiérrez, A; Marín, J; Lahuerta, J J; Sureda, A; Carreras, E; León, A; Arranz, R; Fernández de Sevilla, A; Zuazu, J; García-Laraña, J; Rifon, J; Varela, R; Gandarillas, M; SanMiguel, J; Conde, E

    2003-12-01

    T-cell immunophenotype constitutes an unfavorable prognostic factor in aggressive non-Hodgkin's lymphomas. High-dose chemotherapy with autologous stem-cell rescue (HDC/ASCT) is the best salvage therapy for patients with aggressive B-cell lymphomas. However, results with this therapy in peripheral T-cell lymphoma (PTCL) are not well defined. From January 1990 to December 1999, 115 patients with PTCL underwent HDC/ASCT inside the Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL-TAMO) registry. At diagnosis the median age was 41 years and 60% of patients presented with two or three risk factors from the adjusted International Prognostic Index (a-IPI). Thirty-two per cent of patients were transplanted in first complete response (CR), 62% in chemosensitive disease and 5% in refractory disease. Eighty-six per cent of the patients attained a CR and 5% a partial response (PR). With a median follow-up of 37 months (range 1-133), overall survival (OS), time-to-treatment failure (TTF) and disease-free survival (DFS) at 5 years was 56%, 51% and 60%, respectively; for the 37 patients transplanted in first CR, OS and DFS at 5 years were 80% and 79%, respectively. Lactase dehydrogenase (LDH), a-IPI and disease status pre-transplant were associated with outcome. More than half of patients with chemosensitive disease who were transplanted are expected to be alive at 5 years. We confirm the utility of the pre-transplant IPI system in predicting outcome. Salvage treatment results with HDC/ASCT in PTCL are similar to those found in corresponding aggressive B-cell lymphomas.

  2. Mesenchymal stromal cells improve early lymphocyte recovery and T cell reconstitution after autologous hematopoietic stem cell transplantation in patients with malignant lymphomas.

    PubMed

    Batorov, Egor V; Shevela, Ekaterina Ya; Tikhonova, Marina A; Batorova, Dariya S; Ushakova, Galina Yu; Sizikova, Svetlana A; Sergeevicheva, Vera V; Gilevich, Andrey V; Kryuchkova, Irina V; Ostanin, Alexandr A; Chernykh, Elena R

    2015-10-01

    Mesenchymal stromal cells (MSCs) possess a multi-lineage potential and immunoregulatory activities and provide a great potential in cell-based technologies. However, MSC suppressive activity raises concerns regarding the possible adverse effect of MSCs on the immune recovery. The influence of autologous MSC co-transplantation on recovery of T cell subsets in patients receiving autologous hematopoietic stem cell transplantation (AHSCT) for malignant lymphomas and multiple myeloma were characterized. Co-transplantation of MSCs improved lymphocyte recovery most effectively in patients with low input of hematopoietic stem cells or low absolute lymphocyte count in apheresis product. MSC co-transplantation improved early recovery of both memory and naive T cells with more prominent effect on naive CD4(+) T cells. Patients with MSC co-transplantation showed more effective reconstitution of recent thymic emigrants. These data indicate the positive impact of MSCs on immune reconstitution and note MSC co-transplantation is feasible to optimize the outcomes of AHSCT in malignant lymphoma patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Autologous mesenchymal stem cell (MSCs) transplantation for critical-sized bone defect following a wide excision of osteofibrous dysplasia

    PubMed Central

    Dilogo, Ismail Hadisoebroto; Kamal, Achmad Fauzi; Gunawan, Bambang; Rawung, Rangga Valentino

    2015-01-01

    Introduction Osteofibrous dysplasia is a rare non-neoplastic disease that is almost exclusive to pediatric tibial diaphysis. Wide excision of the lesion is recommended to avoid recurrence. However, such radical surgery will results in large segmental bone defects that will require further extensive reconstructive surgery. We report a novel approach of treating bone defect by implementing the diamond concept of bone healing using autologous bone marrow derived mesenchymal stem cells (BM-MSCs). Presentation of case An eight-year-old Indonesian male presented with severe bowing deformity of the left lower leg. Radiographic and histological analysis confirmed the diagnosis of osteofibrous dysplasia. A wide excision of the defect was made leaving a critical-sized bone defect. A combination of autologous transplantation of 50 million BM-MSCs, hydroxyapatite (HA) granules, bone morphogenic protein 2 (BMP-2) and Djoko-Zarov hybrid circular external fixator was used to treat the defect. The outcomes measured were subjective complaints, functionality based on LEFS and radiological assessments. Discussion Radiographic assessments showed successful new bone tissue formation and integration of implanted HA granules. The external fixator was removed at 42 weeks after adequate callus formation and clinical stability was achieved. The patient underwent progressive functional improvements and reached a near normal functionality of 90% LEFS at 84 week. No therapy side effect or complication was reported. Conclusion Osteofibrous dysplasia was successfully excised without signs of recurrence after 84-week follow-up. Autologous transplantation of augmented BM-MSCs has successfully created new normal bone tissue without causing any side effect and had significantly improved the patient’s quality of life. PMID:26599503

  4. Bilayer hydrogel with autologous stem cells derived from debrided human burn skin for improved skin regeneration.

    PubMed

    Natesan, Shanmugasundaram; Zamora, David O; Wrice, Nicole L; Baer, David G; Christy, Robert J

    2013-01-01

    The objective of this study was to demonstrate that stem cells isolated from discarded skin obtained after debridement can be used with collagen and fibrin-based scaffolds to develop a tissue-engineered vascularized dermal equivalent. Discarded tissue samples were collected from severely burned patients undergoing wound debridement. Stem cells were isolated from the adipose tissue layer and their growth and immunophenotype characterized. To develop a skin equivalent, debrided skin adipose stem cells (dsASCs) were added to a collagen-polyethylene glycol (PEG) fibrin-based bilayer hydrogel and analyzed in vitro. The effect of the bilayered hydrogels on wound healing was demonstrated using an excision wound model in athymic rats. The dsASCs isolated from all samples were CD90, CD105, and stromal cell surface protein-1 positive, similar to adipose stem cells isolated from normal human lipoaspirates. Within the bilayer hydrogels, dsASCs proliferated and differentiated, maintained a spindle-shaped morphology in collagen, and developed a tubular microvascular network in the PEGylated fibrin. Rat excision wounds treated with bilayer hydrogels showed less wound contraction and exhibited better dermal matrix deposition and epithelial margin progression than controls. Stem cells can be isolated from the adipose layer of burned skin obtained during debridement. When dsASCs are incorporated within collagen-PEGylated fibrin bilayer hydrogels, they develop stromal and vascular phenotypes through matrix-directed differentiation without use of growth factors. Preliminary in vivo studies indicate that dsASC-bilayer hydrogels contribute significantly to wound healing and provide support for their use as a vascularized dermal substitute for skin regeneration to treat large surface area burns.

  5. Comparison of SPE, IFE, and FLC in Monitoring Patients with Multiple Myeloma After Autologous Stem Cell Transplantation.

    PubMed

    Li, Wei; Zhou, Jia-Zi; Chang, Hui-Rong; Dai, Li-Jun; Zhu, Zi-Ling; Feng, Yu-Feng; Gong, Fei-Ran; Wu, De-Pei

    2015-12-01

    Conventionally, serum protein electrophoresis (SPE) and serum immunofixation electrophoresis (IFE) are used as primary methods to diagnose and monitor multiple myeloma (MM). Recently, serum-free light chain (FLC) assay has been incorporated into hematological screening programs for myeloma. The purpose of this study is to compare the performance of the three methods in monitoring MM patients after autologous stem cell transplantation (ASCT). SPE, serum IFE and serum FLC assay were performed on 38 MM patients who underwent ASCT. In total, four patients had unexpected protein bands (UPBs) and 13 patients had relapsed after ASCT. Our results indicate that IFE is more sensitive than SPE and FLC assay in detection of UPBs and relapse. The results of IFE may provide useful information in advance of patient relapse.

  6. Germinal center B (GCB) and non-GCB cell-like diffuse large B cell lymphomas have similar outcomes following autologous haematopoietic stem cell transplantation.

    PubMed

    Costa, Luciano J; Feldman, Andrew L; Micallef, Ivana N; Inwards, David J; Johnston, Patrick B; Porrata, Luis F; Ansell, Stephen M

    2008-07-01

    Patients with germinal center B cell-like (GCB) and non-GCB diffuse large B cell lymphomas (DLBCL) receiving first line therapy have distinct prognosis. We explored the differences in outcome following salvage autologous hematopoietic stem cell (HSC) transplantation between patients with GCB and non-GCB DLBCL. Forty-four patients with relapsed and 15 patients with primary refractory chemosensitive disease undergoing BEAM (BCNU [carmustine], etoposide, cytarabine, melphalan) conditioning and autologous HSC were included. Immunohistochemical analysis was performed for CD10, BCL-6, MUM1 (allowing classification into GCB and non-GCB-like DLBCL) and BCL-2. Median follow-up of survivors was 25 months; median age at the time of transplantation was 60 years (range 17-77). Thirty-two patients (54%) were classified as having GCB and 27 (46%) as having non-GCB-like DLBCL. Patients with GCB and non-GCB DLBCL did not differ in the risk of progression after HSC transplant (P = 0.78) or overall survival (P = 0.48). In multivariate analysis, only time to progression after initial treatment impacted overall survival. We conclude that patients with relapsed or primary refractory chemosensitive GCB and non-GCB-like DLBCL derive similar benefit from autologous HSC transplant.

  7. Persistent positive metaiodobenzylguanidine scans after autologous peripheral blood stem cell transplantation may indicate maturation of stage 4 neuroblastoma.

    PubMed

    Okamoto, Yasuhiro; Kodama, Yuichi; Nishikawa, Takuro; Rindiarti, Almitra; Tanabe, Takayuki; Nakagawa, Shunsuke; Yoshioka, Takako; Takumi, Koji; Kaji, Tatsuru; Kawano, Yoshifumi

    2017-10-04

    Metaiodobenzylguanidine (MIBG) scans are sensitive testing tools for neuroblastoma. Persistent positive MIBG scans in patients with stage 3 neuroblastoma have previously been found to indicate maturation rather than regression. We assessed the significance of this finding in stage 4 neuroblastoma in the present study. Fifteen consecutive pediatric patients with stage 4 neuroblastoma treated between 2004 and 2014 at the Kagoshima University Hospital were retrospectively examined. Treatment involved a combination of multiagent chemotherapy, resection, autologous peripheral blood stem cell transplantation (PBSCT), radiotherapy, and maintenance therapy with retinoic acid. The MIBG uptake in each patient during treatment was assessed using a Curie score. The 5-year event-free and overall survival rates in 15 patients were 38.9% and 58.7%, respectively. Four patients with persistent positive MIBG scans who underwent autologous PBSCT but experienced decreased (123)I-MIBG uptake during the clinical course survived without progression, and their event-free survival (EFS) was significantly superior to that of patients who showed negative MIBG scans after PBSCT (5-year EFS rate: 18.2%, p = 0.0176). Therefore, persistent positive MIBG scans with gradually decreased uptake after PBSCT do not always indicate neuroblastoma progression, and may instead indicate tumor maturation in some selected cases, if not all cases, of stage 4 neuroblastoma.

  8. Repeated Autologous Bone Marrow-Derived Mesenchymal Stem Cell Injections Improve Radiation-Induced Proctitis in Pigs

    PubMed Central

    Busson, Elodie; Holler, Valerie; Strup-Perrot, Carine; Lacave-Lapalun, Jean-Victor; Lhomme, Bruno; Prat, Marie; Devauchelle, Patrick; Sabourin, Jean-Christophe; Simon, Jean-Marc; Bonneau, Michel; Lataillade, Jean-Jacques; Benderitter, Marc

    2013-01-01

    The management of proctitis in patients who have undergone very-high-dose conformal radiotherapy is extremely challenging. The fibrosis-necrosis, fistulae, and hemorrhage induced by pelvic overirradiation have an impact on morbidity. Augmenting tissue repair by the use of mesenchymal stem cells (MSCs) may be an important advance in treating radiation-induced toxicity. Using a preclinical pig model, we investigated the effect of autologous bone marrow-derived MSCs on high-dose radiation-induced proctitis. Irradiated pigs received repeated intravenous administrations of autologous bone marrow-derived MSCs. Immunostaining and real-time polymerase chain reaction analysis were used to assess the MSCs' effect on inflammation, extracellular matrix remodeling, and angiogenesis, in radiation-induced anorectal and colon damages. In humans, as in pigs, rectal overexposure induces mucosal damage (crypt depletion, macrophage infiltration, and fibrosis). In a pig model, repeated administrations of MSCs controlled systemic inflammation, reduced in situ both expression of inflammatory cytokines and macrophage recruitment, and augmented interleukin-10 expression in rectal mucosa. MSC injections limited radiation-induced fibrosis by reducing collagen deposition and expression of col1a2/col3a1 and transforming growth factor-β/connective tissue growth factor, and by modifying the matrix metalloproteinase/TIMP balance. In a pig model of proctitis, repeated injections of MSCs effectively reduced inflammation and fibrosis. This treatment represents a promising therapy for radiation-induced severe rectal damage. PMID:24068742

  9. Repeated autologous bone marrow-derived mesenchymal stem cell injections improve radiation-induced proctitis in pigs.

    PubMed

    Linard, Christine; Busson, Elodie; Holler, Valerie; Strup-Perrot, Carine; Lacave-Lapalun, Jean-Victor; Lhomme, Bruno; Prat, Marie; Devauchelle, Patrick; Sabourin, Jean-Christophe; Simon, Jean-Marc; Bonneau, Michel; Lataillade, Jean-Jacques; Benderitter, Marc

    2013-11-01

    The management of proctitis in patients who have undergone very-high-dose conformal radiotherapy is extremely challenging. The fibrosis-necrosis, fistulae, and hemorrhage induced by pelvic overirradiation have an impact on morbidity. Augmenting tissue repair by the use of mesenchymal stem cells (MSCs) may be an important advance in treating radiation-induced toxicity. Using a preclinical pig model, we investigated the effect of autologous bone marrow-derived MSCs on high-dose radiation-induced proctitis. Irradiated pigs received repeated intravenous administrations of autologous bone marrow-derived MSCs. Immunostaining and real-time polymerase chain reaction analysis were used to assess the MSCs' effect on inflammation, extracellular matrix remodeling, and angiogenesis, in radiation-induced anorectal and colon damages. In humans, as in pigs, rectal overexposure induces mucosal damage (crypt depletion, macrophage infiltration, and fibrosis). In a pig model, repeated administrations of MSCs controlled systemic inflammation, reduced in situ both expression of inflammatory cytokines and macrophage recruitment, and augmented interleukin-10 expression in rectal mucosa. MSC injections limited radiation-induced fibrosis by reducing collagen deposition and expression of col1a2/col3a1 and transforming growth factor-β/connective tissue growth factor, and by modifying the matrix metalloproteinase/TIMP balance. In a pig model of proctitis, repeated injections of MSCs effectively reduced inflammation and fibrosis. This treatment represents a promising therapy for radiation-induced severe rectal damage.

  10. Treatment of one case of cerebral palsy combined with posterior visual pathway injury using autologous bone marrow mesenchymal stem cells.

    PubMed

    Li, Min; Yu, Aixue; Zhang, Fangfang; Dai, Guanghui; Cheng, Hongbin; Wang, Xiaodong; An, Yihua

    2012-05-18

    Cerebral palsy is currently one of the major diseases that cause severe paralysis of the nervous system in children; approximately 9-30% of cerebral palsy patients are also visually impaired, for which no effective treatment is available. Bone marrow mesenchymal stem cells (BMSCs) have very strong self-renewal, proliferation, and pluripotent differentiation potentials. Therefore, autologous BMSC transplantation has become a novel method for treating cerebral palsy. An 11-year-old boy had a clear history of dystocia and asphyxia after birth; at the age of 6 months, the family members observed that his gaze roamed and noted that he displayed a lack of attention. A brain MRI examination at the age of 7 years showed that the child had cerebral palsy with visual impairment (i.e., posterior visual pathway injury). The patient was hospitalized for 20 days and was given four infusions of intravenous autologous BMSCs. Before transplantation and 1, 6, and 12 months after transplantation, a visual evoked potential test, an electrocardiogram, routine blood tests, and liver and kidney function tests were performed. The patient did not have any adverse reactions during hospitalization or postoperative follow-up. After discharge, the patient could walk more smoothly than he could before transplantation; furthermore, his vision significantly improved 6 months after transplantation, which was also supported by the electrophysiological examinations. The clinical application of BMSCs is effective for improving vision in a patient with cerebral palsy combined with visual impairment.

  11. Repair of facial nerve defects with decellularized artery allografts containing autologous adipose-derived stem cells in a rat model.

    PubMed

    Sun, Fei; Zhou, Ke; Mi, Wen-Juan; Qiu, Jian-Hua

    2011-07-20

    The purpose of this study was to investigate the effects of a decellularized artery allograft containing autologous adipose-derived stem cells (ADSCs) on an 8-mm facial nerve branch lesion in a rat model. At 8 weeks postoperatively, functional evaluation of unilateral vibrissae movements, morphological analysis of regenerated nerve segments and retrograde labeling of facial motoneurons were all analyzed. Better regenerative outcomes associated with functional improvement, great axonal growth, and improved target reinnervation were achieved in the artery-ADSCs group (2), whereas the cut nerves sutured with artery conduits alone (group 1) achieved inferior restoration. Furthermore, transected nerves repaired with nerve autografts (group 3) resulted in significant recovery of whisking, maturation of myelinated fibers and increased number of labeled facial neurons, and the latter two parameters were significantly different from those of group 2. Collectively, though our combined use of a decellularized artery allograft with autologous ADSCs achieved regenerative outcomes inferior to a nerve autograft, it certainly showed a beneficial effect on promoting nerve regeneration and thus represents an alternative approach for the reconstruction of peripheral facial nerve defects. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Comparison of characteristics of bacterial bloodstream infection between adult patients with allogeneic and autologous hematopoietic stem cell transplantation.

    PubMed

    Hong, Junshik; Moon, Song Mi; Ahn, Hee Kyung; Sym, Sun Jin; Park, Yoon Soo; Park, Jinny; Cho, Yong Kyun; Cho, Eun Kyung; Shin, Dong Bok; Lee, Jae Hoon

    2013-06-01

    Although autologous and allogeneic hematopoietic stem cell transplantation (HSCT) are fundamentally different procedures, a tailored approach to bacterial bloodstream infection (BSI) according to the type of HSCT has not yet been suggested. We evaluated the characteristics of BSI after HSCT, with a focus on comparison of BSIs between recipients of autologous HSCT (auto-HSCT) and allogeneic HSCT (allo-HSCT). Among 134 patients (59 received allo-HSCT and 75 received auto-HSCT) who underwent HSCT, BSIs were reported earlier in patients who underwent auto-HSCT, compared with those who underwent allo-HSCT (mean 12.1 ± 3.4 days versus 32.8 ± 27.1 days, P = .006). Among patients receiving allo-HSCT, postneutrophil-engraftment bacterial BSI showed an association with grade ≥ 2 acute graft-versus-host disease (GVHD). In patients who underwent auto-HSCT, results of multivariate analysis showed that not receiving prophylactic antibiotics (P = .004) and having elevated serum C-reactive protein (P = .034) were risk factors of BSI. Elevated CRP (P = .01) and acute GVHD ≥ grade 2 (P = .002) were independent risk factors in patients who underwent allo-HSCT. Those differences originated mainly from the impact of acute GVHD-related postengraftment BSIs of patients who underwent allo-HSCT. To establish the best defense strategy against BSI, the distinctive natures of bacterial BSI after HSCT between auto-HSCT and allo-HSCT should be considered.

  13. Enhancement of the repair of dog alveolar cleft by an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture.

    PubMed

    Yuanzheng, Chen; Yan, Gao; Ting, Li; Yanjie, Fu; Peng, Wu; Nan, Bai

    2015-05-01

    Autologous bone graft has been regarded as the criterion standard for the repair of alveolar cleft. However, the most prominent issue in alveolar cleft treatment is the high absorption rate of the bone graft. The authors' objective was to investigate the effects of an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture on the repair of dog alveolar cleft. Twenty beagle dogs with unilateral alveolar clefts created by surgery were divided randomly into four groups: group A underwent repair with an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture; group B underwent repair with autologous iliac bone and bone marrow-derived mesenchymal stem cells; group C underwent repair with autologous iliac bone and platelet-rich fibrin; and group D underwent repair with autologous iliac bone as the control. One day and 6 months after transplantation, the transplant volumes and bone mineral density were assessed by quantitative computed tomography. All of the transplants were harvested for hematoxylin and eosin staining 6 months later. Bone marrow-derived mesenchymal stem cells and platelet-rich fibrin transplants formed the greatest amounts of new bone among the four groups. The new bone formed an extensive union with the underlying maxilla in groups A, B, and C. Transplants with the bone marrow-derived mesenchymal stem cells, platelet-rich fibrin, and their mixture retained the majority of their initial volume, whereas the transplants in the control group showed the highest absorption rate. Bone mineral density of transplants with the bone marrow-derived mesenchymal stem cells, platelet-rich fibrin, and their mixture 6 months later was significantly higher than in the control group (p < 0.05), and was the highest in bone marrow-derived mesenchymal stem cells and platelet-rich fibrin mixed transplants. Hematoxylin and eosin staining showed that the structure of new bones formed the best

  14. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study.

    PubMed

    Orozco, Lluis; Munar, Anna; Soler, Robert; Alberca, Mercedes; Soler, Francesc; Huguet, Marina; Sentís, Joan; Sánchez, Ana; García-Sancho, Javier

    2013-06-27

    Osteoarthritis is the most prevalent joint disease and a frequent cause of joint pain, functional loss, and disability. Osteoarthritis often becomes chronic, and conventional treatments have demonstrated only modest clinical benefits without lesion reversal. Cell-based therapies have shown encouraging results in both animal studies and a few human case reports. We designed a pilot study to assess the feasibility and safety of osteoarthritis treatment with mesenchymal stromal cells (MSCs) in humans and to obtain early efficacy information for this treatment. Twelve patients with chronic knee pain unresponsive to conservative treatments and radiologic evidence of osteoarthritis were treated with autologous expanded bone marrow MSCs by intra-articular injection (40×10 cells). Clinical outcomes were followed for 1 year and included evaluations of pain, disability, and quality of life. Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping. Feasibility and safety were confirmed, and strong indications of clinical efficacy were identified. Patients exhibited rapid and progressive improvement of algofunctional indices that approached 65% to 78% by 1 year. This outcome compares favorably with the results of conventional treatments. Additionally, quantification of cartilage quality by T2 relaxation measurements demonstrated a highly significant decrease of poor cartilage areas (on average, 27%), with improvement of cartilage quality in 11 of the 12 patients. MSC therapy may be a valid alternative treatment for chronic knee osteoarthritis. The intervention is simple, does not require hospitalization or surgery, provides pain relief, and significantly improves cartilage quality.

  15. Myeloablative allogeneic hematopoietic stem cell transplantation in patients who experience relapse after autologous stem cell transplantation for lymphoma: a report of the International Bone Marrow Transplant Registry.

    PubMed

    Freytes, César O; Loberiza, Fausto R; Rizzo, J Douglas; Bashey, Asad; Bredeson, Christopher N; Cairo, Mitchell S; Gale, Robert Peter; Horowitz, Mary M; Klumpp, Thomas R; Martino, Rodrigo; McCarthy, Philip L; Molina, Arturo; Pavlovsky, Santiago; Pecora, Andrew L; Serna, Derek S; Tsai, Tsuong; Zhang, Mei-Jie; Vose, Julie M; Lazarus, Hillard M; van Besien, Koen

    2004-12-01

    Myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasingly used in patients with lymphoma who experience disease relapse after autologous hematopoietic stem cell transplantation (auto-HSCT) because the allograft is tumor free and may induce a graft-versus-tumor effect. We analyzed 114 patients treated with this approach from 1990 to 1999 to assess disease progression, progression-free survival (PFS), and overall survival (OS). Cumulative incidence of disease progression at 3 years was 52%, whereas treatment-related mortality was 22%, lower than previously reported. Three-year probabilities of OS and PFS were 33% and 25%, respectively. With prolonged follow-up, however, nearly all patients experienced disease progression, and 5-year probabilities were 24% and 5%, respectively. Complete remission at the time of allo-HSCT and use of total body irradiation (TBI) in patients with non-Hodgkin lymphoma (NHL) were associated with lower rates of disease progression and higher rates of OS. In summary, allo-HSCT is feasible for patients with lymphoma who have relapses after auto-HSCT and can result in prolonged survival for some, but it is usually not curative. Most likely to benefit are patients who have HLA-matched sibling donors, are in remission, and have good performance status.

  16. Presence of osteoclast precursor cells during ex vivo expansion of bone marrow-derived mesenchymal stem cells for autologous use in cell therapy.

    PubMed

    Allers, Carolina; Lasala, Gabriel P; Minguell, José J

    2014-04-01

    To obtain a cell product competent for clinical use in terms of cell dose and biologic properties, bone marrow-derived mesenchymal stem cells (MSCs) must be expanded ex vivo. A retrospective analysis was performed of records of 76 autologous MSC products used in phase I or II clinical studies performed in a cohort of cardiovascular patients. In all cases, native MSCs present in patient bone marrow aspirates were separated and expanded ex vivo. The cell products were classified in two groups (A and B), according to biologic properties and expansion time (ex vivo passages) to reach the protocol-established cell dose. In group A, the population of adherent cells obtained during the expansion period (2 ± 1 passages) was composed entirely of MSCs and met the requirements of cell number and biologic features as established in the respective clinical protocol. In group B, in addition to MSCs, we observed during expansion a high proportion of ancillary cells, characterized as osteoclast precursor cells. In this case, although the biologic properties of the resulting MSC product were not affected, the yield of MSCs was significantly lower. The expansion cycles had to be increased (3 ± 1 passages). These results suggest that the presence of osteoclast precursor cells in bone marrow aspirates may impose a limit for the proper clinical use of ex vivo expanded autologous bone marrow-derived MSCs. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  17. An in vivo study on endothelialized vascular grafts produced by autologous biotubes and adipose stem cells (ADSCs).

    PubMed

    Tseng, Yu Chieh; Roan, Jun Neng; Ho, Ying Chiang; Lin, Chih Chan; Yeh, Ming Long

    2017-09-15

    Currently, commercial synthetic vascular grafts made from Dacron and ePTFE for small-diameter, vascular applications (<6 mm) show limited reendothelization and are less compliant, often resulting in thrombosis and intimal hyperplasia. Although good blood compatibility can be achieved in autologous arteries and veins, the number of high quality harvest sites is limited, and the grafts are size-mismatched for use in the fistula or cardiovascular bypass surgery; thus, alternative small graft substitutes must be developed. A biotube is an in vivo, tissue-engineered approach for the growth of autologous grafts through the subcutaneous implantation of an inert rod through the inflammation process. In the present study, we embedded silicone rods with a diameter of 2 mm into the dorsal subcutaneous tissue of rabbits for 4 weeks to grow biotubes. The formation of functional endothelium cells aligned on the inner wall surface was achieved by seeding with adipose stem cells (ADSCs). The ADSCs-seeded biotubes were implanted into the carotid artery of rabbits for more than 1 month, and the patency rates and remodeling of endothelial cells were observed by angiography and fluorescence staining, respectively. Finally, the mechanical properties of the biotube were also evaluated. The fluorescence staining results showed that the ADSCs differentiated not only into endothelia cells but also into smooth muscle cells. Moreover, the patency of the ADSCs-seeded biotube remained high for at least 5 months. These small-sized ADSCs-seeded vascular biotubes may decrease the rate of intimal hyperplasia during longer implantation times and have potential clinical applications in the future.

