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Sample records for reduced intensity transplant

  1. Antifungal prophylaxis following reduced-intensity stem cell transplantation.

    PubMed

    Kami, M; Murashige, N; Tanaka, Y; Narimatsu, H

    2006-12-01

    Reduced-intensity stem cell transplantation (RIST) has been developed to be a novel curative option for advanced hematologic diseases. Its minimal toxicity allows for transplantation in patients with advanced age or with organ dysfunction. Young patients without comorbidity can undergo RIST as outpatients. However, fungal infection remains an important complication in RIST. Given the poor prognosis of fungal infection, prophylaxis is critical in its management. The prophylactic strategy is recently changing with the development of RIST. Hospital equipment is important for fungal prophylaxis; however, the median day for the development of fungal infection is day 100, when most RIST patients are followed as outpatients. The focus of fungal management after RIST needs to shift from in-hospital equipment to oral antifungals. Various antifungals have recently been developed and introduced for clinical use. A major change in antifungal management will probably occur within several years.

  2. Outcome after Transplantation According to Reduced-Intensity Conditioning Regimen in Patients Undergoing Transplantation for Myelofibrosis.

    PubMed

    Robin, Marie; Porcher, Raphael; Wolschke, Christine; Sicre de Fontbrune, Flore; Alchalby, Haefaa; Christopeit, Maximilian; Cassinat, Bruno; Zabelina, Tatjana; Peffault de Latour, Régis; Ayuk, Francis; Socié, Gérard; Kröger, Nicolaus

    2016-07-01

    Allogeneic hematopoietic stem cell transplantation remains the sole curative option for myelofibrosis. Many transplantation recipients receive a reduced-intensity conditioning (RIC) regimen owing to age or comorbidities; however, there is little published evidence to guide the choice of RIC regimen. In this study, we compared outcomes in patients who received 1 of 2 frequently used RIC regimens for patients with myelofibrosis: fludarabine-busulfan (FB) and fludarabine-melphalan (FM). A total of 160 patients underwent a RIC allograft procedure (FB group, n = 105; FM group, n = 55). We have developed a complex statistical model involving weighting and adjustment to permit comparison between these 2 groups. After weighting, the incidence of acute graft-versus-host disease (GVHD) was 62% in the FM group and 31% in the FB group (P = .001), and the corresponding incidence of chronic GVHD was 49% and 53%, respectively. The 7-year progression-free survival was were 52% in the FM group versus 33% in the FB group, and the 7-year overall survival rate 52% in the FM group versus 59% in the FB group. Nonrelapse mortality (NRM) was 43% in the FM group and 31% in the FB group. Multivariable analyses revealed no significant differences in PFS between the 2 groups; however, the relapse rate was significantly lower in the FM group (hazard ratio, 9.21; P = .008), whereas a trend toward reduced NRM was seen in the FB group (hazard ratio, 0.51; P = .068). In conclusion, both regimens appear to be efficient in mediating disease control and can be used to successfully condition patients with myelofibrosis. The FM regimen appears to induce more NRM than the FB regimen, but with augmented control of disease, leading to comparable overall survival rates for both regimens. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  3. A comparative study of reduced dose alemtuzumab in matched unrelated donor and related donor reduced intensity transplants.

    PubMed

    Jardine, Laura; Publicover, Amy; Bigley, Venetia; Hale, Geoff; Pearce, Kim; Dickinson, Anne; Jackson, Graham; Collin, Matthew

    2015-03-01

    In vivo T cell depletion with 100 mg alemtuzumab prevents graft-versus-host disease (GVHD) in reduced intensity conditioned transplants but is associated with delayed immune reconstitution, a higher risk of infection and relapse. De-escalation studies have shown that a reduced dose of 30 mg is as effective as 100 mg in preventing GVHD in matched related donor (MRD) transplants. Dose reduction in matched unrelated donor (MUD) transplants is feasible but the comparative efficacy of alemtuzumab in this setting is not known and opinions vary widely concerning the optimal level of GVHD prophylaxis that should be achieved. Through retrospective analysis we made an objective comparison of MUD transplants receiving an empirically reduced dose of 60 mg, with MRD transplants receiving a 30 mg dose. We observed proportionate levels of alemtuzumab according to dose but an inverse relationship with body surface area particularly in MRD transplants. MUD transplants experienced more acute and chronic GVHD, higher T cell chimerism, more sustained use of ciclosporin and less need for donor lymphocyte infusion than MRD transplants. Thus, doubling the dose of alemtuzumab to 60 mg did not provide equivalent prevention of GVHD after MUD transplant although there was no difference in non-relapse mortality or survival compared with MRD transplants.

  4. Successful pregnancy and childbirth after reduced intensity conditioning and partially HLA-mismatched bone marrow transplantation

    PubMed Central

    Fuchs, Ephraim J.; Luznik, Leo; Bolaños-Meade, Javier; Miller, Carole B.; Brodsky, Robert A.; Ambinder, Richard F.; Jones, Richard J.

    2011-01-01

    Ovarian failure and permanent infertility occur in nearly all women of childbearing age who are treated with myeloablative conditioning and allogeneic stem cell transplantation (SCT).1,2 Recently, highly immunosuppressive but reduced intensity conditioning regimens have enabled the engraftment of allogeneic cells and their resulting graft-versus-tumor effects.3–5 However, the effect of reduced intensity allogeneic stem cell transplantation, or RIST, on the reproductive function of young women has not been examined. Here we report on two women who had successful pregnancies and childbirths after RIST for lymphoma. PMID:19139737

  5. Fludarabine-based reduced intensity conditioning transplants have a higher incidence of cytomegalovirus reactivation compared with myeloablative transplants.

    PubMed

    George, B; Kerridge, I; Gilroy, N; Huang, G; Hertzberg, M; Gottlieb, D; Bradstock, K

    2010-05-01

    Two hundred and ten adult CMV seropositive patients undergoing myeloablative conditioning (MAC) [n=127] or reduced intensity conditioning (RIC) [n=83] transplants (HCT) were serially monitored for CMV reactivation and disease, using a qualitative polymerase chain reaction (PCR) followed by quantitation with pp65 antigen or quantitative PCR. CMV reactivation occurred in 53 RIC (63.9%) and 61 MAC (48%; P=0.03) transplants at a median of 47 days (range: 24-1977). Risk factors identified included acute GVHD (P=0.001), RIC regimen (P=0.03), unrelated donor (P=0.02), use of anti-thymocyte globulin/alemtuzumb (P=0.02) and use of bone marrow in MAC transplants (P=0.011). On multivariate analysis, RIC transplants and acute GVHD remained independent predictors. Treatment with antiviral drugs resulted in CMV negativity rates of 86.8% in MAC and 88.6% in RIC transplants. CMV disease occurred in 10.8% of RIC and 4.7% of MAC transplants (P=0.15). At a median follow-up of 26 months (range: 3-88), 48.1% of RIC and 50.3% of MAC transplants are alive. The higher incidence of CMV reactivation among RIC transplants suggests the need for novel prophylactic or pre-emptive strategies in this high-risk group of patients.

  6. Bone Marrow or Peripheral Blood for Reduced-Intensity Conditioning Unrelated Donor Transplantation

    PubMed Central

    Eapen, Mary; Logan, Brent R.; Horowitz, Mary M.; Zhong, Xiaobo; Perales, Miguel-Angel; Lee, Stephanie J.; Rocha, Vanderson; Soiffer, Robert J.; Champlin, Richard E.

    2015-01-01

    Purpose There have been no randomized trials that have compared peripheral blood (PB) with bone marrow (BM) grafts in the setting of reduced-intensity conditioning (RIC) transplantations for hematologic malignancy. Because immune modulation plays a significant role in sustaining clinical remission after RIC, we hypothesize that higher graft-versus-host disease (GVHD) associated with PB transplantation may offer a survival advantage. Patients and Methods The primary outcome evaluated was overall survival. Cox regression models were built to study outcomes after transplantation of PB (n = 887) relative to BM (n = 219) for patients with acute myeloid leukemia, myelodysplastic syndrome, or non-Hodgkin lymphoma, the three most common indications for unrelated RIC transplantation. Transplantations were performed in the United States between 2000 and 2008. Conditioning regimens consisted of an alkylating agent and fludarabine, and GVHD prophylaxis involved a calcineurin inhibitor (CNI) with either methotrexate (MTX) or mycophenolate mofetil (MMF). Results After adjusting for age, performance score, donor-recipient HLA-match, disease, and disease status at transplantation (factors associated with overall survival), there were no significant differences in 5-year rates of survival after transplantation of PB compared with BM: 34% versus 38% with CNI-MTX and 27% versus 20% with CNI-MMF GVHD prophylaxis. Conclusion Survival after transplantation of PB and BM are comparable in the setting of nonirradiation RIC regimens for hematologic malignancy. The effect of GVHD prophylaxis on survival merits further evaluation. PMID:25534391

  7. Bone marrow or peripheral blood for reduced-intensity conditioning unrelated donor transplantation.

    PubMed

    Eapen, Mary; Logan, Brent R; Horowitz, Mary M; Zhong, Xiaobo; Perales, Miguel-Angel; Lee, Stephanie J; Rocha, Vanderson; Soiffer, Robert J; Champlin, Richard E

    2015-02-01

    There have been no randomized trials that have compared peripheral blood (PB) with bone marrow (BM) grafts in the setting of reduced-intensity conditioning (RIC) transplantations for hematologic malignancy. Because immune modulation plays a significant role in sustaining clinical remission after RIC, we hypothesize that higher graft-versus-host disease (GVHD) associated with PB transplantation may offer a survival advantage. The primary outcome evaluated was overall survival. Cox regression models were built to study outcomes after transplantation of PB (n = 887) relative to BM (n = 219) for patients with acute myeloid leukemia, myelodysplastic syndrome, or non-Hodgkin lymphoma, the three most common indications for unrelated RIC transplantation. Transplantations were performed in the United States between 2000 and 2008. Conditioning regimens consisted of an alkylating agent and fludarabine, and GVHD prophylaxis involved a calcineurin inhibitor (CNI) with either methotrexate (MTX) or mycophenolate mofetil (MMF). After adjusting for age, performance score, donor-recipient HLA-match, disease, and disease status at transplantation (factors associated with overall survival), there were no significant differences in 5-year rates of survival after transplantation of PB compared with BM: 34% versus 38% with CNI-MTX and 27% versus 20% with CNI-MMF GVHD prophylaxis. Survival after transplantation of PB and BM are comparable in the setting of nonirradiation RIC regimens for hematologic malignancy. The effect of GVHD prophylaxis on survival merits further evaluation. © 2014 by American Society of Clinical Oncology.

  8. Reduced-intensity hematopoietic stem cell transplantation (RIST) for solid malignancies.

    PubMed

    Kami, Masahiro; Makimoto, Atsushi; Heike, Yuji; Takaue, Yoichi

    2004-12-01

    Reduced intensity stem cell transplantation (RIST) is a new approach of stem cell transplantation, which has shown promising features as reported in multiple phase I and II studies. Elderly patients, who are not eligible for conventional myeloablative hematopoietic stem cell transplantation (HSCT), are now treatable with RIST. It has also reduced regimen-related toxicity and provided better prognosis in short-term follow-up than conventional HSCT. Among solid tumors, metastatic renal cell carcinoma was found to respond well to RIST. Clinical studies are currently being conducted to evaluate the efficacy of RIST in other types of solid tumors. However, the mechanism of graft-versus-host disease (GVHD) and graft-versus-tumor (GVT) effects remains unclear. More knowledge on the mechanism is crucial to enhance the antitumor effect and to improve the prognosis further.

  9. Reduced-intensity transplantation for lymphomas using haploidentical related donors vs HLA-matched unrelated donors

    PubMed Central

    Kanate, Abraham S.; Mussetti, Alberto; Kharfan-Dabaja, Mohamed A.; Ahn, Kwang W.; DiGilio, Alyssa; Beitinjaneh, Amer; Chhabra, Saurabh; Fenske, Timothy S.; Freytes, Cesar; Gale, Robert Peter; Ganguly, Siddhartha; Hertzberg, Mark; Klyuchnikov, Evgeny; Lazarus, Hillard M.; Olsson, Richard; Perales, Miguel-Angel; Rezvani, Andrew; Riches, Marcie; Saad, Ayman; Slavin, Shimon; Smith, Sonali M.; Sureda, Anna; Yared, Jean; Ciurea, Stefan; Armand, Philippe; Salit, Rachel; Bolaños-Meade, Javier

    2016-01-01

    We evaluated 917 adult lymphoma patients who received haploidentical (n = 185) or HLA-matched unrelated donor (URD) transplantation either with (n = 241) or without antithymocyte globulin (ATG; n = 491) following reduced-intensity conditioning regimens. Haploidentical recipients received posttransplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, whereas URD recipients received calcineurin inhibitor-based prophylaxis. Median follow-up of survivors was 3 years. The 100-day cumulative incidence of grade III-IV acute GVHD on univariate analysis was 8%, 12%, and 17% in the haploidentical, URD without ATG, and URD with ATG groups, respectively (P = .44). Corresponding 1-year rates of chronic GVHD on univariate analysis were 13%, 51%, and 33%, respectively (P < .001). On multivariate analysis, grade III-IV acute GVHD was higher in URD without ATG (P = .001), as well as URD with ATG (P = .01), relative to haploidentical transplants. Similarly, relative to haploidentical transplants, risk of chronic GVHD was higher in URD without ATG and URD with ATG (P < .0001). Cumulative incidence of relapse/progression at 3 years was 36%, 28%, and 36% in the haploidentical, URD without ATG, and URD with ATG groups, respectively (P = .07). Corresponding 3-year overall survival (OS) was 60%, 62%, and 50% in the 3 groups, respectively, with multivariate analysis showing no survival difference between URD without ATG (P = .21) or URD with ATG (P = .16), relative to haploidentical transplants. Multivariate analysis showed no difference between the 3 groups in terms of nonrelapse mortality (NRM), relapse/progression, and progression-free survival (PFS). These data suggest that reduced-intensity conditioning haploidentical transplantation with posttransplant cyclophosphamide does not compromise early survival outcomes compared with matched URD transplantation, and is associated with significantly reduced risk of chronic GVHD. PMID:26670632

  10. Improved intensive care unit survival for critically ill allogeneic haematopoietic stem cell transplant recipients following reduced intensity conditioning

    PubMed Central

    Townsend, William M; Holroyd, Ailsa; Pearce, Rachel; Mackinnon, Stephen; Naik, Prakesh; Goldstone, Anthony H; Linch, David C; Peggs, Karl S; Thomson, Kirsty J; Singer, Mervyn; Howell, David C J; Morris, Emma C

    2013-01-01

    The use of allogeneic haematopoietic stem cell transplantation (Allo-HSCT) is a standard treatment option for many patients with haematological malignancies. Historically, patients requiring intensive care unit (ICU) admission for transplant-related toxicities have fared extremely poorly, with high ICU mortality rates. Little is known about the impact of reduced intensity Allo-HSCT conditioning regimens in older patients on the ICU and subsequent long-term outcomes. A retrospective analysis of data collected from 164 consecutive Allo-HSCT recipients admitted to ICU for a total of 213 admissions, at a single centre over an 11·5-year study period was performed. Follow-up was recorded until 31 March 2011. Autologous HSCT recipients were excluded. In this study we report favourable ICU survival following Allo-HSCT and, for the first time, demonstrate significantly better survival for patients who underwent Allo-HSCT with reduced intensity conditioning compared to those treated with myeloablative conditioning regimens. In addition, we identified the need for ventilation (invasive or non-invasive) as an independently significant adverse factor affecting short-term ICU outcome. For patients surviving ICU admission, subsequent long-term overall survival was excellent; 61% and 51% at 1 and 5 years, respectively. Reduced intensity Allo-HSCT patients admitted to ICU with critical illness have improved survival compared to myeloablative Allo-HSCT recipients. PMID:23496350

  11. Reduced-intensity conditioning allogeneic hematopoietic-cell transplantation for older patients with acute myeloid leukemia

    PubMed Central

    Goyal, Gaurav; Gundabolu, Krishna; Vallabhajosyula, Saraschandra; Silberstein, Peter T.; Bhatt, Vijaya Raj

    2016-01-01

    Elderly patients (>60 years) with acute myeloid leukemia have a poor prognosis with a chemotherapy-alone approach. Allogeneic hematopoietic-cell transplantation (HCT) can improve overall survival (OS). However, myeloablative regimens can have unacceptably high transplant-related mortality (TRM) in an unselected group of older patients. Reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning regimens preserve the graft-versus-leukemia effects but reduce TRM. NMA regimens result in minimal cytopenia and may not require stem cell support for restoring hematopoiesis. RIC regimens, intermediate in intensity between NMA and myeloablative regimens, can cause prolonged myelosuppresion and usually require stem cell support. A few retrospective and prospective studies suggest a possibility of lower risk of relapse with myeloablative HCT in fit older patients with lower HCT comorbidity index; however, RIC and NMA HCTs have an important role in less-fit patients and those with significant comorbidities because of lower TRM. Whether early tapering of immunosuppression, monitoring of minimal residual disease, and post-transplant maintenance therapy can improve the outcomes of RIC and NMA HCT in elderly patients will require prospective trials. PMID:27247754

  12. A survey on patient perception of reduced-intensity transplantation in adults with sickle cell disease.

    PubMed

    Chakrabarti, S; Bareford, D

    2007-04-01

    The development of reduced-intensity conditioning (RIC) and the success of BMT for paediatric sickle cell disease (SCD) have raised the possibility of revisiting this prospect in adults as well. In a chronic debilitating disorder managed with supportive therapy, the patients' perception is critical in the advancement of any potential curative therapy. To explore this aspect, we undertook a questionnaire-based survey on 30 adults with SCD. Sixty two per cent of the patients were ready to accept a transplant-related mortality (TRM) >10%; 30% of them a TRM >30%. A risk of graft failure (GF) >10% was acceptable to 64%, with a risk >30% acceptable to 41%. Infertility was acceptable to only 50%. Chronic graft-versus-host disease (GVHD) was unacceptable to the majority (80%). Seventy six per cent% of patients had a full sibling and 60% were willing to participate in a clinical trial of RIC transplantation. This survey suggests that the majority of adults with SCD might be willing to consider a curative option such as RIC transplantation even with a high TRM or GF. The major concerns relate to chronic GVHD and infertility. There is an urgent need to explore RIC transplants in SCD patients within the framework of a clinical trial, considering patient perception regarding cure and complications.