  18. Autologous adipocyte derived stem cells favour healing in a minipig model of cutaneous radiation syndrome.

    PubMed

    Forcheron, Fabien; Agay, Diane; Scherthan, Harry; Riccobono, Diane; Herodin, Francis; Meineke, Viktor; Drouet, Michel

    2012-01-01

    Cutaneous radiation syndrome (CRS) is the delayed consequence of localized skin exposure to high doses of ionizing radiation. Here we examined for the first time in a large animal model the therapeutic potential of autologous adipose tissue-derived stroma cells (ASCs). For experiments, Göttingen minipigs were locally gamma irradiated using a (60)Co source at the dose of 50 Gy and grafted (n = 5) or not (n = 8). ASCs were cultured in MEM-alpha with 10% fetal calf serum and basic fibroblast growth factor (2 ng.mL(-1)) and post irradiation were intradermally injected on days 25, 46, 67 and finally between days 95 and 115 (50 × 10(6) ASCs each time) into the exposed area. All controls exhibited a clinical evolution with final necrosis (day 91). In grafted pigs an ultimate wound healing was observed in four out of five grafted animals (day 130 +/- 28). Immunohistological analysis of cytokeratin expression showed a complete epidermis recovery. Grafted ASCs accumulated at the dermis/subcutis barrier in which they attracted numerous immune cells, and even an increased vasculature in one pig. Globally this study suggests that local injection of ASCs may represent a useful strategy to mitigate CRS.

  19. Autologous Adipocyte Derived Stem Cells Favour Healing in a Minipig Model of Cutaneous Radiation Syndrome

    PubMed Central

    Forcheron, Fabien; Agay, Diane; Scherthan, Harry; Riccobono, Diane; Herodin, Francis; Meineke, Viktor; Drouet, Michel

    2012-01-01

    Cutaneous radiation syndrome (CRS) is the delayed consequence of localized skin exposure to high doses of ionizing radiation. Here we examined for the first time in a large animal model the therapeutic potential of autologous adipose tissue-derived stroma cells (ASCs). For experiments, Göttingen minipigs were locally gamma irradiated using a 60Co source at the dose of 50 Gy and grafted (n = 5) or not (n = 8). ASCs were cultured in MEM-alpha with 10% fetal calf serum and basic fibroblast growth factor (2 ng.mL−1) and post irradiation were intradermally injected on days 25, 46, 67 and finally between days 95 and 115 (50×106 ASCs each time) into the exposed area. All controls exhibited a clinical evolution with final necrosis (day 91). In grafted pigs an ultimate wound healing was observed in four out of five grafted animals (day 130 +/− 28). Immunohistological analysis of cytokeratin expression showed a complete epidermis recovery. Grafted ASCs accumulated at the dermis/subcutis barrier in which they attracted numerous immune cells, and even an increased vasculature in one pig. Globally this study suggests that local injection of ASCs may represent a useful strategy to mitigate CRS. PMID:22348120

  20. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury.

    PubMed

    Dai, Guanghui; Liu, Xuebin; Zhang, Zan; Yang, Zhijun; Dai, Yiwu; Xu, Ruxiang

    2013-10-02

    Neuronal injuries have been a challenging problem for treatment, especially in the case of complete and chronic cervical spinal cord injury (SCI). Recently, particular attention is paid to the potential of stem cell in treating SCI, but there are only few clinical studies and insufficient data. This study explored the efficacy of autologous bone marrow mesenchymal stem cells (BMMSCs) transplantation in the treatment of SCI. Forty patients with complete and chronic cervical SCI were selected and randomly assigned to one of the two experimental groups, treatment group and control group. The treatment group received BMMSCs transplantation to the area surrounding injury, while the control group was not treated with any cell transplantation. Both the transplant recipients and the control group were followed up to 6 months, postoperatively. Preoperative and postoperative neurological functions were evaluated with AIS grading, ASIA score, residual urine volume and neurophysiological examination. Results showed that in the treatment group 10 patients had a significant clinical improvement in terms of motor, light touch, pin prick sensory and residual urine volume, while nine patients showed changes in AIS grade. Neurophysiological examination was consistent with clinical observations. No sign of tumor was evident until 6 months postoperatively. In the control group, no improvement was observed in any of the neurological functions specified above. BMMSCs transplantation improves neurological function in patients with complete and chronic cervical SCI, providing valuable information on applications of BMMSCs for the treatment of SCI.

  1. Tweaking the immune system: gene therapy-assisted autologous haematopoietic stem cell transplantation as a treatment for autoimmune disease.

    PubMed

    Alderuccio, Frank; Chan, James; Toh, Ban-Hock

    2008-12-01

    Autoimmune diseases represent a major challenge for medical research. The aberrant self-recognition by the immune system leads to a range of pathologies for which cures have not been forthcoming. Treatments are commonly non-specific and often lead to unwanted side-effects. A number of strategies are currently being explored to tackle autoimmunity; aimed at eliminating existing pathogenic clones and the induction of immune tolerance through resetting or regulating the immune system. Autologous haematopoietic stem cell transplantation (HSCT) is one such strategy and is being trailed in a number of autoimmune diseases. However, a common feature of this strategy is disease relapse and may indicate incomplete tolerance mechanisms. It is well known that bone marrow derived cells have a major influence on immune tolerance. It is also well documented that ectopic expression of antigens within the immune system can promote robust tolerance. This review considers these observations in the context of promoting a strategy involving genetic manipulation of haematopoietic stem cells together with HSCT to induce immune tolerance and tackle autoimmunity.

  2. Dermal Mesenchymal Stem Cells (DMSCs) Inhibit Skin-Homing CD8+ T Cell Activity, a Determining Factor of Vitiligo Patients’ Autologous Melanocytes Transplantation Efficiency

    PubMed Central

    Wu, Ji-long; Lin, Fu-quan; Fu, Li-fang; Wang, Sui-quan; Guan, Cui-ping; Wang, Hong-lin; Xu, Aie

    2013-01-01

    We here investigated the efficiency of autologous melanocyte transplantation of 23 vitiligo patients by focusing on perilesional skin homing CD8+ T lymphocytes, and studied the potential effect of dermal mesenchymal stem cells (DMSCs) on CD8+ T cell activities in vitro. Out of 23 patients with the autologous melanocyte transplantation, 12 patients (52.17%) had an excellent re-pigmentation, 6 patients (26.09%) had a good re-pigmentation, 5 patients (21.74%) had a fair or poor re-pigmentation. CD8+ T cells infiltrating was observed in the perilesional vitiligo area of all patients. Importantly, the efficiency of the transplantation was closely associated with skin-homing CD8+ T cell activities. The patients with high number of perilesional CD8+ T cells or high level of cytokines/chemokines were associated with poor re-pigmentation efficiency. For in-vitro experiments, we successfully isolated and characterized human DMSCs and skin-homing CD8+ T cells. We established DMSCs and CD8+ T cell co-culture system, where DMSCs possessed significant inhibitory effects against skin homing CD8+ T lymphocytes. DMSCs inhibited CD8+ T cells proliferation, induced them apoptosis and regulated their cytokines/chemokines production. Our results suggest that vitiligo patients’ autologous melanocytes transplantation efficiency might be predicted by perilesional skin-homing CD8+ T cell activities, and DMSCs might be used as auxiliary agent to improve transplantation efficacy. PMID:23577097

  3. Persistent complete remission of acute leukemic-phase CCR4-positive gamma-delta peripheral T-cell lymphoma by autologous stem cell transplantation with mogamulizumab.

    PubMed

    Furukawa, Miki; Ikeda, Kazuhiko; Ohkawara, Hiroshi; Saito, Shunichi; Takahashi, Hiroshi; Ueda, Koki; Matsumoto, Hayato; Hashimoto, Yuko; Ohto, Hitoshi; Ogawa, Kazuei; Takeishi, Yasuchika

    2015-10-01

    Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), frequently shows a poor outcome. Especially, expressions of CC chemokine receptor 4 (CCR4) and γδ T-cell receptor (TCR) are associated with worse prognosis in PTCL-NOS. We here report successful treatment with autologous peripheral blood stem cell transplantation (auto-PBSCT) combined with anti-CCR4 antibody mogamulizumab for a very rare case of CCR4+γδTCR+ PTCL-NOS that coexisted with Hodgkin's lymphoma. PTCL-NOS in this patient progressed to leukemic phase, whereas Hodgkin's lymphoma disappeared with standard chemotherapies within 4 years of the initial diagnosis. Leukemic-phase PTCL-NOS was refractory to several chemotherapies. However, auto-PBSCT following high-dose chemotherapy combined with pre- and post-transplant mogamulizumab, which is a humanized monoclonal antibody to CCR4, provided persistent complete remission of PTCL-NOS, despite residual γδTCR+ in the transplanted stem cell product, suggesting a purging effect of mogamulizumab. At 15 months after transplantation, we also found markedly fewer effector regulatory T cells, which may have contributed to prolonged remission. This case suggests that autologous stem cell transplantation combined with mogamulizumab may have a potential to cure T-cell neoplasms that express CCR4 including leukemic-phase PTCL-NOS.

  4. The Impact of the German Tissue Act on the Manufacturing of Autologous and Allogeneic Stem Cell Preparations.

    PubMed

    Schlenke, Peter; Tapernon, Karin; Ahlke, Christoph; Mertens, Alexandra; Sibrowski, Walter

    2008-01-01

    SUMMARY: Cellular therapeutic agents considerably contribute to the optimal treatment of patients with hematological malignancies such as leukemia or nonhematological disorders. Over the last 50 years especially the transplantation of autologous and allogeneic stem cells from different sources after high-dose or myeloablative chemotherapy became a well-established standard therapy that cures or alleviates the symptoms in more than 50,000 patients/year worldwide. In the near future, the current progress in fundamental research on stem cells and immunobiology will allow for the clinical implementation of novel advanced cellular therapies, including gene therapeutic options. The European and German legislation have realized the need of international regulations for improved standardization and harmonization of stem cell transplants, associated cell-therapeutic agents as well as various tissue-engineered preparations in the emerging field of regenerative medicine. The Tissue Directive 2004/23/EC, issued and ratified by the European Parliament in March 2004, and its national transition into the German Tissue Act which came into force in July 2007 define the quality and safety standards for the donation, procurement, testing, processing, preservation, storage, and distribution of human tissues and cells. These standards are of high relevance to ensure the efficient prevention of the transmission of viral and nonviral infectious pathogens and to achieve the same safeguards as in the population's blood supply. This review discusses the pros and cons of the new legislation and argues for keeping the administrative and regulative demands in reasonable limits and for offering innovative approaches of cellular therapies to the European citizens.

  5. Ifosfamide, Cisplatin or Carboplatin, and Etoposide (ICE)-based Chemotherapy for Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Lymphomas

    PubMed Central

    Zhou, Ping; Liu, Peng; Zhou, Sheng-Yu; He, Xiao-Hui; Han, Xiao-Hong; Qin, Yan; Yang, Sheng; Zhang, Chang-Gong; Gui, Lin; Yao, Jia-Rui; Zhao, Li-Ya; Zhang, Shu-Xiang; Sun, Yan; Shi, Yuan-Kai

    2015-01-01

    Background: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a promising approach for lymphomas. This study aimed to evaluate the effect of ifosfamide, cisplatin or carboplatin, and etoposide (ICE)-based regimen as a mobilization regimen on relapsed, refractory, or high-risk aggressive lymphoma. Methods: From June 2001 to May 2013, patients with lymphomas who mobilized by ICE-based regimen for ASCT were analyzed in this retrospective study. The results of the autologous peripheral blood stem cells collection, toxicity, engraftment after ICE-based mobilization regimen were analyzed in this study. Furthermore, risk factors for overall survival (OS) and progression free survival (PFS) were evaluated by univariate analysis. Results: The stem cells were mobilized using ICE-based regimen plus rituximab or ICE-based regimen alone in 12 patients and 54 patients, respectively. The results of stem cell mobilization were excellent. Ninety-seven percentages of the patients had the stem cell collection of at least 2.0 × 106 CD34+ cells/kg and 68% had at least 5 × 106 CD34+ cells/kg. Fifty-eight percentage of the patients experienced Grade 4 neutropenia, 20% developed febrile neutropenia, and only 12% had Grade 4 thrombocytopenia. At a median follow-up of 63.8 months, the 5-year PFS and OS were 64.4% and 75.3%, respectively. Conclusion: ICE is a powerful regimen for stem cell mobilization in patients with lymphomas. PMID:26365969

  6. The Role of Autologous and Allogeneic Stem Cell Transplantation in Follicular Lymphoma in The New Drugs Era

    PubMed Central

    Maura, Francesco; Farina, Lucia; Corradini, Paolo

    2016-01-01

    Follicular lymphoma (FL) is the second most common histotype of non-Hodgkin’s lymphoma, and it is generally characterized by a heterogeneous clinical course. Despite recent therapeutic and diagnostic improvements, a significant fraction of FL patients still relapsed. In younger and/or fit FL relapsed patients bone marrow transplant (BMT) has represented the main salvage therapy for many years. Thanks to the ability of high-dose chemotherapy to overcome the lymphoma resistance and refractoriness, autologous stem cell transplantation (ASCT) can achieve a high complete remission rate (CR) and favorable outcome regarding progression-free survival (PFS) and overall survival (OS). Allogeneic stem cell transplantation (alloSCT) combines the high dose chemotherapy effect together with the immune reaction of the donor immune system against lymphoma, the so-called ‘graft versus lymphoma’ (GVL) effect. Considering the generally higher transplant-related mortality (TRM), alloSCT is mostly indicated for FL relapsed after ASCT. During the last years, there have been a great spread of novel effective and feasible drugs Although these and future novel drugs will probably change our current approach to FL, the OS post-BMT (ASCT and alloSCT) has never been reproduced by any novel combination. In this scenario, it is important to correctly evaluate the disease status, the relapse risk and the comorbidity profile of the relapsed FL patients in order to provide the best salvage therapy and eventually transplant consolidation. PMID:27648208

  7. Five Questions Answered: A Review of Autologous Hematopoietic Stem Cell Transplantation for the Treatment of Multiple Sclerosis.

    PubMed

    Atkins, Harold L; Freedman, Mark S

    2017-08-18

    Multiple sclerosis (MS) is thought to be an autoimmune disease targeting the central nervous system leading to demyelination, and axonal and neuronal damage, resulting in progressive disability. More intensive therapies such as immunodepletion with hematopoietic stem-cell rescue are being used at a time prior to patients becoming irreversibly disabled. Over the last 15 years, there has been a shift away from using autologous hematopoietic stem-cell transplants (aHSCT) to treat patients with progressive MS, towards treating those with active inflammation and relapses. There is an increasing body of evidence that aHSCT improves all measured MS outcomes, including burden of disease on MRI, clinical relapses, accumulation of disability, and quality of life of patients with active MS not controlled with standard therapy. Importantly, the progression-free survival curves of these patients plateau after the first few years demonstrating the impact that aHSCT has in changing the natural history of MS, potentially freeing patients from the relentless accumulation of disability. Concurrently there has been a reduction in procedure-related mortality. The results of randomized trials will likely spur further development of this field.

  8. High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Transplantation in Metastatic Breast Cancer: Overview of Six Randomized Trials

    PubMed Central

    Berry, Donald A.; Ueno, Naoto T.; Johnson, Marcella M.; Lei, Xiudong; Caputo, Jean; Smith, Dori A.; Yancey, Linda J.; Crump, Michael; Stadtmauer, Edward A.; Biron, Pierre; Crown, John P.; Schmid, Peter; Lotz, Jean-Pierre; Rosti, Giovanni; Bregni, Marco; Demirer, Taner

    2011-01-01

    Purpose High doses of effective chemotherapy are compelling if they can be delivered safely. Substantial interest in supporting high-dose chemotherapy with bone marrow or autologous hematopoietic stem-cell transplantation in the 1980s and 1990s led to the initiation of randomized trials to evaluate its effect in the treatment of metastatic breast cancer. Methods We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support. We assembled a single database containing individual patient information from these trials. The primary analysis of overall survival was a log-rank test comparing high dose versus control. We also used Cox proportional hazards regression, adjusting for known covariates. We addressed potential treatment differences within subsets of patients. Results The effect of high-dose chemotherapy on overall survival was not statistically different (median, 2.16 v 2.02 years; P = .08). A statistically significant advantage in progression-free survival (median, 0.91 v 0.69 years) did not translate into survival benefit. Subset analyses found little evidence that there are groups of patients who might benefit from high-dose chemotherapy with hematopoietic support. Conclusion Overall survival of patients with metastatic breast cancer in the six randomized trials was not significantly improved by high-dose chemotherapy; any benefit from high doses was small. No identifiable subset of patients seems to benefit from high-dose chemotherapy. PMID:21768454

  9. In Vivo Confocal Microscopy 1 Year after Autologous Cultured Limbal Stem Cell Grafts.

    PubMed

    Pedrotti, Emilio; Passilongo, Mattia; Fasolo, Adriano; Nubile, Mario; Parisi, Graziella; Mastropasqua, Rodolfo; Ficial, Sara; Bertolin, Marina; Di Iorio, Enzo; Ponzin, Diego; Marchini, Giorgio

    2015-08-01

    To correlate clinical, impression cytologic, and in vivo confocal microscopy findings on the corneal surface after cultured limbal stem cell transplantation. Prospective, interventional, noncomparative, masked case series. Thirteen patients with limbal stem cell deficiency after unilateral (9 eyes) or bilateral (2 eyes) chemical burn, liquid nitrogen injury (1 eye), or herpes simplex virus infection (1 eye). Limbal cells were harvested from healthy or less affected eyes, cultured on 3T3 cells and fibrin glue, and transplanted to the patient's injured eye. Patients underwent clinical examination and impression cytologic examination of the central cornea before and 1 year after intervention. In vivo confocal microscopy scans were obtained in all corneal quadrants after 1 year. The interexamination agreement was established by calculation of the Cohen's κ coefficient. Results of surgery were assessed considering clinical signs (successful: restoration of transparent, avascular, and stable corneal epithelium without neovascularization in central corneal surface; partially successful: recurrence of superficial neovascularization; failed: recurrent epithelial defects, pannus, and inflammation), phenotype of cells covering the corneal surface (conjunctivalized corneal surface: cytokeratin 12 [cK12]-negative and mucin 1 [MUC1]-positive cells; mixed epithelium: cK12-positive and MUC1-positive cells; corneal epithelium: cK12-positive and MUC1-negative cells), and cell morphologic features (corneal epithelium: multilayered polygonal and flat cells with hyperreflective nuclei; conjunctival epithelium: stratified cuboidal or polygonal cells, hyperreflective cytoplasm, and barely defined borders; epithelial transition: transition of epithelial cells from the cornea to the conjunctiva over the corneal surface). We found a moderate to substantial degree of concordance between confocal microscopy and clinical evaluation (κ = 0.768) and between confocal microscopy and impression

  10. Immunological correlates of favorable long-term clinical outcome in multiple sclerosis patients after autologous hematopoietic stem cell transplantation.

    PubMed

    Arruda, Lucas C M; de Azevedo, Júlia T C; de Oliveira, Gislane L V; Scortegagna, Gabriela T; Rodrigues, Evandra S; Palma, Patrícia V B; Brum, Doralina G; Guerreiro, Carlos T; Marques, Vanessa D; Barreira, Amilton A; Covas, Dimas T; Simões, Belinda P; Voltarelli, Júlio C; Oliveira, Maria Carolina; Malmegrim, Kelen C R

    2016-08-01

    High dose immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) induces prolonged clinical remission in multiple sclerosis (MS) patients. However, how patient immune profiles are associated with clinical outcomes has not yet been completely elucidated. In this study, 37 MS patients were assessed for neurological outcomes, thymic function and long-term immune reconstitution after AHSCT. Patients were followed for a mean (SD) of 68.5 (13.9) months post-transplantation and were retrospectively clustered into progression- and non-progression groups, based on Expanded Disease Status Scale (EDSS) outcomes at last visit. After AHSCT, both patient groups presented increased regulatory T-cell subset counts, early expansion of central- and effector-memory CD8(+)T-cells and late thymic reactivation. However, the non-progression group presented early expansion of PD-1(+)CD8(+)T-cells and of PD-1-expressing CD19(+) B-cells. Here, we suggest that along with increased numbers of regulatory T-cell subsets, PD-1 inhibitory signaling is one possible immunoregulatory mechanism by which AHSCT restores immune tolerance in MS patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Autologous Bioscaffolds based on Different Concentrations of Platelet Rich Plasma and Synovial Fluid as a Vehicle for Mesencymal Stem Cells.

    PubMed

    Garate, Ane; Sánchez, Pello; Delgado, Diego; Bilbao, Ane Miren; Muiños-López, Emma; Granero-Moltó, Froilán; Orive, Gorka; Prosper, Felipe; Pedraz, José Luis; Sánchez, Mikel

    2017-09-27

    In the field of tissue engineering, diverse types of bioscaffolds are being developed currently for osteochondral defect applications. In this work, a novel scaffold based on Platelet Rich Plasma and hyaluronic acid with Mesenchymal stem cells (MSCs) has been evaluated to observe its effect on immobilized cells. The bio-scaffolds were prepared by mixing different volumes of synovial fluid (SF) with Platelet Rich Plasma (PRP) from patients obtaining 3 formulations at PRP-SF ratios of 3:1, 1:1 and 1:3 (vol/vol). The live/dead staining revealed that although the cell number of each type of bioscaffold was different, this constructs provide cells with a suitable environment for their viability and proliferation. Moreover, immobilized MSCs showed their ability to secrete fibrinolytic enzymes, which vary depending on the fibrin amount of the scaffold. Immunohistochemical analysis revealed the positive staining for collagen type II in all cases, proving the biologic action of synovial fluid derived MSCs together with the suitable characteristics of the bioscaffold for chondrogenic differentiation. Considering all these aspects, this study demonstrates that these cells-based constructs respresent an attractive method for cell immobilization, achieving completely autologous and biocompatible scaffolds. This article is protected by copyright. All rights reserved. © 2017 Wiley Periodicals, Inc.

  12. High-dose therapy and autologous stem cell transplantation in patients with POEMS syndrome: a retrospective study of the Plasma Cell Disorder sub-committee of the Chronic Malignancy Working Party of the European Society for Blood & Marrow Transplantation.

    PubMed

    Cook, Gordon; Iacobelli, Simona; van Biezen, Anja; Ziagkos, Dimitris; LeBlond, Veronique; Abraham, Julie; McQuaker, Grant; Schoenland, Stefan; Rambaldi, Alessandro; Halaburda, Kazimierz; Rovira, Maria; Sica, Simona; Byrne, Jenny; Sanz, Ramon Garcia; Nagler, Arnon; van de Donk, Niels W C J; Sinisalo, Marjatta; Cook, Mark; Kröger, Nicolaus; De Witte, Theo; Morris, Curly; Garderet, Laurant

    2017-01-01

    POEMS syndrome is a rare para-neoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment can control the disease-related symptom complex. We describe the clinical outcome of autologous stem cell transplantation for patients with POEMS syndrome, determining the impact of patient- and disease-specific factors on prognosis. One hundred and twenty-seven patients underwent an autologous stem cell transplantation between 1997-2010 with a median age of 50 years (range 26-69 years). Median time from diagnosis to autologous stem cell transplantation was 7.5 months with 32% of patients receiving an autologous stem cell transplantation more than 12 months from diagnosis. Engraftment was seen in 97% patients and engraftment syndrome was documented in 23% of autologous stem cell transplantation recipients. Hematologic response was characterized as complete response in 48.5%, partial response in 20.8%, less than partial repsonse in 30.7%. With a median follow up of 48 months (95%CI: 38.3, 58.6), 90% of patients are alive and 16.5% of patients have progressed. The 1-year non-relapse mortality was 3.3%. The 3-year probabilities of progression-free survival and overall survival are 84% and 94%, respectively, with 5-year probabilities of progression-free survival and overall survival of 74% and 89%. In a cohort of graft recipients, detailed organ-specific symptom response demonstrated clear symptom benefit after autologous stem cell transplantation especially in relation to neurological symptom control. The data analyzed in this study demonstrate the clinical utility of autologous stem cell transplantation for patients with POEMS syndrome.

  13. High-dose therapy and autologous stem cell transplantation in patients with POEMS syndrome: a retrospective study of the Plasma Cell Disorder sub-committee of the Chronic Malignancy Working Party of the European Society for Blood & Marrow Transplantation

    PubMed Central

    Cook, Gordon; Iacobelli, Simona; van Biezen, Anja; Ziagkos, Dimitris; LeBlond, Veronique; Abraham, Julie; McQuaker, Grant; Schoenland, Stefan; Rambaldi, Alessandro; Halaburda, Kazimierz; Rovira, Maria; Sica, Simona; Byrne, Jenny; Sanz, Ramon Garcia; Nagler, Arnon; van de Donk, Niels W.C.J.; Sinisalo, Marjatta; Cook, Mark; Kröger, Nicolaus; De Witte, Theo; Morris, Curly; Garderet, Laurant

    2017-01-01

    POEMS syndrome is a rare para-neoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment can control the disease-related symptom complex. We describe the clinical outcome of autologous stem cell transplantation for patients with POEMS syndrome, determining the impact of patient- and disease-specific factors on prognosis. One hundred and twenty-seven patients underwent an autologous stem cell transplantation between 1997–2010 with a median age of 50 years (range 26–69 years). Median time from diagnosis to autologous stem cell transplantation was 7.5 months with 32% of patients receiving an autologous stem cell transplantation more than 12 months from diagnosis. Engraftment was seen in 97% patients and engraftment syndrome was documented in 23% of autologous stem cell transplantation recipients. Hematologic response was characterized as complete response in 48.5%, partial response in 20.8%, less than partial repsonse in 30.7%. With a median follow up of 48 months (95%CI: 38.3, 58.6), 90% of patients are alive and 16.5% of patients have progressed. The 1-year non-relapse mortality was 3.3%. The 3-year probabilities of progression-free survival and overall survival are 84% and 94%, respectively, with 5-year probabilities of progression-free survival and overall survival of 74% and 89%. In a cohort of graft recipients, detailed organ-specific symptom response demonstrated clear symptom benefit after autologous stem cell transplantation especially in relation to neurological symptom control. The data analyzed in this study demonstrate the clinical utility of autologous stem cell transplantation for patients with POEMS syndrome. PMID:27634201

  14. Melphalan Culprit or Confounder in Acute Encephalopathy during Autologous Hematopoietic Stem Cell Transplantation?

    PubMed Central

    Alayón-Laguer, Diógenes; Alsina, Melissa; Ochoa-Bayona, Jose L.; Ayala, Ernesto

    2012-01-01

    We report a case of a female patient with Durie-Salmon stage 3A/ISS stage I IgG kappa multiple myeloma (MM) who developed encephalopathy after high-dose melphalan and hematopoietic stem cell transplant (HSCT). The most common etiologies for encephalopathy such as infection, narcotic medications, metabolic-electrolyte disturbance, stroke, and central nervous system (CNS) hemorrhages were ruled out. The patient recovered from the altered mental status spontaneously. The possibilities of melphalan-induced encephalopathy versus critical-state delirium versus hypercytokinemia induce encephalopathy were contemplated. PMID:23259145

  15. Clinical-scale laser-based scanning and processing of live cells: selective photothermal killing of fluorescent tumor targets for autologous stem cell transplantation

    NASA Astrophysics Data System (ADS)

    Koller, Manfred R.; Hanania, Elie G.; Eisfeld, Timothy; O'Neal, Robert A.; Khovananth, Kevin M.; Palsson, Bernhard O.