  13. Feasibility of early tapering of cyclosporine following reduced-intensity stem cell transplantation for advanced hematologic or solid malignancies.

    PubMed

    Hori, Akiko; Kami, Masahiro; Ohnishi, Mutsuko; Murashige, Naoko; Kojima, Rie; Takaue, Yoichi

    2005-07-01

    Although some researchers have reported that early tapering of cyclosporine is feasible and beneficial to augment graft-versus-leukemia effects after conventional stem-cell transplantation, there is little information on the feasibility of this strategy following reduced-intensity stem cell transplantation (RIST). We summarized outcomes of 17 patients who underwent early tapering of cyclosporine following RIST from HLA-identical siblings.

  14. Pushing the envelope—nonmyeloablative and reduced intensity preparative regimens for allogeneic hematopoietic transplantation

    PubMed Central

    Pingali, SR; Champlin, RE

    2016-01-01

    Allogeneic hematopoietic cell transplantation (HCT) was originally developed to allow delivery of myeloablative doses of chemotherapy and radiotherapy. With better understanding of disease pathophysiology, the graft vs malignancy (GVM) effect of allogeneic hematopoietic transplantation and toxicities associated with myeloablative conditioning (MAC) regimens, the focus shifted to developing less toxic conditioning regimens to reduce treatment-related morbidity without compromising survival. Although HCT with MAC is preferred to reduced intensity conditioning (RIC) for most patients ≤ 60 years with AML/myelodysplastic syndrome and ALL, RIC and nonmyeloablative (NMA) regimens allow HCT for many otherwise ineligible patients. Reduced intensity preparative regimens have produced high rates of PFS for diagnoses, which are highly sensitive to GVM. Relapse of the malignancy is the major cause of treatment failure with RIC/NMA HCT. Incorporation of novel agents like bortezomib or lenalidomide, addition of cellular immunotherapy and use of targeted radiation therapies could further improve outcome. In this review, we discuss commonly used RIC/NMA regimens and promising novel regimens. PMID:25985053

  15. Graft failure following reduced-intensity cord blood transplantation for adult patients.

    PubMed

    Narimatsu, Hiroto; Kami, Masahiro; Miyakoshi, Shigesaburo; Murashige, Naoko; Yuji, Koichiro; Hamaki, Tamae; Masuoka, Kazuhiro; Kusumi, Eiji; Kishi, Yukiko; Matsumura, Tomoko; Wake, Atsushi; Morinaga, Shinichi; Kanda, Yoshinobu; Taniguchi, Shuichi

    2006-01-01

    We reviewed the medical records of 123 adult reduced-intensity cord blood transplantation (RI-CBT) recipients to investigate the clinical features of graft failure after RI-CBT. Nine (7.3%) had graft failure, and were classified as graft rejection rather than primary graft failure; they showed peripheral cytopenia with complete loss of donor-type haematopoiesis, implying destruction of donor cells by immunological mechanisms rather than poor graft function. Three of them died of bacterial or fungal infection during neutropenia. Two recovered autologous haematopoiesis. The remaining four patients underwent a second RI-CBT and developed severe regimen-related toxicities. One died of pneumonia on day 8, and the other three achieved engraftment. Two of them died of transplant-related mortality, and the other survived without disease progression for 9.0 months after the second RI-CBT. In total, seven of the nine patients with graft failure died. The median survival of those with graft failure was 3.8 months (range, 0.9-15.4). Graft failure is a serious complication of RI-CBT. As host T cells cannot completely be eliminated by reduced-intensity preparative regimens, we need to be aware of the difficulty in differentiating graft rejection from other causes of graft failure following RI-CBT. Further studies are warranted to establish optimal diagnostic and treatment strategies.

  16. Current status of reduced-intensity allogeneic stem cell transplantation using alternative donors.

    PubMed

    Chen, Y-B; Spitzer, T R

    2008-01-01

    The optimal donor for a patient undergoing reduced-intensity stem cell transplantation remains a human leukocyte antigen (HLA)-matched relative. Alternative donors such as matched unrelated donors (MUDs), mismatched related donors (haploidentical), or unrelated umbilical cord blood (UCB) units have emerged as options as well. The most experience thus far has been with MUD donors, mostly attributed to the development of allele-specific DNA-based HLA-typing methods. The biggest drawback remains the significant delay needed to locate a donor. Haploidentical donors exist for almost all patients, and offer the convenience of a living related donor. However, significant rates of graft-versus-host disease (GVHD) and other toxicities continue to complicate such HLA mismatching. UCB is the most recent option for source of stem cells. Frozen cord blood units can be acquired almost immediately and are able to safely traverse 1 or 2-HLA antigen mismatch barriers. The experience with UCB has been limited by the low cell dose, although recent innovations are attempting to overcome this. In this review, we summarize the current experience and knowledge with alternative donors as stem cell sources for reduced-intensity transplantation.

  17. Early central nervous system complications after reduced-intensity stem cell transplantation.

    PubMed

    Kishi, Yukiko; Miyakoshi, Shigesaburo; Kami, Masahiro; Ikeda, Masayuki; Katayama, Yuta; Murashige, Naoko; Kusumi, Eiji; Yuji, Koichiro; Kobayashi, Kazuhiko; Kato, Daisuke; Hamaki, Tamae; Matsumura, Tomoko; Kim, Sung-Won; Morinaga, Shinichi; Mori, Shinichiro; Kanemaru, Mineo; Hayashi, Tatsuyuki; Takaue, Yoichi; Taniguchi, Shuichi

    2004-08-01

    To investigate clinical characteristics of early central nervous system (CNS) complications after reduced-intensity stem cell transplantation (RIST), we reviewed the medical records of 232 patients who had undergone RIST for hematologic diseases at our institutions between September 1999 and June 2003. All patients had received purine analog-based preparative regimens. Stem cell sources comprised granulocyte colony-stimulating factor-mobilized blood from HLA-identical or 1 locus-mismatched related donors (n = 151), unrelated bone marrow (n = 44), or unrelated cord blood (n = 37). Graft-versus-host disease prophylaxis incorporated cyclosporine with or without methotrexate. Diagnosis of CNS complications was based on clinical, radiologic, and microbiological findings. CNS complications occurred in 18 patients (7.8%), with a median onset of 22 days, and were infectious (n = 1), metabolic (n = 15), or cerebrovascular (n = 2). Symptoms included seizures (n = 7), visual disturbance (n = 2), headache (n = 8), nausea (n = 8), vomiting (n = 6), impaired consciousness (n = 16), and hemiparesis (n = 3). Complications improved promptly in 10 patients, and 8 patients died without improvement within 30 days. Multivariate analysis with logistic regression identified umbilical cord blood transplantation as a significant risk factor for early CNS complications (odds ratio, 14.5; 95% confidence interval, 3.7-56.9; P <.0001). CNS complications are a significant problem after RIST, particularly with umbilical cord blood. Limbic encephalopathy is an unrecognized subtype of neurotoxicity after umbilical cord blood transplantation.

  18. Disseminated tuberculosis following reduced-intensity cord blood transplantation for adult patients with hematological diseases.

    PubMed

    Maeda, T; Kusumi, E; Kami, M; Kawabata, M; Le Pavoux, A; Hara, S; Chizuka, A; Murashige, N; Tanimoto, T E; Matsumura, T; Yuji, K; Yuji, Ko; Wake, A; Miyakoshi, S; Morinaga, S; Taniguchi, S

    2005-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-SCT) recipients are prone to infections. The incidences of mycobacterial infections after allo-SCT in several case series vary from less than 0.1-5.5%. However, no study has been published on tuberculosis following unrelated cord blood transplantation (UCBT). We retrospectively reviewed medical records of 113 adult patients with a median age of 54 years who underwent reduced-intensity UCBT (RI-UCBT) at Toranomon Hospital from March 2002 to May 2004. Mycobacterium tuberculosis infections were diagnosed in three patients (2.7%), of these two patients developed primary infection and one patient developed reactivation of latent tuberculosis. The interval between RI-UCBT and the diagnosis of tuberculosis was 34, 41 and 61 days. All the patients had disseminated disease at diagnosis. Histological examination showed the lack of granuloma in caseous necrosis. Combination antituberculous treatments showed limited efficacy, and two patients died immediately after diagnosis. M. tuberculosis caused life-threatening illness, rapidly progressing in RI-UCBT recipients. The lack of granuloma in caseous necrosis suggests the impaired T-cell function in early post transplant phase of RI-UCBT. We should consider M. tuberculosis in the differential diagnoses of fever of unknown source after RI-UCBT.

  19. Cytomegalovirus infections following umbilical cord blood transplantation using reduced intensity conditioning regimens for adult patients.

    PubMed

    Matsumura, Tomoko; Narimatsu, Hiroto; Kami, Masahiro; Yuji, Koichiro; Kusumi, Eiji; Hori, Akiko; Murashige, Naoko; Tanaka, Yuji; Masuoka, Kazuhiro; Wake, Atsushi; Miyakoshi, Shigesaburo; Kanda, Yoshinobu; Taniguchi, Shuichi

    2007-05-01

    Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem cell transplantation (Allo-HSCT); however, we have little information on the clinical features of CMV reactivation after cord blood transplantation using reduced-intensity regimens (RI-CBT) for adults. We reviewed medical records of 140 patients who underwent RI-CBT at Toranomon Hospital between January 2002 and March 2005. All the patients were monitored for CMV-antigenemia weekly, and, if turned positive, received preemptive foscarnet or ganciclovir. Seventy-seven patients developed positive antigenemia at a median onset of day 35 (range, 4-92) after transplant. Median of the maximal number of CMV pp65-positive cells per 50,000 cells was 22 (range, 1-1806). CMV disease developed in 22 patients on a median of day 35 (range, 15-106); 21 had enterocolitis and 1 had adrenalitis. CMV antigenemia had not been detected in 2 patients, when CMV disease was diagnosed. CMV disease was successfully treated using ganciclovir or foscarnet in 14 patients. The other 8 patients died without improvement of CMV disease. In multivariate analysis, grade II-IV acute graft-versus-host disease was a risk factor of CMV disease (relative risk 3.48, 95% confidential interval 1.47-8.23). CMV reactivation and disease develop early after RI-CBT. CMV enterocolitis may be a common complication after RI-CBT.

  20. Reduced intensity allogeneic hematopoietic transplantation is an established standard of care for treatment of older patients with acute myeloid leukemia.

    PubMed

    Champlin, Richard

    2013-09-01

    Allogeneic hematopoietic transplantation, an effective treatment for acute myeloid leukemia (AML), was originally developed as a means of delivering high-dose myeloablative chemotherapy or radiation. The transplant itself allowed stem cells to restore normal hematopoiesis and immunity. Yet older people were denied this treatment because the myeloablative therapy has considerable toxicity. More recently, reduced-intensity conditioning has been used, allowing older or medically infirm patients to receive a transplant. This review explores the feasibility of transplant as a standard of care for older patients. Copyright © 2013. Published by Elsevier Ltd.

  1. Reduced-intensity conditioning allogeneic stem cell transplantation in malignant lymphoma: current status

    PubMed Central

    Zhang, Le; Zhang, Yi-Zhuo

    2013-01-01

    Allogeneic stem cell transplantation (allo-SCT) is a potential cure for patients with malignant lymphoma that is based on the graft-versus-lymphoma (GVL) effect. Myeloablative conditioning allo-SCT is associated with high mortality and morbidity, particularly in patients older than 45 years, heavily pretreated patients (prior hematopoietic stem cell transplantation or more than two lines of conventional chemotherapy) or patients affected by other comorbidities. Therefore, conventional allo-SCT is restricted to younger patients (<50 to 55 years) in good physical condition. Over the last decade, allo-SCT with reduced-intensity conditioning (RIC-allo-SCT) has been increasingly used to treat patients with lymphoma. This treatment is associated with lower toxicity and substantial decrease in the incidence of transplant-related mortality, and has the potential to lead to long-term remissions. Therefore, patients who are not suitable to undergo conventional allo-SCT can benefit from the potentially curative GVL effects of allo-SCT. Although RIC-allo-SCT has improved the survival of lymphoma patients, high post-transplant relapse rates or disease progression mainly results in treatment failure. Thus, further improvement is clearly needed. The role and timing of RIC-allo-SCT in the treatment of lymphoma remains unclear. Therefore, more prospective studies should clarify the effectiveness of this method. In this article, we review the recent literature on RIC-allo-SCT as a treatment for major lymphoma subtypes. Areas that require further investigation in the context of clinical trials are also highlighted. PMID:23691438

  2. Stem cell transplantation after reduced-intensity conditioning for sickle cell disease.

    PubMed

    Matthes-Martin, Susanne; Lawitschka, Anita; Fritsch, Gerhard; Lion, Thomas; Grimm, Brigitte; Breuer, Sabine; Boztug, Heidrun; Karlhuber, Susanne; Holter, Wolfgang; Peters, Christina; Minkov, Milen

    2013-04-01

    Sickle cell disease (SCD) is still associated with substantial morbidity and reduced life expectancy. Disease-related mortality rises to 14% in adolescents and young adults. Overall and disease-free survival following haematopoietic stem cell transplantation (HSCT) is 90% and 95%, respectively. To reduce transplant-associated late effects, the feasibility of a highly immunosuppressive reduced-intensity conditioning (RIC) regimen was explored in children with SCD and a matched sibling donor. Eight patients (median age, 9 yr) and symptomatic SCD were included. The conditioning regimen consisted of fludarabine, melphalan and either thiotepa or total lymphoid irradiation plus antithymocyte globuline or alemtuzumab. The graft was bone marrow in seven and cord blood in one case. The conditioning regimen was well tolerated and no severe infectious complications occurred. All patients displayed mixed chimaerism on day +28. After a median follow-up of 4 yr, 3/8 patients have mixed leucocyte chimaerism and 8/8 patients have 100% donor erythropoiesis. HSCT from matched sibling donors following a RIC regimen was well tolerated and resulted in cure in all patients studied. If confirmed in larger patient cohorts, these observations will have important implications for the indications of HSCT in children with SCD.

  3. Prognostic Value of the Hematopoietic Cell Transplantation Comorbidity Index for Patients Undergoing Reduced-Intensity Conditioning Cord Blood Transplantation.

    PubMed

    Salit, Rachel B; Oliver, David C; Delaney, Colleen; Sorror, Mohamed L; Milano, Filippo

    2017-04-01

    The Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) has been validated as a tool for evaluating the risk of treatment-related mortality (TRM) in HLA-matched sibling and matched unrelated donor bone marrow and peripheral blood stem cell transplantation patients. However, the role of the HCT-CI after cord blood transplantation (CBT) has not been fully investigated. In this analysis, we sought to evaluate the predictive value of the HCT-CI in patients undergoing reduced-intensity conditioning (RIC) CBT. Between 2006 and 2013, HCT-CI scores were prospectively tabulated for patients with hematologic malignancies sequentially enrolled on multicenter RIC CBT studies coordinated by the Fred Hutchinson Cancer Research Center: 151 patients with acute myeloid leukemia/myelodysplastic syndrome (n = 101), chronic myeloid leukemia (n = 3), acute lymphocytic leukemia (n = 24), non-Hodgkin lymphoma (n = 8), Hodgkin lymphoma (n = 3), and other hematologic malignancies (n = 12) underwent RIC CBT and were included. Two patients received a single CBT and the remaining 149 received a double CBT. All patients received cyclosporine and mycophenolate mofetil for graft-versus-host disease prophylaxis. Median HCT-CI for the whole group was 3 (range, 0 to 8). Using the HCT-CI categories of low (0), intermediate (1 or 2), and high risk (>3), there was no significant difference in TRM between the 3 groups. However, when the patients were divided into 2 groups, HCT-CI ≤ 3 or > 3, the incidence of TRM at 3 years after transplantation was 26% (95% confidence interval [CI], 17 to 36) in the HCT-CI ≤ 3 group versus 50% (95% CI, 30 to 67) in the HCT-CI > 3 group (P = .01). Overall survival for patients with HCT-CI ≤ 3 was 40% (95% CI, 27 to 51) versus 29% in patients with HCT-CI >3 (95% CI, 12 to 48) (P = .08). Our study demonstrates that HCT-CI score > 3 is associated with an increased risk of TRM at 3 years after

  4. Reduced intensity allogeneic hematopoietic stem cell transplantion for MDS using tacrolimus/sirolimus-based GVHD prophylaxis

    PubMed Central

    Nakamura, Ryotaro; Palmer, Joycelynne M.; O'Donnell, Margaret R.; Stiller, Tracey; Thomas, Sandra H.; Chao, Joseph; Alvarnas, Joseph; Parker, Pablo M.; Pullarkat, Vinod; Maegawa, Rodrigo; Stein, Anthony S.; Snyder, David S.; Bhatia, Ravi; Chang, Karen; Wang, Shirong; Cai, Ji-Lian; Senitzer, David; Forman, Stephen J.