    2001-04-01

    High-dose chemotherapy, followed by autologous hematopoietic stem cell (HSC) transplantation, is widely used for the treatment of cancer. However, contaminating tumor cells within HSC harvests continue to be of major concern since re-infused tumor cells have proven to contribute to disease relapse. Many tumor purging methods have been evaluated, but all leave detectable tumor cells in the transplant and result in significant loss of HSCs. These shortcomings cause engraftment delays and compromise the therapeutic value of purging. A novel approach integrating automated scanning cytometry, image analysis, and selective laser-induced killing of labeled cells within a cell mixture is described here. Non-Hodgkin's lymphoma (NHL) cells were spiked into cell mixtures, and fluorochrome-conjugated antibodies were used to label tumor cells within the mixture. Cells were then allowed to settle on a surface, and as the surface was scanned with a fluorescence excitation source, a laser pulse was fired at every detected tumor cell using high-speed beam steering mirrors. Tumor cells were selectively killed with little effect on adjacent non-target cells, demonstrating the feasibility of this automated cell processing approach. This technology has many potential research and clinical applications, one example of which is tumor cell purging for autologous HSC transplantation.

  16. Evaluating the effects of lenalidomide induction therapy on peripheral stem cells collection in patients undergoing autologous stem cell transplant for multiple myeloma.

    PubMed

    Bhutani, Divaya; Zonder, Jeffrey; Valent, Jason; Tageja, Nishant; Ayash, Lois; Deol, Abhinav; Al-Kadhimi, Zaid; Abrams, Judith; Lum, Lawrence; Ratanatharathorn, Voravit; Uberti, Joseph; Abidi, Muneer H

    2013-09-01

    Lenalidomide (LEN) is a relatively new and very effective therapy for multiple myeloma (MM). Prior LEN therapy is associated with an increased risk of peripheral blood stem cell collection (PBSC) failure, particularly with filgrastim (G-CSF) alone. We performed a retrospective chart review of 319 consecutive MM patients who underwent apheresis to collect PBSCs for the first autologous stem cell transplant (ASCT). The median number of PBSCs collected in the LEN (+) group was significantly less than the LEN (-) group (6.34 vs. 7.52 × 10(6) CD34(+) cells/kg; p = 0.0004). In addition, the median number of apheresis sessions required for adequate PBSCs collection were significantly more in the LEN (+) group as compared to LEN (-) group (2 vs. 1 sessions; p = 0.002). In the LEN (+) group, there was a negative correlation between PBSCs collected and prior number of cycles of LEN (p = 0.0001). Rate of PBSC collection failure was 9% in the LEN (+) group and 5% in the LEN (-) group (p = 0.16). Only six patients who failed PBSC collection with G-CSF were able to collect adequate PBSCs with G-CSF + plerixafor. LEN exposure had no effect on neutrophil or platelet recovery post-ASCT. Up to four cycles of LEN exposure have minimal negative impact on PBSC collection. Despite prolong exposure of LEN, PBSC collection was adequate for two ASCTs in the majority of patients and post-ASCT engraftment was not longer than expected; however, clinical relevance (complication rate, quality of life, cost) of prolonged LEN exposure on both PBSC and ASCT, should be evaluated in prospective clinical trials.

  17. Hepatic veno-occlusive disease (VOD) with complete occlusion of liver venules after tandem autologous stem cell transplantation-- successful treatment with high-dose methylprednisolone and defibrotide.

    PubMed

    Sayer, H G; Will, U; Schilling, K; Vogt, T; Wollina, K; Höffken, K

    2002-03-01

    Veno-occlusive disease (VOD) is a life-threatening complication following allogeneic or autologous stem cell transplantation. We report on a patient with a high grade B-cell lymphoma who presented 28 days after the second autologous stem cell transplantation with weight gain, ascites, hyperbilirubinemia, and liver venules occlusion as demonstrated by sonography. Starting with high-dose methylprednisolone treatment followed by defibrotide maintenance therapy the patient showed dramatic complete response of VOD, resulting in a normal sonography of the liver and normalization of laboratory values. The response of the occlusion of nearly all liver venules underlines the value of anti-inflammatory treatment combined with new thrombolytic medication such as defibrotide for the treatment of severe VOD.

  18. [Immunology in the medical practice.XXXII. Transplantation of autologous hematopoietic stem cells for treatment of refractory auto-immune diseases; preliminary favorable results with 35 patients].

    PubMed

    Vlieger, A M; van den Hoogen, F H; Brinkman, D M; van Laar, J M; Schipperus, M; Kruize, A A; Wulffraat, N M

    2000-08-12

    The objective of this study was to document the experiences in the first Dutch pilot studies of the effect of transplantation of autologous haematopoietic stem cells in patients with therapy-resistant autoimmune disease. The first results in 21 adults and 14 children are promising: remission of the disease was achieved in 13 patients, while in the others a significant reduction of disease activity was seen with a corresponding improvement of the quality of life. Infectious complications were frequently observed. Two children with systemic juvenile idiopathic arthritis developed a fatal infection-associated macrophage activation syndrome. Multicentre randomised studies are necessary to study the effects of autologous stem cell transplantation and modifications such as T-cell depletion.

  19. Involved Field Radiation After Autologous Stem Cell Transplant for Diffuse Large B-Cell Lymphoma in the Rituximab Era

    SciTech Connect

    Biswas, Tithi; Dhakal, Sughosh; Chen Rui; Hyrien, Ollivier; Bernstein, Steven; Friedberg, Jonathan W.; Fisher, Richard I.; Liesveld, Jane; Phillips, Gordon; Constine, Louis S.

    2010-05-01

    Purpose: For patients with recurrent or refractory large B-cell non-Hodgkin's lymphoma, high-dose chemotherapy and autologous stem cell transplant (ASCT) is the treatment of choice. We evaluated the role of involved field radiation therapy (IFRT) post-ASCT for patients initially induced with cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) or, more recently, rituximab-CHOP (R-CHOP). Materials and Methods: Between May 1992 and April 2005, 176 patients underwent ASCT for recurrent or refractory large B-cell non-Hodgkin's lymphoma; 164 patients were evaluable for endpoint analysis. Fifty percent of the CHOP group (n = 131), and 39% of the R-CHOP group (n = 33), received IFRT. Follow-up from the time of transplant was a median/mean of 1.7/3 years (range, 0.03-13 years). Results: The 5-year overall survival (OS) and disease-specific survival (DSS) improved with IFRT in both the R-CHOP (p = 0.006 and 0.02, respectively) and CHOP (p = 0.02 and p = 0.04, respectively) groups. IFRT was associated with a 10% (p = 0.17) reduction in local failure, alone or with a distant site. On univariate analysis, IFRT was associated with superior OS (hazard ratio [HR] = 0.50 [95% CI 0.32, 0.78]; p = 0.002) and DSS (HR = 0.53 [95% CI 0.33, 0.86]; p = 0.009). Presence of B symptoms was adverse (p = 0.03). On multivariate analysis, only IFRT was associated with significant improvement in OS (HR = 0.35 [0.18, 0.68]; p = 0.002) and DSS (HR = 0.39 [95% CI 0.18, 0.84]; p = 0.01). Conclusions: Recognizing that positive and negative patient selection bias exists for the use of IFRT post-ASCT, patients initially treated with CHOP or R-CHOP and who undergo ASCT for recurrent or refractory disease may benefit from subsequent IFRT presumably due to enhanced local control that can translate into a survival advantage.

  20. The separation of a mixture of bone marrow stem cells from tumor cells: an essential step for autologous bone marrow transplantation

    SciTech Connect

    Rubin, P.; Wheeler, K.T.; Keng, P.C.; Gregory, P.K.; Croizat, H.

    1981-10-01

    KHT tumor cells were mixed with mouse bone marrow to simulate a sample of bone marrow containing metastatic tumor cells. This mixture was separated into a bone marrow fraction and a tumor cell fraction by centrifugal elutriation. Elutriation did not change the transplantability of the bone marrow stem cells as measured by a spleen colony assay and an in vitro erythroid burst forming unit assay. The tumorogenicity of the KHT cells was similarly unaffected by elutriation. The data showed that bone marrow cells could be purified to less than 1 tumor cell in more than 10/sup 6/ bone marrow cells. Therefore, purification of bone marrow removed prior to lethal radiation-drug combined therapy for subsequent autologous transplantation appears to be feasible using modifications of this method if similar physical differences between human metastatic tumor cells and human bone marrow cells exist. This possibility is presently being explored.

  1. Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial.

    PubMed

    Atkins, Harold L; Bowman, Marjorie; Allan, David; Anstee, Grizel; Arnold, Douglas L; Bar-Or, Amit; Bence-Bruckler, Isabelle; Birch, Paul; Bredeson, Christopher; Chen, Jacqueline; Fergusson, Dean; Halpenny, Mike; Hamelin, Linda; Huebsch, Lothar; Hutton, Brian; Laneuville, Pierre; Lapierre, Yves; Lee, Hyunwoo; Martin, Lisa; McDiarmid, Sheryl; O'Connor, Paul; Ramsay, Timothy; Sabloff, Mitchell; Walker, Lisa; Freedman, Mark S

    2016-08-06

    Strong immunosuppression, including chemotherapy and immune-depleting antibodies followed by autologous haemopoietic stem-cell transplantation (aHSCT), has been used to treat patients with multiple sclerosis, improving control of relapsing disease. We addressed whether near-complete immunoablation followed by immune cell depleted aHSCT would result in long-term control of multiple sclerosis. We did this phase 2 single-arm trial at three hospitals in Canada. We enrolled patients with multiple sclerosis, aged 18-50 years with poor prognosis, ongoing disease activity, and an Expanded Disability Status Scale of 3.0-6.0. Autologous CD34 selected haemopoietic stem-cell grafts were collected after mobilisation with cyclophosphamide and filgrastim. Immunoablation with busulfan, cyclophosphamide, and rabbit anti-thymocyte globulin was followed by aHSCT. The primary outcome was multiple sclerosis activity-free survival (events were clinical relapse, appearance of a new or Gd-enhancing lesion on MRI, and sustained progression of Expanded Disability Status Scale score). This study was registered at ClinicalTrials.gov, NCT01099930. Between diagnosis and aHSCT, 24 patients had 167 clinical relapses over 140 patient-years with 188 Gd-enhancing lesions on 48 pre-aHSCT MRI scans. Median follow-up was 6.7 years (range 3.9-12.7). The primary outcome, multiple sclerosis activity-free survival at 3 years after transplantation was 69.6% (95% CI 46.6-84.2). With up to 13 years of follow-up after aHSCT, no relapses occurred and no Gd enhancing lesions or new T2 lesions were seen on 314 MRI sequential scans. The rate of brain atrophy decreased to that expected for healthy controls. One of 24 patients died of transplantation-related complications. 35% of patients had a sustained improvement in their Expanded Disability Status Scale score. We describe the first treatment to fully halt all detectable CNS inflammatory activity in patients with multiple sclerosis for a prolonged period in the

  2. Preparation of a nano- and micro-fibrous decellularized scaffold seeded with autologous mesenchymal stem cells for inguinal hernia repair

    PubMed Central

    Zhang, Yinlong; Zhou, Yuanyuan; Zhou, Xu; Zhao, Bin; Chai, Jie; Liu, Hongyi; Zheng, Yifei; Wang, Jinling; Wang, Yaozong; Zhao, Yilin

    2017-01-01

    Prosthetic meshes used for hernioplasty are usually complicated with chronic pain due to avascular fibrotic scar or mesh shrinkage. In this study, we developed a tissue-engineered mesh (TEM) by seeding autologous bone marrow-derived mesenchymal stem cells onto nanosized fibers decellularized aorta (DA). DA was achieved by decellularizing the aorta sample sequentially with physical, mechanical, biological enzymatic digestion, and chemical detergent processes. The tertiary structure of DA was constituted with micro-, submicro-, and nanosized fibers, and the original strength of fresh aorta was retained. Inguinal hernia rabbit models were treated with TEMs or acellular meshes (AMs). After implantation, TEM-treated rabbit models showed no hernia recurrence, whereas AM-treated animals displayed bulges in inguinal area. At harvest, TEMs were thicker, have less adhesion, and have stronger mechanical strength compared to AMs (P<0.05). Moreover, TEM showed better cell infiltration, tissue regeneration, and neovascularization (P<0.05). Therefore, these cell-seeded DAs with nanosized fibers have potential for use in inguinal hernioplasty. PMID:28260890

  3. Follow-up of relapsed B-cell lymphoma patients treated with iodine-131-labeled anti-CD20 antibody and autologous stem-cell rescue

    SciTech Connect

    Liu, S Y.; Eary, Janet F.; Petersdorf, S H.; Martin, P J.; Maloney, D G.; Applebaum, F. R.; Matthews, D. C.; Bush, S A.; Durack, L. D.; Fisher, Darrell R. ); Gooley, T A.; Bernstein, I. D.; Press, O. W.

    1997-11-01

    Radioimmunotherapy (RIT) is a promising treatment approach for B-cell lymphomas. This is our first opportunity to report long-term follow-up data and late toxicities in 29 patients treated with myeloablative doses of iodine-131-anti-CD20 antibody (anti-B1) and autologous stem-cell rescue. PATIENTS AND METHODS: Trace-labeled biodistribution studies first determined the ability to deliver higher absorbed radiation doses to tumor sites than to lung, liver, or kidney at varying amounts of anti-B1 protein (0.35, 1.7, or 7 mg/kg). Twenty- nine patients received therapeutic infusions of single-agent (131)I- anti-B1, given at the protein dose found optimal in the biodistribution study, labeled with amounts of (131)I (280 to 785 mCi[10.4 to 29.0 GBq]) calculated to deliver specific absorbed radiation doses to the normal organs, followed by autologous stem-cell support. RESULTS: Major responses occurred in 25 patients (86%), with 23 complete responses (CRs; 79%). The nonhematopoietic do se-limiting toxicity was reversible cardiopulmonary insufficiency, which occurred in two patients at RIT doses that delivered > or = 27 Gy to the lungs. With a median follow-up time of 42 months, the estimated overall and progression-free survival rates are 68% and 42%, respectively. Currently, 14 of 29 patients remain in unmaintained remissions that range from 27+ to 87+ months after RIT. Late toxicities have been uncommon except for elevated thyroid-stimulating hormone (TSH) levels found in approximately 60% of the subjects. Two patients developed second malignancies, but none have developed myelodysplasia (MDS). CONCLUSION: Myeloablative (131)I-anti- B1 RIT is relatively well tolerated when given with autologous stem- cell support and often results in prolonged remission durations with few late toxicities.

  4. Addition of plerixafor to mobilization regimens in autologous peripheral blood stem cell transplants does not affect the correlation of preharvest hematopoietic precursor cell enumeration with first-harvest CD34+ stem cell yield.

    PubMed

    Villa, Carlos H; Shore, Tsiporah; Van Besien, Koen; Cushing, Melissa

    2012-12-01

    The CXCR4 antagonist plerixafor is increasingly used in the mobilization regimens for autologous peripheral blood stem cell (PBSC) transplantation. This agent may mobilize a different subset of the stem cell population than traditional regimens, such as growth factors (with and without chemotherapy). Thus, it is important to determine whether plerixafor has an effect on the utility of measurements used to predict the yield of CD34(+) cells, usually either preharvest peripheral blood CD34(+) enumeration by flow cytometry or hematopoietic precursor cell (HPC) enumeration by automated hematology analysis. Although HPC enumeration has a weaker correlation with first-harvest CD34(+) cell yield, this parameter still plays an important role in the timing of apheresis procedures for autologous PBSC transplantation because of its technical simplicity and low cost. In the present study, we retrospectively examined the correlation of HPC measurements with CD34(+) cell yields in patients with multiple myeloma and lymphoma undergoing autologous PBSC transplantation, and investigated how the mobilization regimen affected these results. We found that the correlation coefficients ranged from 0.5877 to 0.7668 and were not significantly impacted by differences in diagnosis or inclusion of plerixafor in the mobilization regimen. The predictive ability of HPC enumeration for various target yields was also examined, and receiver-operating characteristic curves were generated. An HPC cutoff of 20 should result in adequate initial CD34(+) cell yields (>2.5 × 10(6) cell/kg) in >80% of autologous donors with or without plerixafor. This study confirms the utility of HPC enumeration in prediction of adequate initial cell yields, and demonstrates that this utility is maintained regardless of whether or not plerixafor is included in the mobilization regimen.

  5. Procedure-related complications and adverse events associated with pediatric autologous peripheral blood stem cell collection.

    PubMed

    Cooling, Laura; Hoffmann, Sandra; Webb, Dawn; Meade, Micheal; Yamada, Chisa; Davenport, Robertson; Yanik, Gregory

    2017-02-01

    Autologous peripheral blood hematopoietic progenitor cell collection (A-HPCC) in pediatric patients is considered relatively safe although technically challenging. Very little is known regarding the incidence, risk factors and impact of procedure-related adverse events (AE) on pediatric A-HPCC outcomes. Prospective 4.5-year review of AE associated with pediatric A-HPCC. AE were graded by severity and type. Potential demographic and procedural risk factors, and the impact on product quality, were compared by t-test, chi-square, and linear regression. Sixty-two children underwent 110 A-HPCC, including 36 (58%) under 20 kg. Fifty-five AE were documented in 25.4% A-HPCCs and 39% of children (citrate 25%, access 19%, technical 11%, cardiovascular 0%, allergic 1.8%). No AE were noted in children < 10 kg anticoagulated with heparin. Access and technical AE accounted for 73% of severe AE, with line-related problems underlying most technical AE (87.5%, P = 0.006). AE were more likely in older (P = 0.012), heavier patients (P = 0.02), who frequently required more than one A-HPCC (P = 0.012). In contrast, young children were more likely to experience citrate AE with gastrointestinal symptoms (median age, 6 years; P = 0.076). AE had no impact on CD34 collection rates; however, mean CD34 yields (4.2 vs. 20.4 million/kg; P = 0.0035) were decreased in patients with technical AE due to lower peripheral CD34 counts and a high number of aborted procedures (37%). Venous access and flow-related issues are a major factor associated with moderate and severe AE, effecting ∼10% of patients. AE are more frequent with increasing patient age, weight, and number of procedures. J. Clin. Apheresis 32:35-48, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial.

    PubMed

    van Laar, Jacob M; Farge, Dominique; Sont, Jacob K; Naraghi, Kamran; Marjanovic, Zora; Larghero, Jérôme; Schuerwegh, Annemie J; Marijt, Erik W A; Vonk, Madelon C; Schattenberg, Anton V; Matucci-Cerinic, Marco; Voskuyl, Alexandre E; van de Loosdrecht, Arjan A; Daikeler, Thomas; Kötter, Ina; Schmalzing, Marc; Martin, Thierry; Lioure, Bruno; Weiner, Stefan M; Kreuter, Alexander; Deligny, Christophe; Durand, Jean-Marc; Emery, Paul; Machold, Klaus P; Sarrot-Reynauld, Francoise; Warnatz, Klaus; Adoue, Daniel F P; Constans, Joël; Tony, Hans-Peter; Del Papa, Nicoletta; Fassas, Athanasios; Himsel, Andrea; Launay, David; Lo Monaco, Andrea; Philippe, Pierre; Quéré, Isabelle; Rich, Éric; Westhovens, Rene; Griffiths, Bridget; Saccardi, Riccardo; van den Hoogen, Frank H; Fibbe, Willem E; Socié, Gérard; Gratwohl, Alois; Tyndall, Alan

    2014-06-25

    High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation-registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. HSCT vs intravenous pulse cyclophosphamide. The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year

  7. [The BCTRIMS Expanded Consensus on treatment of multiple sclerosis: I. The evidences for the use of immunosuppressive agents, plasma exchange and autologous hematopoietic stem cell transplantation].

    PubMed

    Callegaro, Dagoberto; Lana-Peixoto, Marco Aurélio; Moreira, Marcos Aurélio; Marchiori, Paulo Eurípedes; Bacheschi, Luiz Alberto; Arruda, Walter Oleschko; Campos, Gilberto Belisário; Lino, Angelina Maria Martins; Melo, Aílton Souza; Rocha, Fernando Coronetti Gomes; Ferreira, Maria Lúcia Brito; Ataide, Luiz; Maciel, Damacio Ramón Kaimen

    2002-09-01

    Since the sixties immunosuppressive agents have been used in the treatment of multiple sclerosis as there was cumulating evidence of the inflammatory nature of the disease. Cyclophosphamide, azathioprine and methotrexate have been the most frequently employed drugs whereas other agents such as cyclosporine and cladribine have been recently tested for RRMS. Mithoxantrone, on the other hand, was approved by the FDA for treatment of aggressive forms of the disease. Other immunointerventions such as plasma exchange and autologous hematopoietic stem cell transplantation have recently been employed in some special circumstances. This paper analyses the most important published data on the use of the immunosuppressive agents, plasma exchange and autologous hematopoietic stem cell transplantation according to the classes of evidences and types of recommendations of these drugs and immunointerventions. It provides sufficient information to support the guidelines expressed in the BCTRIMS Expanded Consensus on Treatment of MS.

  8. Adoptive immunotherapy with donor lymphocyte infusions and interleukin-2 after high-dose therapy and autologous stem cell rescue for multiple myeloma.

    PubMed

    Ballester, O F; Fang, T; Raptis, A; Ballester, G; Wilcox, P; Hiemenz, J; Tan, B

    2004-09-01

    In an attempt to induce a graft-versus-myeloma effect, we administered donor lymphocyte infusions (DLI) after high-dose therapy with autologous stem cell transplant rescue to seven patients with refractory or relapsed multiple myeloma. High-dose therapy consisted of melphalan, idarubicin and etoposide (days -9 to -6) followed by autologous stem cell infusion on day 0. DLI (five of seven donors with two or three HLA antigens mismatched) were administered on days +1, +5 and +10 along with IL-2 (from day +1 through +12). Six of the seven patients developed acute graft-versus-host disease (GVHD), which resolved spontaneously, coincidentally with autologous hematopoietic reconstitution. One patient failed to engraft and received a second autologous graft. One patient died from complications of a pulmonary hemorrhage after experiencing GVHD. With a minimum follow-up of 38 months, five patients remain without disease progression in complete remission or with minimal residual disease. In this setting, DLI/IL-2 is biologically active resulting in GVHD. A graft-versus-myeloma effect is suggested by the improved outcome of our small cohort of high-risk patients. The use of partially mismatched related donors makes this approach potentially available to nearly all patients.

  9. Autologous bone marrow stem cell neurotransplantation in stroke patients. An open study.

    PubMed

    Suárez-Monteagudo, Carlos; Hernández-Ramírez, Porfirio; Alvarez-González, Lázaro; García-Maeso, Iván; de la Cuétara-Bernal, Karelys; Castillo-Díaz, Lázara; Bringas-Vega, María L; Martínez-Aching, Gilda; Morales-Chacón, Lilia M; Báez-Martín, Margarita M; Sánchez-Catasús, Carlos; Carballo-Barreda, Maylen; Rodríguez-Rojas, Rafael; Gómez-Fernández, Lázaro; Alberti-Amador, Esteban; Macías-Abraham, Consuelo; Balea, Elvira Dorticós; Rosales, Lázaro Cortina; Del Valle Pérez, Lázaro; Ferrer, Berta B Socarrás; González, Raúl Macías; Bergado, Jorge A

    2009-01-01

    Bone marrow stem cells (BMSC) were transplanted into the perilesional area in five patients bearing sequels of stroke, to evaluate the safety of the procedure and tolerance to the transplanted cells. Cells were obtained from bone marrow samples taken from the same patient and stereotactically implanted into the targets, determined using a combination of images, and trans-operative recording of multiunit activity. The cells were implanted in several points along tracts in the perilesional region. No important adverse events derived from surgery or transplant were observed during the one year follow-up period, or detected using a combination of tests and functional measurements applied pre- and post-surgically. In contrast, some improvements were observed regarding the neurological condition of the patients, but the small number of patients in the study does not allow any conclusive statement. Our results demonstrate that BMSC can be safely transplanted into the brain of patients, with excellent tolerance and without complications, using the methods described here.

  10. High-dose therapy and autologous stem cell transplant for transformed non-Hodgkin lymphoma in the rituximab era

    PubMed Central

    Ban-Hoefen, Makiko; Kelly, Jennifer L.; Bernstein, Steven H.; Liesveld, Jane; Constine, Louis; Becker, Michael; Milner, Laurie; Phillips, Gordon; Friedberg, Jonathan W.

    2013-01-01

    The impact of rituximab on outcome of high dose therapy and autologous stem cell transplantation (HD-ASCT) for transformed NHL has not been previously described. We analyzed eighteen consecutive patients with indolent NHL who transformed to diffuse large B-cell lymphoma (DLBCL), received rituximab-containing therapy either before or after transformation and underwent subsequent HD-ASCT. With a median follow-up of 40 months, the 2-year PFS was 59% and the 2-year OS was 82%. Six patients did not receive rituximab pre-transformation; this group had a significantly better PFS at 2 years post HD-ASCT compared to 12 patients who were exposed to rituximab pre-transformation (p=0.03). HD-ASCT remains an effective therapeutic option for transformed NHL in the rituximab era. However, patients exposed to rituximab pre-transformation appear to have inferior HD-ASCT outcomes, and thus may benefit from novel conditioning and maintenance regimens in the setting of HD-ASCT. PMID:22023518

  11. Absolute lymphocyte count as predictor of overall survival for patients with multiple myeloma treated with single autologous stem cell transplant.

    PubMed

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

    2015-01-01

    Post-autologous stem cell transplant (ASCT) studies have demonstrated that absolute lymphocyte count (ALC) recovery is associated with prolonged survival in some hematological malignancies. To assess whether ALC recovery has prognostic significance in patients with multiple myeloma (MM) undergoing single ASCT, we conducted a retrospective analysis of ALC at different time-points in patients with MM. In total 769 consecutive patients who underwent single ASCT from January 2000 to December 2007 were evaluated. An ALC of ≥ 1400 cells/μL at day 0, day 15 and day 90 significantly correlated with a better overall survival (OS) (median OS of 111, 90.7 and 84 months vs. 74, 70.5 and 65 months, respectively, p < 0.001 for all time-points). Multivariate analysis showed that ALC is an independent prognostic factor for OS after ASCT. In conclusion, ALC is a surrogate marker of the host immune system that correlates with better survival in patients with MM undergoing single ASCT. Immunomodulatory drugs, vaccination strategies and cellular therapies in MM should be investigated.