    2012-01-01

    We report a consecutive series of 59 patients with MDS who underwent reduced-intensity hematopoietic stem cell transplantation (RI-HSCT) with fludarabine/melphalan conditioning and tacrolimus/sirolimus-based GVHD prophylaxis. Two-year OS, EFS, and relapse incidences were 75.1%, 65.2%, and 20.9%, respectively. The cumulative incidence of non-relapse mortality at 100 days, 1 year, and 2 years was 3.4%, 8.5%, and 10.5%, respectively. The incidence of grade II-IV acute GVHD was 35.4%; grade III-IV was 18.6%. Forty of 55 evaluable patients developed chronic GVHD, 35 extensive grade. This RI-HSCT protocol produces encouraging outcomes in MDS patients, and tacrolimus/sirolimus-based GVHD prophylaxis may contribute to that promising result. PMID:22677229

  5. Intestinal thrombotic microangiopathy following reduced-intensity umbilical cord blood transplantation.

    PubMed

    Narimatsu, H; Kami, M; Hara, S; Matsumura, T; Miyakoshi, S; Kusumi, E; Kakugawa, Y; Kishi, Y; Murashige, N; Yuji, K; Masuoka, K; Yoneyama, A; Wake, A; Morinaga, S; Kanda, Y; Taniguchi, S

    2005-09-01

    Thrombotic microangiopathy (TMA) is a significant complication after hematopoietic stem-cell transplantation (HSCT); however, there is little information on it following reduced-intensity cord blood transplantation (RI-CBT). We reviewed the medical records of 123 adult patients who received RI-CBT at Toranomon Hospital between January 2002 and August 2004. TMA was diagnosed in seven patients based on intestinal biopsy (n = 6) or autopsy results (n = 1). While these patients showed some clinical symptoms such as diarrhea and/or abdominal pain, mental status alterations or neurological disorders were not observed in any of them. Laboratory results were mostly normal at the onset of TMA; >2% fragmented erythrocytes (n = 1), <10 mg/dl haptoglobin (n = 1), and >200 IU/dl lactic dehydrogenase (LD) (n = 4). On endoscopic examination, TMA lesions, consisting of ulcers, erosions, and diffuse exfoliation, were distributed spottily from terminal ileum to rectum. Intestinal graft-versus-host disease (GVHD) and cytomegalovirus (CMV) colitis were confirmed in five and four patients, respectively. With therapeutic measures including supportive care (n = 4), fresh frozen plasma (n = 1), and a reduction of immunosuppressive agents (n = 1), TMA improved in four patients. The present study demonstrates that intestinal TMA is a significant complication after RI-CBT. Since conventional diagnostic criteria can overlook TMA, its diagnosis requires careful examination of the gastrointestinal tract using endoscopy with biopsy.

  6. Reduced-intensity unrelated cord blood transplantation for patients with advanced malignant lymphoma.

    PubMed

    Yuji, Koichiro; Miyakoshi, Shigesaburo; Kato, Daisuke; Miura, Yuji; Myojo, Tomohiro; Murashige, Naoko; Kishi, Yukiko; Kobayashi, Kazuhiro; Kusumi, Eiji; Narimatsu, Hiroto; Hamaki, Tamae; Matsumura, Tomoko; Kami, Masahiro; Fukuda, Takahiro; Masuo, Shigeru; Masuoka, Kazuhiro; Wake, Atsushi; Ueyama, Junichi; Yoneyama, Akiko; Miyamoto, Ko; Nagoshi, Haruhisa; Matsuzaki, Michio; Morinaga, Shinichi; Muto, Yoshitomo; Takeue, Yoichi; Taniguchi, Shuichi

    2005-04-01

    We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor.

  7. Invasive fungal infection following reduced-intensity cord blood transplantation for adult patients with hematologic diseases.

    PubMed

    Miyakoshi, Shigesaburo; Kusumi, Eiji; Matsumura, Tomoko; Hori, Akiko; Murashige, Naoko; Hamaki, Tamae; Yuji, Koichiro; Uchida, Naoyuki; Masuoka, Kazuhiro; Wake, Atsushi; Kanda, Yoshinobu; Kami, Masahiro; Tanaka, Yuji; Taniguchi, Shuichi

    2007-07-01

    Invasive fungal infection (IFI) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT); however, we have little information on its clinical features after reduced intensity cord blood transplantation (RICBT) for adults. We reviewed medical records of 128 patients who underwent RICBT at Toranomon Hospital between March 2002 and November 2005. Most of the patients received purine-analogbased preparative regimens. Graft-versus-host disease (GVHD) prophylaxis was a continuous infusion of either tacrolimus 0.03 mg/kg or cyclosporine 3 mg/kg. IFI was diagnosed according to the established EORTC/NIH-MSG criteria. IFI was diagnosed in 14 patients. Thirteen of the 14 had probable invasive pulmonary aspergillosis and the other had fungemia resulting from Trichosporon spp. Median onset of IFI was day 20 (range: 1-82), and no patients developed IFI after day 100. Three-year cumulative incidence of IA was 10.2%. Four of the 13 patients with invasive aspergillosis (IA) developed grade II-IV acute GVHD, and their IA was diagnosed before the onset of acute GVHD. The mortality rate of IFI was 86%. Multivariate analysis revealed that the use of prednisolone >0.2 mg/kg (relative risk 7.97, 95% confidence interval 2.24-28.4, P = .0014) was a significant risk factor for IA. This study suggests that IFI is an important cause of deaths after RICBT, and effective strategies are warranted to prevent IFI.

  8. Achieving stringent CR is essential before reduced-intensity conditioning allogeneic hematopoietic cell transplantation in AML.

    PubMed

    Ustun, C; Wiseman, A C; Defor, T E; Yohe, S; Linden, M A; Oran, B; Burke, M; Warlick, E; Miller, J S; Weisdorf, D

    2013-11-01

    Reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (allo-HCT) can cure patients with AML in CR. However, relapse after RIC allo-HCT may indicate heterogeneity in the stringency of CR. Strict definition of CR requires no evidence of leukemia by both morphologic and flow cytometric criteria. We re-evaluated 85 AML patients receiving RIC allo-HCT in CR to test if a strict definition of CR had direct implications for the outcome. These patients had leukemia immunophenotype documented at diagnosis and analyzed at allo-HCT. Eight (9.4%) had persistent leukemia by flow cytometric criteria at allo-HCT. The patients with immunophenotypic persistent leukemia had a significantly increased relapse (hazard ratio (HR): 3.7; 95% confidence interval (CI): 1.3-10.3, P=0.01) and decreased survival (HR: 2.9; 95% CI: 1.3-6.4, P<0.01) versus 77 patients in CR by both morphology and flow cytometry. However, the pre-allo-HCT bone marrow (BM) blast count (that is, 0-4%) was not significantly associated with risks of relapse or survival. These data indicate the presence of leukemic cells, but not the BM blast count affects survival. A strict morphologic and clinical lab flow cytometric definition of CR predicts outcomes after RIC allo-HCT, and therefore is critical to achieve at transplantation.

  9. Bloodstream infection after umbilical cord blood transplantation using reduced-intensity stem cell transplantation for adult patients.

    PubMed

    Narimatsu, Hiroto; Matsumura, Tomoko; Kami, Masahiro; Miyakoshi, Shigesaburo; Kusumi, Eiji; Takagi, Shinsuke; Miura, Yuji; Kato, Daisuke; Inokuchi, Chiho; Myojo, Tomohiro; Kishi, Yukiko; Murashige, Naoko; Yuji, Koichiro; Masuoka, Kazuhiro; Yoneyama, Akiko; Wake, Atsushi; Morinaga, Shinichi; Kanda, Yoshinobu; Taniguchi, Shuichi

    2005-06-01

    Bloodstream infection (BSI) is a significant problem after cord blood transplantation (CBT). However, little information has been reported on BSI after reduced-intensity CBT (RI-CBT). We retrospectively reviewed the medical records of 102 patients. The median age of the patients was 55 years (range, 17-79 years). Preparative regimens comprised fludarabine 125 to 150 mg/m 2 , melphalan 80 to 140 mg/m 2 , or busulfan 8 mg/kg and total body irradiation 2 to 8 Gy. Prophylaxis against graft-versus-host disease comprised cyclosporin or tacrolimus. BSI developed within 100 days of RI-CBT in 32 patients. The cumulative incidence of BSI was 25% at day 30 and 32% at day 100. The median onset was day 15 (range, 1-98 days). Causative organisms included Pseudomonas aeruginosa (n = 12), Staphylococcus epidermidis (n = 11), Staphylococcus aureus (n = 6), Enterococcus faecium (n = 4), Enterococcus faecalis (n = 4), Stenotrophomonas maltophilia (n = 4), and others (n = 7). Of the 32 patients with BSI, 25 (84%) died within 100 days after RI-CBT. BSI was the direct cause of death in 8 patients (25%). Univariate analysis failed to identify any significant risk factors. BSI clearly represents a significant and fatal complication after RI-CBT. Further studies are warranted to determine clinical characteristics, identify patients at high risk of BSI, and establish therapeutic strategies.

  10. Hepatic injury following reduced intensity unrelated cord blood transplantation for adult patients with hematological diseases.

    PubMed

    Kusumi, Eiji; Kami, Masahiro; Kanda, Yoshinobu; Murashige, Naoko; Seki, Kunihiko; Fujiwara, Masayo; Koyama, Rikako; Komatsu, Tsunehiko; Hori, Akiko; Tanaka, Yuji; Yuji, Koichiro; Matsumura, Tomoko; Masuoka, Kazuhiro; Wake, Atsushi; Miyakoshi, Shigesaburo; Taniguchi, Shuichi

    2006-12-01

    Liver injury is a common complication in allogeneic hematopoietic stem cell transplantation. Its major causes comprise graft-versus-host disease (GVHD), infection, and toxicities of preparative regimens and immunosuppressants; however, we have little information on liver injuries after reduced intensity cord blood transplantation (RICBT). We reviewed medical records of 104 recipients who underwent RICBT between March 2002 and May 2004 at Toranomon Hospital. Preparative regimen and GVHD prophylaxis comprised fludarabine/melphalan/total body irradiation and cyclosporine or tacrolimus. We assessed the etiology of liver injuries based on the clinical presentation, laboratory results, comorbid events, and imaging studies in 85 patients who achieved primary engraftment. The severity of liver dysfunction was assessed according to the National Cancer Institute Common Toxicity Criteria version 2.0. Hyperbilirubinemia was graded according to a report by Hogan et al (Blood. 2004;103:78-84). Moderate to very severe liver injuries were observed in 36 patients. Their causes included cholestatic liver disease (CLD) related to GVHD or sepsis (n = 15), GVHD (n = 7), cholangitis lenta (n = 5), and others (n = 9). Median onsets of CLD, GVHD, and cholangitis lenta were days 37, 40, and 22, respectively. Frequencies of grade 3-4 alanine aminotransferase elevation were comparable across the 3 types of hepatic injuries. Serum gamma-glutamil transpeptidase was not elevated in any patients with cholangitis lenta, whereas 27% and 40% of patients with CLD and GVHD, respectively, developed grade 3-4 gamma-glutamil transpeptidase elevation. Multivariate analysis identified 2 risk factors for hyperbilirubinemia; grade II-IV acute GVHD (relative risk, 2.23; 95% confidential interval, 1.11-4.47; P = .024) and blood stream infection (relative risk, 3.77; 95% confidential interval, 1.91-7.44; P = .00013). In conclusion, the present study has demonstrated that the hepatic injuries are significant

  11. Effect of postremission therapy before reduced-intensity conditioning allogeneic transplantation for acute myeloid leukemia in first complete remission.

    PubMed

    Warlick, Erica D; Paulson, Kristjan; Brazauskas, Ruta; Zhong, Xiaobo; Miller, Alan M; Camitta, Bruce M; George, Biju; Savani, Bipin N; Ustun, Celalettin; Marks, David I; Waller, Edmund K; Baron, Frédéric; Freytes, César O; Socie, Gérard; Akpek, Gorgun; Schouten, Harry C; Lazarus, Hillard M; Horwitz, Edwin M; Koreth, John; Cahn, Jean-Yves; Bornhauser, Martin; Seftel, Matthew; Cairo, Mitchell S; Laughlin, Mary J; Sabloff, Mitchell; Ringdén, Olle; Gale, Robert Peter; Kamble, Rammurti T; Vij, Ravi; Gergis, Usama; Mathews, Vikram; Saber, Wael; Chen, Yi-Bin; Liesveld, Jane L; Cutler, Corey S; Ghobadi, Armin; Uy, Geoffrey L; Eapen, Mary; Weisdorf, Daniel J; Litzow, Mark R

    2014-02-01

    The impact of pretransplant (hematopoietic cell transplantation [HCT]) cytarabine consolidation therapy on post-HCT outcomes has yet to be evaluated after reduced-intensity or nonmyeloablative conditioning. We analyzed 604 adults with acute myeloid leukemia in first complete remission (CR1) reported to the Center for International Blood and Marrow Transplant Research who received a reduced-intensity or nonmyeloablative conditioning HCT from an HLA-identical sibling, HLA-matched unrelated donor, or umbilical cord blood donor from 2000 to 2010. We compared transplant outcomes based on exposure to cytarabine postremission consolidation. Three-year survival rates were 36% (95% confidence interval [CI], 29% to 43%) in the no consolidation arm and 42% (95% CI, 37% to 47%) in the cytarabine consolidation arm (P = .16). Disease-free survival was 34% (95% CI, 27% to 41%) and 41% (95% CI, 35% to 46%; P = .15), respectively. Three-year cumulative incidences of relapse were 37% (95% CI, 30% to 44%) and 38% (95% CI, 33% to 43%), respectively (P = .80). Multivariate regression confirmed no effect of consolidation on relapse, disease-free survival, and survival. Before reduced-intensity or nonmyeloablative conditioning HCT, these data suggest pre-HCT consolidation cytarabine does not significantly alter outcomes and support prompt transition to transplant as soon as morphologic CR1 is attained. If HCT is delayed while identifying a donor, our data suggest that consolidation does not increase transplant treatment-related mortality and is reasonable if required.

  12. Infused total nucleated cell dose is a better predictor of transplant outcomes than CD34+ cell number in reduced-intensity mobilized peripheral blood allogeneic hematopoietic cell transplantation.

    PubMed

    Martin, Paul S; Li, Shuli; Nikiforow, Sarah; Alyea, Edwin P; Antin, Joseph H; Armand, Philippe; Cutler, Corey S; Ho, Vincent T; Kekre, Natasha; Koreth, John; Luckey, C John; Ritz, Jerome; Soiffer, Robert J

    2016-04-01

    Mobilized peripheral blood is the most common graft source for allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning. In assessing the effect of donor cell dose and graft composition on major transplant outcomes in the reduced-intensity setting, prior studies focused primarily on CD34(+)cell dose and reported conflicting results, especially in relation to survival end-points. While the impact of total nucleated cell dose has been less frequently evaluated, available studies suggest higher total nucleated cell dose is associated with improved survival outcomes in the reduced-intensity setting. In order to further explore the relationship between CD34(+)cell dose and total nucleated cell dose on reduced-intensity transplant outcomes, we analyzed the effect of donor graft dose and composition on outcomes of 705 patients with hematologic malignancies who underwent reduced-intensity peripheral blood stem cell transplantation at the Dana Farber Cancer Institute from 2000 to 2010. By multivariable analysis we found that higher total nucleated cell dose (top quartile; ≥10.8 × 10(10)cells) was associated with improved overall survival [HR 0.69 (0.54-0.88),P=0.0028] and progression-free survival [HR 0.68 (0.54-0.85),P=0.0006]. Higher total nucleated cell dose was independently associated with decreased relapse [HR 0.66 (0.51-0.85),P=0.0012] and increased incidence of chronic graft-versus-host disease [HR 1.4 (1.12-1.77),P=0.0032]. In contrast, higher doses of CD34(+)cells (top quartile; ≥10.9 × 10(6)/kg) had no significant effect on graft-versus-host disease or survival outcomes. These data suggest total nucleated cell dose is a more relevant prognostic variable for reduced-intensity transplant outcomes than the more commonly studied CD34(+)cell dose.