  12. Detection of Minimal Residual Disease by Flow Cytometry for Patients with Multiple Myeloma Submitted to Autologous Hematopoietic Stem Cell Transplantation

    PubMed Central

    Dal Bó, Suzane; Pezzi, Annelise; Amorin, Bruna; Valim, Vanessa; Isabel Bittencourt, Rosane; Silla, Lucia

    2013-01-01

    The treatment strategy in multiple myeloma (MM) is to get complete remission followed by high-dose chemotherapy and autologous Hematopoietic Stem Cell Transplantation (HSCT). Neoplastic Plasma Cells (NPCs) are CD45−/dim, CD38+high, CD138+, CD19−, and  CD56+high in most cases. The description of this immunophenotype is of major importance as it leads to the correct identification of minimal residual disease (MRD). Samples from 44 Patients were analyzed prospectively in this study. We analyzed if the presence of MRD at three months after HSCT was predictive of relapse or death. There were 40 evaluable patients of whom 16/40 patients had MRD at three moths after HSCT and there were none in cytological relapse. The mean overall survival (OS) was 34 months and disease-free survival (RFS) was 28 months after HSCT. There was no significant difference in the log rank analysis comparing OS and the presence of MRD (P = 0,611) and RFS (P = 0,3106). Here, we demonstrate that three color flow cytometry (FCM) is more sensitive for MDR evaluation than cytological analyzes. However, based in our data we can not affirm that MRD is a good predictor of MM relapse or death. In conclusion, our results could be attributed to a short followup, small sample size, and over most to the inability of a three-color FCM to detect the NPC population. PMID:23864957

  13. Thiotepa-based high-dose therapy for autologous stem cell transplantation in lymphoma: a retrospective study from the EBMT.

    PubMed

    Sellner, L; Boumendil, A; Finel, H; Choquet, S; de Rosa, G; Falzetti, F; Scime, R; Kobbe, G; Ferrara, F; Delmer, A; Sayer, H; Amorim, S; Bouabdallah, R; Finke, J; Salles, G; Yakoub-Agha, I; Faber, E; Nicolas-Virelizier, E; Facchini, L; Vallisa, D; Zuffa, E; Sureda, A; Dreger, P

    2016-02-01

    Clinical information about thiotepa-based autologous stem cell transplantation (auto-SCT) outside the primary central nervous system lymphoma (PCNSL) field is sparse. In this registry-based retrospective study, we evaluated potential risks and benefits of thiotepa-based preparative regimens compared with BEAM (carmustine, etoposide, cytarabine, melphalan) in auto-SCT for diffuse large B-cell lymphoma (DLBCL, excluding PCNSL), follicular lymphoma (FL) or Hodgkin lymphoma (HL). A total of 14 544 patients (589 thiotepa and 13 955 BEAM) met the eligibility criteria, and 535 thiotepa- and 1031 BEAM-treated patients were matched in a 1:2 ratio for final comparison. No significant differences between thiotepa and BEAM groups for any survival end point were identified in the whole sample or disease entity subsets. For a more detailed analysis, 47 TEAM (thiotepa, etoposide, cytarabine, melphalan)-treated patients were compared with 75 matched BEAM patients with additional collection of toxicity data. Again, there were no significant differences between the two groups for any survival end point. In addition, the frequency of common infectious and non-infectious complications including secondary malignancies was comparable between TEAM and BEAM. These results indicate that thiotepa-based high-dose therapy might be a valuable alternative to BEAM in DLBCL, HL and FL. Further evaluation by prospective clinical trials is warranted.

  14. Canadian cost analysis comparing maintenance therapy with bortezomib versus lenalidomide for patients with multiple myeloma post autologous stem cell transplant.

    PubMed

    LeBlanc, R; Hollmann, S; Tay, J

    2016-01-01

    Multiple myeloma (MM) is a cancer caused by malignant plasma cells that accumulate mostly in the bone marrow. In Canada, the most common maintenance therapy options after autologous stem cell transplant (ASCT) are bortezomib and lenalidomide. To determine the incremental cost between bortezomib and lenalidomide maintenance therapies for patients with MM post ASCT. Analyses were conducted to compare the annual costs of bortezomib and lenalidomide maintenance treatments for patients with MM post ASCT in Canada. The base case analysis included the acquisition costs of the drugs and administration costs. Additional analyses were conducted which considered the cost of experiencing adverse events (AEs) and the cost of treating second primary malignancies (SPMs). In the Canadian healthcare system, the total annual per patient cost was $33,967 for bortezomib maintenance therapy versus $131,765 for lenalidomide maintenance therapy. One-way sensitivity analyses demonstrated that both AEs and SPMs had little impact on the incremental cost, and that differences between the two maintenance therapies were mainly due to the acquisition costs of the drugs. Bortezomib is significantly less costly than lenalidomide, and is an economically reasonable maintenance treatment option for patients with MM post ASCT.

  15. Effectiveness of Etoposide Chemomobilization in Lymphoma Patients Undergoing Autologous Stem Cell Transplantation

    PubMed Central

    Wood, William A; Whitley, Julia; Goyal, Ravi; Sharf, Andrew; Irons, Robert; Rao, Kamakshi V.; Essenmacher, Amber; Serody, Jonathan S.; Coghill, Jay M.; Armistead, Paul M.; Sarantopoulos, Stefanie; Gabriel, Don A.; Shea, Thomas C.; Brown, Paul

    2015-01-01

    The effectiveness of stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) in lymphoma patients is suboptimal. We reviewed our institutional experience using chemomobilization with etoposide (VP-16; 375mg/m2 on days +1 and +2) and G-CSF (5ug/kg twice daily from day +3 through the final day of collection) in 159 patients with lymphoma. This approach resulted in successful mobilization (> 2 × 106 CD34 cells collected) in 94% of patients (83% within 4 apheresis sessions). 57% of patients collected at least 5 × 106 cells in ≤ 2 days and were defined as good mobilizers. The regimen was safe with a low rate of rehospitalization. Average costs were $14,923 for good mobilizers and $27,044 for poor mobilizers (p<0.05). Using our data, we performed a ‘break-even’ analysis that demonstrated that adding two doses of Plerixafor to predicted poor mobilizers at the time of first CD34 count would achieve cost neutrality if the frequency of good mobilizers were to increase by 21%, while the frequency of good mobilizers would need to increase by 25% if three doses of Plerixafor were used. We conclude that chemomobilization with etoposide and G-CSF in patients with lymphoma is effective, with future opportunities for cost-neutral improvement using novel agents. PMID:23165501

  16. Tantalum coating of porous carbon scaffold supplemented with autologous bone marrow stromal stem cells for bone regeneration in vitro and in vivo

    PubMed Central

    Wei, Xiaowei; Wang, Benjie; Wang, Wei; Kang, Kai; Xie, Hui; Liu, Baoyi; Zhang, Xiuzhi; Zhang, Jinsong; Yang, Zhenming

    2016-01-01

    Porous tantalum metal with low elastic modulus is similar to cancellous bone. Reticulated vitreous carbon (RVC) can provide three-dimensional pore structure and serves as the ideal scaffold of tantalum coating. In this study, the biocompatibility of domestic porous tantalum was first successfully tested with bone marrow stromal stem cells (BMSCs) in vitro and for bone tissue repair in vivo. We evaluated cytotoxicity of RVC scaffold and tantalum coating using BMSCs. The morphology, adhesion, and proliferation of BMSCs were observed via laser scanning confocal microscope and scanning electron microscopy. In addition, porous tantalum rods with or without autologous BMSCs were implanted on hind legs in dogs, respectively. The osteogenic potential was observed by hard tissue slice examination. At three weeks and six weeks following implantation, new osteoblasts and new bone were observed at the tantalum–host bone interface and pores. At 12 weeks postporous tantalum with autologous BMSCs implantation, regenerated trabecular equivalent to mature bone was found in the pore of tantalum rods. Our results suggested that domestic porous tantalum had excellent biocompatibility and could promote new bone formation in vivo. Meanwhile, the osteogenesis of porous tantalum associated with autologous BMSCs was more excellent than only tantalum implantation. Future clinical studies are warranted to verify the clinical efficacy of combined implantation of this domestic porous tantalum associated with autologous BMSCs implantation and compare their efficacy with conventional autologous bone grafting carrying blood vessel in patients needing bone repairing. PMID:26843518

  17. Tantalum coating of porous carbon scaffold supplemented with autologous bone marrow stromal stem cells for bone regeneration in vitro and in vivo.

    PubMed

    Wei, Xiaowei; Zhao, Dewei; Wang, Benjie; Wang, Wei; Kang, Kai; Xie, Hui; Liu, Baoyi; Zhang, Xiuzhi; Zhang, Jinsong; Yang, Zhenming

    2016-03-01

    Porous tantalum metal with low elastic modulus is similar to cancellous bone. Reticulated vitreous carbon (RVC) can provide three-dimensional pore structure and serves as the ideal scaffold of tantalum coating. In this study, the biocompatibility of domestic porous tantalum was first successfully tested with bone marrow stromal stem cells (BMSCs) in vitro and for bone tissue repair in vivo. We evaluated cytotoxicity of RVC scaffold and tantalum coating using BMSCs. The morphology, adhesion, and proliferation of BMSCs were observed via laser scanning confocal microscope and scanning electron microscopy. In addition, porous tantalum rods with or without autologous BMSCs were implanted on hind legs in dogs, respectively. The osteogenic potential was observed by hard tissue slice examination. At three weeks and six weeks following implantation, new osteoblasts and new bone were observed at the tantalum-host bone interface and pores. At 12 weeks postporous tantalum with autologous BMSCs implantation, regenerated trabecular equivalent to mature bone was found in the pore of tantalum rods. Our results suggested that domestic porous tantalum had excellent biocompatibility and could promote new bone formation in vivo. Meanwhile, the osteogenesis of porous tantalum associated with autologous BMSCs was more excellent than only tantalum implantation. Future clinical studies are warranted to verify the clinical efficacy of combined implantation of this domestic porous tantalum associated with autologous BMSCs implantation and compare their efficacy with conventional autologous bone grafting carrying blood vessel in patients needing bone repairing. © 2016 by the Society for Experimental Biology and Medicine.

  18. Cost-Effectiveness of Autologous Stem Cell Treatment as Compared to Conventional Chemotherapy for Treatment of Multiple Myeloma in India.

    PubMed

    Prinja, Shankar; Kaur, Gunjeet; Malhotra, Pankaj; Jyani, Gaurav; Ramachandran, Raja; Bahuguna, Pankaj; Varma, Subhash

    2017-03-01

    Recent innovations in treatment of multiple myeloma include autologous stem cell transplantation (ASCT) along with high dose chemotherapy (HDC). We undertook this study to estimate incremental cost per quality adjusted life year gained (QALY) with use of ASCT along with HDC as compared to conventional chemotherapy (CC) alone in treatment of multiple myeloma. A combination of decision tree and markov model was used to undertake the analysis. Incremental costs and effects of ASCT were compared against the baseline scenario of CC (based on Melphalan and Prednisolone regimen) in the patients of multiple myeloma. A lifetime study horizon was used and future costs and consequences were discounted at 5%. Consequences were valued in terms of QALYs. Incremental cost per QALY gained using ASCT as against CC for treatment of multiple myeloma was estimated using both a health system and societal perspective. The cost of providing ASCT (with HDC) for multiple myeloma patients was INR 500,631, while the cost of CC alone was INR 159,775. In the long run, cost per patient per year for ASCT and CC arms was estimated to be INR 119,740 and INR 111,565 respectively. The number of QALYs lived per patient in case of ASCT and HDC alone were found to be 4.1 and 3.5 years respectively. From a societal perspective, ASCT was found to incur an incremental cost of INR 334,433 per QALY gained. If the ASCT is initiated early to patients, the incremental cost for ASCT was found to be INR 180,434 per QALY gained. With current mix of patients, stem cell treatment for multiple myeloma is not cost effective at a threshold of GDP per capita. It becomes marginally cost-effective at 3-times the GDP per capita threshold. However, accounting for the model uncertainties, the probability of ASCT to be cost effective is 59%. Cost effectiveness of ASCT can be improved with early detection and initiation of treatment.

  19. Real-world costs of autologous and allogeneic stem cell transplantations for haematological diseases: a multicentre study.

    PubMed

    Blommestein, H M; Verelst, S G R; Huijgens, P C; Blijlevens, N M A; Cornelissen, J J; Uyl-de Groot, C A

    2012-12-01

    Haematopoietic stem cell transplantation (SCT) is an expensive lifesaving procedure, which is increasingly performed in patients with haematological diseases. Developments in the protocol for SCT have resulted in cost estimates that require updating. We aimed to calculate actual costs for SCT and to identify major cost drivers by means of a daily practice cost study. We randomly selected 191 patients, treated at three university hospitals, who underwent an autologous (auto) SCT or allogeneic (allo) SCT in 2007, 2008 or 2009. Allo-SCT included sibling donors, matched unrelated donors (MUD) and umbilical cord blood (UCB). Resource use was collected from the hospital registration systems and medical files. The total costs included selection and harvesting of stem cells, transplantation and 1-year follow-up. The average costs per patient were 45,670 € for auto-SCT and 101,919 € for sibling allo-SCT. The costs of transplantations from unrelated donors were much higher: 171,478 € for allo-SCT-MUD and 254,689 € for allo-SCT-UCB. Hospital inpatient days together with laboratory and other activities were the main cost drivers across all types of SCT. Besides, donor search costs were a large cost component in allo-SCT-sib (18 %) and allo-SCT-MUD (12 %). Real-world costs were above routine reimbursement and appropriate financing is necessary to guarantee the continuation of SCT. The costs calculated in this study provide reliable up-to-date input for cost-effectiveness studies and budget revision.

  20. Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis.

    PubMed

    Casanova, Bonaventura; Jarque, Isidro; Gascón, Francisco; Hernández-Boluda, Juan Carlos; Pérez-Miralles, Francisco; de la Rubia, Javier; Alcalá, Carmen; Sanz, Jaime; Mallada, Javier; Cervelló, Angeles; Navarré, Arantxa; Carcelén-Gadea, María; Boscá, Isabel; Gil-Perotin, Sara; Solano, Carlos; Sanz, Miguel Angel; Coret, Francisco

    2017-07-01

    The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.

  1. Pegfilgrastim compared with filgrastim for cytokine-alone mobilization of autologous haematopoietic stem and progenitor cells.

    PubMed

    Herbert, K E; Gambell, P; Link, E K; Mouminoglu, A; Wall, D M; Harrison, S J; Ritchie, D S; Seymour, J F; Prince, H M

    2013-03-01

    Haematopoietic stem and progenitor cells (HSPC) mobilization, using cytokine-alone, is a well-tolerated regimen with predictable mobilization kinetics. Single-dose pegfilgrastim mobilizes HSPC efficiently; however, there is surprisingly little comparative data on its use without chemotherapy for HSPC mobilization. Pegfilgrastim-alone and filgrastim-alone mobilization regimens were compared in 52 patients with haematological malignancy. Pegfilgrastim 12 mg (n=20) or 6 mg (n=2) was administered Day 1 (D1) in 22 patients (lymphoma n=17; myeloma n=5). Thirty historical controls (lymphoma n=18; myeloma n=12) received filgrastim 10 mcg/kg daily from D1. Peripheral blood (PB) CD34(+) counts reached threshold (5 × 10(6)/L) and apheresis commenced on D4(4-5) and D4(4-6). Median PB CD34(+) cell count on D1 of apheresis was similar (26.0 × 10(6)/L (2.5-125.0 × 10(6)/L) and 16.2 × 10(6)/L (2.6-50.7 × 10(6)/L); P=0.06), for pegfilgrastim and filgrastim groups, respectively. Target yield (2 × 10(6) per kg CD34(+) cells) was collected in 20/22 (91%) pegfilgrastim patients and 24/30 (80%) in the filgrastim group (P=0.44), in a similar median number of aphereses (3(1-4) versus 3(2-6), respectively; P=0.85). A higher proportion of pegfilgrastim patients tended to yield 4 × 10(6) per kg CD34(+) cells; 16/22 (73%) versus 14/30 (47%) filgrastim patients (P=0.09). One pegfilgrastim patient developed hyperleukocytosis that resolved without incident. Pegfilgrastim-alone is a simple, well-tolerated, and attractive option for outpatient-based HSPC mobilization with similar mobilization kinetics and efficacy to regular filgrastim.

  2. Comparison of autologous peripheral blood stem cell dosing by ideal vs actual body weight.

    PubMed

    Waples, J M; Moreb, J S; Sugrue, M; Belanger, G; Kubilis, P; Lynch, J W; Gian, V; Weeks, F; Wingard, J

    1999-05-01

    In this retrospective study, we evaluated the predictability of PBSC dose for hematopoietic engraftment comparing that calculated by ideal body weight (IBW) vs another calculated by actual body weight (ABW) for each patient. Sixty-three consecutive patients treated similarly using one transplant protocol were analyzed. While all patients had data available on CFU-GM and nucleated cells (NC), data on CD34+ enumeration was present only in 34 patients. We found that 49% of the patients were greater than 25% over their IBW. In addition, least-squares linear regression was used to assess the strength of the linear relationship between the inverse of cell dose/kg of ABW or IBW and time to AGC or platelet engraftment and showed no difference in r2 values for platelet engraftment, while using dose/kg of IBW greatly improved the ability of NC (r2 improved from 0.19 for ABW to 0.35 for IBW) and CFU-GM (r2 improved from 0.35 for ABW to 0.53 for IBW) to predict time to AGC engraftment, but did not change the CD34 r2. Hazard ratios were estimated using Cox proportional hazards regression and in all instances were found greater than 1.0 indicating that the probability of engraftment increased as cell dose/kg ABW or IBW increased. Finally, our data showed that 10 patients (16%) could have had one less apheresis procedure performed to obtain their set target stem cell dose calculated per kg IBW rather than ABW. In conclusion, PBSC dose per kg IBW is as good or better predictor of engraftment of AGC and may lead to cost savings in a certain subset of patients.

  3. 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

  4. Long-term follow-up of fertility and pregnancy in autoimmune diseases after autologous haematopoietic stem cell transplantation.

    PubMed

    Massenkeil, G; Alexander, T; Rosen, O; Dörken, B; Burmester, G; Radbruch, A; Hiepe, F; Arnold, R

    2016-11-01

    Issues of fertility and pregnancy require special attention in the long-term care of patients with autoimmune diseases (AD), who are candidates for haematopoietic stem cell transplantation (HSCT). In this single-centre observational study, we report fertility status and pregnancy outcomes in 15 patients (11 female and 4 male) after immunoablation with cyclophosphamide, antithymocyte globulin and autologous CD34(+)-selected HSCT for severe, refractory AD. The median follow-up after HSCT was 12 years (range 2-16 years). Impaired fertility was observed in six patients (five females and one male) before HSCT based on sexual hormone measurements. Higher age and cumulative cyclophosphamide dosage before HSCT correlated with fertility impairment. Median serum level of follicle-stimulating hormone (FSH) was significantly higher in female patients at 1 year after HSCT compared to baseline values, but premature ovarian failure developed in only one patient. Four women had five pregnancies and six healthy offsprings during follow-up, and no miscarriages were observed. The mothers were in treatment-free remissions during conception. No peripartal flare of their AD occurred. Although AD patients undergoing HSCT are at risk of developing infertility, pre-HSCT treatment and patients' age seem to have higher impact on long-term fertility status than HSCT itself. HSCT offers the opportunity to conceive during treatment-free remissions with favourable pregnancy outcomes.

  5. Miconazole mucoadhesive buccal tablet in high-dose therapy with autologous stem cell transplantation (HDT/ASCT)-induced mucositis.

    PubMed

    Orvain, C; Moles-Moreau, M P; François, S; Mercier, M; Moal, F; Hamel, J F; Parot-Schinkel, E; Ifrah, N; Hunault-Berger, M; Tanguy-Schmidt, A

    2015-02-01

    Oral mucositis is a major cause of morbidity in high-dose therapy/autologous stem cell transplantation (HDT/ASCT), where microbial colonization has an important pathological implication. In this study, we evaluated the impact of miconazole mucoadhesive buccal tablet (MBT) on mucositis-related complications. During two consecutive 34-month periods, patients treated with HDT/ASCT in our hematology department received either miconazole MBT (60 patients) or conventional oral amphotericin B suspensions three times a day (44 patients) in order to prevent or decrease chemotherapy-induced mucositis. The use of miconazole MBT is associated with less infectious complications as indicated by shorter antibiotic use (7.8 vs. 12.3 days; p < 0.0001), shorter intravenous antifungal use (1.4 vs. 3.6 days; p = 0.02), and a trend towards less yeast contamination in stool samples. Less patients required any analgesic drugs during hospitalization in the miconazole MBT group (18 vs. 7 %; p = 0.09). Indirect indicators of chemotherapy-induced mucositis (duration of hospitalization, morphine use) were in favor of miconazole MBT in patients with multiple myeloma (MM) but not for those with lymphoma. This study suggests that miconazole MBT provides a valid alternative to oral amphotericin B suspensions in regards to mucositis-related complications. A prospective and randomized study is warranted to establish the definite role of miconazole MBT.

  6. Successful management of gastropulmonary fistula due to invasive fungal infection after chemotherapy and autologous stem cell transplantation: a case report

    PubMed Central

    Ričardas, Janilionis; Lina, Lukoševičiūtė; Virgilijus, Beiša; Valdemaras, Jotautas; Roberta, Petrauskaitė; Valdas, Pečeliūnas; Renata, Jucaitienė

    2016-01-01

    Background. Invasive fungal infections (IFI) contribute significantly to mortality and morbidity in patients receiving myelosuppressive chemotherapy for hematologic malignancies. Acquired gastropulmonary fistula is a rare complication of IFI. Material and methods. We present a case history of a patient with malignant myeloma. She was treated with autologous stem cell transplantation and chemotherapy for three years. She had been treated with antifungal agents as well. Following a specific treatment, she developed an invasive fungal infection (IFI) of the left lung which had been complicated with left gastropulmonary fistula. The patient’s general condition was deteriorating, so it was decided to perform a surgical intervention. At the first procedure, open-window thoracostomy was created in order to facilitate treatment by daily packing of the cavity. Four weeks after the thoracostomy, a thoracomyoplasty was performed to repair a gastropleural fistula. During the laparotomy, the gastric fundus was freed from adjacent tissues and repaired. Intrathoracic transposition of the latissimus dorsi and anterior serratus muscle flaps was performed simultaneously to create a new diaphragm. The open-window thoracostomy was left open due to some small bronchial fistulas. The thoracostomy opening healed spontaneously during the following six months. Conclusion. We report what is, to the best of our knowledge, the first case of an invasive fungal infection (Geotrichum capitatum) successfully treated with intravenous amphotericin B, voriconazole, and surgery on infected soft tissues (organs) for a patient with multiple myeloma in prolonged neutropenia. The efficacy and safety of the surgery for infected soft tissues requires further evaluation. PMID:28356805

  7. Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet-Rich Plasma Accelerate Distraction Osteogenesis in A Canine Model

    PubMed Central

    Dehghan, Mohammad Mehdi; Baghaban Eslaminejad, Mohamadreza; Motallebizadeh, Nader; Ashrafi Halan, Javad; Tagiyar, Leila; Soroori, Sarang; Nikmahzar, Agbibi; Pedram, Mirsepehr; Shahverdi, Abdolhossein; Kazemi Mehrjerdi, Hossein; Izadi, Sadra

    2015-01-01

    Objective Distraction osteogenesis (DO) is a surgical procedure used to generate large volumes of new bone for limb lengthening. Materials and Methods In this animal experimental study, a 30% lengthening of the left tibia (mean distraction distance: 60.8 mm) was performed in ten adult male dogs by callus distraction after osteotomy and application of an Ilizarov fixator. Distraction was started on postoperative day seven with a distraction rate of 0.5 mm twice per day and carried out at a rate of 1.5 mm per day until the end of the study. Autologous bone marrow mesenchymal stem cells (BM-MSCs) and platelet-rich plasma (PRP) as the treatment group (n=5) or PRP alone (control group, n=5) were injected into the distracted callus at the middle and end of the distraction period. At the end of the consolidation period, the dogs were sacrificed after which computerized tomography (CT) and histomorphometric evaluations were performed. Results Radiographic evaluationsrevealed that the amount and quality of callus formations were significantly higher in the treatment group (P<0.05). As measured by CT scan, the healing parametersin dogs of the treatment group were significantly greater (P<0.05). New bone formation in the treatment group was significantly higher (P<0.05). Conclusion The present study showed that the transplantation of BM-MSCs positively affects early bony consolidation in DO. The use of MSCs might allow a shortened period of consolidation and therefore permit earlier device removal. PMID:26199903

  8. Therapeutic effects of massage therapy and handling touch on caregivers of patients undergoing autologous hematopoietic stem cell transplant.

    PubMed

    Rexilius, Stephanie J; Mundt, Carla; Erickson Megel, Mary; Agrawal, Sangeeta

    2002-04-01

    To examine the effect of massage therapy and Healing Touch on anxiety, depression, subjective caregiver burden, and fatigue experienced by caregivers of patients undergoing autologous hematopoietic stem cell transplant. Quasi-experimental repeated measures. Oncology/hematology outpatient clinic in a large midwestern city. 36 caregivers: 13 in the control group, 13 in the massage therapy group, and 10 in the Healing Touch group. Average age was 51.5 years; most participants were Caucasian. All caregivers completed the Beck Anxiety Inventory, the Center for Epidemiologic Studies Depression Scale, the Subjective Burden Scale, and the Multidimensional Fatigue Inventory-20 before and after treatment consisting of two 30-minute massages or Healing Touch treatments per week for three weeks. Caregivers in the control group received usual nursing care and a 10-minute supportive visit from one of the researchers. Anxiety, depression, subjective burden, fatigue, Healing Touch, massage therapy. Results showed significant declines in anxiety scores, depression, general fatigue, reduced motivation fatigue, and emotional fatigue for individuals in the massage therapy group only. In the Healing Touch group, anxiety and depression scores decreased, and fatigue and subjective burden increased, but these changes did not achieve statistical significance. Caregivers can benefit from massage therapy in the clinic setting. Oncology nurses care for both patients and their caregivers. Although some transplant programs provide services to support lay caregivers, studies indicate that these individuals continue to feel stressed by their situation. Massage might be one intervention that can be used by nurses to decrease feelings of stress in patients' caregivers.

  9. Autologous stem cell transplantation versus novel drugs or conventional chemotherapy for patients with relapsed multiple myeloma after previous ASCT.

    PubMed

    Grövdal, M; Nahi, H; Gahrton, G; Liwing, J; Waage, A; Abildgaard, N; Pedersen, P T; Hammerstrøm, J; Laaksonen, A; Bazia, P; Terava, V; Ollikainen, H; Silvennoinen, R; Putkonen, M; Anttila, P; Porkka, K; Remes, K

    2015-06-01

    High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is the most common first-line treatment for patients with multiple myeloma (MM) under 65 years of age. A second ASCT at first relapse is frequently used but is challenged by the use of novel drugs. We retrospectively studied the outcome of second-line treatment in MM patients from the Nordic countries with relapse after first-line HDT and ASCT. Patients that underwent a second ASCT (n=111) were compared with patients re-treated with conventional cytotoxic drugs only (n=91) or with regimens including novel drugs (proteasome inhibitors and/or immunomodulatory drugs) (n=362) without a second ASCT. For patients receiving a second ASCT median overall survival was 4.0 years compared with 3.3 years (P<0.001) for the group treated with novel drugs and 2.5 years (P<0.001) for those receiving conventional cytotoxic drugs only. A second ASCT also resulted in a significantly longer second time to progression and a significantly longer time to next treatment. We conclude that, irrespective of the addition of novel drugs, MM patients in first relapse after ASCT still appear to benefit from a second ASCT. A second ASCT should be considered for all physically fit patients.

  10. Reduced nutritional status among multiple myeloma patients during treatment with high-dose chemotherapy and autologous stem cell support.

    PubMed

    Iversen, Per Ole; Wisløff, Finn; Gulbrandsen, Nina

    2010-08-01

    Multiple myeloma (MM) ranks among the most frequent blood cancers in adults. Optimal treatment consists of high-dose chemotherapy and autologous stem cell transplantation. Health-related quality of life (HRQoL) is reduced before, during, and after therapy. Several HRQoL items are associated with nutritional health, e.g., nausea/vomiting, appetite loss and fatigue. It is unknown whether nutritional status in MM is affected by treatment. Hence we assessed nutritional status before, during and (1/2) year after treatment-start. We applied anthropometry (height, weight, hand-grip strength, triceps skinfold) and plasma concentrations of biomarkers to assess nutritional status. HRQoL was determined with the EORTC QLQ-C30 questionnaire. The anthropometrical parameters all decreased (p<0.05) during treatment, but were restored at the end of the observation period. Albumin and the fat-soluble vitamins D and E followed a similar pattern, whereas transferrin and vitamin A were unchanged (p>0.05). Interestingly, markers of thyroid function declined and remained low (p<0.05) even 6 months after start of therapy. Nutrition-associated symptoms used as markers of HRQoL worsened during therapy, but returned to pre-therapy levels. Intensive therapy in MM is associated with a decline in both nutritional status and health-related quality of life. Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  11. Tolerability of piperacillin/tazobactam in children and adolescents after high dose radio-/chemotherapy and autologous stem cell transplantation.

    PubMed

    Nürnberger, W; Bönig, H; Burdach, S; Göbel, U

    1998-01-01

    The combination of piperacillin with tazobactam (PIP/TAZ) extends the activity of piperacillin against gram-positive, gram-negative, and anaerobic bacteria. The broad-spectrum of this formulation, together with its low degree of organ toxicity observed in adults, makes PIP/TAZ a tempting choice for children with radio-/chemotherapy-induced neutropenia. However, the use of PIP/TAZ is not yet approved for children under 12 years of age. The tolerability of PIP/TAZ was assessed in 19 children and adolescents between 2 and 18 years of age who developed a fever during aplasia after high dose radio-/chemotherapy and autologous stem cell transplantation (HD-SCT) for primary multifocal or relapsed solid tumours. Treatment with PIP/TAZ was initiated on average 3 days after HD-SCT, and the treatment was continued for approximately 10 days. Both clinical observation and laboratory studies showed no relevant alterations that would have been attributable to PIP/TAZ treatment. These results indicate that PIP/TAZ appears to be well tolerated in children during the acute phase of HD-SCT.

  12. Prophylactic intravenous immunoglobulin during autologous haemopoietic stem cell transplantation for multiple myeloma is not associated with reduced infectious complications.

    PubMed

    Blombery, Piers; Prince, H Miles; Worth, Leon J; Main, Jo; Yang, Melissa; Wood, Erica M; Westerman, David A

    2011-10-01

    Patients with multiple myeloma undergoing autologous haemopoietic stem cell transplantation (ASCT) are at high risk for infectious complications. Peri-transplant intravenous immunoglobulin (IVIG) has been used with the aim of reducing these risks. Our retrospective, non-randomised study of peri-transplant IVIG use and effect on infectious complications in 266 ASCTs for myeloma from 2000 to 2009 at a major metropolitan referral centre for haematological malignancies found no difference between those receiving peri-transplant IVIG (0.4 g/kg) (n=130) and those who were not (n=110) with regard to bloodstream infections, pneumonia, urinary tract or gastrointestinal infections. When analysed according to pre-transplant therapy (conventional chemotherapy versus novel agents), there was no significant difference in infectious complications between those who did or did not receive peri-transplant IVIG. In conclusion, our study did not show a benefit for the use of peri-transplant IVIG (0.4 g/kg) to reduce infectious complications in a large cohort of patients with myeloma undergoing ASCT. In the absence of data supporting efficacy in this context, there appears to be no benefit in the routine use of IVIG for this purpose.

  13. Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation

    PubMed Central

    Paiva, Bruno; Vidriales, Maria-Belén; Cerveró, Jorge; Mateo, Gema; Pérez, Jose J.; Montalbán, Maria A.; Sureda, Anna; Montejano, Laura; Gutiérrez, Norma C.; de Coca, Alfonso García; de las Heras, Natalia; Mateos, Maria V.; López-Berges, Maria C.; García-Boyero, Raimundo; Galende, Josefina; Hernández, Jose; Palomera, Luis; Carrera, Dolores; Martínez, Rafael; de la Rubia, Javier; Martín, Alejandro; Bladé, Joan; Lahuerta, Juan J.; Orfao, Alberto

    2008-01-01

    Minimal residual disease (MRD) assessment is standard in many hematologic malignancies but is considered investigational in multiple myeloma (MM). We report a prospective analysis of the prognostic importance of MRD detection by multiparameter flow cytometry (MFC) in 295 newly diagnosed MM patients uniformly treated in the GEM2000 protocol VBMCP/VBAD induction plus autologous stem cell transplantation [ASCT]). MRD status by MFC was determined at day 100 after ASCT. Progression-free survival (PFS; median 71 vs 37 months, P < .001) and overall survival (OS; median not reached vs 89 months, P = .002) were longer in patients who were MRD negative versus MRD positive at day 100 after ASCT. Similar prognostic differentiation was seen in 147 patients who achieved immunofixation-negative complete response after ASCT. Moreover, MRD− immunofixation-negative (IFx−) patients and MRD− IFx+ patients had significantly longer PFS than MRD+ IFx− patients. Multivariate analysis identified MRD status by MFC at day 100 after ASCT as the most important independent prognostic factor for PFS (HR = 3.64, P = .002) and OS (HR = 2.02, P = .02). Our findings demonstrate the clinical importance of MRD evaluation by MFC, and illustrate the need for further refinement of MM re-sponse criteria. This trial is registered at http://clinicaltrials.gov under identifier NCT00560053. PMID:18669875

  14. Infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and hematopoietic stem cells in post-traumatic paraplegia offers a viable therapeutic approach

    PubMed Central

    Thakkar, Umang G.; Vanikar, Aruna V.; Trivedi, Hargovind L.; Shah, Veena R.; Dave, Shruti D.; Dixit, Satyajit B.; Tiwari, Bharat B.; Shah, Harda H.

    2016-01-01

    Background: Spinal cord injury (SCI) is not likely to recover by current therapeutic modalities. Stem cell (SC) therapy (SCT) has promising results in regenerative medicine. We present our experience of co-infusion of autologous adipose tissue derived mesenchymal SC differentiated neuronal cells (N-Ad-MSC) and hematopoietic SCs (HSCs) in a set of patients with posttraumatic paraplegia. Materials and Methods: Ten patients with posttraumatic paraplegia of mean age 3.42 years were volunteered for SCT. Their mean age was 28 years, and they had variable associated complications. They were subjected to adipose tissue resection for in vitro generation of N-Ad-MSC and bone marrow aspiration for generation of HSC. Generated SCs were infused into the cerebrospinal fluid (CSF) below injury site in all patients. Results: Total mean quantum of SC infused was 4.04 ml with a mean nucleated cell count of 4.5 × 104/μL and mean CD34+ of 0.35%, CD45−/90+ and CD45−/73+ of 41.4%, and 10.04%, respectively. All of them expressed transcription factors beta-3 tubulin and glial fibrillary acid protein. No untoward effect of SCT was noted. Variable and sustained improvement in Hauser's index and American Spinal Injury Association score was noted in all patients over a mean follow-up of 2.95 years. Mean injury duration was 3.42 years against the period of approximately 1-year required for natural recovery, suggesting a positive role of SCs. Conclusion: Co-infusion of N-Ad-MSC and HSC in CSF is safe and viable therapeutic approach for SCIs. PMID:27110548

  15. Infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and hematopoietic stem cells in post-traumatic paraplegia offers a viable therapeutic approach.

    PubMed

    Thakkar, Umang G; Vanikar, Aruna V; Trivedi, Hargovind L; Shah, Veena R; Dave, Shruti D; Dixit, Satyajit B; Tiwari, Bharat B; Shah, Harda H

    2016-01-01

    Spinal cord injury (SCI) is not likely to recover by current therapeutic modalities. Stem cell (SC) therapy (SCT) has promising results in regenerative medicine. We present our experience of co-infusion of autologous adipose tissue derived mesenchymal SC differentiated neuronal cells (N-Ad-MSC) and hematopoietic SCs (HSCs) in a set of patients with posttraumatic paraplegia. Ten patients with posttraumatic paraplegia of mean age 3.42 years were volunteered for SCT. Their mean age was 28 years, and they had variable associated complications. They were subjected to adipose tissue resection for in vitro generation of N-Ad-MSC and bone marrow aspiration for generation of HSC. Generated SCs were infused into the cerebrospinal fluid (CSF) below injury site in all patients. Total mean quantum of SC infused was 4.04 ml with a mean nucleated cell count of 4.5 × 10(4)/μL and mean CD34+ of 0.35%, CD45-/90+ and CD45-/73+ of 41.4%, and 10.04%, respectively. All of them expressed transcription factors beta-3 tubulin and glial fibrillary acid protein. No untoward effect of SCT was noted. Variable and sustained improvement in Hauser's index and American Spinal Injury Association score was noted in all patients over a mean follow-up of 2.95 years. Mean injury duration was 3.42 years against the period of approximately 1-year required for natural recovery, suggesting a positive role of SCs. Co-infusion of N-Ad-MSC and HSC in CSF is safe and viable therapeutic approach for SCIs.

  16. Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma

    ClinicalTrials.gov

    2016-02-23

    Prolymphocytic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; T-Cell Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  17. Immunological Balance Is Associated with Clinical Outcome after Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetes

    PubMed Central

    Malmegrim, Kelen C. R.; de Azevedo, Júlia T. C.; Arruda, Lucas C. M.; Abreu, Joana R. F.; Couri, Carlos E. B.; de Oliveira, Gislane L. V.; Palma, Patricia V. B.; Scortegagna, Gabriela T.; Stracieri, Ana B. P. L.; Moraes, Daniela A.; Dias, Juliana B. E.; Pieroni, Fabiano; Cunha, Renato; Guilherme, Luiza; Santos, Nathália M.; Foss, Milton C.; Covas, Dimas T.; Burt, Richard K.; Simões, Belinda P.; Voltarelli, Júlio C.; Roep, Bart O.; Oliveira, Maria C.

    2017-01-01

    Autologous hematopoietic stem cell transplantation (AHSCT) increases C-peptide levels and induces insulin independence in patients with type 1 diabetes. This study aimed to investigate how clinical outcomes may associate with the immunological status, especially concerning the balance between immunoregulation and autoreactivity. Twenty-one type 1 diabetes patients were monitored after AHSCT and assessed every 6 months for duration of insulin independence, C-peptide levels, frequencies of islet-specific autoreactive CD8+ T cells (CTL), regulatory lymphocyte subsets, thymic function, and T-cell repertoire diversity. In median follow-up of 78 (range 15–106) months, all patients became insulin-independent, resuming insulin after median of 43 (range 6–100) months. Patients were retrospectively divided into short- or prolonged-remission groups, according to duration of insulin independence. For the entire follow-up, CD3+CD4+ T-cell numbers remained lower than baseline in both groups, whereas CD3+CD8+ T-cell levels did not change, resulting in a CD4/CD8 ratio inversion. Memory CTL comprehended most of T cells detected on long-term follow-up of patients after AHSCT. B cells reconstituted to baseline levels at 2–3 months post-AHSCT in both patient groups. In the prolonged-remission-group, baseline islet-specific T-cell autoreactivity persisted after transplantation, but regulatory T cell counts increased. Patients with lower frequencies of autoreactive islet-specific T cells remained insulin-free longer and presented greater C-peptide levels than those with lower frequencies of these cells. Therefore, immune monitoring identified a subgroup of patients with superior clinical outcome of AHSCT. Our study shows that improved immunoregulation may balance autoreactivity endorsing better metabolic outcomes in patients with lower frequencies of islet-specific T cells. Development of new strategies of AHSCT is necessary to increase frequency and function of T and B

  18. Flow cytometric minimal residual disease monitoring in patients with multiple myeloma undergoing autologous stem cell transplantation: a retrospective study.

    PubMed

    Liu, Hong; Yuan, Constance; Heinerich, Jeremy; Braylan, Raul; Chang, Myron; Wingard, John; Moreb, Jan

    2008-02-01

    We retrospectively reviewed the flow cytometry (FCM) data from bone marrow aspirates of multiple myeloma (MM) patients before and after autologous stem cell transplantation (ASCT). Light scatter properties and CD38 expression were used to identify plasma cells, and CD19/CD45/CD56 further distinguished normal from abnormal plasma cells (NPC and APC, respectively), the latter defined as plasma cells with aberrant CD56, decreased or absent CD19 and/or CD45 expression. Forty-seven patients were screened. After ASCT, 66% (31/47) patients achieved complete remission (CR)/very good partial remission (VGPR), as compared to only 40% (19/47) prior to ASCT (P = 0.01). In 39 patients with data before and after ASCT, all 39 (100%) had a detectable APC population prior to ASCT. Twenty-six out of 39 patients (67%) also had detectable NPC. Following ASCT, the number of patients with detectable NPC increased to 35/39 (89%), while 3/39 (8%) had no detectable NPC and 1/39 (3%) had neither NPC nor APC. The proportion of APC decreased significantly after transplant from a median of 79% to 52% post-transplant (P < 0.001). The APC/total events ratio decreased significantly (P < 0.0001) after transplant. Prior to transplant, patients with less than 1.8% APC had significantly longer progression free survival (PFS) than patients with greater than 1.8% (P = 0.017, by log rank test), while the difference in overall survival did not achieve statistical significance (P = 0.081). Patients who achieved CR/VGPR after transplant had significantly longer PFS in comparison to all others (26 months vs. 11 months, P = 0.004). In conclusion, the detection of a significant population of APC by FCM prior to ASCT significantly correlates with poorer PFS in MM patients.

  19. Development of autologous blood cell therapies.

    PubMed

    Kim, Ah Ram; Sankaran, Vijay G

    2016-10-01

    Allogeneic hematopoietic stem cell transplantation and blood cell transfusions are performed commonly in patients with a variety of blood disorders. Unfortunately, these donor-derived cell therapies are constrained due to limited supplies, infectious risk factors, a lack of appropriately matched donors, and the risk of immunologic complications from such products. The use of autologous cell therapies has been proposed to overcome these shortcomings. One can derive such therapies directly from hematopoietic stem and progenitor cells of individuals, which can then be manipulated ex vivo to produce the desired modifications or differentiated to produce a particular target population. Alternatively, pluripotent stem cells, which have a theoretically unlimited self-renewal capacity and an ability to differentiate into any desired cell type, can be used as an autologous starting source for such manipulation and differentiation approaches. Such cell products can also be used as a delivery vehicle for therapeutics. In this review, we highlight recent advances and discuss ongoing challenges for the in vitro generation of autologous hematopoietic cells that can be used for cell therapy. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  20. Improved survival of children with advanced tumors by myeloablative chemotherapy and autologous peripheral blood stem cell transplantation in complete remission.

    PubMed

    Sato, A; Imaizumi, M; Saisho, T; Saito, T; Yoshinari, M; Cui, Y; Suzuki, H; Koizumi, Y; Ito, T; Takai, Y; Hayashi, Y; Tamura, M; Iinuma, K

    1998-12-01

    Five children with neuroblastoma (NB) stage IV and five children with rhabdomyosarcoma (RMS) stage III were treated with myeloablative chemotherapy and autologous peripheral blood stem cell transplantation (MCT/PBSCT) in the state of complete remission (CR) achieved by conventional therapy. PBSCs were collected in CR status using a cell separator with blood access through a double-lumen central venous catheter. PBSCs with 1.9+/-0.8x10(5) of CFU-GM per patient weights (kg) were infused following MCT after a period of conventional therapy for 11.1+/-2.1 or 9.7+/-0.9 months in NB or RMS patients, respectively. Regimen-related toxicity of MCT was tolerable and peripheral white blood cell count recovered beyond 1.0x10(3)/microl 10-12 days after infusion of PBSCs in all patients. All of RMS patients and three of five NB patients survived for an average of 31.6 months (ranged 10.8-58.1). The survival rate of these patients was improved as compared with our historical controls, and presumably, with that of conventional chemotherapy previously reported. Despite a limited number of patients, it appears that MCT/PBSCT may be effective in improving survival by preventing relapse which may occur thereafter if treated with conventional therapy alone. Furthermore, MCT/PBSCT reduced the duration of treatment, as compared with that of conventional chemo-therapy. Therefore, this study may suggest the feasibility and promise of the therapy including MCT/PBSCT for children with advanced stages of NB and RMS.

  1. Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture

    PubMed Central

    Muir, Peter; Hans, Eric C.; Racette, Molly; Volstad, Nicola; Sample, Susannah J.; Heaton, Caitlin; Holzman, Gerianne; Schaefer, Susan L.; Bloom, Debra D.; Bleedorn, Jason A.; Hao, Zhengling; Amene, Ermias; Suresh, M.; Hematti, Peiman

    2016-01-01

    Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response

  2. Immunological characteristics and T-cell receptor clonal diversity in children with systemic juvenile idiopathic arthritis undergoing T-cell-depleted autologous stem cell transplantation.

    PubMed

    Wu, Qiong; Pesenacker, Anne M; Stansfield, Alka; King, Douglas; Barge, Dawn; Foster, Helen E; Abinun, Mario; Wedderburn, Lucy R

    2014-06-01

    Children with systemic Juvenile Idiopathic Arthritis (sJIA), the most severe subtype of JIA, are at risk from destructive polyarthritis and growth failure, and corticosteroids as part of conventional treatment can result in osteoporosis and growth delay. In children where there is failure or toxicity from drug therapies, disease has been successfully controlled by T-cell-depleted autologous stem cell transplantation (ASCT). At present, the immunological basis underlying remission after ASCT is unknown. Immune reconstitution of T cells, B cells, natural killer cells, natural killer T cells and monocytes, in parallel with T-cell receptor (TCR) diversity by analysis of the β variable region (TCRVb) complementarity determining region-3 (CDR3) using spectratyping and sequencing, were studied in five children with sJIA before and after ASCT. At time of follow up (mean 11.5 years), four patients remain in complete remission, while one child relapsed within 1 month of transplant. The CD8(+) TCRVb repertoire was highly oligoclonal early in immune reconstitution and re-emergence of pre-transplant TCRVb CDR3 dominant peaks was observed after transplant in certain TCRVb families. Further, re-emergence of pre-ASCT clonal sequences in addition to new sequences was identified after transplant. These results suggest that a chimeric TCR repertoire, comprising T-cell clones developed before and after transplant, can be associated with clinical remission from severe arthritis. © 2014 The Authors. Immunology published by John Wiley & Sons Ltd.

  3. Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.

    PubMed

    Llufriu, Sara; Sepúlveda, María; Blanco, Yolanda; Marín, Pedro; Moreno, Beatriz; Berenguer, Joan; Gabilondo, Iñigo; Martínez-Heras, Eloy; Sola-Valls, Nuria; Arnaiz, Joan-Albert; Andreu, Enrique J; Fernández, Begoña; Bullich, Santi; Sánchez-Dalmau, Bernardo; Graus, Francesc; Villoslada, Pablo; Saiz, Albert

    2014-01-01

    Uncontrolled studies of mesenchymal stem cells (MSCs) in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL) on magnetic resonance imaging (MRI) at 6 months and at the end of the study. Patients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS) 3.0-6.5 were randomized to receive IV 1-2×10(6) bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite), and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects. At baseline 9 patients were randomized to receive MSCs (n = 5) or placebo (n = 4). One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1-8.8 vs 12.3, 95% CI = 4.4-34.5, p = 0.064), and at the end of study to reduced mean GEL (-2.8±5.9 vs 3±5.4, p = 0.075). No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+) cells in blood of MSCs treated patients. Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266.

  4. Randomized Placebo-Controlled Phase II Trial of Autologous Mesenchymal Stem Cells in Multiple Sclerosis

    PubMed Central

    Blanco, Yolanda; Marín, Pedro; Moreno, Beatriz; Berenguer, Joan; Gabilondo, Iñigo; Martínez-Heras, Eloy; Sola-Valls, Nuria; Arnaiz, Joan-Albert; Andreu, Enrique J.; Fernández, Begoña; Bullich, Santi; Sánchez-Dalmau, Bernardo; Graus, Francesc; Villoslada, Pablo; Saiz, Albert

    2014-01-01

    Objective Uncontrolled studies of mesenchymal stem cells (MSCs) in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL) on magnetic resonance imaging (MRI) at 6 months and at the end of the study. Methods Patients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS) 3.0–6.5 were randomized to receive IV 1–2×106 bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite), and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects. Results At baseline 9 patients were randomized to receive MSCs (n = 5) or placebo (n = 4). One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1–8.8 vs 12.3, 95% CI = 4.4–34.5, p = 0.064), and at the end of study to reduced mean GEL (−2.8±5.9 vs 3±5.4, p = 0.075). No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+) cells in blood of MSCs treated patients. Conclusion Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266 PMID:25436769

  5. Defibrotide prevents the activation of macrovascular and microvascular endothelia caused by soluble factors released to blood by autologous hematopoietic stem cell transplantation.

    PubMed

    Palomo, Marta; Diaz-Ricart, Maribel; Rovira, Montserrat; Escolar, Ginés; Carreras, Enric

    2011-04-01

    Endothelial activation and damage occur in association with autologous hematopoietic stem cell transplantation (HSCT). Several of the early complications associated with HSCT seem to have a microvascular location. Through the present study, we have characterized the activation and damage of endothelial cells of both macro (HUVEC) and microvascular (HMEC) origin, occurring early after autologous HSCT, and the potential protective effect of defibrotide (DF). Sera samples from patients were collected before conditioning (Pre), at the time of transplantation (day 0), and at days 7, 14, and 21 after autologous HSCT. Changes in the expression of endothelial cell receptors at the surface, presence and reactivity of extracellular adhesive proteins, and the signaling pathways involved were analyzed. The expression of ICAM-1 at the cell surface increased progressively in both HUVEC and HMEC. However, a more prothrombotic profile was denoted for HMEC, in particular at the time of transplantation (day 0), reflecting the deleterious effect of the conditioning treatment on the endothelium, especially at a microvascular location. Interestingly, this observation correlated with a higher increase in the expression of both tissue factor and von Willebrand factor on the extracellular matrix, together with activation of intracellular p38 MAPK and Akt. Previous exposure and continuous incubation of cells with DF prevented the signs of activation and damage induced by the autologous sera. These observations corroborate that conditioning treatment in autologous HSCT induces a proinflammatory and a prothrombotic phenotype, especially at a microvascular location, and indicate that DF has protective antiinflammatory and antithrombotic effects in this setting. Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  6. Induction of apoptosis and effect on CD20+ using rituximab on autologous peripheral blood stem cell harvests from patients with B cell lymphomas.

    PubMed

    Borbolla-Escoboza, Jose R; Leon, Maria I; Collados, Maria T; Baez, Enrique; Baltasar, Severiano; Hernández, Roberto; Rojas, Julio C

    2004-04-01

    Purging of neoplastic cells for autologous stem cell transplantation is usually done in vivo by administering chemotherapy and/or other agents before harvesting. It is also possible to decrease malignant cells counts directly in the cell harvest. In this study, we ascertained the effect of anti-CD20 monoclonal antibody and rituximab administration on peripheral blood hematopoietic stem cells. Five samples of stem cell harvests from different patients with B cell lymphoma were obtained. Each sample was divided in two tubes with calcium gluconate (20 mEq/50 microl). Rituximab (1 mg/600,000 mononuclear cells) was added to one of the tubes. Using flow cytometry, CD19, CD20 (B cell markers), and CD95 (apoptosis marker), expression was measured at baseline and 24 h after the addition of rituximab. A one-sided t-test with equal variances was used to analyze the results. Immediately after rituximab addition, CD20 expression became null. No significant difference in variation of CD19 expression was detected after the addition of rituximab (-3.64% control vs. 0.63% rituximab, p = 0.69). Mean variations of percentage of CD95 expression were 2.9% (controls) and 10.52% (rituximab tubes) (p = 0.06). We conclude that rituximab is capable of initiating apoptosis in vitro. We found no decrease in the CD19+ cell count, used as a surrogate marker for CD20+ cells, meaning that, at least in 24 h, apoptosis activation is not capable of decreasing CD20+ cell numbers. In vitro purging of peripheral blood stem cells harvests with rituximab could be part of a broader therapeutic strategy to be offered to lymphoproliferative disorder patients. Copyright Mary Ann Liebert, Inc.

  7. Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn's fistula.

    PubMed

    Lee, Woo Yong; Park, Kyu Joo; Cho, Yong Beom; Yoon, Sang Nam; Song, Kee Ho; Kim, Do Sun; Jung, Sang Hun; Kim, Mihyung; Yoo, Hee-Won; Kim, Inok; Ha, Hunjoo; Yu, Chang Sik

    2013-11-01

    Fistula is a representative devastating complication in Crohn's patients due to refractory to conventional therapy and high recurrence. In our phase I clinical trial, adipose tissue-derived stem cells (ASCs) demonstrated their safety and therapeutic potential for healing fistulae associated with Crohn's disease. This study was carried out to evaluate the efficacy and safety of ASCs in patients with Crohn's fistulae. In this phase II study, forty-three patients were treated with ASCs. The amount of ASCs was proportioned to fistula size and fistula tract was filled with ASCs in combination with fibrin glue after intralesional injection of ASCs. Patients without complete closure of fistula at 8 weeks received a second injection of ASCs containing 1.5 times more cells than the first injection. Fistula healing at week 8 after final dose injection and its sustainability for 1-year were evaluated. Healing was defined as a complete closure of external opening without any sign of drainage and inflammation. A modified per-protocol analysis showed that complete fistula healing was observed in 27/33 patients (82%) by 8 weeks after ASC injection. Of 27 patients with fistula healing, 26 patients completed additional observation study for 1-year and 23 patients (88%) sustained complete closure. There were no adverse events related to ASC administration. ASC treatment for patients with Crohn's fistulae was well tolerated, with a favorable therapeutic outcome. Furthermore, complete closure was well sustained. These results strongly suggest that autologous ASC could be a novel treatment option for the Crohn's fistula with high-risk of recurrence. Copyright © 2013 AlphaMed Press.