  13. [Chronic active Epstein-Barr virus infection treated with reduced intensity stem cell transplantation].

    PubMed

    Sakata, Naoki; Sato, Emiko; Sawada, Akihisa; Yasui, Masahiro; Inoue, Masami; Kawa, Keisei

    2004-05-01

    A 31-year-old woman had been suffering from fever and a sore throat since January 1999, and had a left neck lymphadenopathy in December 1999. Pathological findings of the biopsied lymphnode suggested malignant lymphoma. She was finally diagnosed as having a chronic active Epstein-Barr virus(EBV) infection because of abnormal antibody titers against EBV antigens and an increased EBV load in her peripheral blood. After receiving chemotherapy consisting of CHOP and high dose cytarabine, the amount of the EBV genome decreased below the detection limit before BMT. Therefore, instead of a conventional myeloablative transplant, we performed BMT using reduced-intensity conditioning regimens consisting of fludarabine and melphalan from an HLA-identical sibling donor. After 14 months, the patient remained in complete remission. Menstruation occurred on day 83 following BMT, and the serum level of LH and FSH on day 316 were within normal range. Under these circumstances, RIST seems to be one of the curative treatments for the patients with CAEBV with minimal late side effects.

  14. Reduced dose of foscarnet as preemptive therapy for cytomegalovirus infection following reduced-intensity cord blood transplantation.

    PubMed

    Narimatsu, H; Kami, M; Kato, D; Matsumura, T; Murashige, N; Kusumi, E; Yuji, K; Hori, A; Shibata, T; Masuoka, K; Wake, A; Miyakoshi, S; Morinaga, S; Taniguchi, S

    2007-03-01

    Although foscarnet is a promising alternative for the treatment of cytomegalovirus (CMV) infection, its toxicity can be significant in patients with advanced age. We retrospectively reviewed medical records of 123 patients (median age of 55; range, 17-79) who received reduced-intensity cord blood transplantation (RI-CBT). Patients preemptively received reduced-dose foscarnet 30 mg/kg twice daily when CMV antigenemia exceeded 10/50,000. Sixty-three patients developed CMV antigenemia on a median of day 34, and 29 received foscarnet preemptively. The median level of CMV antigenemia at the initiation of foscarnet was 30. Median duration of foscarnet administration was 24 days. Adverse effects included electrolyte abnormalities (n=19), renal impairment (n=13), and skin eruption requiring discontinuation of foscarnet (n=1). Preemptive therapy of foscarnet was completed in 18 patients. Seven patients died during foscarnet use without developing CMV disease. The remaining 3 developed CMV enterocolitis 5, 14, and 17 days after initiation of foscarnet. All of them were successfully treated with ganciclovir or foscarnet. Reduced dose of foscarnet is beneficial to control CMV reactivation following RI-CBT; however, it has considerable toxicities in RI-CBT recipients with advanced age. Further studies are warranted to minimize toxicities and identify optimal dosages.

  15. Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation

    PubMed Central

    Sobecks Ronald, M; Tao, Wang; Medhat, Askar; Gallagher Meighan, M; Michael, Haagenson; Stephen, Spellman; Marcelo, Fernandez-Vina; Karl-Johan, Malmberg; Carlheinz, Muller; Minoo, Battiwalla; James, Gajewski; Verneris Michael, R; Olle, Ringden; Marino Susana, R; Stella, Davies; Jason, Dehn; Martin, Bornhäuser; Yoshihiro, Inamoto; Ann, Woolfrey; Peter, Shaw; Marilyn, Pollack; Daniel, Weisdorf; Jeffrey, Miller; Hurley Carolyn, K; Lee Stephanie, J; Hsu Katharine, C

    2015-01-01

    Natural killer (NK) cells are regulated killer immunoglobulin-like receptor (KIR) interactions with HLA class I ligands. Several models of NK reactivity have been associated with improved outcomes following myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute myeloid leukemia (AML, n=612) lacking ≥1 KIR ligands experienced higher grade III–IV acute graft-vs.-host disease (GvHD) (HR 1.6, 95%CI 1.16–2.28, p=0.005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II–IV (HR 1.4, p=0.002) and III–IV acute GvHD (HR 1.5, p=0.01) compared to HLA-C2+patients. AML patients with KIR2DS1+, HLA-C2 homozygous donors had greater treatment-related mortality compared to others (HR 2.4, 95%CI 1.4–4.2, p=0.002), but did not experience lower relapse. There were no significant associations with outcomes for AML when assessing donor activating KIRs or centromeric KIR content, nor for any donor-recipient KIR-HLA assessments in patients with myelodysplastic syndrome (n=297). KIR-HLA combinations in RIC-URD HCT recapitulate some but not all KIR-HLA effects observed in myeloablative HCT. PMID:25960307

  16. Donor Chimerism Early after Reduced-intensity Conditioning Hematopoietic Stem Cell Transplantation Predicts Relapse and Survival

    PubMed Central

    Koreth, John; Kim, Haesook T.; Nikiforow, Sarah; Milford, Edgar L.; Armand, Philippe; Cutler, Corey; Glotzbecker, Brett; Ho, Vincent T.; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome; Alyea, Edwin P.

    2015-01-01

    The impact of early donor cell chimerism on outcomes of T-replete reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) is ill-defined. We evaluated day 30 (D30) and 100 (D100) total donor cell chimerism after RIC HSCT undertaken between 2002 and 2010 at our institution, excluding patients who died or relapsed before D30. When available, donor T-cell chimerism was also assessed. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), relapse and non-relapse mortality (NRM). 688 patients with hematologic malignancies (48% myeloid; 52% lymphoid) and a median age of 57 years (range, 18-74) undergoing RIC HSCT with T-replete donor grafts (97% peripheral blood; 92% HLA-matched) and median follow-up of 58.2 months (range, 12.6-120.7) were evaluated. In multivariable analysis total donor cell and T-cell chimerism at D30 and D100 each predicted RIC HSCT outcomes, with D100 total donor cell chimerism most predictive. D100 total donor cell chimerism <90% was associated with increased relapse (HR 2.54, 95% CI 1.83-3.51, p<0.0001), impaired PFS (HR 2.01, 95% CI 1.53-2.65, p<0.0001) and worse OS (1.50, 95% CI 1.11-2.04, p=0.009), but not NRM (HR 0.76; 95% CI 0.44-2.27, p=0.33). There was no additional utility of incorporating sustained D30-D100 total donor cell chimerism, or T-cell chimerism. Low donor chimerism early after RIC HSCT is an independent risk factor for relapse and impaired survival. Donor chimerism assessment early after RIC HSCT can prognosticate for long-term outcomes and help identify high-risk patient cohorts that may benefit from additional therapeutic interventions. PMID:24907627

  17. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    PubMed

    Scott, Bart L; Pasquini, Marcelo C; Logan, Brent R; Wu, Juan; Devine, Steven M; Porter, David L; Maziarz, Richard T; Warlick, Erica D; Fernandez, Hugo F; Alyea, Edwin P; Hamadani, Mehdi; Bashey, Asad; Giralt, Sergio; Geller, Nancy L; Leifer, Eric; Le-Rademacher, Jennifer; Mendizabal, Adam M; Horowitz, Mary M; Deeg, H Joachim; Horwitz, Mitchell E

    2017-04-10

    Purpose The optimal regimen intensity before allogeneic hematopoietic cell transplantation (HCT) is unknown. We hypothesized that lower treatment-related mortality (TRM) with reduced-intensity conditioning (RIC) would result in improved overall survival (OS) compared with myeloablative conditioning (MAC). To test this hypothesis, we performed a phase III randomized trial comparing MAC with RIC in patients with acute myeloid leukemia or myelodysplastic syndromes. Patients and Methods Patients age 18 to 65 years with HCT comorbidity index ≤ 4 and < 5% marrow myeloblasts pre-HCT were randomly assigned to receive MAC (n = 135) or RIC (n = 137) followed by HCT from HLA-matched related or unrelated donors. The primary end point was OS 18 months post-random assignment based on an intent-to-treat analysis. Secondary end points included relapse-free survival (RFS) and TRM. Results Planned enrollment was 356 patients; accrual ceased at 272 because of high relapse incidence with RIC versus MAC (48.3%; 95% CI, 39.6% to 56.4% and 13.5%; 95% CI, 8.3% to 19.8%, respectively; P < .001). At 18 months, OS for patients in the RIC arm was 67.7% (95% CI, 59.1% to 74.9%) versus 77.5% (95% CI, 69.4% to 83.7%) for those in the MAC arm (difference, 9.8%; 95% CI, -0.8% to 20.3%; P = .07). TRM with RIC was 4.4% (95% CI, 1.8% to 8.9%) versus 15.8% (95% CI, 10.2% to 22.5%) with MAC ( P = .002). RFS with RIC was 47.3% (95% CI, 38.7% to 55.4%) versus 67.8% (95% CI, 59.1% to 75%) with MAC ( P < .01). Conclusion OS was higher with MAC, but this was not statistically significant. RIC resulted in lower TRM but higher relapse rates compared with MAC, with a statistically significant advantage in RFS with MAC. These data support the use of MAC as the standard of care for fit patients with acute myeloid leukemia or myelodysplastic syndromes.

  18. Autologous or Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation for Chemotherapy-Sensitive Mantle-Cell Lymphoma: Analysis of Transplantation Timing and Modality

    PubMed Central

    Fenske, Timothy S.; Zhang, Mei-Jie; Carreras, Jeanette; Ayala, Ernesto; Burns, Linda J.; Cashen, Amanda; Costa, Luciano J.; Freytes, César O.; Gale, Robert P.; Hamadani, Mehdi; Holmberg, Leona A.; Inwards, David J.; Lazarus, Hillard M.; Maziarz, Richard T.; Munker, Reinhold; Perales, Miguel-Angel; Rizzieri, David A.; Schouten, Harry C.; Smith, Sonali M.; Waller, Edmund K.; Wirk, Baldeep M.; Laport, Ginna G.; Maloney, David G.; Montoto, Silvia; Hari, Parameswaran N.

    2014-01-01

    Purpose To examine the outcomes of patients with chemotherapy-sensitive mantle-cell lymphoma (MCL) following a first hematopoietic stem-cell transplantation (HCT), comparing outcomes with autologous (auto) versus reduced-intensity conditioning allogeneic (RIC allo) HCT and with transplantation applied at different times in the disease course. Patients and Methods In all, 519 patients who received transplantations between 1996 and 2007 and were reported to the Center for International Blood and Marrow Transplant Research were analyzed. The early transplantation cohort was defined as those patients in first partial or complete remission with no more than two lines of chemotherapy. The late transplantation cohort was defined as all the remaining patients. Results Auto-HCT and RIC allo-HCT resulted in similar overall survival from transplantation for both the early (at 5 years: 61% auto-HCT v 62% RIC allo-HCT; P = .951) and late cohorts (at 5 years: 44% auto-HCT v 31% RIC allo-HCT; P = .202). In both early and late transplantation cohorts, progression/relapse was lower and nonrelapse mortality was higher in the allo-HCT group. Overall survival and progression-free survival were highest in patients who underwent auto-HCT in first complete response. Multivariate analysis of survival from diagnosis identified a survival benefit favoring early HCT for both auto-HCT and RIC allo-HCT. Conclusion For patients with chemotherapy-sensitive MCL, the optimal timing for HCT is early in the disease course. Outcomes are particularly favorable for patients undergoing auto-HCT in first complete remission. For those unable to achieve complete remission after two lines of chemotherapy or those with relapsed disease, either auto-HCT or RIC allo-HCT may be effective, although the chance for long-term remission and survival is lower. PMID:24344210

  19. Personalized Fludarabine Dosing To Reduce Non-Relapse Mortality In Hematopoietic Stem Cell Transplant Recipients Receiving Reduced Intensity Conditioning

    PubMed Central

    Sanghavi, Kinjal; Wiseman, Anthony; Kirstein, Mark N.; Cao, Qing; Brundage, Richard; Jensen, Kyle; Rogosheske, John; Kurtzweil, Andy; Long-Boyle, Janel; Wagner, John; Warlick, Erica D.; Brunstein, Claudio G; Weisdorf, Daniel J.; Jacobson, Pamala A.

    2016-01-01

    Patients undergoing hematopoietic cell transplantation (HCT) with reduced intensity conditioning (RIC) commonly receive fludarabine. Higher exposure of F-ara-A, the active component of fludarabine, has been associated with a greater risk of non-relapse mortality (NRM). We sought to develop a model for fludarabine dosing in adult HCT recipients that would allow for precise dose targeting and predict adverse clinical outcomes. We developed a pharmacokinetic model from 87 adults undergoing allogeneic RIC HCT that predicts F-ara-A population clearance (Clpop) accounting for ideal body weight and renal function. We then applied the developed model to an independent cohort of 240 patients to identify whether model predictions were associated with NRM and acute graft vs host disease (GVHD). Renal mechanisms accounted for 35.6% of total F-ara-A Clpop. In the independent cohort the hazard ratio of NRM at day 100 was significantly higher in patients with predicted F-ara-A clearance (Clpred) <8.50 L/hr (p<0.01) and area under the curve (AUCpred)>6.00 μg*hr/mL (p=0.01). A lower Clpred was also associated with more NRM at month 6 (p=0.01) and trended towards significance at 12 months (p=0.05). In multivariate analysis, low fludarabine clearance trended towards higher risk of acute GVHD (p=0.05). We developed a model that predicts an individual's systemic F-ara-A exposure accounting for kidney function and weight. This model may provide guidance in dosing in overweight individuals and those with altered kidney function. PMID:27094990

  20. Reduced intensity conditioning allogeneic hematopoietic cell transplantation for adult acute myeloid leukemia in complete remission - a review from the Acute Leukemia Working Party of the EBMT

    PubMed Central

    Sengsayadeth, Salyka; Savani, Bipin N.; Blaise, Didier; Malard, Florent; Nagler, Arnon; Mohty, Mohamad

    2015-01-01

    Acute myeloid leukemia is the most common indication for an allogeneic hematopoietic cell transplant. The introduction of reduced intensity conditioning has expanded the recipient pool for transplantation, which has importantly made transplant an option for the more commonly affected older age groups. Reduced intensity conditioning allogeneic transplantation is currently the standard of care for patients with intermediate or high-risk acute myeloid leukemia and is now most often employed in older patients and those with medical comorbidities. Despite being curative for a significant proportion of patients, post-transplant relapse remains a challenge in the reduced intensity conditioning setting. Herein we discuss the studies that demonstrate the feasibility of reduced intensity conditioning allogeneic transplants, compare the outcomes of reduced intensity conditioning versus chemotherapy and conventional myeloablative conditioning regimens, describe the optimal donor and stem cell source, and consider the impact of post-remission consolidation, comorbidities, center experience, and more intensive (reduced toxicity conditioning) regimens on outcomes. Additionally, we discuss the need for further prospective studies to optimize transplant outcomes. PMID:26130513

  1. Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival.

    PubMed

    van Besien, Koen; Hari, Parameswaran; Zhang, Mei-Jie; Liu, Hong-Tao; Stock, Wendy; Godley, Lucy; Odenike, Olatoyosi; Larson, Richard; Bishop, Michael; Wickrema, Amittha; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; Tsai, Stephanie; Rhodes, Joanna; Cushing, Melissa M; Korman, Sandra; Artz, Andrew

    2016-05-01

    Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, P<0.0001) recovery, lower risk of grade II-IV acute graft-versus-host disease (HR=0.26, P<0.0001) and chronic graft-versus-host disease (HR=0.06, P<0.0001). Haplo-cord was associated with decreased risk of relapse (HR 0.48, P=0.001). Graft-versus-host disease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588.

  2. Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

    PubMed Central

    van Besien, Koen; Hari, Parameswaran; Zhang, Mei-Jie; Liu, Hong-Tao; Stock, Wendy; Godley, Lucy; Odenike, Olatoyosi; Larson, Richard; Bishop, Michael; Wickrema, Amittha; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; Tsai, Stephanie; Rhodes, Joanna; Cushing, Melissa M.; Korman, Sandra; Artz, Andrew

    2016-01-01

    Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, P<0.0001) recovery, lower risk of grade II–IV acute graft-versus-host disease (HR=0.26, P<0.0001) and chronic graft-versus-host disease (HR=0.06, P<0.0001). Haplo-cord was associated with decreased risk of relapse (HR 0.48, P=0.001). Graft-versus-host disease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588. PMID

  3. Brentuximab vedotin enables successful reduced-intensity allogeneic hematopoietic cell transplantation in patients with relapsed or refractory Hodgkin lymphoma

    PubMed Central

    Palmer, Joycelynne M.; Thomas, Sandra H.; Tsai, Ni-Chun; Farol, Len; Nademanee, Auayporn; Forman, Stephen J.; Gopal, Ajay K.

    2012-01-01

    Brentuximab vedotin induces an overall response rate of 75% in patients with relapsed/refractory Hodgkin lymphoma, but its impact on future allogeneic transplantation (allo-HCT) is not known. We retrospectively examined the records of 18 patients with relapsed/refractory Hodgkin lymphoma who were treated on brentuximab vedotin clinical trials to evaluate the efficacy and safety of subsequent reduced-intensity allo-HCT. Seventeen patients had previous autologous transplant; 6 were in complete remission, and 8 were in partial remission before allo-HCT with 12 grafts from unrelated or mismatched donors. The 1-year overall survival was 100%, progression-free survival was 92.3%, and nonrelapse mortality was 0% (median follow-up, 14 months). The incidence of acute GVHD was 27.8% and chronic GVHD was 56.3%. Brentuximab vedotin before reduced-intensity allo-HCT does not appear to adversely affect engraftment, GVHD, or survival and may provide sufficient disease control to enable reduced-intensity allo-HCT. PMID:22611160

  4. Reduced-intensity stem-cell transplantation for adult acute lymphoblastic leukemia: a retrospective study of 33 patients.

    PubMed

    Hamaki, T; Kami, M; Kanda, Y; Yuji, K; Inamoto, Y; Kishi, Y; Nakai, K; Nakayama, I; Murashige, N; Abe, Y; Ueda, Y; Hino, M; Inoue, T; Ago, H; Hidaka, M; Hayashi, T; Yamane, T; Uoshima, N; Miyakoshi, S; Taniguchi, S

    2005-03-01

    Efficacy of reduced-intensity stem-cell transplantation (RIST) for acute lymphoblastic leukemia (ALL) was investigated in 33 patients (median age, 55 years). RIST sources comprised 20 HLA-identical related donors, five HLA-mismatched related, and eight unrelated donors. Six patients had undergone previous transplantation. Disease status at RIST was first remission (n=13), second remission (n=6), and induction failure or relapse (n=14). All patients tolerated preparatory regimens and achieved neutrophil engraftment (median, day 12.5). Acute and chronic graft-versus-host disease (GVHD) developed in 45 and 64%, respectively. Six patients received donor lymphocyte infusion (DLI), for prophylaxis (n=1) or treatment of recurrent ALL (n=5). Nine patients died of transplant-related mortality, with six deaths due to GVHD. The median follow-up of surviving patients was 11.6 months (range, 3.5-37.3 months). The 1-year relapse-free and overall survival rates were 29.8 and 39.6%, respectively. Of the 14 patients transplanted in relapse, five remained relapse free for longer than 6 months. Cumulative rates of progression and progression-free mortality at 3 years were 50.9 and 30.4%, respectively. These findings suggest the presence of a graft-versus-leukemia effect for ALL. RIST for ALL is worth considering for further evaluation.

  5. Predictive value of risk assessment scores in patients with hematologic malignancies undergoing reduced-intensity conditioning allogeneic stem cell transplantation.

    PubMed

    Yamamoto, Wataru; Ogusa, Eriko; Matsumoto, Kenji; Maruta, Atsuo; Ishigatsubo, Yoshiaki; Kanamori, Heiwa

    2014-09-01

    Reduced-intensity conditioning allogeneic stem cell transplantation (RIC allo-SCT) is associated with less toxicity and is used for older patients. We retrospectively studied the predictive value of two risk assessment scores, which were the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and the pre-transplantation assessment of mortality (PAM) score, for assessing the outcome of RIC allo-SCT. Seventy-eight patients underwent transplantation between 2005 and 2013 at a single institution. RIC was performed with fludarabine and melphalan with/without total body irradiation. The 3-year overall survival of patients with an HCT-CI >3 was significantly worse than that of patients with an HCT-CI 0-3 (31.6% vs. 59.6%, P = 0.020). Also, the 3-year overall survival of patients with a PAM score >24 was significantly worse than that of those with a PAM score ≤24 (29.2% vs. 61.4%, P = 0.005). The present findings suggest that changing the cut-off values of these risk assessment scores can improve prediction of outcomes in patients receiving RIC allo-SCT with this conditioning regimen and we need validation by large-scale study with other regimens. © 2014 Wiley Periodicals, Inc.

  6. Effect of post remission therapy prior to reduced intensity conditioning allogeneic transplantation for acute myeloid leukemia in first complete remission

    PubMed Central

    Warlick, Erica D.; Paulson, Kristjan; Brazauskas, Ruta; Zhong, Xiaobo; Miller, Alan M.; Camitta, Bruce M.; George, Biju; Savani, Bipin N.; Ustun, Celalettin; Marks, David I.; Waller, Edmund K.; Baron, Frédéric; Freytes, César O.; Socie, Gérard; Akpek, Gorgun; Schouten, Harry C.; Lazarus, Hillard M.; Horwitz, Edwin M.; Koreth, John; Cahn, Jean-Yves; Bornhauser, Martin; Seftel, Matthew; Cairo, Mitchell S.; Laughlin, Mary J.; Sabloff, Mitchell; Ringdén, Olle; Gale, Robert Peter; Kamble, Rammurti T.; Vij, Ravi; Gergis, Usama; Mathews, Vikram; Saber, Wael; Chen, Yi-Bin; Liesveld, Jane L.; Cutler, Corey S.; Ghobadi, Armin; Uy, Geoffrey L.; Eapen, Mary; Weisdorf, Daniel J.; Litzow, Mark R.

    2013-01-01

    The impact of pre transplant (HCT) cytarabine consolidation therapy on post HCT outcomes has yet to be evaluated after reduced intensity or non-myeloablative conditioning. We analyzed 604 adults with acute myeloid leukemia (AML) in first complete remission (CR1) reported to the CIBMTR who received a RIC or NMA HCT from an HLA-identical sibling, HLA-matched unrelated donor (URD), or umbilical cord blood (UCB) donor in 2000–2010. We compared transplant outcomes based on exposure to cytarabine post remission consolidation. Three year survival rates were 36% (29–43%, 95% CI) in the no consolidation arm and 42% (37–47%, 95% CI) in the cytarabine consolidation arm (p=0.16). Disease free survival was 34% (27–41%, 95% CI) and 41% (35–46%, 95% CI) (p=0.15), respectively. Three year cumulative incidences of relapse were 37% (30–44%, 95% CI) and 38% (33–43%, 95% CI), respectively (p=0.80). Multivariate regression confirmed no effect of consolidation on relapse, DFS and survival. Prior to RIC/NMA HCT, these data suggest pre-HCT consolidation cytarabine does not significantly alter outcomes and support prompt transition to transplant as soon as morphologic CR1 is attained. If HCT is delayed while identifying a donor, our data suggest that consolidation does not increase transplant TRM and is reasonable if required. PMID:24184335

  7. Donor-derived mycosis fungoides following reduced intensity haematopoietic stem cell transplantation from a matched unrelated donor

    PubMed Central

    Kinsella, Francesca A M; Amel Kashipaz, Mohammad Rasoul; Scarisbrick, Julia; Malladi, Ram

    2017-01-01

    A 46-year-old woman with a history of dasatinib-resistant chronic myeloid leukaemia, clonal evolution and monosomy 7 underwent reduced intensity conditioned in vivo T-cell-depleted allogeneic haematopoietic stem cell transplantation (HSCT) from a matched unrelated donor. Following the transplantation, she developed recurrent cutaneous graft versus host disease (GvHD), which required treatment with systemic immunosuppression and electrocorporeal photophoresis. Concurrently, she developed a lichenoid rash with granulomatous features suggestive of cutaneous sarcoidosis. Additional treatment with hydroxychloroquine was initially successful, but 2 months later, she developed erythroderma with palpable lymphadenopathy. Repeated histological analysis established a diagnosis of folliculotropic mycosis fungoides stage IVA2, and the malignant clone was confirmed to be of donor origin. A positive response to brentuximab has been shown. This is the first reported case of primary mycosis fungoides after matched unrelated donor HSCT, and in a patient still undergoing treatment for GvHD. PMID:28073814

  8. HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide after Busulfan-Containing Reduced-Intensity Conditioning.

    PubMed

    Sugita, Junichi; Kawashima, Naomi; Fujisaki, Tomoaki; Kakihana, Kazuhiko; Ota, Shuichi; Matsuo, Keitaro; Miyamoto, Toshihiro; Akashi, Koichi; Taniguchi, Shuichi; Harada, Mine; Teshima, Takanori

    2015-09-01

    Allogeneic hematopoietic stem cell transplantation (allo-SCT) using post-transplant cyclophosphamide (PTCy) is increasingly performed. We conducted a multicenter phase II study to evaluate the safety and efficacy of PTCy-based HLA-haploidentical peripheral blood stem cell transplantation (PTCy-haploPBSCT) after busulfan-containing reduced-intensity conditioning. Thirty-one patients were enrolled; 61% patients were not in remission and 42% patients had a history of prior allo-SCT. Neutrophil engraftment was achieved in 87% patients with a median of 19 days. The cumulative incidence of grades II to IV and III to IV acute graft-versus-host disease (GVHD) and chronic GVHD at 1 year were 23%, 3%, and 15%, respectively. No patients developed severe chronic GVHD. Day 100 nonrelapse mortality (NRM) rate was 19.4%. Overall survival, relapse, and disease-free survival rates were 45%, 45%, and 34%, respectively, at 1 year. Subgroup analysis showed that patients who had a history of prior allo-SCT had lower engraftment, higher NRM, and lower overall survival than those not receiving a prior allo-SCT. Our results suggest that PTCy-haploPBSCT after busulfan-containing reduced-intensity conditioning achieved low incidences of acute and chronic GVHD and NRM and stable donor engraftment and low NRM, particularly in patients without a history of prior allo-SCT.

  9. Reduced-intensity bone marrow transplantation from an alternative unrelated donor for myelodysplastic syndrome of first-donor origin.

    PubMed

    Komeno, Yukiko; Kanda, Yoshinobu; Kandabashi, Koji; Kawazu, Masahito; Goyama, Susumu; Takeshita, Masataka; Nannya, Yasuhito; Niino, Miyuki; Nakamoto, Tetsuya; Kurokawa, Mineo; Tsujino, Shiho; Ogawa, Seishi; Aoki, Katsunori; Chiba, Shigeru; Motokura, Toru; Hirai, Hisamaru

    2003-03-01

    A male patient had a relapse of myelodysplastic syndrome (MDS) 2 years after BMT from a female matched unrelated donor. Conventional cytogenetics, FISH, and short-tandem repeat chimerism analysis proved a relapse of donor origin. He underwent reduced-intensity BMT after a conditioning with fludarabine and busulfan, since he had impaired renal, liver, and pulmonary functions. Chimerism analysis on day 28 after the second BMT showed mixed chimerism of the first and the second donors, which later turned to full second-donor chimerism on day 60. He developed grade II acute GVHD of the skin and cytomegalovirus reactivation, but both were improved with methylprednisolone and ganciclovir, respectively. He remains in complete remission 6 months after the second BMT. Reduced-intensity second BMT from an alternative donor appeared to be a tolerable treatment option for donor-derived leukemia/MDS after the first conventional transplantation.

  10. The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation.

    PubMed

    Marks, David I; Lush, Richard; Cavenagh, Jamie; Milligan, Donald W; Schey, Steven; Parker, Anne; Clark, Fiona J; Hunt, Linda; Yin, John; Fuller, Steven; Vandenberghe, Elisabeth; Marsh, Judith; Littlewood, Timothy; Smith, Graeme M; Culligan, Dominic; Hunter, Ann; Chopra, Rajesh; Davies, Andrew; Towlson, Keiren; Williams, Catherine D

    2002-11-01

    We describe the toxicity and efficacy of donor lymphocyte infusions (DLIs) given to 81 patients (median age, 50 years) after reduced-intensity conditioning (RIC) transplantations performed at 16 centers in the United Kingdom. The diseases treated included non-Hodgkin lymphoma (NHL; n = 29), chronic myeloid leukemia (CML; n = 12), myeloma (n = 11), acute myeloid leukemia (AML; n = 10), and chronic lymphocytic leukemia (CLL; n = 9). Eighty-eight percent received stem cells from sibling donors. The patients received 130 infusions (median, 1; range, 1-4). Indications for DLI were unsatisfactory response/disease progression in 51 patients, mixed chimerism in 18, preemptive in 10, and other in 2. Graft hypoplasia was uncommon (11%). Grade II to IV graft-versus-host disease (GVHD) occurred in 23 of 81 patients (28%) and limited and extensive chronic GVHD in 5 of 69 and 18 of 69 evaluable patients (total incidence 33%). Conversion from mixed to full donor chimerism occurred in 19 of 55 evaluable patients (35%) at a median of 48 days after the DLI; partial responses occurred in 6 patients (total response rate 45%). Eighteen of 51 (35%) patients with measurable disease after stem cell transplantation had a complete response (2 molecular), and 5 a partial response (total response rate 45%). Eleven of 17 evaluable complete responders had full donor chimerism. Eight of 13 patients with follicular NHL had complete responses as did 4 of 12 patients with CML. Clinical and chimeric responses correlated strongly with acute and chronic GVHD. Forty-seven patients (58%) survive at a median of 508 days after transplantation (range, 155-1171 days) with a median Karnofsky score of 90. Thirty-four patients (42%) died at a median of 211 days after transplantation with the major causes being progressive disease (26%) and GVHD (9%). Further systematic studies are required to determine the efficacy and optimum use of DLI for patients with each disease treated by nonmyeloablative stem cell

  11. No improvement of survival with reduced- versus high-intensity conditioning for allogeneic stem cell transplants in Ewing tumor patients.

    PubMed

    Thiel, U; Wawer, A; Wolf, P; Badoglio, M; Santucci, A; Klingebiel, T; Basu, O; Borkhardt, A; Laws, H-J; Kodera, Y; Yoshimi, A; Peters, C; Ladenstein, R; Pession, A; Prete, A; Urban, E-C; Schwinger, W; Bordigoni, P; Salmon, A; Diaz, M A; Afanasyev, B; Lisukov, I; Morozova, E; Toren, A; Bielorai, B; Korsakas, J; Fagioli, F; Caselli, D; Ehninger, G; Gruhn, B; Dirksen, U; Abdel-Rahman, F; Aglietta, M; Mastrodicasa, E; Torrent, M; Corradini, P; Demeocq, F; Dini, G; Dreger, P; Eyrich, M; Gozdzik, J; Guilhot, F; Holler, E; Koscielniak, E; Messina, C; Nachbaur, D; Sabbatini, R; Oldani, E; Ottinger, H; Ozsahin, H; Schots, R; Siena, S; Stein, J; Sufliarska, S; Unal, A; Ussowicz, M; Schneider, P; Woessmann, W; Jürgens, H; Bregni, M; Burdach, S

    2011-07-01

    Outcomes of Ewing tumor (ET) patients treated with allogeneic stem cell transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts. We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts. Median overall survival was 7.9 months [±1.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (±1.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE). There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocols.

  12. Role of reduced-intensity conditioning allogeneic hematopoietic cell transplantation in older patients with de novo acute myeloid leukemia.

    PubMed

    Yamasaki, Satoshi; Hirakawa, Akihiro; Aoki, Jun; Uchida, Naoyuki; Fukuda, Takahiro; Ogawa, Hiroyasu; Ohashi, Kazuteru; Kondo, Tadakazu; Eto, Tetsuya; Kanamori, Heiwa; Okumura, Hirokazu; Iwato, Koji; Ichinohe, Tatsuo; Kanda, Junya; Onizuka, Makoto; Kuwatsuka, Yachiyo; Yanada, Masamitsu; Atsuta, Yoshiko; Takami, Akiyoshi; Yano, Shingo

    2017-02-01

    Reduced-intensity conditioning (RIC) regimens extend the therapeutic use of allogeneic hematopoietic cell transplantation (HCT) to older patients. The survival trend in 2325 patients aged >50 years presenting with de novo acute myeloid leukemia (AML) who underwent first reduced-intensity HCT (RIC-HCT) was assessed by retrospectively analyzing outcomes between 2000 and 2013. The annual number of RIC-HCTs in Japan was higher in the 2008-2013 period (n = 205/year [1229/6 years]) than in the 2000-2007 period (n = 137/year [1096/8 years]). Overall and disease-free survival were higher in the 2008-2013 period (P < 0.001) because of the improvement in transplant-related mortality (TRM). Survival regarding RIC-HCT for AML has improved over time, with an increased number of RIC-HCTs in patients with a Karnofsky performance status (KPS) ≥80. However, TRM remains high and the relapse rate has not improved over time. Multivariate analyses showed that a KPS ≥80 and complete remission at HCT were associated with less TRM and relapse, and better survival regardless of age ≥65 years. Accurate timing and prospective identification of patients at risk of TRM may aid the development of risk-adapted strategies for RIC-HCT in AML patients regardless of age.