  8. High-dose chemotherapy followed by autologous stem cell transplantation changes prognosis of IgD multiple myeloma.

    PubMed

    Maisnar, V; Hájek, R; Scudla, V; Gregora, E; Büchler, T; Tichý, M; Kotoucek, P; Kafková, A; Forraiová, L; Minarík, J; Radocha, J; Bláha, V; Malý, J

    2008-01-01

    Immunoglobulin D (IgD) multiple myeloma (MM) is a rare plasma cell disorder constituting less than 2% of all MM cases. Survival of patients with IgD MM is generally shorter than that of patients with other types of monoclonal (M-) protein. We have retrospectively analyzed patients with IgD MM participating in clinical trials of the Czech Myeloma Group. Twenty-six IgD MM patients treated between 1996 and 2006 were identified, 14 (54%) men and 12 (46%) women. The median age was 61 years (range: 37-79 years). Ten of 26 patients (39%) were treated with first-line high-dose chemotherapy (HDCT) using melphalan 200 mg/m(2) followed by autologous stem cell transplantation (ASCT). Thirteen of 26 patients (50%) received conventional chemotherapy (CHT), mostly melphalan and prednisone or a vincristine/doxorubicin/dexamethasone (VAD) regimen. Treatment responses were evaluable for 23 of 26 (89%) patients. All HDCT patients had treatment responses, including seven patients (70%) with complete responses and three patients (30%) with partial responses. The median progression-free survival was 18 months for HDCT patients and 20 months for CHT patients. The median overall survival (OS) for all patients was 34 months. The median OS for the HDCT group has not yet been reached (70% of the patients are still alive). In contrast, the median OS for CHT patients was only 16 months. The difference in OS between the two groups was statistically significant (P=0.005). In conclusion, the overall response rate for patients with IgD MM aged 65 years or less treated with HDCT and ASCT is similar to that seen in other MM types.

  9. Delineation of the timing of second-line therapy post-autologous stem cell transplant in patients with AL amyloidosis.

    PubMed

    Hwa, Yi L; Warsame, Rahma; Gertz, Morie A; Buadi, Francis K; Lacy, Martha Q; Kumar, Shaji K; Dingli, David; Zeldenrust, Steve R; Leung, Nelson; Hayman, Susanne R; Kapoor, Prashant; Gonsalves, Wilson I; Kourelis, Taxiarchis V; Russell, Stephen; Go, Ronald S; Hobbs, Miriam A; Fonder, Amie L; Rajkumar, S Vincent; Dispenzieri, Angela

    2017-09-28

    Among patients with immunoglobulin light chain (AL) amyloidosis, there is little consensus on when reinstitution of chemotherapy should occur. We conducted a retrospective study to evaluate the patterns of relapse or progression (R/P) and the timing of reinitiating therapy among 235 patients initially treated with autologous stem cell transplant (ASCT) at Mayo Clinic. The median time from ASCT to second-line therapy was 24.3 months. At the time of restarting therapy, median difference of free light chain (dFLC) was 9.9 mg/dL (42% of diagnosis value), 32% had a dFLC <5 mg/dL, and 63% met criteria for organ R/P. The indications for retreatment were (1) clinical suspicion of R/P, 10%; 92) hematologic R/P only, 23%; (3) organ R/P only, 32%; (4) both hematologic and organ R/P, 31%; and (5) suboptimal response to ASCT and second-line therapy as consolidation, 4%. Patients with organ progression at the time of second-line therapy had inferior survival. Although a dFLC of >5 mg/dL at the time of reinstituting therapy was associated with risk, patients relapsing from very good partial response (VGPR) or better had a longer time to develop organ progression after hematologic R/P (24.2 vs 3.2 months, P = .007). These data suggest that the best candidates for clinical trials testing novel plasma cell-directed chemotherapy beyond first line may be those patients who are either relapsing from VGPR or better (dFLC at diagnosis was >5 mg/dL) or having inadequate response to prior therapy. This strategy should allow for hematologic response assessment while avoiding the risk of deleterious organ progression. Implementation of more stringent progression criteria may also be warranted. © 2017 by The American Society of Hematology.

  10. Allogenic stem cell transplantation as salvage therapy for patients relapsing after autologous transplantation: experience from a single institution.

    PubMed

    Martínez, C; Carreras, E; Rovira, M; Urbano-Ispizua, A; Esteve, J; Fernández-Avilés, F; Perales, M; Rives, S; Gómez, M; Montserrat, E

    2001-05-01

    The prognosis of patients relapsing after an autologous transplant (autoSCT) is very poor. Allogenic stem cell transplantation (alloSCT) offers the possibility of curing some of these patients, at the cost, however, of a high transplant related mortality (TRM). The aim of this study was to analyze the outcome of 14 consecutive patients with hematologic malignancies, from a single institution, who underwent alloSCT for progressive disease after autoSCT. Patients had relapsed at a median of 11.5 months (range 2-72) after autoSCT and they underwent alloSCT at a median of 25.5 months (range 7-73) from the first transplant. Ten patients received HLA-identical related peripheral blood progenitor cells, three patients underwent matched-unrelated donor marrow transplants, and one patient received a mismatched related transplant. Conditioning regimens consisted of total body irradiation plus cyclophosphamide (n=5) or melphalan (n=1), or high-dose combination chemotherapy (n=8). Cyclosporin A and methotrexate were administered as graft-versus-host disease (GVHD) prophylaxis. Eight patients (57%) developed grade II-IV acute GVHD. All evaluable patients (n=6) presented extensive chronic GVHD. Overall survival at 1 year was 16% (median 3.5 months, 95% CI 0.7-10.3). Ten patients (71%) died from transplant related complications at a median of 3.5 months (range 0.7-11). Only one patient died of recurrent disease. Three patients remain alive and in complete remission at the time of this report (4, 20 and 20 months, respectively). In conclusion, alloSCT offers the possibility of a sustained control of the disease in some patients who relapse after an autoSCT. However, the procedure is associated with a high transplant-related mortality. Better results might be obtained by carefully selecting patients and by reducing the intensity of the preparative regimen.

  11. Defective expression of apoptosis-related molecules in multiple sclerosis patients is normalized early after autologous haematopoietic stem cell transplantation.

    PubMed

    de Oliveira, G L V; Ferreira, A F; Gasparotto, E P L; Kashima, S; Covas, D T; Guerreiro, C T; Brum, D G; Barreira, A A; Voltarelli, J C; Simões, B P; Oliveira, M C; de Castro, F A; Malmegrim, K C R

    2017-03-01

    Defective apoptosis might be involved in the pathogenesis of multiple sclerosis (MS). We evaluated apoptosis-related molecules in MS patients before and after autologous haematopoietic stem cell transplantation (AHSCT) using BCNU, Etoposide, AraC and Melphalan (BEAM) or cyclophosphamide (CY)-based conditioning regimens. Patients were followed for clinical and immunological parameters for 2 years after AHSCT. At baseline, MS patients had decreased proapoptotic BAD, BAX and FASL and increased A1 gene expression when compared with healthy counterparts. In the BEAM group, BAK, BIK, BIMEL , FAS, FASL, A1, BCL2, BCLXL , CFLIPL and CIAP2 genes were up-regulated after AHSCT. With the exception of BIK, BIMEL and A1, all genes reached levels similar to controls at day + 720 post-transplantation. Furthermore, in these patients, we observed increased CD8(+) Fas(+) T cell frequencies after AHSCT when compared to baseline. In the CY group, we observed increased BAX, BCLW, CFLIPL and CIAP1 and decreased BIK and BID gene expressions after transplantation. At day + 720 post-AHSCT, the expression of BAX, FAS, FASL, BCL2, BCLXL and CIAP1 was similar to that of controls. Protein analyses showed increased Bcl-2 expression before transplantation. At 1 year post-AHSCT, expression of Bak, Bim, Bcl-2, Bcl-xL and cFlip-L was decreased when compared to baseline values. In summary, our findings suggest that normalization of apoptosis-related molecules is associated with the early therapeutic effects of AHSCT in MS patients. These mechanisms may be involved in the re-establishment of immune tolerance during the first 2 years post-transplantation.

  12. [Successful autologous haematopoietic stem cell transplantation in severe, therapy-resistant childhood Crohn's disease. Report on the first case in Hungary].

    PubMed

    Kriván, Gergely; Szabó, Dolóresz; Kállay, Krisztián; Benyó, Gábor; Kassa, Csaba; Sinkó, János; Goda, Vera; Arató, András; Veres, Gábor

    2014-05-18

    The biological therapy of Crohn's disease, such as infliximab is a powerful approach in the therapy of inflammatory bowel diseases. However, in some patients with aggressive disease course, even a combined immunosuppressive therapy will not result in permanent remission. Hematopoietic stem cell transplantation has emerged as a new potential therapeutic tool for inflammatory bowel diseases. The authors report the case of a 15-year-old boy with severe Crohn's disease resistant to combined immunosuppressive therapy. After a 3-years course of unsuccessful conventional therapy including infliximab, autologous hematopoietic stem cell transplantation was performed which resulted in a complete remission. One year after transplantation the patient has relapsed, but he could be treated effectively with conventional therapy regiments. To the best of knowledge of the authors, this is the first report in Hungary presenting hematopoietic stem cell therapy in patient with severe Crohn's disease.

  13. Granulomatosis after autologous stem cell transplantation in nonHodgkin lymphoma – experience of single institution and a review of literature

    PubMed Central

    Boltezar, Lucka; Zagar, Ivana

    2016-01-01

    Abstract Background Sarcoidosis before and after treatment of malignancy is an important differential diagnosis that has to be distinguished from lymphoma. Patients and methods Hodgkin lymphoma, diffuse large B-cell lymphoma and aggressive follicular lymphoma are being staged and treatment effect is evaluated with PET-CT. We report three cases of aggressive lymphoma after high dose therapy and autologous stem cell transplantation with positive lymph nodes on PET-CT, which were histologically diagnosed as sarcoidosis/granulomatosis. In the literature, we found that false positive lymph nodes were more common after allogeneic than after autologous transplantation. Conclusions Post-treatment PET-CT positive lymph nodes should always be examined histologically prior to any further treatment decision to avoid unnecessary toxic procedures. PMID:27904442

  14. Autologous Stem Cell Application in Periodontal Regeneration Technique (SAI-PRT) Using PDLSCs Directly From an Extracted Tooth···An Insight

    PubMed Central

    Vandana, KL; Desai, Rajendra; Dalvi, Priyanka Jairaj

    2015-01-01

    Periodontal regeneration represents the ultimate goal of periodontal therapy. The current regenerative techniques have limited success rates especially in advanced periodontal defects. Currently the research is focused on novel cell-based approaches for periodontal regeneration to overcome the limitations of existing treatment. The human clinical trial on stem cells based periodontal regeneration is promising. The plethora of animal studies provide sound evidence to support the belief that periodontal ligament stem cells (PDLSCs) can be used for periodontal regeneration. The direct application of autologous periodontal stem cells in treatment of intrabony defects is attempted for the first time in periodontal literature. Stem cell Application in Periodontal Regeneration Technique (SAI-PRT) using direct PDLSCs has overcome the limitations and concerns of ex- vivo stem cell culture methods like high cost, technique sensitivity, loss of stemness during cell passage, genetic manipulation and tumorigenic potential. Clinical feasibility, success and cost effectiveness over currently available techniques are encouraging. The clinical utility of this novel idea is recommended. PMID:26634072

  15. Single or tandem autologous stem-cell transplantation for first-relapsed or refractory Hodgkin lymphoma: 10-year follow-up of the prospective H96 trial by the LYSA/SFGM-TC study group.

    PubMed

    Sibon, David; Morschhauser, Franck; Resche-Rigon, Matthieu; Ghez, David; Dupuis, Jehan; Marçais, Ambroise; Deau-Fischer, Bénédicte; Bouabdallah, Reda; Sebban, Catherine; Salles, Gilles; Brice, Pauline

    2016-04-01

    We assessed the long-term results of autologous stem-cell transplantation for patients with first-relapsed or refractory Hodgkin lymphoma included in the prospective Lymphoma Study Association/Société Française de Greffe de Moelle H96 trial. This large multicenter phase II trial evaluated a risk-adapted strategy with single or tandem autologous stem-cell transplantation for 245 Hodgkin lymphoma patients. Poor-risk patients (n=150) had primary refractory Hodgkin lymphoma (n=77) or ≥2 risk factors at first relapse (n=73) and were eligible for tandem autologous stem-cell transplantation. Intermediate-risk patients (n=95) had one risk factor at first relapse and were eligible for single autologous stem-cell transplantation. With a median follow-up of 10.3 years, 10-year freedom from second failure and overall survival rates were, respectively: 64% (95% CI, 54% to 74%) and 70% (95% CI, 61% to 80%) for the intermediate-risk group, and 41% (95% CI, 33% to 49%) and 47% (95% CI, 39% to 55%) for the poor-risk group. Considering only patients who did not relapse after completing autologous stem-cell transplantation, the 15-year cumulative incidences of second primary malignancies were 24% for the 70 intermediate-risk patients and 2% for the 75 poor-risk ones. With long-term follow-up, the risk-adapted strategy remains appropriate. Tandem autologous stem-cell transplantation can still be considered an option for poor-risk patients, but integration of positron-emission tomography findings and new drugs may help to refine the need for a second autologous stem-cell transplant and possibly improve outcomes of patients with first-relapsed or refractory Hodgkin lymphoma.

  16. Single or tandem autologous stem-cell transplantation for first-relapsed or refractory Hodgkin lymphoma: 10-year follow-up of the prospective H96 trial by the LYSA/SFGM-TC study group

    PubMed Central

    Sibon, David; Morschhauser, Franck; Resche-Rigon, Matthieu; Ghez, David; Dupuis, Jehan; Marçais, Ambroise; Deau-Fischer, Bénédicte; Bouabdallah, Reda; Sebban, Catherine; Salles, Gilles; Brice, Pauline

    2016-01-01

    We assessed the long-term results of autologous stem-cell transplantation for patients with first-relapsed or refractory Hodgkin lymphoma included in the prospective Lymphoma Study Association/Société Française de Greffe de Moelle H96 trial. This large multicenter phase II trial evaluated a risk-adapted strategy with single or tandem autologous stem-cell transplantation for 245 Hodgkin lymphoma patients. Poor-risk patients (n=150) had primary refractory Hodgkin lymphoma (n=77) or ≥2 risk factors at first relapse (n=73) and were eligible for tandem autologous stem-cell transplantation. Intermediate-risk patients (n=95) had one risk factor at first relapse and were eligible for single autologous stem-cell transplantation. With a median follow-up of 10.3 years, 10-year freedom from second failure and overall survival rates were, respectively: 64% (95% CI, 54% to 74%) and 70% (95% CI, 61% to 80%) for the intermediate-risk group, and 41% (95% CI, 33% to 49%) and 47% (95% CI, 39% to 55%) for the poor-risk group. Considering only patients who did not relapse after completing autologous stem-cell transplantation, the 15-year cumulative incidences of second primary malignancies were 24% for the 70 intermediate-risk patients and 2% for the 75 poor-risk ones. With long-term follow-up, the risk-adapted strategy remains appropriate. Tandem autologous stem-cell transplantation can still be considered an option for poor-risk patients, but integration of positron-emission tomography findings and new drugs may help to refine the need for a second autologous stem-cell transplant and possibly improve outcomes of patients with first-relapsed or refractory Hodgkin lymphoma. PMID:26721893

  17. Cell adhesion molecule expression on CD34+ cells in grafts and time to myeloid and platelet recovery after autologous stem cell transplantation.

    PubMed

    Watanabe, T; Dave, B; Heimann, D G; Jackson, J D; Kessinger, A; Talmadge, J E

    1998-01-01

    The relationship between cell adhesion receptor expression on CD34+ cells in stem cell grafts and the time to neutrophil and platelet recovery after autologous stem cell transplantation (ASCT [n = 25]) was studied with granulocyte/monocyte-colony stimulating factor (GM-CSF)-mobilized peripheral blood stem cells (PBSCs) and steady-state bone marrow (BM) harvests. Cell adhesion receptor expression was analyzed using flow cytometry after CD34+ cell enrichment. Significantly higher expression of L-selectin and CD44, and significantly lower expression of VLA-4, LFA-1, ICAM-1, Sialyl Lewis(x), Sialyl Lewis(A), and Thy-1 were observed on PBSCs compared with BM CD34+ cells. The log of the number of reinfused CD34+ cells, colony forming units granulocyte/macrophage (CFU-GM), and CD34+ cells coexpressing VLA-4, VLA-5, LAF-1, Mac-1, LFA-3, or CD38 but not ICAM-1, Sialyl Lewis(x), Sialyl Lewis(A), or Thy-1 correlated with the time required to reach an absolute neutrophil count (ANC) of > or =0.5 x 10(9)/L. In addition, the log of the number of CD34+ L-selectin+ and CD34+CD44+ cells reinfused after ASCT correlated better with the time required to reach an ANC of > or =0.5 x 10(9)/L than did the log of the number of CD34+ cells or CFU-GM reinfused. The log of the number of reinfused CD34+ cells, CFU-GM, and CD34+ cells coexpressing CD44, L-selectin, VLA-5 Mac-1, or CD38, but not VLA-4, LAF-1, ICAM-1, LAF-3, Sialyl Lewis(X), Sialyl Lewis(A), or Thy-1, correlated with the time required to reach a platelet count of >20 x 10(9)/L. Thus, L-selectin or CD44 may play an important role in the homing of progenitors after ASCT. In addition, the higher proportion of CD34+L-selectin+ or CD34+CD44+ cells in leukapheresis products may provide one explanation for the more rapid hematologic reconstitution observed after PBSC transplantation.

  18. Autologous Stem-Cell Transplantation Without Hematopoietic Support for the Treatment of Hematologic Malignancies in Jehovah's Witnesses

    PubMed Central

    Ford, Patricia A.; Grant, Shakira J.; Mick, Rosemarie; Keck, Gina

    2015-01-01

    Purpose Autologous stem-cell transplantation (ASCT) has shown to provide curative benefit in patients with relapsed lymphoma and multiple myeloma (MM), often requiring hematopoietic support until marrow engraftment. Because of Jehovah's Witnesses' (JW) refusal of blood products, treatment challenges arise. This study represents 125 JWs with lymphoma (n = 55), MM (n = 68), or amyloidosis (n = 2), treated with high-dose chemotherapy (HDC) and ASCT without transfusions. Patients and Methods Priming with intravenous iron and erythropoietin occurred to increase hemoglobin (Hb) pretransplantation. Cytokine mobilization of stem-cells was used. Delay to HDC was done to allow Hb and platelets to approach 11 g/dL and 100 × 103/μL, respectively. Patients with MM received a standard dose of melphalan 200 mg/m2, with dose reduction for severe kidney dysfunction. Patients with lymphoma received carmustine 300 mg/m2, cyclophosphamide 1,500 mg/m2 on days 2 through 5 (total 6 g/m2), and etoposide 700 mg/m2 per day on days 2 through 4 (total 2,100 mg/m2). Post-transplantation, a combination of granulocyte colony-stimulating factor, erythropoietin, aminocaproic acid, and phytonadione was administered. Results There were two major and 15 minor bleeding complications, none occurring at platelets less than 5.0 × 103/μL, with six (4.8%) treatment-related mortalities. The median decrease in Hb was 5.0 g/dL, with median Hb nadir of 7.0 g/dL. The median number of days with platelet count less than 10 × 103/μL was 3, with median platelet nadir of 5.0 × 103/μL. Cardiac complications occurred in 40 patients (32%). Conclusion ASCT can safely be performed without transfusion support. A platelet transfusion trigger of ≤ 5 × 103/μL may be appropriate in select patients. Pharmacotherapy and cardiac monitoring are effective in the management of cardiac complications. PMID:25870085

  19. Randomized Comparison of Allogeneic Vs. Autologous Mesenchymal Stem Cells for Non-lschemic Dilated Cardiomyopathy: POSEIDON-DCM Trial

    PubMed Central

    Hare, Joshua M.; DiFede, Darcy L; Castellanos, Angela M; Florea, Victoria; Landin, Ana M; El-Khorazaty, Jill; Khan, Aisha; Mushtaq, Muzammil; Lowery, Maureen H; Byrnes, John J; Hendel, Robert C; Cohen, Mauricio G; Alfonso, Carlos E; Valasaki, Krystalenia; Pujol, Marietsy V; Golpanian, Samuel; Ghersin, Eduard; Fishman, Joel E; Pattany, Pradip; Gomes, Samirah A; Delgado, Cindy; Miki, Roberto; Abuzeid, Fouad; Vidro-Casiano, Mayra; Premer, Courtney; Medina, Audrey; Porras, Valeria; Hatzistergos, Konstantinos E.; Anderson, Erica; Mendizabal, Adam; Mitrani, Raul; Heldman, Alan W.

    2016-01-01

    Background While human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic non-ischemic dilated cardiomyopathy (NIDCM). Objectives The POSEIDON-DCM trial is a randomized comparison of safety and efficacy of autologous (auto) vs. allogeneic (allo) bone marrow-derived hMSCs in NIDCM. Methods Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients (age: 55.8 ± 11.2; 32% female) received hMSCs (100 million) by transendocardial stem cell injection (TESI) in ten left ventricular sites by NOGA Catheter. Treated patients were evaluated at baseline, 30 days, 3-, 6-, and 12-months for safety: serious adverse events (SAE), and efficacy endpoints: Ejection Fraction (EF), Minnesota Living with Heart Failure Questionnaire (MLHFQ), Six Minute Walk Test (6MWT), MACE, and immune-biomarkers. This trial is registered with ClinicalTrials.gov, #NCT01392625. Results There were no 30-day treatment-emergent (TE)-SAEs. 12-month SAE incidence was 28.2% (95% CI: 12.8, 55.1) in allo, and 63.5% (95% CI: 40.8, 85.7; p=0.1004) in auto. One allo-group patient developed an elevated donor specific cPRA. EF increased in allo by 8.0 units (95% Cl: 2.8, 13.2; p=0.004), and in auto: 5.4 units (95% Cl: −1.4, 12.1; p=0.116, allo vs. auto p=0.4887). 6MWT increased for allo: 37.0 meters (95% Cl: 2.0 to 72.0; p=0.04), but not auto: 7.3 meters (95% Cl: −47.8, 33.3; p=0.71, auto vs. allo p=0.0168). MLHFQ score decreased in allo (p=0.0022), and auto (p=0.463; p=0.172). The MACE rate was lower in allo vs. auto (p=0.0186). Tumor necrosis factor alpha (TNF-α) decreased (p=0.0001 for each), to a greater extent in allo vs. auto at six-months (p=0.05). Conclusion These findings demonstrate safety and support greater, clinically meaningful efficacy of allo-hMSC vs. auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are

  20. Addition of Mesenchymal Stem Cells to Autologous Platelet-Enhanced Fibrin Scaffolds in Chondral Defects: Does It Enhance Repair?

    PubMed

    Goodrich, Laurie R; Chen, Albert C; Werpy, Natasha M; Williams, Ashley A; Kisiday, John D; Su, Alvin W; Cory, Esther; Morley, Paul S; McIlwraith, C Wayne; Sah, Robert L; Chu, Constance R

    2016-01-06

    The chondrogenic potential of culture-expanded bone-marrow-derived mesenchymal stem cells (BMDMSCs) is well described. Numerous studies have also shown enhanced repair when BMDMSCs, scaffolds, and growth factors are placed into chondral defects. Platelets provide a rich milieu of growth factors and, along with fibrin, are readily available for clinical use. The objective of this study was to determine if the addition of BMDMSCs to an autologous platelet-enriched fibrin (APEF) scaffold enhances chondral repair compared with APEF alone. A 15-mm-diameter full-thickness chondral defect was created on the lateral trochlear ridge of both stifle joints of twelve adult horses. In each animal, one defect was randomly assigned to receive APEF+BMDMSCs and the contralateral defect received APEF alone. Repair tissues were evaluated one year later with arthroscopy, histological examination, magnetic resonance imaging (MRI), micro-computed tomography (micro-CT), and biomechanical testing. The arthroscopic findings, MRI T2 map, histological scores, structural stiffness, and material stiffness were similar (p > 0.05) between the APEF and APEF+BMDMSC-treated repairs at one year. Ectopic bone was observed within the repair tissue in four of twelve APEF+BMDMSC-treated defects. Defects repaired with APEF alone had less trabecular bone edema (as seen on MRI) compared with defects repaired with APEF+BMDMSCs. Micro-CT analysis showed thinner repair tissue in defects repaired with APEF+BMDMSCs than in those treated with APEF alone (p < 0.05). APEF alone resulted in thicker repair tissue than was seen with APEF+BMDMSCs. The addition of BMDMSCs to APEF did not enhance cartilage repair and stimulated bone formation in some cartilage defects. APEF supported repair of critical-size full-thickness chondral defects in horses, which was not improved by the addition of BMDMSCs. This work supports further investigation to determine whether APEF enhances cartilage repair in humans. Copyright © 2016

  1. Incidence, risk factors, and outcome of bacteremia following autologous hematopoietic stem cell transplantation in 720 adult patients.

    PubMed

    Piñana, José Luis; Montesinos, Pau; Martino, Rodrigo; Vazquez, Lourdes; Rovira, Montserrat; López, Javier; Batlle, Montserrat; Figuera, Ángela; Barba, Pere; Lahuerta, Juan José; Debén, Guillermo; Perez-Lopez, Cristina; García, Raimundo; Rosique, Pedro; Lavilla, Esperanza; Gascón, Adriana; Martínez-Cuadrón, David; Sanz, Miguel Ángel

    2014-02-01

    Bacteremia is the most frequent infectious complication during neutropenia in patients receiving autologous hematopoietic stem cell transplantation (ASCT). The objective of this study was to analyze the incidence, characteristics, risk factors, and outcome of bacteremia during the early period after ASCT. A total of 720 patients undergoing ASCT in two observational prospective consecutive multicenter studies of the Programa Español para el Tratamiento de las Hemopatías group were analyzed. Bacteremia occurred in 20 % of patients. Coagulase-negative Staphylococcus was the most frequent (66 %) among the gram-positive agents and Escherichia coli (49 %) among the gram-negative agents. Multivariate analysis showed that the length of neutropenia <1 × 10(9)/L (more than 9 days) [relative risk (RR) of 2.6, p < 0.001] was the sole risk factor for overall bacteremia. We identified the length of neutropenia <1 × 10(9)/L (more than 9 days) (RR 4.98, p < 0.001) and the use of prophylactic fluoroquinolones (RR 0.46, p < 0.01) as specific risk factors for gram-negative bacteremia. Risk factors for gram-positive bacteremia were the use of total parenteral nutrition (RR 1.92, p < 0.01) and deep neutropenia (<0.1 × 10(9)/L), with duration over 5 days (RR 1.67, p < 0.027). Bacteremia showed an increased morbidity with no impact on neither overall nor infectious related mortality. The identification of such risk factors may be helpful to implement prophylactic and therapeutic risk-adapted strategies to reduce the incidence of bacteremia in ASCT.

  2. Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience.

    PubMed

    Mancardi, G L; Sormani, M P; Di Gioia, M; Vuolo, L; Gualandi, F; Amato, M P; Capello, E; Currò, D; Uccelli, A; Bertolotto, A; Gasperini, C; Lugaresi, A; Merelli, E; Meucci, G; Motti, L; Tola, M R; Scarpini, E; Repice, A M; Massacesi, L; Saccardi, R

    2012-06-01

    Over recent years numerous patients with severe forms of multiple sclerosis (MS) refractory to conventional therapies have been treated with intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT). The clinical outcome and the toxicity of AHSCT can be diverse, depending on the various types of conditioning protocols and on the disease phase. To report the Italian experience on all the consecutive patients with MS treated with AHSCT with an intermediate intensity conditioning regimen, named BEAM/ATG, in the period from 1996 to 2008. Clinical and magnetic resonance imaging outcomes of 74 patients were collected after a median follow-up period of 48.3 (range = 0.8-126) months. Two patients (2.7%) died from transplant-related causes. After 5 years, 66% of patients remained stable or improved. Among patients with a follow-up longer than 1 year, eight out of 25 subjects with a relapsing-remitting course (31%) had a 6-12 months confirmed Expanded Disability Status Scale improvement > 1 point after AHSCT as compared with one out of 36 (3%) patients with a secondary progressive disease course (p = 0.009). Among the 18 cases with a follow-up longer than 7 years, eight (44%) remained stable or had a sustained improvement while 10 (56%), after an initial period of stabilization or improvement with median duration of 3.5 years, showed a slow disability progression. This study shows that AHSCT with a BEAM/ATG conditioning regimen has a sustained effect in suppressing disease progression in aggressive MS cases unresponsive to conventional therapies. It can also cause a sustained clinical improvement, especially if treated subjects are still in the relapsing-remitting phase of the disease.

  3. Incidence of infection according to intravenous immunoglobulin use in autologous hematopoietic stem cell transplant recipients with multiple myeloma.

    PubMed

    Park, S; Jung, C W; Jang, J H; Kim, S J; Kim, W S; Kim, K

    2015-10-01

    Although intravenous immunoglobulin (IVIG) is not routinely recommended, many centers still use IVIG during the post-hematopoietic stem cell transplant (HSCT) period. A total of 162 multiple myeloma (MM) patients who underwent autologous (auto-) HSCT between January 2008 and June 2013 were retrospectively reviewed. Primary objective was determination of the impact of IVIG on post-transplant infection, and secondary objectives included identification of overall incidence of infection, type of infection, and risk factors for infection after auto-HSCT in MM patients. After auto-HSCT, 53 of 162 patients (32.7%) experienced 104 infectious events. Upper respiratory infection was most common (n = 31, 29.8%) and pneumonia (n = 27, 26.0%) and herpes zoster (n = 15, 14.4%) came next. Among the identifiable organisms causing respiratory infection, influenza virus (n = 10) and Pneumococcus (n = 9) were predominant. Incidence of infection was not statistically different according to IVIG use (34.8% in IVIG (-) vs. 31.3% in IVIG (+), P = 0.631). Incidence of infection requiring hospitalization and multiple episodes of infection showed no difference between the groups (P = 0.147, P = 0.156). In a Cox proportional hazard model, none of the factors including age, gender, type of disease, stage, tandem (vs. single) transplantation,and IVIG was prognostic for infectious event after auto-HSCT (P = 0.955, hazard ratio 0.980 with 95% confidence interval 0.481-1.997 for IVIG). In auto-HSCT recipients with MM, incidence of post-transplant infection was not different according to prophylactic IVIG use. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Comparison of outcomes after autologous stem cell transplantation between myeloma patients with skeletal and soft tissue plasmacytoma.

    PubMed

    Shin, Ho-Jin; Kim, Kihyun; Lee, Ji Won; Song, Moo-Kon; Lee, Je-Jung; Lee, Ho-Sup; Lee, Won Sik; Kim, Seok Jin; Chung, Joo Seop

    2014-11-01

    We aimed to compare the characteristics of skeletal and soft tissue plasmacytomas and to analyze clinical outcomes and prognostic factors of autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients with plasmacytoma. We retrospectively reviewed data from 93 myeloma patients with detectable extramedullary (EM) plasmacytoma at diagnosis or during the course of the disease, who underwent ASCT. Soft tissue plasmacytoma occurred more frequently in male patients and had higher levels of serum β2-microglobulin and lactate dehydrogenase and high frequency of advanced disease according to International Staging System compared to the skeletal plasmacytoma group. Both soft tissue and skeletal plasmacytoma groups showed similar plasmacytoma relapse patterns after ASCT and relapsed with EM plasmacytoma slightly more frequently in the bone compared to soft tissue sites. Compared to patients with skeletal plasmacytoma, patients with soft tissue plasmacytoma had worse median progression-free survival (PFS) (12 vs. 28 months) (P = 0.001) and overall survival (OS) (37 vs. 67 months) (P = 0.037) after ASCT. In a multivariate analysis, soft tissue plasmacytoma was an only independent poor prognostic factor for both PFS (HR, 2.398; 95% CI, 1.304-4.410) and OS (HR, 2.811; 95% CI, 1.107-7.135) after ASCT. These results demonstrate that, even though ASCT achieved a strong response in myeloma patients with soft tissue plasmacytoma, the presence of EM disease still contributed to a poor prognosis after ASCT compared to skeletal plasmacytoma, and these poor outcomes were not overcome by ASCT. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Autologous Peripheral Blood Stem Cell Transplantation Improves Portal Hemodynamics in Patients with Hepatitis B Virus-related Decompensated Cirrhosis

    PubMed Central

    Deng, Qinzhi; Cai, Ting; Zhang, Shun; Hu, Airong; Zhang, Xingfen; Wang, Yinyin; Huang, Jianrong

    2015-01-01

    Background: Chronic hepatitis B virus (HBV) infection may eventually lead to decompensated liver cirrhosis, which is a terminal illness. Objectives: The aim of this study was to investigate the therapeutic efficacy of autologous peripheral blood stem cell (APBSC) transplantation to improve portal vein hemodynamics in patients with HBV-related decompensated cirrhosis. Patients and Methods: This prospective study included 68 hospitalized patients who were diagnosed with HBV-related decompensated cirrhosis. These patients were divided into two groups: the transplantation group included 33 patients, while the control group included 35. Both groups received conventional medical treatment simultaneously, and APBSC transplantation was performed on the patients in the transplantation group. We evaluated the effects of APBSC transplantation on postoperative liver function using the following indices: total bilirubin, serum prothrombin and albumin, spleen size, and portal vein hemodynamics. Postoperatively, all of the patients were followed up at 24, 36, and 48 weeks. Results: The transplantation group had no serious reactions. Compared with the control group, albumin and prothrombin activity in the transplantation group was significantly improved at 24, 36, and 48 weeks after the procedure, and spleen length and portal vein diameter were substantially reduced at 48 weeks. The velocity of peak portal vein blood flow and mean maximum portal vein blood flow were greatly increased in the APBSC transplantation group at 36 and 48 weeks, respectively; however, there was also decreased portal vein diameter, which reduced portal vein pressure in patients with HBV-related decompensated cirrhosis. Conclusions: APBSC transplantation greatly benefits HBV-linked decompensated cirrhosis patients and should be recommended in clinical practice. PMID:26977164

  6. Cost-effectiveness analysis of consolidation with brentuximab vedotin for high-risk Hodgkin lymphoma after autologous stem cell transplantation.

    PubMed

    Hui, Lucy; von Keudell, Gottfried; Wang, Rong; Zeidan, Amer M; Gore, Steven D; Ma, Xiaomei; Davidoff, Amy J; Huntington, Scott F

    2017-10-01

    In a recent randomized, placebo-controlled trial, consolidation treatment with brentuximab vedotin (BV) decreased the risk of Hodgkin lymphoma (HL) progression after autologous stem cell transplantation (ASCT). However, the impact of BV consolidation on overall survival, quality of life, and health care costs remain unclear. A Markov decision-analytic model was constructed to measure the costs and clinical outcomes for BV consolidation therapy compared with active surveillance in a cohort of patients aged 33 years who were at risk for HL relapse after ASCT. Life-time costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each post-ASCT strategy. After quality-of-life adjustments and standard discounting, upfront BV consolidation was associated with an improvement of 1.07 QALYs compared with active surveillance plus BV as salvage. However, the strategy of BV consolidation led to significantly higher health care costs ($378,832 vs $219,761), resulting in an ICER for BV consolidation compared with active surveillance of $148,664/QALY. If indication-specific pricing was implemented, then the model-estimated BV price reductions of 18% to 38% for the consolidative setting would translate into ICERs of $100,000 and $50,000 per QALY, respectively. These findings were consistent on 1-way and probabilistic sensitivity analyses. BV as consolidation therapy under current US pricing is unlikely to be cost effective at a willingness-to-pay threshold of $100,000 per QALY. However, indication-specific price reductions for the consolidative setting could reduce ICERs to widely acceptable values. Cancer 2017. © 2017 American Cancer Society. Cancer 2017;123:3763-3771. © 2017 American Cancer Society. © 2017 American Cancer Society.

  7. Prolonged survival with a longer duration of maintenance lenalidomide after autologous hematopoietic stem cell transplantation for multiple myeloma.

    PubMed

    Mian, Idrees; Milton, Denái R; Shah, Nina; Nieto, Yago; Popat, Uday R; Kebriaei, Partow; Parmar, Simrit; Oran, Betul; Shah, Jatin J; Manasanch, Elisabet E; Orlowski, Robert Z; Shpall, Elizabeth J; Champlin, Richard E; Qazilbash, Muzaffar H; Bashir, Qaiser

    2016-12-15

    Although lenalidomide maintenance therapy has demonstrated improved outcomes after autologous hematopoietic stem cell transplantation (auto-HCT) for patients with multiple myeloma (MM), the impact of the duration of this therapy is not clearly known. This study retrospectively analyzed all MM patients who were placed on maintenance lenalidomide after auto-HCT between January 2007 and December 2013. Progression-free survival (PFS) and overall survival (OS) were analyzed in multivariate Cox proportional hazards regression models that included the duration of maintenance as a time-dependent covariate. Of the 464 patients identified, 46% initiated therapy early (<4 months after auto-HCT). The median PFS and OS were 38 and 78 months, respectively. Improvements in PFS (hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.04-0.38; P < .001) and OS (HR, 0.09; 95% CI, 0.03-0.26; P < .001) were seen for those on maintenance for >2 years versus those on maintenance for ≤2 years. For those on maintenance for >3 versus those on maintenance for ≤3 years, this trend continued with improvements seen in PFS (HR, 0.02; 95% CI, 0.00-0.44; P = .012) and OS (HR, 0.05; 95% CI, 0.00-0.83; P = .037). The incidence of second primary malignancies (SPMs) in the entire cohort was 3%. No differences were seen in survival between early and late initiators of maintenance lenalidomide. A longer duration of maintenance therapy was associated with longer survival. The incidence of SPMs was low, and they were not associated with the duration of maintenance. The timing of the initiation of maintenance had no effect on survival. Cancer 2016;122:3831-3837. © 2016 American Cancer Society. © 2016 American Cancer Society.

  8. Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Grade Gliomas in Children and Adolescents

    PubMed Central

    2017-01-01

    With the aim to investigate the outcome of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) for high-grade gliomas (HGGs), we retrospectively reviewed the medical records of 30 patients with HGGs (16 glioblastomas, 7 anaplastic astrocytomas, and 7 other HGGs) between 2006 and 2015. Gross or near total resection was possible in 11 patients. Front-line treatment after surgery was radiotherapy (RT) in 14 patients and chemotherapy in the remaining 16 patients including 3 patients less than 3 years of age. Eight of 12 patients who remained progression free and 5 of the remaining 18 patients who experienced progression during induction treatment underwent the first HDCT/auto-SCT with carboplatin + thiotepa + etoposide (CTE) regimen and 11 of them proceeded to the second HDCT/auto-SCT with cyclophosphamide + melphalan (CyM) regimen. One patient died from hepatic veno-occlusive disease (VOD) during the second HDCT/auto-SCT; otherwise, toxicities were manageable. Four patients in complete response (CR) and 3 of 7 patients in partial response (PR) or second PR at the first HDCT/auto-SCT remained event free: however, 2 patients with progressive tumor experienced progression again. The probabilities of 3-year overall survival (OS) after the first HDCT/auto-SCT in 11 patients in CR, PR, or second PR was 58.2% ± 16.9%. Tumor status at the first HDCT/auto-SCT was the only significant factor for outcome after HDCT/auto-SCT. There was no difference in survival between glioblastoma and other HGGs. This study suggests that the outcome of HGGs in children and adolescents after HDCT/auto-SCT is encouraging if the patient could achieve CR or PR before HDCT/auto-SCT. PMID:28049229

  9. Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft

    SciTech Connect

    Fermand, J.P.; Levy, Y.; Gerota, J.; Benbunan, M.; Cosset, J.M.; Castaigne, S.; Seligmann, M.; Brouet, J.C.

    1989-01-01

    Eight patients with stage III aggressive multiple myeloma, refractory to current chemotherapy in six cases, were treated by high-dose chemotherapy (nitrosourea, etoposide, and melphalan) (HDC) and total body irradiation (TBI), followed by autografting with blood stem cells. These cells were previously collected by leukapheresis performed during hematologic recovery following cytotoxic drug-induced bone marrow aplasia. Seven patients were alive 9 to 17 months after HDC-TBI and graft. One died at day 40 from cerebral bleeding. All living patients achieved a 90% or greater reduction in tumor mass. In two cases, a complete remission (CR) has persisted at a follow-up of 15 and 16 months. Three patients have been well and off therapy with stable minimal residual disease (RD) since 10, 11, and 17 months, respectively. A patient in apparent CR and another with RD have relapsed 9 to 12 months posttreatment. Autologous blood-derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. These results, although still preliminary, indicate that HDC and TBI, followed by blood stem cells autograft, which has both practical and theoretical interest over allogeneic or autologous bone marrow transplantation, deserve consideration in selected patients with multiple myeloma.

  10. Safety and Feasibility of Autologous Mesenchymal Stem Cell Transplantation in Chronic Stroke in Indian patients. A four-year follow up.

    PubMed

    Bhasin, Ashu; Kumaran, Senthil S; Bhatia, Rohit; Mohanty, Sujata; Srivastava, M V Padma

    2017-01-01

    Introduction: Stem cell (SC) therapy has been envisioned as a therapeutic vehicle to promote recovery in resistant neurological diseases. Knowing the logistics and paradigms in recovery processes after Stroke, clinicians have pioneered the transplantation therapy. This study presents four-year follow up of our previous trial transplanting bone-marrow-derived animal-free culture expanded intravenous mesenchymal stem cells (MSCs) in chronic stroke which was published in 2010. Methods: We performed an open-label, pilot trial on 12 patients with chronic stroke. Patients were allocated to two groups, those who received intravenous autologous ex vivo cultured mesenchymal stem cells (MSC group) or those who did not (control group), all followed for four years from the day of cell transplantation. Results: The reports have been optimistic regarding safety as we did not find any cell related side effects / mortality till 208th week. We observed that modified Barthel Index showed statistical significant improvement at 156 and 208 weeks of transplantation (95 % CI : -10.27 to 0.07; p =0.041) follow up in the MSC group as compared to controls. The 2nd and 3rd quartile for mBI in MSC group was 89 & 90 respectively suggesting good performance of patients in the stem cell group. The impairment scales i.e., Fugl Meyer, Ashworth tone scale, strength of hand muscles (MRC) did not show any significant improvement at 208th week which is similar to our previous published report. Conclusion: This follow up study primarily indicates safety, tolerance and applicability of autologous mesenchymal stem cells in Stroke. MSCs may act as "chaperones" or work through paracrine mechanisms leading to functional recovery post stroke.

  11. Brief report: Autologous stem cell transplantation restores immune tolerance in experimental arthritis by renewal and modulation of the Teff cell compartment.

    PubMed

    Delemarre, Eveline M; Roord, Sarah T A; van den Broek, Theo; Zonneveld-Huijssoon, Evelien; de Jager, Wilco; Rozemuller, Henk; Martens, Anton C; Broere, Femke; Wulffraat, Nico M; Glant, Tibor T; Prakken, Berent J; van Wijk, Femke

    2014-02-01

    Autologous stem cell transplantation (ASCT) induces long-term drug-free disease remission in patients with juvenile idiopathic arthritis. This study was undertaken to further unravel the immunologic mechanisms underlying ASCT by using a mouse model of proteoglycan-induced arthritis (PGIA). For initiation of PGIA, BALB/c mice received 2 intraperitoneal injections of human PG in a synthetic adjuvant on days 0 and 21. Five weeks after the first immunization, the mice were exposed to total body irradiation (7.5 Gy) and received (un)manipulated bone marrow (BM) grafts from mice with PGIA. Clinical scores, T cell reconstitution, (antigen-specific) T cell cytokine production, and intracellular cytokine expression were determined following autologous BM transplantation (ABMT). ABMT resulted in amelioration and stabilization of arthritis scores. BM grafts containing T cells and T cell-depleted grafts provided the same clinical benefit, with similar reductions in PG-induced T cell proliferation and the number of PG-specific autoantibodies. In vivo reexposure to PG did not exacerbate disease. Following ABMT, basal levels of disease-associated proinflammatory cytokines (interferon-γ [IFNγ], interleukin-17 [IL-17], and tumor necrosis factor α [TNFα]) were reduced. In addition, restimulation of T cells with PG induced a strong reduction in disease-associated proinflammatory cytokine production. Finally, although the remaining host T cells displayed a proinflammatory phenotype following ABMT, IFNγ, IL-17, and TNFα production by the newly reconstituted donor-derived T cells was significantly lower. Taken together, our data suggest that ABMT restores immune tolerance by renewal and modulation of the Teff cell compartment, leading to a strong reduction in proinflammatory (self antigen-specific) T cell cytokine production. Copyright © 2014 by the American College of Rheumatology.

  12. Percutaneous injection of autologous, culture-expanded mesenchymal stem cells into carpometacarpal hand joints: a case series with an untreated comparison group.

    PubMed

    Centeno, Christopher J; Freeman, Michael D

    2014-03-01

    In the present study, we describe six patients who received autologous mesenchymal stem cell (MSC) therapy for symptomatic carpometacarpal (CMC) joint and hand osteoarthritis (OA). Six patients who received injections of adult autologous culture expanded MSCs in their thumb CMC joints were followed for 1 year posttreatment, and matched with four procedure candidates who remained untreated. We observed positive outcomes in the treatment group for both symptoms and function related to the OA, compared with a reported worsening among the untreated controls. While these results should be interpreted with caution because of the small number of treated subjects and lack of placebo control and randomization, we find sufficient evidence for further investigation of MSC therapy as an alternative to more invasive surgery in patients with OA of the hand.

  13. Repair of large full-thickness cartilage defect by activating endogenous peripheral blood stem cells and autologous periosteum flap transplantation combined with patellofemoral realignment.

    PubMed

    Fu, Wei-Li; Ao, Ying-Fang; Ke, Xiao-Yan; Zheng, Zhuo-Zhao; Gong, Xi; Jiang, Dong; Yu, Jia-Kuo

    2014-03-01

    Minimal-invasive procedure and one-step surgery offer autologous mesenchymal stem cells derived from peripheral blood (PB-MSCs) a promising prospective in the field of cartilage regeneration. We report a case of a 19-year-old male athlete of kickboxing with ICRS grade IV chondral lesions at the 60° region of lateral femoral trochlea, which was repaired by activating endogenous PB-MSCs plus autologous periosteum flap transplantation combined with correcting the patellofemoral malalignment. After a 7.5 year follow-up, the result showed that the patient returned to competitive kickboxing. Second-look under arthroscopy showed a smooth surface at 8 months postoperation. The IKDC 2000 subjective score, Lysholm score and Tegner score were 95, 98 and 9 respectively at the final follow up. CT and MRI evaluations showed a significant improvement compared with those of pre-operation. © 2013.

  14. Outcome of intensive immunosuppression and autologous stem cell transplantation in patients with severe rheumatoid arthritis is associated with the composition of synovial T cell infiltration

    PubMed Central

    Verburg, R; Flierman, R; Sont, J; Ponchel, F; van Dreunen, L; Levarht, E; Welling, M; Toes, R; Isaacs, J; van Laar, J M

    2005-01-01

    Objective: To determine clinical and immunological correlates of high dose chemotherapy (HDC) + autologous stem cell transplantation (ASCT) in patients with severe rheumatoid arthritis (RA), refractory to conventional treatment. Methods: Serial samples of peripheral blood and synovial tissue were obtained from seven patients with RA treated with HDC and autologous peripheral blood grafts enriched for CD34+ cells. Disease activity was assessed with the Disease Activity Score (DAS), serum concentrations of C reactive protein (CRP), and human immunoglobulin (HIg) scans, and the extent of immunoablation was determined by immunophenotyping of peripheral blood mononuclear cells, and immunohistochemistry and double immunofluorescence of synovium. Results: Clinical responders (n = 5) had a larger number of cells at baseline expressing CD3, CD4, CD27, CD45RA, CD45RB, and CD45RO in synovium (p<0.05), higher activity on HIg scans (p = 0.08), and a trend towards higher concentrations of CRP in serum than non-responders (n = 2). Subsequent remissions and relapses in responders paralleled reduction and re-expression, respectively, of T cell markers. A relatively increased expression of CD45RB and CD45RO on synovial CD3+ T cells was seen after HDC + ASCT. No correlations were found between DAS and changes in B cells or macrophage infiltration or synoviocytes. Conclusions: HDC + ASCT results in profound but incomplete immunoablation of both the memory and naïve T cell compartment, which is associated with longlasting clinical responses in most patients. The findings provide strong circumstantial evidence for a role of T cells in established RA, and demonstrate a role for the synovium in post-transplantation T cell reconstitution. PMID:15829573

  15. Clinical outcomes of osteonecrosis of the femoral head after autologous bone marrow stem cell implantation: a meta-analysis of seven case-control studies.

    PubMed

    Yuan, Heng-Feng; Zhang, Jing; Guo, Chang-An; Yan, Zuo-Qin

    2016-02-01

    The purpose of this study was to evaluate the clinical outcomes of osteonecrosis of the femoral head after autologous bone marrow stem cell implantation. We searched the PubMed, Embase and Web of Science databases and included all case-control trials that reported on the clinical outcomes of osteonecrosis progression, incidence of total hip arthroplasty and improvement in Harris hip scores. Overall, seven case-control trials were included. Compared with the controls, patients treated with the bone marrow stem cells implantation treatment showed improved clinical outcomes with delayed osteonecrosis progression (odds ratio = 0.17, 95% CI: 0.09 - 0.32; p <0.001), a lower total hip arthroplasty incidence (odds ratio = 0.30, 95% CI: 0.12 - 0.72; p <0.01) and increased Harris hip scores (mean difference = 4.76, 95% CI: 1.24 - 8.28; p<0.01). The heterogeneity, publication bias, and sensitivity analyses showed no statistical difference significant differences between studies. Thus, our study suggests that autologous bone marrow stem cells implantation has a good therapeutic effect on osteonecrosis of the femoral, resulting in beneficial clinical outcomes. However, trials with larger sample sizes are needed to confirm these findings.

  16. Phase I/II Trial of Autologous Bone Marrow Stem Cell Transplantation with a Three-Dimensional Woven-Fabric Scaffold for Periodontitis

    PubMed Central

    Baba, Shunsuke; Komuro, Akira; Yotsui, Yoritaka; Umeda, Makoto; Shimuzutani, Kimishige; Nakamura, Sayaka

    2016-01-01

    Regenerative medicine is emerging as a promising option, but the potential of autologous stem cells has not been investigated well in clinical settings of periodontal treatment. In this clinical study, we evaluated the safety and efficacy of a new regenerative therapy based on the surgical implantation of autologous mesenchymal stem cells (MSCs) with a biodegradable three-dimensional (3D) woven-fabric composite scaffold and platelet-rich plasma (PRP). Ten patients with periodontitis, who required a surgical procedure for intrabony defects, were enrolled in phase I/II trial. Once MSCs were implanted in each periodontal intrabony defect, the patients were monitored during 36 months for a medical exam including laboratory tests of blood and urine samples, changes in clinical attachment level, pocket depth, and linear bone growth (LBG). All three parameters improved significantly during the entire follow-up period (p < 0.0001), leading to an average LBG of 4.7 mm after 36 months. Clinical mobility measured by Periotest showed a decreasing trend after the surgery. No clinical safety problems attributable to the investigational MSCs were identified. This clinical trial suggests that the stem cell therapy using MSCs-PRP/3D woven-fabric composite scaffold may constitute a novel safe and effective regenerative treatment option for periodontitis. PMID:27990164

  17. Phase I/II Trial of Autologous Bone Marrow Stem Cell Transplantation with a Three-Dimensional Woven-Fabric Scaffold for Periodontitis.

    PubMed

    Baba, Shunsuke; Yamada, Yoichi; Komuro, Akira; Yotsui, Yoritaka; Umeda, Makoto; Shimuzutani, Kimishige; Nakamura, Sayaka

    2016-01-01

    Regenerative medicine is emerging as a promising option, but the potential of autologous stem cells has not been investigated well in clinical settings of periodontal treatment. In this clinical study, we evaluated the safety and efficacy of a new regenerative therapy based on the surgical implantation of autologous mesenchymal stem cells (MSCs) with a biodegradable three-dimensional (3D) woven-fabric composite scaffold and platelet-rich plasma (PRP). Ten patients with periodontitis, who required a surgical procedure for intrabony defects, were enrolled in phase I/II trial. Once MSCs were implanted in each periodontal intrabony defect, the patients were monitored during 36 months for a medical exam including laboratory tests of blood and urine samples, changes in clinical attachment level, pocket depth, and linear bone growth (LBG). All three parameters improved significantly during the entire follow-up period (p < 0.0001), leading to an average LBG of 4.7 mm after 36 months. Clinical mobility measured by Periotest showed a decreasing trend after the surgery. No clinical safety problems attributable to the investigational MSCs were identified. This clinical trial suggests that the stem cell therapy using MSCs-PRP/3D woven-fabric composite scaffold may constitute a novel safe and effective regenerative treatment option for periodontitis.

  18. Human breast adipose‑derived stem cells: characterization and differentiation into mammary gland‑like epithelial cells promoted by autologous activated platelet‑rich plasma.

    PubMed

    Cui, Shi-En; Li, Hong-Mian; Liu, Da-Lie; Nan, Hua; Xu, Kun-Ming; Zhao, Pei-Ran; Liang, Shuang-Wu

    2014-08-01

    Human adipose‑derived stem cells (ASCs) isolated from various body sites have been widely investigated in basic and clinical studies. However, ASCs derived from human breast tissue (hbASCs) have not been extensively investigated. In order to expand our understanding of hbASCs and examine their potential applications in stem cell research and cell‑based therapy, hbASCs were isolated from discarded surgical fat tissue following reduction mammoplasty and a comprehensive characterization of these hbASCs was performed, including analysis of their cellular morphology, growth features, cell surface protein markers and multilineage differentiation capacity. These hbASCs expressed cluster of differentiation (CD)44, CD49d, CD90 and CD105, but did not express CD31 and CD34. Subsequently, the hbASCs were differentiated into adipocytes, osteocytes and chondrocytes in vitro. In order to examine the potential applications of hbASCs in breast reconstruction, an approach to promote in vitro differentiation of hbASCs into mammary gland‑like epithelial cells (MGECs) was developed using activated autologous platelet‑rich plasma (PRP). A proliferation phase and a subsequent morphological conversion phase were observed during this differentiation process. PRP significantly promoted the growth of hbASCs in the proliferation phase and increased the eventual conversion rate of hbASCs into MGECs. Thus, to the best of our knowledge, the present study provided the first comprehensive characterization of hbASCs and validated their multipotency. Furthermore, it was revealed that activated autologous PRP was able to enhance the differentiation efficiency of hbASCs into MGECs. The present study and other studies of hbASCs may aid the development of improved breast reconstruction strategies.