  13. Reduced-intensity hematopoietic stem-cell transplantation for malignant lymphoma: a retrospective survey of 112 adult patients in Japan.

    PubMed

    Kusumi, E; Kami, M; Kanda, Y; Murashige, N; Kishi, Y; Suzuki, R; Takeuchi, K; Tanimoto, T E; Mori, T; Muta, K; Tamaki, T; Tanaka, Y; Ogawa, H; Yamane, T; Taniguchi, S; Takaue, Y

    2005-08-01

    We conducted a nation-wide survey of 112 adult Japanese patients who underwent reduced-intensity stem cell transplantation (RIST) from 1999 to 2002. Underlying diseases included indolent (n=45), aggressive (n=58) and highly aggressive lymphomas (n=9). Median age of the patients was 49 years. A total of 40 patients (36%) had relapsed diseases after autologous stem cell transplantation and 36 patients (32%) had received radiotherapy. RIST regimens were fludarabine-based (n=95), low-dose total body irradiation-based (n=6) and others (n=11). Cumulative incidences of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD were, respectively, 49 and 59%. Cumulative incidences of progression and progression-free mortality were 18 and 25%, respectively. With a median follow-up of 23.9 months, 3-year overall survival rates were 59%. A multivariate analysis identified three significant factors for progression, which are history of radiation (relative risk (RR) 3.45, confidential interval (CI) 1.12-10.0, P=0.03), central nervous system involvement (RR 6.25, CI 2.08-20.0, P=0.001) and development of GVHD (RR 0.28, CI 0.090-0.86, P=0.026). RIST may have decreased the rate of transplant-related mortality, and GVHD may have induced a graft-versus-lymphoma effect. However, whether or not these potential benefits can be directly translated into improved patient survival should be evaluated in further studies.

  14. Cytomegalovirus Status and the Outcome of T Cell-Replete Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Verduyn Lunel, Frans M; Raymakers, Reinier; van Dijk, Anette; van der Wagen, Lotte; Minnema, Monique C; Kuball, Jurgen

    2016-10-01

    Cytomegalovirus (CMV) serostatus of donor and recipient are frequently used in algorithms of donor selection, whereas the impact of CMV reactivation on transplantation-related mortality, leukemia control, and overall survival (OS) remains controversial. Therefore, we retrospectively studied the impact of latent or active CMV infections on the outcome and occurrence of graft-versus-host disease (GVHD) after reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (SCT) in 294 patients during the period from 2004 to 2010. CMV viral load was routinely monitored in plasma using a quantitative PCR. Preemptive antiviral therapy was initiated when the viral load in plasma exceeded a predefined threshold. In a proportional hazards model, a seropositive recipient was significantly associated with increased occurrence of acute GVHD. However the CMV serostatus of both recipient and donor and the presence of active CMV infection was not associated with the occurrence of relapses, chronic GVHD, or OS. We conclude that in the presence of viral load monitoring and preemptive treatment, latent or active CMV infection does not substantially affect the OS after T cell-replete RIC allogeneic SCT. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  15. [Successful treatment with reduced-intensity cord blood transplantation for acute myeloid leukemia with complete tetraploidy (92, XXXX)].

    PubMed

    Iwasaki, Junko; Onozawa, Masahiro; Takahashi, Shojiro; Okada, Kohei; Takahata, Mutsumi; Shigematsu, Akio; Kahata, Kaoru; Kondo, Takeshi; Hashino, Satoshi; Imamura, Masahiro; Asaka, Masahiro

    2011-03-01

    A 56-year-old female was diagnosed with acute myeloid leukemia (FAB: AML-M1). G-banding karyotype of her bone marrow showed complete tetraploidy (92, XXXX [24/24]). Although she achieved complete remission (CR) after induction therapy and maintained CR during consolidation therapy, relapse occurred only 2 months after discharge. When the relapse occurred, bone marrow karyotypic analysis showed complete tetraploidy again. The patient received reduced-intensity cord blood transplantation (RI-CBT), which induced CR for the second time. The patient is currently alive 24 months after transplantation and there have not been any signs of recurrence to date. There have been a few reports of AML with near-tetraploidy, but cases of AML with complete tetraploidy are extremely rare. Tetraploid AML has been reported to have a poor prognosis and there have been very few cases maintaining CR over the long term after chemotherapy alone. This is the first case of complete tetraploid AML successfully treated by RI-CBT. The clinical course of this case suggests that hematopoietic stem cell transplantation during the first CR phase should be considered a treatment option for tetraploid AML.

  16. Reduced intensity conditioning for allogeneic hematopoietic stem-cell transplant determines the kinetics of acute graft-versus-host disease.

    PubMed

    Turner, Brie E; Kambouris, Melinda E; Sinfield, Laura; Lange, Janusz; Burns, Ann M; Lourie, Rohan; Atkinson, Kerry; Hart, Derek N J; Munster, David J; Rice, Alison M

    2008-10-15

    Preparative myeloablative conditioning regimens for allogeneic hematopoietic stem-cell transplantation (HSCT) may control malignancy and facilitate engraftment but also contribute to transplant related mortality, cytokine release, and acute graft-versus-host disease (GVHD). Reduced intensity conditioning (RIC) regimens have decreased transplant related mortality but the incidence of acute GVHD, while delayed, remains unchanged. There are currently no in vivo allogeneic models of RIC HSCT, limiting studies into the mechanism behind RIC-associated GVHD. We developed two RIC HSCT models that result in delayed onset GVHD (major histocompatibility complex mismatched (UBI-GFP/BL6 [H-2]-->BALB/c [H-2]) and major histocompatibility complex matched, minor histocompatibility mismatched (UBI-GFP/BL6 [H-2]-->BALB.B [H-2])) enabling the effect of RIC on chimerism, dendritic cell (DC) chimerism, and GVHD to be investigated. In contrast with myeloablative conditioning, we observed that RIC-associated delayed-onset GVHD is characterized by low production of tumor necrosis factor-alpha, maintenance of host DC, phenotypic DC activation, increased T-regulatory cell numbers, and a delayed emergence of activated donor DC. Furthermore, changes to the peritransplant milieu in the recipient after RIC lead to the altered activation of DC and the induction of T-regulatory responses. Reduced intensity conditioning recipients suffer less early damage to GVHD target organs. However, as donor cells engraft, activated donor DC and rising levels of tumor necrosis factor-alpha are associated with a later onset of severe GVHD. Delineating the mechanisms underlying delayed onset GVHD in RIC HSCT recipients is vital to improve the prediction of disease onset and allow more targeted interventions for acute GVHD.

  17. Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia

    PubMed Central

    Mohty, Mohamad; Malard, Florent; Blaise, Didier; Milpied, Noel; Socié, Gérard; Huynh, Anne; Reman, Oumédaly; Yakoub-Agha, Ibrahim; Furst, Sabine; Guillaume, Thierry; Tabrizi, Resa; Vigouroux, Stéphane; Peterlin, Pierre; El-Cheikh, Jean; Moreau, Philippe; Labopin, Myriam; Chevallier, Patrice

    2017-01-01

    The prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients’ outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included. Cytogenetic risk was poor in 15 patients (62%) and intermediate in nine (38%). The sequential regimen consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a 3-day rest, by reduced-intensity conditioning and allogeneic stem-cell transplantation combining cyclophosphamide (60 mg/kg), intravenous busulfan (3.2 mg/kg/day) for 2 days and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Patients in complete remission at day +120 received prophylactic donor lymphocyte infusion. Eighteen patients (75%) achieved complete remission. With a median follow-up of 24.6 months, the Kaplan-Meier estimate of overall survival was 54% (95% CI: 33–71) at 1 year and 38% (95% CI: 18–46) at 2 years. The Kaplan-Meier estimate of leukemia-free survival was 46% (95% CI: 26–64) at 1 year and 29% (95% CI: 13–48) at 2 years. The cumulative incidence of non-relapse mortality was 8% (95% CI: 1–24) at 1 year and 12% (95% CI: 3–19) at 2 years. Results from this phase 2 prospective multicenter trial endorsed the safety and efficacy of a clofarabine-based sequential reduced-toxicity conditioning regimen, which warrants further investigation. This study was registered at www.clinicaltrials.gov, identifier number: NCT01188174. PMID:27561720

  18. A Review of Myeloablative vs Reduced Intensity/Non-Myeloablative Regimens in Allogeneic Hematopoietic Stem Cell Transplantations

    PubMed Central

    Atilla, Erden; Ataca Atilla, Pınar; Demirer, Taner

    2017-01-01

    Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative treatment option for both malignant and some benign hematological diseases. During the last decade, many of the newer high-dose regimens in different intensity have been developed specifically for patients with hematologic malignancies and solid tumors. Today there are three main approaches used prior to allogeneic transplantation: Myeloablative (MA), Reduced Intensity Conditioning (RIC) and Non-MA (NMA) regimens. MA regimens cause irreversible cytopenia and there is a requirement for stem cell support. Patients who receive NMA regimen have minimal cytopenia and this type of regimen can be given without stem cell support. RIC regimens do not fit the criteria of MA and NMA: the cytopenia is reversible and the stem cell support is necessary. NMA/RIC for Allo-HSCT has opened a new era for treating elderly patients and those with comorbidities. The RIC conditioning was used for 40% of all Allo-HSCT and this trend continue to increase. In this paper, we will review these regimens in the setting of especially allogeneic HSCT and our aim is to describe the history, features and impact of these conditioning regimens on specific diseases. PMID:28251017

  19. Review of allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in solid tumors excluding breast cancer

    PubMed Central

    Karadurmus, Nuri; Sahin, Ugur; Basgoz, Bilgin Bahadir; Arpaci, Fikret; Demirer, Taner

    2016-01-01

    Solid tumors in adults constitute a heterogeneous group of malignancy originating from various organ systems. Solid tumors are not completely curable by chemotherapy, even though some subgroups are very chemo-sensitive. Recently, oncologists have focused on the use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced intensity conditioning (RIC) for the treatment of some refractory solid tumors. After the demonstration of allogeneic graft-versus-leukemia effect in patients with hematological malignancies who received allo-HSCT, investigators evaluated this effect in patients with refractory metastatic solid tumors. According to data from experimental animal models and preliminary clinical trials, a graft-versus-tumor (GvT) effect may also be observed in the treatment of some solid tumors (e.g., renal cell cancer, colorectal cancer, etc.) after allo-HSCT with RIC. The use of RIC regimens offers an opportunity of achieving full-donor engraftment with GvT effect, as well as, a reduced transplant-related mortality. Current literature suggests that allo-HSCT with RIC might become a choice for elderly and medically fragile patients with refractory metastatic solid tumors. PMID:28058217

  20. Reduced-intensity conditioning with combined haploidentical and cord blood transplantation results in rapid engraftment, low GVHD, and durable remissions

    PubMed Central

    Liu, Hongtao; Rich, Elizabeth S.; Godley, Lucy; Odenike, Olatoyosi; Joseph, Loren; Marino, Susana; Kline, Justin; Nguyen, Vu; Cunningham, John; Larson, Richard A.; del Cerro, Paula; Schroeder, Linda; Pape, Lisa; Stock, Wendy; Wickrema, Amittha; Artz, Andrew S.

    2011-01-01

    We conducted a 45 patient prospective study of reduced-intensity conditioning (RIC) and transplantation of unrelated umbilical cord blood (UCB) and CD34+ stem cells from a haploidentical family member. Median age was 50 years; weight was 80 kg. Fifty-eight percent had active disease. Neutrophil engraftment occurred at 11 days (interquartile range [IQR], 9-15) and platelet engraftment at 19 days (IQR, 15-33). In the majority of patients, early haploidentical engraftment was replaced by durable engraftment of UCB by 100 days, with regular persistence of minor host and/or haplo-hematopoiesis. Percentage of haplochimerism at day 100 correlated with the haplo-CD34 dose (P = .003). Cumulative incidence of acute GVHD (aGVHD) was 25% and chronic GVHD (cGVHD) was 5%. Actuarial survival at 1 year was 55%, progression-free survival (PFS) was 42%, nonrelapse mortality (NRM) was 28%, and relapse was 30%. RIC and haplo-cord transplantation results in fast engraftment of neutrophils and platelets, low incidences of aGVHD and cGVHD, low frequency of delayed opportunistic infections, reduced transfusion requirements, shortened length of hospital stay, and promising long-term outcomes. UCB cell dose had no impact on time to hematopoietic recovery. Therefore, UCB selection can prioritize matching, and better matched donors can be identified rapidly for most patients. This study is registered at http://clinicaltrials.gov as NCI clinical trial no. NCT00943800. PMID:21976674

  1. Long-term survival outcomes of reduced-intensity allogeneic or autologous transplantation in relapsed grade 3 follicular lymphoma.

    PubMed

    Klyuchnikov, E; Bacher, U; Woo Ahn, K; Carreras, J; Kröger, N M; Hari, P N; Ku, G H; Ayala, E; Chen, A I; Chen, Y-B; Cohen, J B; Freytes, C O; Gale, R P; Kamble, R T; Kharfan-Dabaja, M A; Lazarus, H M; Martino, R; Mussetti, A; Savani, B N; Schouten, H C; Usmani, S Z; Wiernik, P H; Wirk, B; Smith, S M; Sureda, A; Hamadani, M

    2016-01-01

    Grade 3 follicular lymphoma (FL) has aggressive clinical behavior. To evaluate the optimal first transplantation approach in relapsed/refractory grade 3 FL patients, we compared the long-term outcomes after allogeneic (allo-) vs autologous hematopoietic cell transplantation (auto-HCT) in the rituximab era. A total of 197 patients undergoing first reduced-intensity conditioning (RIC) allo-HCT or first auto-HCT during 2000-2012 were included. Rituximab-naive patients were excluded. Allo-HCT recipients were younger, more heavily pretreated and had a longer interval between diagnosis and HCT. The 5-year probabilities of non-relapse mortality (NRM), relapse/progression, PFS and overall survival (OS) for auto-HCT vs allo-HCT groups were 4% vs 27% (P<0.001), 61% vs 20% (P<0.001), 36% vs 51% (P=0.07) and 59% vs 54% (P=0.7), respectively. On multivariate analysis, auto-HCT was associated with reduced risk of NRM (relative risk (RR)=0.20; P=0.001). Within the first 11 months post HCT, auto- and allo-HCT had similar risks of relapse/progression and PFS. Beyond 11 months, auto-HCT was associated with higher risk of relapse/progression (RR=21.3; P=0.003) and inferior PFS (RR=3.2; P=0.005). In the first 24 months post HCT, auto-HCT was associated with improved OS (RR=0.42; P=0.005), but in long-time survivors (beyond 24 months) it was associated with inferior OS (RR=3.6; P=0.04). RIC allo-HCT as the first transplant approach can provide improved PFS and OS, in long-term survivors.

  2. Fatal deep vein thrombosis after allogeneic reduced intensity hematopoietic stem cell transplantation for the treatment of metastatic gastric cancer.

    PubMed

    Kamitsuji, Yuri; Mori, Shin-Ichiro; Kami, Masahiro; Yamada, Hirofumi; Shirakawa, Kazuo; Kishi, Yukiko; Murashige, Naoko; Kim, Sung-Won; Heike, Yuji; Takaue, Yoichi

    2004-08-01

    A 61-year-old man received reduced intensity stem cell transplantation (RIST) for the treatment of metastatic gastric cancer. The cytoreductive course of RIST was uneventful until day 0, when fever suddenly developed and his performance status deteriorated. Edema developed in the bilateral lower extremities by day 7, which was diagnosed by Doppler ultrasonography as deep vein thrombosis (DVT) involving the femoral veins to the inferior vena cava. While the edema improved with anticoagulation treatment, gastrointestinal graft-versus-host disease (GVHD) followed on day 13. Diarrhea subsided spontaneously, but hypoalbuminemia persisted, with the subsequent development of oliguria and jaundice on day 18. He died of sepsis on day 30, without any evidence of cancer progression. This case demonstrates that DVT is a potentially significant problem following RIST for solid tumors.

  3. Reduced-intensity stem cell transplantation from an HLA-identical sibling donor in patients with myeloid malignancies.

    PubMed

    Hamaki, T; Kami, M; Kim, S-W; Onishi, Y; Kishi, Y; Murashige, N; Hori, A; Kojima, R; Sakiyama, M; Imataki, O; Heike, Y; Tanosaki, R; Masuo, S; Miyakoshi, S; Taniguchi, S; Tobinai, K; Takaue, Y

    2004-05-01

    The purpose of this study was to evaluate the feasibility and efficacy of allogeneic hematopoietic stem cell transplantation with a reduced-intensity regimen (RIST) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). In all, 36 patients (median age 55 years) underwent RIST from an HLA-matched related donor between September 1999 and December 2002. The diagnoses included AML (n=14), leukemia evolving from MDS (n=10), and MDS (refractory anemia with excess blasts n=6, refractory anemia n=6). The RIST regimen consisted of purine analog (cladribine or fludarabine)/busulfan, with or without antithymocyte globulin. The regimen was well tolerated, and 34 patients achieved durable engraftment and most achieved remission after RIST. A total of 17 patients developed grade II-IV acute GVHD, and 27 developed chronic GVHD. Eight patients relapsed, and five of them received antithymocyte globulin (ATG) as part of the preparative regimen. A total of 12 patients died (four disease progression, six transplantation-related complications, and two others). Estimated 1-year disease-free survival (DFS) in low- and high-risk groups was 85 and 64%, respectively. We conclude that RIST can be performed safely in elderly patients with myeloid malignancies, and has therapeutic potential for those who fail conventional chemotherapy. In view of the significant association between GVHD or ATG and DFS, defined management of GVHD following RIST should become a major target of clinical research.