  19. Human breast adipose-derived stem cells transfected with the stromal cell-derived factor-1 receptor CXCR4 exhibit enhanced viability in human autologous free fat grafts.

    PubMed

    Xu, Fang-tian; Li, Hong-mian; Yin, Qing-Shui; Liu, Da-lie; Nan, Hua; Zhao, Pei-ran; Liang, Shuang-wu

    2014-01-01

    The main complication of autologous free fat tissue transplantation is fat resorption and calcification due to the ischemic necrosis of fat. The promotion of transplant neovascularization soon after autologous free fat grafts may reduce these outcomes. In adulthood, stromal cell-derived factor-1 (SDF-1) and its membrane receptor C-X-C chemokine receptor type 4 (CXCR4) are involved in the homing and migration of multiple stem cell types, neovascularization, and cell proliferation. We hypothesized that CXCR4 may improve the long-term survival of free fat tissue transplants by recruiting endothelial progenitor cells (EPCs) and may therefore improve graft revascularization. In this study, we aimed to determine the effect of human breast adipose-derived stem cells (HBASCs) transfected with the CXCR4 gene on the survival rate of human autologous free fat transplants in nude mice. Human breast adipose-derived stem cells (HBASCs) were expanded ex vivo for 3 passages, labeled with green fluorescent protein (GFP) and transfected with CXCR4 or left untransfected. Autologous fat tissues were mixed with the GFP-labeled, CXCR4-transfected HBASCs (group A), GFP-labeled HBASCs (group B), the known vascularization-promoting agent VEGF (group C), or medium (group D) and then injected subcutaneously into 32 nude mice at 4 spots in a random fashion. Six months later, the transplanted tissue volume and histology were evaluated, and neo-vascularization was quantified by counting the capillaries. CXCR4 and SDF-1α mRNA expression in the transplants was determined using real-time quantitative PCR analysis (qPCR). The data revealed that the control (group D) transplant volume survival was 28.3 ± 4.5%. Mixing CXCR4-transfected (group A) and untransfected (group B) HBASCs significantly increased transplant volume survival (79.5 ± 8.3% and 67.2 ± 5.9%, respectively), whereas VEGF-transfected HBASCs (group C) were less effective (41.2 ± 5.1%). Histological analysis revealed that both types

  20. Phase I-II study of high-dose busulfan and cyclophosphamide followed by autologous peripheral blood stem cell transplantation for hematological malignancies: toxicities and hematopoietic recovery.

    PubMed

    Ballester, O F; Agaliotis, D P; Hiemenz, J W; Janssen, W E; Fields, K K; Zorksy, P E; Goldstein, S C; Perkins, J B; Elfenbein, G J

    1996-07-01

    In a phase I-II study, we evaluated toxicities, tolerability, pace of engraftment, and tumor responses to high-dose bulsulfan and cyclophosphamide followed by autologous peripheral blood stem cell transplantation in patients with hematological malignancies. We treated 51 patients with various hematological malignancies involving the bone marrow with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) followed by reinfusion of autologous peripheral blood stem cells. Stem cells were previously collected during hematopoietic recovery after cyclophosphamide (100 mg/kg) and etoposide (600 mg/m2) followed by G-CSF (5 micrograms/kg/day). Neutrophil recovery (>0.5 x 10(9)/I) was rapid in the majority of patients (median 10 days after transplant, range 7-91 days), resulting in a low number of days with severe neutropenia (median 7 days, range 5-85 days) and with fever (median 5 days, range 1-13 days). Platelet recovery, however, was delayed in 60% of patients. There was one acute transplant-related death (2%). Four patients died of late, presumed infections, pulmonary complications (interstitial pneumonia). Tumor responses were documented in a significant proportion of these patients with high-risk hematological malignancies. We conclude that peripheral blood stem cell transplantation results in rapid recovery of neutrophils but variable recovery of platelets after high-dose busulfan and cyclophosphamide, when stem cells are harvested following priming with cyclophosphamide/etoposide and G-CSF. The regimen is well-tolerated with limited non-hematological toxicities and transplant-related mortality. While significant tumor responses were documented in this trial, the ultimate efficacy of the regimen needs to be further defined.

  1. Retinoic acid postconsolidation therapy for high-risk neuroblastoma patients treated with autologous haematopoietic stem cell transplantation.

    PubMed

    Peinemann, Frank; van Dalen, Elvira C; Enk, Heike; Berthold, Frank

    2017-08-25

    Neuroblastoma is a rare malignant disease and mainly affects infants and very young children. The tumours mainly develop in the adrenal medullary tissue, with an abdominal mass as the most common presentation. About 50% of patients have metastatic disease at diagnosis. The high-risk group is characterised by metastasis and other features that increase the risk of an adverse outcome. High-risk patients have a five-year event-free survival of less than 50%. Retinoic acid has been shown to inhibit growth of human neuroblastoma cells and has been considered as a potential candidate for improving the outcome of patients with high-risk neuroblastoma. This review is an update of a previously published Cochrane Review. To evaluate the efficacy and safety of additional retinoic acid as part of a postconsolidation therapy after high-dose chemotherapy (HDCT) followed by autologous haematopoietic stem cell transplantation (HSCT), compared to placebo retinoic acid or to no additional retinoic acid in people with high-risk neuroblastoma (as defined by the International Neuroblastoma Risk Group (INRG) classification system). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2016, Issue 11), MEDLINE in PubMed (1946 to 24 November 2016), and Embase in Ovid (1947 to 24 November 2016). Further searches included trial registries (on 22 December 2016), conference proceedings (on 23 March 2017) and reference lists of recent reviews and relevant studies. We did not apply limits by publication year or languages. Randomised controlled trials (RCTs) evaluating additional retinoic acid after HDCT followed by HSCT for people with high-risk neuroblastoma compared to placebo retinoic acid or to no additional retinoic acid. Primary outcomes were overall survival and treatment-related mortality. Secondary outcomes were progression-free survival, event-free survival, early toxicity, late toxicity, and health-related quality of life. We used standard

  2. Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases

    ClinicalTrials.gov

    2005-06-23

    Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis

  3. Impact of Prophylactic Levofloxacin on Rates of Bloodstream Infection and Fever in Neutropenic Patients with Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation.

    PubMed

    Satlin, Michael J; Vardhana, Santosh; Soave, Rosemary; Shore, Tsiporah B; Mark, Tomer M; Jacobs, Samantha E; Walsh, Thomas J; Gergis, Usama

    2015-10-01

    Few studies have evaluated the role of antibacterial prophylaxis during neutropenia in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (HSCT). At our center, levofloxacin prophylaxis was initiated in June 2006 in patients with myeloma who were undergoing autologous HSCT. We compared the incidence of bloodstream infection (BSI) and fever and neutropenia (FN) within 30 days of transplantation before (January 2003 to May 2006) and after (June 2006 to April 2010) the initiation of levofloxacin prophylaxis in patients undergoing autologous HSCT for myeloma. We also compared rates of BSI and FN during the same time periods in autologous HSCT recipients with lymphoma who did not receive antibacterial prophylaxis during either time period. After the initiation of levofloxacin prophylaxis, the BSI rate decreased from 41.2% (49 of 119) to 14.7% (23 of 156) and the rate of FN decreased from 91.6% to 60.9% in patients with myeloma (P < .001, for each). In contrast, rates of BSI (43.1% versus 47.3%; P = .50) and FN (98.8% versus 97.1%; P = .63) did not change in patients with lymphoma. Levofloxacin prophylaxis was independently associated with decreased odds of BSI (odds ratio, .27; 95% confidence interval, .14 to .51; P < .001) and FN (odds ratio, .18; 95% confidence interval, .09 to .36; P < .001) in multivariate analysis. Patients with myeloma had a nonsignificant increase in the risk of BSI due to levofloxacin-resistant Enterobacteriaceae (5% versus 1%, P = .08) and Clostridium difficile infection (7% versus 3%, P = .12) after the initiation of levofloxacin prophylaxis but did not have higher rates of BSI due to other resistant bacteria. Levofloxacin prophylaxis is associated with decreased risk of BSI and FN in patients with myeloma undergoing autologous HSCT.

  4. Evaluation of a laminin-alginate biomaterial, adipocytes, and adipocyte-derived stem cells interaction in animal autologous fat grafting model using 7-Tesla magnetic resonance imaging.

    PubMed

    Chen, Yo-Shen; Hsueh, Yu-Sheng; Chen, Yen-Yu; Lo, Cheng-Yu; Tai, Hao-Chih; Lin, Feng-Huei

    2017-01-01

    Biomaterials are often added to autologous fat grafts both as supporting matrices for the grafted adipocytes and as cell carrier for adipose-derived stem cells (ADSCs). This in vivo study used an autologous fat graft model to test a lamininalginate biomaterial, adipocytes, and ADSCs in immune-competent rats. We transplanted different combinations of shredded autologous adipose tissue [designated "A" for adipose tissue]), laminin-alginate beads [designated "B" for bead], and ADSCs [designated "C" for cell]) into the backs of 15 Sprague-Dawley rats. Group A received only adipocytes, Group B received only laminin-alginate beads, Group AB received adipocytes mixed with laminin-alginate beads, Group BC received laminin-alginate beads encapsulating ADSCs, and Group ABC received adipocytes and laminin-alginate beads containing ADSCs. Seven-tesla magnetic resonance imaging was used to evaluate the rats at the 1st, 6th, and 12th weeks after transplantation. At the 12th week, the rats were sacrificed and the implanted materials were retrieved for gross examination and histological evaluation. The results based on MRI, gross evaluation, and histological data all showed that implants in Group ABC had better resorption of the biomaterial, improved survival of the grafted adipocytes, and adipogenic differentiation of ADSCs. Volume retention of grafts in Group ABC (89%) was also significantly greater than those in Group A (58%) (p < 0.01). Our findings support that the combination of shredded adipose tissue with ADSCs in laminin-alginate beads provided the best overall outcome.

  5. Transplantation of Reprogrammed Autologous Stem Cells for Chronic Pain and Drug Abuse

    DTIC Science & Technology

    2016-07-01

    dissected medulla by mechanical dissociation . The harvested cells were filtered through a 70-μm nylon mesh (BD Falcon, Bedford, MA, USA) and then...5) were performed by using the same method described for co-cultures of SH-SY5Y cells and hMSCs at identical condition, as shown in Fig. 1a & b... dissociation solution followed by washing once with HBSS buffer. cAMP accumulation in SH-SY5Y cells was assayed by using a LANCE™ cAMP kit (PerkinElmer

  6. Transplantation of Reprogrammed Autologous Stem Cells for Chronic Pain and Drug Abuse

    DTIC Science & Technology

    2013-10-01

    chromaffin-like cells by reprogramming human MSCs (hMSCs) with the extracts of porcine adrenal chromaffin cells. We have harvested bone marrow tissues from...into the spinal subarachnoid space produces antinociceptive effects on both Aδ and C fiber-mediated responses in a thermal pain model of rat and non ...can be used in hundreds of thousands of patients with a wide range of cancer and non -cancer pain states to improve quality of life and save billions

  7. Cytomegalovirus reactivation after autologous stem cell transplantation in myeloma and lymphoma patients: A single-center study

    PubMed Central

    Marchesi, Francesco; Pimpinelli, Fulvia; Gumenyuk, Svitlana; Renzi, Daniela; Palombi, Francesca; Pisani, Francesco; Romano, Atelda; Spadea, Antonio; Papa, Elena; Canfora, Marco; Ensoli, Fabrizio; Mengarelli, Andrea

    2015-01-01

    AIM: To determine the incidence of and the risk factors for cytomegalovirus (CMV) symptomatic infection and end-organ disease after autologous stem cell transplantation (ASCT). METHODS: A total of 327 consecutive non CD34+ selected autografts performed from the Hematology and Stem Cell Transplantation Unit of Regina Elena National Cancer Institute of Rome (Italy) in the period comprised between January 2003 to January 2015, were reviewed. Over the 327 autografts, 201 were performed in patients with multiple myeloma, whereas the remaining 126 in patients affected by non-Hodgkin’s lymphoma and Hodgkin’s lymphoma. The patients who underwent an ASCT for an acute leukemia (n = 20) in the same period were excluded from this analysis. CMV DNA load in the blood has been determined by polymerase-chain reaction in the case of a clinical suspicion of reactivation, therefore, no routine monitoring strategy was adopted. In the presence of signs and symptoms of CMV reactivation an antiviral treatment was performed. RESULTS: Overall, 36 patients (11%) required a specific antiviral treatment for a symptomatic CMV reactivation (n = 32) or an end-organ disease (n = 4). We observed 20 and 16 cases of CMV reactivation among lymphoma (16%) and myeloma patients (8%), respectively. Among cases of end-organ disease, 3 were diagnosed as interstitial pneumonia and one remaining case as hemorrhagic enteritis. All cases of CMV reactivation were observed in IgG seropositive patients, with no documented cases of primary CMV infection. All patients were treated with a specific antiviral therapy, with a global rate of hospitalization of 55%; four patients received intravenous immunoglobulins. Transplant-related mortality was significantly higher in patients who experienced a CMV reactivation (8.4% ± 4.7% vs 1.7% ± 0.8%; P = 0.047). In univariate analysis, a pre-transplant HBcIgG seropositivity, a diagnosis of T-cell non-Hodgkin’s lymphoma and higher median age at transplant were

  8. [Efficacy of autologous peripheral blood stem cell transplantation (auto-PBSCT) on the neuropathic manifestations in POEMS syndrome].

    PubMed

    Gronier, S; Delmont, E; Legros, L; Launay, M; Jeandel, P Y; Fuzibet, J G; Desnuelle, C

    2014-01-01

    POEMS syndrome (polyneuropathy, organomegaly, endocrynopathy, M-protein, and skin changes) is a rare multisystem disease associated with plasma cell dyscrasia. The efficacy of autologous peripheral blood stem cell transplantation (auto-PBSCT) reported in case series has been mainly based on hematologic criteria and clinical recovery of peripheral neuropathy dysfunctions but has not been specifically evaluated. This retrospective study aimed to analyze the efficacy of auto-PBSCT on disability and electrophysiological patterns in patients with POEMS syndrome. Five patients presenting with POEMS syndrome received auto-PBSCT. Disability was evaluated before treatment and at 6 and 12 months using the Overall Neuropathy Limitation Scale (ONLS) and MRC sumscore of 28 muscles. Nerve conduction studies were performed before and one year after treatment, on median, ulnar, fibular and tibial nerves. Mean age was 60.6 years (49-70). Disease duration between first symptoms and auto-PBSCT was 15.4 months (2-33). Before auto-PBSCT, mean ONLS score was 4.2 (1-10) and mean MRC sumscore 115.8/140 (74-140). At M6, mean ONLS score decreased and mean MRC sumscore increased; both were improved in all patients at M12: mean ONLS score 3 (range 0-8) at M6 and 2.2 (range 0-7) at M12; mean MRC sumscore 118/140 (77-140) at M6 and 122.4/140 (80-140) at M12. Significant recovery in electrophysiological patterns was observed in all patients on ulnar and median nerves: before-after treatment differences were observed for motor conduction velocities (34.41 vs. 45.47 m/s; P<0.001), distal CMAP amplitudes (5.04 vs. 5.96 mV; P=0.004), and sensory conduction velocities (43.20 vs. 49.20 m/s; P=0.001). Distal CMAP amplitude remained low in fibular and tibial nerves (0.41 vs. 0.17 mV). Clinical and electrophysiological improvement is obvious in POEMS syndrome peripheral neuropathy within one year after treatment with auto-PBSCT, undoubtedly resulting from extensive remyelinisation and axonal regeneration

  9. Prolonged survival of patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation: the GELTAMO experience.

    PubMed

    Rodríguez, José; Conde, Eulogio; Gutiérrez, Antonio; Arranz, Reyes; Gandarillas, Marcos; Leon, Angel; Ojanguren, Jesus; Sureda, Anna; Carrera, Dolores; Bendandi, Mauricio; Moraleda, Jose; Ribera, Jose Maria; Albo, Carmen; Morales, Alfonso; García, Juan Carlos; Fernández, Pascual; Cañigral, Guillermo; Bergua, Juan; Caballero, María Dolores

    2007-04-01

    Angioimmunoblastic T-cell lymphoma (AIL) is a rare lymphoma with a poor prognosis and no standard treatment. Here, we report our experiences with 19 patients treated with high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) within the GELTAMO co-operative group between 1992 and 2004. The median age at transplantation was 46 yr. Fifteen patients underwent the procedure as front-line therapy and four patients as salvage therapy. Most patients received peripheral stem cells (90%) coupled with BEAM or BEAC as conditioning regimen (79%). A 79% of patients achieved complete response, 5% partial response and 16% failed the procedure. After a median follow-up of 25 months, eight patients died (seven of progressive disease and secondary neoplasia), while actuarial overall survival and progression-free survival at 3 yr was 60% and 55%. Prognostic factors associated with a poor outcome included bone marrow involvement, transplantation in refractory disease state, attributing more than one factor of the age-adjusted-International Prognostic Index, Pretransplant peripheral T-cell lymphoma (PTCL) Score or Prognostic Index for PTCL. More than half of the patients with AIL that display unfavourable prognostic factors at diagnosis or relapse would be expected to be alive and disease-free after 3 yr when treated with HDC/ASCT. Patients who are transplanted in a refractory disease state do not benefit from this procedure.

  10. 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.

  11. Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma.

    PubMed

    Thomas, Alissa A; Abrey, Lauren E; Terziev, Robert; Raizer, Jeffrey; Martinez, Nina L; Forsyth, Peter; Paleologos, Nina; Matasar, Matthew; Sauter, Craig S; Moskowitz, Craig; Nimer, Stephen D; DeAngelis, Lisa M; Kaley, Thomas; Grimm, Sean; Louis, David N; Cairncross, J Gregory; Panageas, Katherine S; Briggs, Samuel; Faivre, Geraldine; Mohile, Nimish A; Mehta, Jayesh; Jonsson, Philip; Chakravarty, Debyani; Gao, Jianjiong; Schultz, Nikolaus; Brennan, Cameron W; Huse, Jason T; Omuro, Antonio

    2017-10-01

    Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are chemotherapy-sensitive tumors with prolonged survival after radiochemotherapy. We report a prospective trial using induction temozolomide (TMZ) followed by myeloablative high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) as a potential strategy to defer radiotherapy. Patients with AO/AOA received 6 cycles of TMZ (200 mg/m2 × 5/28 day). Responding patients were eligible for HDC (thiotepa 250 mg/m2/day × 3 days, then busulfan 3.2 mg/kg/day × 3 days), followed by ASCT. Genomic characterization was performed using next-generation sequencing. Forty-one patients were enrolled; 85% had 1p/19q codeleted tumors. After induction, 26 patients were eligible for HDC-ASCT and 21 agreed to proceed. There were no unexpected adverse events or toxic deaths. After median follow-up of 66 months, 2-year progression-free survival (PFS) for transplanted patients was 86%, 5-year PFS 60%, and no patient has died. Among all 1p/19q codeleted patients (N = 33), 5-year PFS was 50% and 5-year overall survival (OS) 93%, with median time to radiotherapy not reached. Next-generation sequencing disclosed typical oligodendroglioma-related mutations, including IDH1, TERT, CIC, and FUBP1 mutations in 1p/19q codeleted patients, and glioblastoma-like signatures in 1p/19q intact patients. Aside from IDH1, potentially oncogenic/actionable mutations were variable, depicting wide molecular heterogeneity within oligodendroglial tumors. TMZ followed by HDC-ASCT can be safely administered to patients with newly diagnosed 1p/19q codeleted AO. This strategy was associated with promising PFS and OS, suggesting that a chemotherapy-based approach may delay the need for radiotherapy and radiation-related toxicities. Raw data for further genomic and meta-analyses are publicly available at http://cbioportal.org/study?id=odg_msk_2017, accessed 6 January 2017. NCT00588523.

  12. Role of Salvage Radiation Therapy for Patients With Relapsed or Refractory Hodgkin Lymphoma Who Failed Autologous Stem Cell Transplant

    SciTech Connect

    Goda, Jayant S.; Massey, Christine; Kuruvilla, John; Gospodarowicz, Mary K.; Wells, Woodrow; Hodgson, David C.; Sun, Alexander; Keating, Armand; Crump, Michael; Tsang, Richard W.

    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 plus 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.

  13. Autologous Stem Cell Transplantation for Follicular Lymphoma: Favorable Long-Term Survival Irrespective of Pretransplantation Rituximab Exposure.

    PubMed

    Jiménez-Ubieto, Ana; Grande, Carlos; Caballero, Dolores; Yáñez, Lucrecia; Novelli, Silvana; Hernández-Garcia, Miguel Teodoro; Manzanares, María; Arranz, Reyes; Ferreiro, José Javier; Bobillo, Sabella; Mercadal, Santiago; Galeo, Andrea; López Jiménez, Javier; Moraleda, José María; Vallejo, Carlos; Albo, Carmen; Pérez, Elena; Marrero, Carmen; Magnano, Laura; Palomera, Luis; Jarque, Isidro; Martínez-Sánchez, Pilar; Martín, Alejandro; Coria, Erika; López-Guillermo, Armando; Salar, Antonio; Lahuerta, Juan José

    2017-10-01

    High-dose chemotherapy supported by autologous stem cell transplantation (HDT/ASCT) has contributed to modify the natural history of follicular lymphoma (FL); however, an overall survival (OS) benefit has been demonstrated at relapse only after a rituximab-free chemotherapy regimen. A total of 655 patients with FL were reported to the Spanish GELTAMO (Grupo Español de Linfomas y Trasplantes de Médula Ósea) registry and underwent first ASCT between 1989 and 2007. A total of 203 patients underwent ASCT in first complete response (CR1), 174 in second complete response (CR2), 28 in third complete response (CR3), 140 in first partial response (PR1), 81 in subsequent PR, and 29 with resistant/refractory disease; 184 patients received rituximab before ASCT. With a median follow-up of 12 years from ASCT, median progression-free survival (PFS) and overall survival (OS) were 9.7 and 21.3 years, respectively. Actuarial 12-year PFS and OS were 63% (95% confidence interval [CI], 58%-68%) and 73% (95% CI, 68%-78%), respectively, for patients in CR (with a plateau in the curve beyond 15.9 years), 25% (95% CI, 19%-28%) and 49% (95% CI 42%-56%), respectively, for patients in PR, and 23% (95% CI, 8%-48%) and 28% (95% CI, 9%-45%), respectively, for patients with resistant/refractory disease (P < .001). In patients who received rituximab before ASCT, the estimated 9-year PFS and OS from ASCT were 59.5% (95% CI, 51%-67%) and 75% (95% CI, 68%-83%), respectively. Interestingly, for patients who underwent transplantation in CR ≥2 or PR ≥2 who had received rituximab before ASCT (n = 90), 9-year PFS and OS were 61% (95% CI, 51%-73%) and 75% (95% CI, 65%-80%), respectively, with no relapses occurring beyond 5.1 years after ASCT. The cumulative incidence of second malignancies in the global series was 6.7% at 5 years and 12.8% at 10 years. This analysis strongly suggests that ASCT is a potentially curative option for eligible patients with FL. In the setting of relapse, it is

  14. Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis.

    PubMed

    McCarthy, Philip L; Holstein, Sarah A; Petrucci, Maria Teresa; Richardson, Paul G; Hulin, Cyrille; Tosi, Patrizia; Bringhen, Sara; Musto, Pellegrino; Anderson, Kenneth C; Caillot, Denis; Gay, Francesca; Moreau, Philippe; Marit, Gerald; Jung, Sin-Ho; Yu, Zhinuan; Winograd, Benjamin; Knight, Robert D; Palumbo, Antonio; Attal, Michel

    2017-10-10

    Purpose Lenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized controlled trials (RCTs) of patients with newly diagnosed multiple myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting. Patients and Methods The meta-analysis was conducted using primary-source patient-level data and documentation from three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Myélome 2005-02) that met the following prespecified inclusion criteria: an RCT in patients with NDMM receiving ASCT followed by lenalidomide maintenance versus placebo or observation with patient-level data available and achieved database lock for primary efficacy analysis. Results Overall, 1,208 patients were included in the meta-analysis (605 patients in the lenalidomide maintenance group and 603 in the placebo or observation group). The median PFS was 52.8 months for the lenalidomide group and 23.5 months for the placebo or observation group (hazard ratio, 0.48; 95% CI, 0.41 to 0.55). At a median follow-up time of 79.5 months for all surviving patients, the median OS had not been reached for the lenalidomide maintenance group, whereas it was 86.0 months for the placebo or observation group (hazard ratio, 0.75; 95% CI, 0.63 to 0.90; P = .001). The cumulative incidence rate of a second primary malignancy before disease progression was higher with lenalidomide maintenance versus placebo or observation, whereas the cumulative incidence rates of progression, death, or death as a result of myeloma were all higher with placebo or observation versus lenalidomide maintenance. Conclusion This meta

  15. Technological progress and challenges towards cGMP manufacturing of human pluripotent stem cells based therapeutic products for allogeneic and autologous cell therapies.

    PubMed

    Abbasalizadeh, Saeed; Baharvand, Hossein

    2013-12-01

    Recent technological advances in the generation, characterization, and bioprocessing of human pluripotent stem cells (hPSCs) have created new hope for their use as a source for production of cell-based therapeutic products. To date, a few clinical trials that have used therapeutic cells derived from hESCs have been approved by the Food and Drug Administration (FDA), but numerous new hPSC-based cell therapy products are under various stages of development in cell therapy-specialized companies and their future market is estimated to be very promising. However, the multitude of critical challenges regarding different aspects of hPSC-based therapeutic product manufacturing and their therapies have made progress for the introduction of new products and clinical applications very slow. These challenges include scientific, technological, clinical, policy, and financial aspects. The technological aspects of manufacturing hPSC-based therapeutic products for allogeneic and autologous cell therapies according to good manufacturing practice (cGMP) quality requirements is one of the most important challenging and emerging topics in the development of new hPSCs for clinical use. In this review, we describe main critical challenges and highlight a series of technological advances in all aspects of hPSC-based therapeutic product manufacturing including clinical grade cell line development, large-scale banking, upstream processing, downstream processing, and quality assessment of final cell therapeutic products that have brought hPSCs closer to clinical application and commercial cGMP manufacturing.

  16. What's It Like to Donate Stem Cells?

    MedlinePlus

    ... for Cancer What’s It Like to Donate Stem Cells? People usually volunteer to donate stem cells for ... autologous transplant. If you want to donate stem cells for someone else People who want to donate ...