  4. Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen.

    PubMed

    Mohty, M; Jacot, W; Faucher, C; Bay, J O; Zandotti, C; Collet, L; Choufi, B; Bilger, K; Tournilhac, O; Vey, N; Stoppa, A M; Coso, D; Gastaut, J A; Viens, P; Maraninchi, D; Olive, D; Blaise, D

    2003-11-01

    In the setting of reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT), the epidemiology of transplant-related infections is still poorly defined. In 101 high-risk patients who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan and antithymocyte globulin (ATG), we report during the first 6 months a cumulative incidence of positive CMV antigenemia of 42% (95% CI 32-52%), developing at a median of 37 (range 7-116) days without evidence of CMV disease (median follow-up, 434 days). The cumulative incidence of bacteremia was 25% (95% CI 17-33%), occurring at a median of 67 (range 7-172) days, while patients had recovered a full neutrophil count. In all, 65% of the bacteremia (95% CI 49-81%) were gram negative. The cumulative incidence of fungal infections was 8% (95% CI 3-13%), with a median onset of 89 (range 7-170) days. In multivariate analysis, stem cell source (bone marrow; P=0.0002) was significantly associated with the risk of positive CMV antigenemia, while higher doses of prednisone (>2 mg/kg) represented the major risk factor for bacteremia (P=0.0001). Infectious-related mortality was 5% (95% CI 1-9%), with aspergillosis being the principal cause. Collectively, these results suggest that prospective efforts are warranted to develop optimal antimicrobial preventive strategies after RIC allo-SCT.

  5. Pre-transplant MRD predicts outcome following reduced-intensity and myeloablative allogeneic hemopoietic SCT in AML.

    PubMed

    Anthias, C; Dignan, F L; Morilla, R; Morilla, A; Ethell, M E; Potter, M N; Shaw, B E

    2014-05-01

    The presence of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) has been associated with adverse outcomes in AML patients treated with chemotherapy alone, but its impact in the setting of allogeneic hematopoietic SCT (HSCT) is less clear. We studied 88 patients who underwent myeloablative (MA) or reduced-intensity conditioned allogeneic HSCT for AML in first or subsequent remission at our center. MRD status was determined using three-color MFC on pre-HSCT BM aspirates, and patients were stratified by MRD status into MRD-negative, low-level MRD-positive (<1%) or high-level MRD-positive groups (1-4.9%). Two-year survival estimates in these groups were 66.8%, 51% and 30%, respectively (P=0.012), and 2-year estimates of relapse were 7.6, 37 and 70% (P<0.001). Pre-HSCT MRD was related to disease characteristics including secondary AML (P=0.002) and primary induction failure (P=0.005), but, despite these strong correlations, MRD remained independently associated with poorer survival in multivariate analysis (hazard ratio, 1.92; P=0.014). Pre-HSCT MRD is associated with adverse clinical outcomes in AML patients undergoing reduced-intensity or MA HSCT in first or subsequent remission and should be integrated into transplant strategies for patients with AML.

  6. A prospective PETHEMA study of tandem autologous transplantation versus autograft followed by reduced-intensity conditioning allogeneic transplantation in newly diagnosed multiple myeloma.

    PubMed

    Rosiñol, Laura; Pérez-Simón, José Antonio; Sureda, Anna; de la Rubia, Javier; de Arriba, Felipe; Lahuerta, Juan José; González, José David; Díaz-Mediavilla, Joaquín; Hernández, Belén; García-Frade, Javier; Carrera, Dolores; León, Angel; Hernández, Miguel; Abellán, Pascual Fernández; Bergua, Juan Miguel; San Miguel, Jesús; Bladé, Joan

    2008-11-01

    One hundred ten patients with multiple myeloma (MM) failing to achieve at least near-complete remission (nCR) after a first autologous stem cell transplantation (ASCT) were scheduled to receive a second ASCT (85 patients) or a reduced-intensity-conditioning allograft (allo-RIC; 25 patients), depending on the human leukocyte antigen (HLA)-identical sibling donor availability. There was a higher increase in complete remission (CR) rate (40% vs 11%, P = .001) and a trend toward a longer progression-free survival (PFS; median, 31 months vs not reached, P = .08) in favor of allo-RIC. In contrast, it was associated with a trend toward a higher transplantation-related mortality (16% vs 5%, P = .07), a 66% chance of chronic graft-versus-host disease and no statistical difference in event-free survival and overall survival. Although the PFS plateau observed with allo-RIC is very encouraging, this procedure is associated with high morbidity and mortality, and therefore it should still be considered investigational and restricted to well-designed prospective clinical trials. This trial is registered at ClinicalTrials.gov ID number NCT00560053.

  7. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts

    PubMed Central

    Carter, Shelly L.; Karanes, Chatchada; Costa, Luciano J.; Wu, Juan; Devine, Steven M.; Wingard, John R.; Aljitawi, Omar S.; Cutler, Corey S.; Jagasia, Madan H.; Ballen, Karen K.; Eapen, Mary; O'Donnell, Paul V.

    2011-01-01

    The Blood and Marrow Transplant Clinical Trials Network conducted 2 parallel multicenter phase 2 trials for individuals with leukemia or lymphoma and no suitable related donor. Reduced intensity conditioning (RIC) was used with either unrelated double umbilical cord blood (dUCB) or HLA-haploidentical related donor bone marrow (Haplo-marrow) transplantation. For both trials, the transplantation conditioning regimen incorporated cyclophosphamide, fludarabine, and 200 cGy of total body irradiation. The 1-year probabilities of overall and progression-free survival were 54% and 46%, respectively, after dUCB transplantation (n = 50) and 62% and 48%, respectively, after Haplo-marrow transplantation (n = 50). The day +56 cumulative incidence of neutrophil recovery was 94% after dUCB and 96% after Haplo-marrow transplantation. The 100-day cumulative incidence of grade II-IV acute GVHD was 40% after dUCB and 32% after Haplo-marrow transplantation. The 1-year cumulative incidences of nonrelapse mortality and relapse after dUCB transplantation were 24% and 31%, respectively, with corresponding results of 7% and 45%, respectively, after Haplo-marrow transplantation. These multicenter studies confirm the utility of dUCB and Haplo-marrow as alternative donor sources and set the stage for a multicenter randomized clinical trial to assess the relative efficacy of these 2 strategies. The trials are registered at www.clinicaltrials.gov under NCT00864227 (BMT CTN 0604) and NCT00849147 (BMT CTN 0603). PMID:21527516

  8. Impact of ATG-containing reduced-intensity conditioning after single- or double-unit allogeneic cord blood transplantation.

    PubMed

    Pascal, Laurent; Tucunduva, Luciana; Ruggeri, Annalisa; Blaise, Didier; Ceballos, Patrice; Chevallier, Patrice; Cornelissen, Jan; Maillard, Natacha; Tabrizi, Reza; Petersen, Eefke; Linkesch, Werner; Sengeloev, Henrik; Kenzey, Chantal; Pagliuca, Antonio; Holler, Ernst; Einsele, Hermann; Gluckman, Eliane; Rocha, Vanderson; Yakoub-Agha, Ibrahim

    2015-08-20

    We analyzed 661 adult patients who underwent single-unit (n = 226) or double-unit (n = 435) unrelated cord blood transplantation (UCBT) following a reduced-intensity conditioning (RIC) consisting of low-dose total body irradiation (TBI), cyclophosphamide, and fludarabine (Cy/Flu/TBI200). Eighty-two patients received rabbit antithymocyte globulin (ATG) as part of the conditioning regimen (ATG group), whereas 579 did not (non-ATG group). Median age at UCBT was 54 years, and diagnoses were acute leukemias (51%), myelodysplastic syndrome/myeloproliferative neoplasm (19%), and lymphoproliferative diseases (30%). Forty-four percent of patients were transplanted with advanced disease. All patients received ≥4 antigens HLA-matched UCBT. Median number of collected total nucleated cells was 4.4 × 10(7)/kg. In the ATG group, on 64 evaluable patients, ATG was discontinued 1 (n = 27), 2 (n = 20), or > 2 days before the graft infusion (n = 17). In multivariate analyses, the use of ATG was associated with decreased incidence of acute graft-versus-host disease (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.17-0.55; P < .0001), higher incidence of nonrelapse mortality (HR, 1.68; 95% CI, 1.16-2.43; P = .0009), and decreased overall survival (HR, 1.69; 95% CI, 1.19-2.415; P = .003). Collectively, our results suggest that the use of ATG could be detrimental, especially if given too close to graft infusion in adults undergoing UCBT following Cy/Flu/TBI200 regimen. © 2015 by The American Society of Hematology.

  9. Double reduced-intensity allogeneic hematopoietic stem cell transplantation: a retrospective study from the SFGM-TC.

    PubMed

    Bay, J O; Cabrespine, A; Faucher, C; Tabrizi, R; Bordigoni, P; Berceanu, A; Coiteux, V; Renaud, M; Mialou, V; Robin, M; Kuentz, M; Chevallier, P; Dhédin, N; Huynh, A; Garban, F; Witz, F; Buzyn, A; De Revel, T; Galambrun, C; Deconinck, E; Contentin, N; François, S; Gratecos, N; Blaise, D; Michallet, M

    2012-02-01

    The purpose of this paper is to describe the outcome of patients who underwent double allogeneic hematopoietic stem cell transplantation (AHSCT) with reduced-intensity conditioning regimens (RIC). Forty-five patients who received double RIC-AHSCT between 1997 and 2006 were retrospectively studied. The predominant diagnosis was acute myeloid leukemia (AML) (n = 17). Other diagnoses were aplasic anemia (AA) (n = 5), myelodysplasic disorder (n = 5), acute lymphoblastic leukemia (ALL) (n = 4), chronic myelomonocytic leukemia (CML) (n = 3), myeloma (n = 3), non-Hodgkin lymphoma (NHL) (n = 3), chronic lymphocytic leukemia (CLL) (n = 2), Hodgkin's disease (HD) (n = 2), and chronic myelomonocytic leukemia (n = 1). Main indications for RIC-AHSCT 2 were relapse (n = 25, 56%) and early (n = 8, 18%) or late (n = 12, 26%) graft failure. Median delays to reach a neutrophil count of 0.5 × 10(9)/L and platelet counts of 50 × 10(9)/L were significantly smaller after the second AHSCT. Among 25 patients who relapsed after RIC-AHSCT 1, 14 patients (56%) presented a response improvement after RIC-AHSCT 2. In this group, 9 patients sustained a complete response and 5 patients a partial response. Moreover, among the 20 patients who had early or late graft failure following RIC-AHSCT 1, 9 (45%) finally reached an engraftment. Disease-free survival (DFS) was significantly improved after RIC-AHSCT 2. Thirteen patients (28%) died of transplant-related mortality (TRM) at a median delay of 69 days (range: 0-451) after RIC-AHSCT 2. Double RIC-AHSCT is a feasible procedure that allows a response or engraftment not observed after RIC-AHSCT 1. The main indication is relapse. However, TRM remains high.

  10. Prospective Study of Single vs. Two Unit Umbilical Cord Blood Transplantation Following Reduced Intensity Conditioning in Adults with Hematologic Malignancies

    PubMed Central

    Kindwall-Keller, Tamila L.; Hegerfeldt, Yael; Meyerson, Howard J.; Margevicius, Seunghee; Fu, Pingfu; van Heeckeren, Willem; Lazarus, Hillard M.; Cooper, Brenda W.; Gerson, Stanton L.; Barr, Paul; Tse, William W.; Curtis, Christine; Fanning, Laura R.; Creger, Richard J.; Carlson-Barko, Joanne M.; Laughlin, Mary J.

    2011-01-01

    As the threshold nucleated cell dose for single unit umbilical cord blood (UCB) in adults has not to date been firmly established, we prospectively compared single vs. 2-unit UCB transplantation after reduced intensity conditioning (RIC) in adult patients with hematologic malignancies. Study design specified one UCB unit if the cryopreserved total nucleated cell (TNC) dose was ≥2.5×107/kg recipient weight, otherwise 2-units matched at minimum 4/6 HLA loci to the patient and 3/6 to each other were infused. Twenty-seven patients received 1 unit; 23 patients received 2 units. Median time to absolute neutrophil count (ANC) >500/μL was 24 days (95% CI 22–28 days), 25 days for 1-unit and 23 days for 2-units (p=0.99). At day 100, ANC >500/μL was 88.4% and 91.3% in the 1 and 2-unit groups (p=0.99), respectively. Three-year event free survival (EFS) was 28.6% and 39.1% in the 1 and 2-unit groups (p=0.71), respectively. Infusion of 2 units was associated with significantly lower relapse risk, 30.4% vs. 59.3% (p=0.045). Infused cell doses (TNC, CD3+, CD34+, CD56+CD3neg) did not impact engraftment, overall survival (OS), or EFS. Taken together, single unit UCB transplantation with threshold cell dose ≥2.5×107/kg recipient weight after RIC is a viable option for adults, although infusion of 2 units confers a lower relapse incidence. PMID:22002488

  11. Bone marrow as stem cell source for allogeneic HLA-identical sibling transplantation following reduced-intensity preparative regimen.

    PubMed

    Faucher, Catherine; Mohty, Mohamad; Vey, Norbert; Gaugler, Béatrice; Bilger, Karin; Moziconnacci, Marie-Joelle; Stoppa, Anne-Marie; Coso, Diane; Ladaique, Patrick; Chabannon, Christian; Reviron, Denis; Maraninchi, Dominique; Gastaut, Jean-Albert; Olive, Daniel; Blaise, Didier

    2003-10-01

    Reduced-intensity conditioning regimens (RIC) and peripheral blood stem cells (PBSC) are increasingly used for allogeneic stem cell transplantation (allo-BMT). RIC has been shown to allow engraftment with minimal early transplant-related mortality (TRM). However, in the context of RIC, the use of bone marrow (BM) as stem cell source is still little evaluated. In this report, we analyzed the outcome of 32 high-risk patients with hematological malignancies who received an HLA-identical sibling allo-BMT after RIC including fludarabine, busulfan, and anti-thymocyte globulin (ATG). Sustained neutrophil and platelet recovery occurred at a median of 13 days (range, 10-19) and 17 days (range, 0-45) respectively. Early and durable full donor chimerism could be established as soon as the first month after allo-BMT. Also, a sustained and early CD8(+) T-cell recovery was observed, but the CD4(+) T-cell compartment remained profoundly low. The cumulative incidences of grade II-IV acute GVHD and chronic GVHD were 26% (95% CI, 11-41%) and 31% (95% CI, 15-47%) respectively. The overall cumulative incidence of TRM was 28% (95% CI, 12-44%) occurring mainly in patients aged over 50. In this setting, GVHD showed a protective effect on disease progression or relapse with better progression-free survival for patients with GVHD as compared to patients without GVHD (p=0.03). Collectively, these results confirm that the use of BM grafts for RIC is feasible with durable donor engraftment and no detrimental GVHD.

  12. Reduced intensity conditioning HLA identical sibling donor allogeneic stem cell transplantation for patients with follicular lymphoma: long-term follow-up from two prospective multicenter trials

    PubMed Central

    Piñana, José Luis; Martino, Rodrigo; Gayoso, Jorge; Sureda, Anna; de la Serna, Javier; Díez-Martín, Jose Luis; Vazquez, Lourdes; Arranz, Reyes; Tomás, José Francisco; Sampol, Antonia; Solano, Carlos; Delgado, Julio; Sierra, Jorge; Caballero, Dolores

    2010-01-01

    Background Allogeneic hematopoietic stem cell transplantation is an effective treatment for patients with poor risk lymphoma, at least in part because of the graft-versus-lymphoma effect. Over the past decade, reduced intensity conditioning regimens have been shown to offer results similar to those of conventional high-dose conditioning regimens but with lower toxicity early after transplantation, especially in patients with chemosensitive disease at transplant. Design and Methods The aim of this study was to analyze the long-term outcome of patients with follicular lymphoma who received an HLA identical sibling allogeneic stem cell transplant with a reduced intensity conditioning regimen within prospective trials. The prospective multicenter studies considered included 37 patients with follicular lymphoma who underwent allogeneic stem cell transplantation between 1998 and 2007 with a fludarabine plus melphalan-based reduced intensity conditioning regimen. Results The median age of the patients was 50 years (range, 34–62 years) and the median follow-up was 52 months (range, 0.6 to 113 months). Most patients (77%) had stage III-IV at diagnosis, and patients had received a median of three lines of therapy before the reduced intensity conditioning allogeneic stem cell transplantation. At the time of transplantation, 14 patients were in complete remission, 16 in partial remission and 7 had refractory or progressive disease after salvage chemotherapy. The 4-year overall survival rates for patients in complete remission, partial remission, or with refractory or progressive disease were 71%, 48% and 29%, respectively (P=0.09), whereas the 4-year cumulative incidences of non-relapse mortality were 26% (95% CI, 11–61), 33% (95% CI, 16–68) and 71% (95% CI, 44–100), respectively. The incidence of relapse for the whole group was only 8% (95% CI, 2–23). Conclusions We conclude that this strategy of reduced intensity conditioning allogeneic stem cell transplantation

  13. Lowering the alemtuzumab dose in reduced intensity conditioning allogeneic hematopoietic cell transplantation is associated with a favorable early intense natural killer cell recovery.

    PubMed

    Gärtner, Frank; Hieke, Stefanie; Finke, Jürgen; Bertz, Hartmut

    2013-10-01

    The anti-CD52 monoclonal antibody alemtuzumab is employed in allogeneic hematopoietic cell transplantation (alloHCT) for the prevention of graft-versus-host disease (GVHD). However, its optimal dosing in this setting has not been determined yet. We compared three different alemtuzumab dose levels in reduced intensity conditioning (RIC) alloHCT with respect to lymphocyte recovery and outcome. In 127 consecutive patients with predominantly advanced stage hematologic malignancies, a first alloHCT after RIC was performed, applying a fludarabine-based protocol (in 93% FBM: fludarabine, bis-chloroethyl-nitrosourea [BCNU], and melphalan). For GVHD prophylaxis, cyclosporine and alemtuzumab at three different dose levels (40 mg, 20 mg, 10 mg) were administered. Recovery of the peripheral blood (PB) lymphocyte sub-populations and clinical outcome were determined with regard to the alemtuzumab dose. Natural killer (NK) cell concentrations in PB around day +30 correlated inversely with the alemtuzumab dose, whereas other PB lymphocyte subtypes remained essentially unaffected by dosing of alemtuzumab. Lower alemtuzumab doses were associated with a tendency toward improved overall survival mainly during the early post-transplantation months. With regard to the PB NK cell concentration around day +30, "early intense NK cell reconstituters" tended to show an overall survival benefit. An alemtuzumab dose reduction to only 10-20 mg provides sufficient GVHD prophylaxis and supports improved NK cell regeneration early after alloHCT in PB ("NK cell saving effect"), which may have a positive effect on overall survival. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  14. Reduced-intensity hematopoietic cell transplantation for patients with primary myelofibrosis: a cohort analysis from the center for international blood and marrow transplant research.

    PubMed

    Gupta, Vikas; Malone, Adriana K; Hari, Parameswaran N; Ahn, Kwang Woo; Hu, Zhen-Huan; Gale, Robert Peter; Ballen, Karen K; Hamadani, Mehdi; Olavarria, Eduardo; Gerds, Aaron T; Waller, Edmund K; Costa, Luciano J; Antin, Joseph H; Kamble, Rammurti T; van Besien, Koen M; Savani, Bipin N; Schouten, Harry C; Szer, Jeffrey; Cahn, Jean-Yves; de Lima, Marcos J; Wirk, Baldeep; Aljurf, Mahmoud D; Popat, Uday; Bejanyan, Nelli; Litzow, Mark R; Norkin, Maxim; Lewis, Ian D; Hale, Gregory A; Woolfrey, Ann E; Miller, Alan M; Ustun, Celalettin; Jagasia, Madan H; Lill, Michael; Maziarz, Richard T; Cortes, Jorge; Kalaycio, Matt E; Saber, Wael

    2014-01-01

    We evaluated outcomes and associated prognostic factors in 233 patients undergoing allogeneic hematopoietic cell transplantation (HCT) for primary myelofibrosis (MF) using reduced-intensity conditioning (RIC). The median age at RIC HCT was 55 yr. Donors were a matched sibling donor (MSD) in 34% of RIC HCTs, an HLA well-matched unrelated donor (URD) in 45%, and a partially matched/mismatched URD in 21%. Risk stratification according to the Dynamic International Prognostic Scoring System (DIPSS) was 12% low, 49% intermediate-1, 37% intermediate-2, and 1% high. The probability of survival at 5 yr was 47% (95% confidence interval [CI], 40% to 53%). In a multivariate analysis, donor type was the sole independent factor associated with survival. Adjusted probabilities of survival at 5-yr were 56% (95% CI, 44% to 67%) for MSD, 48% (95% CI, 37% to 58%) for well-matched URD, and 34% (95% CI, 21% to 47%) for partially matched/mismatched URD (P = .002). The relative risk (RR) for NRM was 3.92 (P = .006) for well-matched URD and 9.37 (P < .0001) for partially matched/mismatched URD. Trends toward increased NRM (RR, 1.7; P = .07) and inferior survival (RR, 1.37; P = .10) were observed in DIPSS intermediate-2/high-risk patients compared with DIPSS low/intermediate-1 risk patients. Our data indicate that RIC HCT is a potentially curative option for patients with MF, and that donor type is the most important factor influencing survival in these patients. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  15. Successful engraftment of mismatched unrelated cord blood transplantation following reduced intensity preparative regimen using fludarabine and busulfan.

    PubMed

    Komatsu, Tsunehiko; Narimatsu, Hiroto; Yoshimi, Ai; Kurita, Naoki; Kusakabe, Manabu; Hori, Akiko; Murashige, Naoko; Matsumura, Tomoko; Kobayashi, Kazuhiko; Yuji, Koichiro; Tanaka, Yuji; Kami, Masahiro

    2007-01-01

    We conducted a pilot study to evaluate the feasibility of reduced-intensity cord blood transplantation (RI-CBT) using a non-total body irradiation (TBI) regimen in adult patients with advanced hematologic malignancies. Seventeen patients with a median age of 58 years (range, 38-74) underwent RI-CBT at Tsukuba Memorial Hospital between April 2004 and November 2005. Preparative regimens were fludarabine 30 mg/m(2) for 6 days, and busulfan 4 mg/kg for 2 days. Tacrolimus was used for prophylaxis of graft-vs-host disease (GVHD). Median numbers of infused total nucleated were 2.6 x 10(7)/kg (range, 2.0-3.3). HLA disparity was found in 2/6 antigens (n=16) and 1/6 antigens (n=1). Underlying diseases progressed despite preparative regimens in four patients. Of the remaining 13 patients, nine patients achieved engraftment at a median of day 18 (range, 17-28). Six of the nine patients with engraftment achieved complete donor-type chimerism by day 100. Six patients were alive in remission at median follow-up of 13.1 months (range, 1.0-19.0). This study demonstrated the feasibility of RI-CBT using a non-TBI regimen in adults. When disease progression is controlled by the preparative regimen, RI-CBT carries a clinically significant graft-vs-tumor effect. Further studies are required to identify patients who benefit from this regimen.

  16. Mycophenolate mofetil and cyclosporine for graft-versus-host disease prophylaxis following reduced intensity conditioning allogeneic stem cell transplantation.

    PubMed

    Mohty, M; de Lavallade, H; Faucher, C; Bilger, K; Vey, N; Stoppa, A-M; Gravis, G; Coso, D; Viens, P; Gastaut, J-A; Blaise, D

    2004-09-01

    The use of reduced intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT) can result in a significant decrease in early procedure-related toxicity in patients not eligible for standard myeloablative regimens. However, acute graft-versus-host disease (aGVHD) remains a matter of concern after RIC allo-SCT, and its incidence might be expected to be higher in elderly and high-risk patients. This report investigated mycophenolate mofetil (MMF) and cyclosporin A (CsA) combination (n=14) in comparison to CsA alone (n=20) for GVHD prophylaxis in cancer patients aged over 50 years (27 haematological malignancies and seven solid tumours) receiving an HLA-identical sibling antithymocyte-globulin (ATG)-based RIC allo-SCT. Baseline demographic characteristics and risk factors for aGVHD were comparable between both groups. Although MMF administration was not associated with any significant toxicity, the cumulative incidence of any form of GVHD was comparable between both groups (cumulative incidence of grade II-IV aGVHD, 50% (95% CI, 28-72%) for CsA alone, as compared to 64% (95% CI, 39-89%) to CsA and MMF, P=NS), suggesting that adjunction of MMF to CsA is feasible, but does not translate towards a significant reduction of aGVHD, at least in the context ATG-based RIC allo-SCT.

  17. Reduced-intensity conditioning regimen using low-dose total body irradiation before allogeneic transplant for hematologic malignancies: Experience from the European Group for Blood and Marrow Transplantation

    SciTech Connect

    Belkacemi, Yazid . E-mail: y-belkacemi@o-lambret.fr; Labopin, Myriam; Hennequin, Christophe; Hoffstetter, Sylvette; Mungai, Raffaello; Wygoda, Marc; Lundell, Marie; Finke, Jurgen; Aktinson, Chris; Lorchel, Frederic; Durdux, Catherine; Basara, Nadezda

    2007-02-01

    Purpose: The high rate of toxicity is the limitation of myelobalative regimens before allogeneic transplantation. A reduced intensity regimen can allow engraftment of stem cells and subsequent transfer of immune cells for the induction of a graft-vs.-tumor reaction. Methods and Materials: The data from 130 patients (80 males and 50 females) treated between 1998 and 2003 for various hematologic malignancies were analyzed. The median patient age was 50 years (range, 3-72 years). Allogeneic transplantation using peripheral blood or bone marrow, or both, was performed in 104 (82%), 22 (17%), and 4 (3%) patients, respectively, from HLA identical sibling donors (n = 93, 72%), matched unrelated donors (n = 23, 18%), mismatched related donors (4%), or mismatched unrelated donors (6%). Total body irradiation (TBI) at a dose of 2 Gy delivered in one fraction was given to 101 patients (78%), and a total dose of 4-6 Gy was given in 29 (22%) patients. The median dose rate was 14.3 cGy/min (range, 6-16.4). Results: After a median follow-up period of 20 months (range, 1-62 months), engraftment was obtained in 122 patients (94%). Acute graft-vs.-host disease of Grade 2 or worse was observed in 37% of patients. Multivariate analysis showed three favorable independent factors for event-free survival: HLA identical sibling donor (p < 0.0001; relative risk [RR], 0.15), complete remission (p < 0.0001; RR, 3.08), and female donor to male patient (p = 0.006; RR 2.43). For relapse, the two favorable prognostic factors were complete remission (p < 0.0001, RR 0.11) and HLA identical sibling donor (p = 0.0007; RR 3.59). Conclusions: In this multicenter study, we confirmed high rates of engraftment and chimerism after the reduced intensity regimen. Our results are comparable to those previously reported. Radiation parameters seem to have no impact on outcome. However, the lack of a statistically significant difference in terms of dose rate may have been due, in part, to the small population

  18. Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis.

    PubMed

    Ghosh, Nilanjan; Karmali, Reem; Rocha, Vanderson; Ahn, Kwang Woo; DiGilio, Alyssa; Hari, Parameswaran N; Bachanova, Veronika; Bacher, Ulrike; Dahi, Parastoo; de Lima, Marcos; D'Souza, Anita; Fenske, Timothy S; Ganguly, Siddhartha; Kharfan-Dabaja, Mohamed A; Prestidge, Tim D; Savani, Bipin N; Smith, Sonali M; Sureda, Anna M; Waller, Edmund K; Jaglowski, Samantha; Herrera, Alex F; Armand, Philippe; Salit, Rachel B; Wagner-Johnston, Nina D; Fuchs, Ephraim; Bolaños-Meade, Javier; Hamadani, Mehdi

    2016-09-10

    Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor-based GVHD prophylaxis. Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD. © 2016 by American Society of Clinical Oncology.

  19. Persistence of Recipient Human Leucocyte Antigen (HLA) Antibodies and Production of Donor HLA antibodies Following Reduced Intensity Allogeneic Haematopoietic Stem Cell Transplantation

    PubMed Central

    Fasano, Ross M.; Mamcarz, Ewelina; Adams, Sharon; Jerussi, Theresa Donohue; Sugimoto, Kyoko; Tian, Xin; Flegel, Willy A.; Childs, Richard W.

    2014-01-01

    The effects of reduced intensity conditioning (RIC) on human leucocyte antigen (HLA)-alloimmunization and platelet transfusion refractoriness (PTR) following allogeneic haematopoietic stem cell transplantation (Allo-HSCT) are unknown. We studied HLA-alloantibodies in a cohort of 16 patients (8 HLA-alloimmunized with pre-transplant histories of PTR and 8 non-alloimmunized controls) undergoing Allo-HSCT using fludarabine/cyclophosphamide-based RIC. Pre- and post-transplant serum samples were analysed for HLA-antibodies and compared to myeloid, T-cell and bone marrow plasma cell chimaerism. Among alloimmunized patients, the duration that HLA-antibodies persisted post-transplant correlated strongly with pre-transplant HLA-antibody mean fluorescence intensity (MFI) and PRA levels (Spearman’s rank correlation = 0.954 (p=0.0048) and 0.865 (p=0.0083) respectively). Pre-transplant MFI >10,000 was associated with post-transplant HLA antibody persistence >100 days (p=0.029). HLA-antibodies persisted ≥100 days in 3/8 patients despite recipient chimaerism being undetectable in all lympho-haematopoietic lineages including plasma cells. Post-transplant de-novo HLA-antibodies developed in 3 control patients with 2 developing PTR; the donors for 2 of these patients demonstrated pre-existing HLA-antibodies of equivalent specificity to those in the patient, confirming donor origin. These data show HLA-antibodies may persist for prolonged periods following RIC. Further study is needed to determine the incidence of post-transplant PTR as a consequence of donor–derived HLA alloimmunization before recommendations on donor HLA-antibody screening can be made. PMID:24750103

  20. Graft-versus-lymphoma effect in refractory cutaneous T-cell lymphoma after reduced-intensity HLA-matched sibling allogeneic stem cell transplantation.

    PubMed

    Herbert, K E; Spencer, A; Grigg, A; Ryan, G; McCormack, C; Prince, H M

    2004-09-01

    Cutaneous T-cell lymphomas (CTCL) are rare diseases that, in their advanced stages or in transformation, have a poor prognosis. Autologous stem cell transplantation (Au-SCT) after high-dose therapy has yielded disappointing results. Allogeneic transplantation (allo-SCT) provides the potential advantage of an immune-mediated graft-versus-lymphoma (GVL) effect. Reduced-intensity allo-SCT potentially offers a GVL effect, but with diminished toxicity related to the induction regimen; however, published experience with this approach in CTCL is limited. We report a series of three patients (age 35-49) with advanced, refractory (n=2) or transformed (n=1) CTCL who underwent reduced-intensity allo-SCT in the context of active disease. All three survived the peri-transplant period and, despite later having disease relapse, all exhibited evidence of a GVL effect. Relapses of the disease were in the context of immune suppression for graft-versus-host disease (GVHD), and when immune suppression was reduced, responses were regained. A comparison is made of these results to those in a review of the published literature to date. We conclude that while a GVL can be achieved for CTCL with reduced-intensity allogeneic transplantation, the clinical benefits are short lived and novel approaches are required to obtain sustained remissions.

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

    PubMed

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

    2016-07-01

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

  2. REDUCED INTENSITY HEMATOPOIETIC CELL TRANSPLANTATION FOR PATIENTS WITH PRIMARY MYELOFIBROSIS: A COHORT ANALYSIS FROM THE CENTER FOR INTERNATIONAL BLOOD AND MARROW TRANSPLANT RESEARCH

    PubMed Central

    Gupta, Vikas; Malone, Adriana K.; Hari, Parameswaran N.; Ahn, Kwang Woo; Hu, Zhen-Huan; Gale, Robert Peter; Ballen, Karen K.; Hamadani, Mehdi; Olavarria, Eduardo; Gerds, Aaron T.; Waller, Edmund K.; Costa, Luciano J.; Antin, Joseph H.; Kamble, Rammurti T.; van Besien, Koen M.; Savani, Bipin N.; Schouten, Harry C.; Szer, Jeffrey; Cahn, Jean-Yves; de Lima, Marcos J.; Wirk, Baldeep; Aljurf, Mahmoud D.; Popat, Uday; Bejanyan, Nelli; Litzow, Mark R.; Norkin, Maxim; Lewis, Ian D.; Hale, Gregory A.; Woolfrey, Ann E.; Miller, Alan M.; Ustun, Celalettin; Jagasia, Madan H.; Lill, Michael; Maziarz, Richard T.; Cortes, Jorge; Kalaycio, Matt E.; Saber, Wael

    2014-01-01

    We evaluated the outcomes and associated prognostic factors in 233 patients undergoing allogeneic hematopoietic cell transplantation (HCT) for primary myelofibrosis (MF) using reduced intensity conditioning (RIC). Median age at HCT was 55 years. Donors were: matched sibling donor (MSD), 34%; HLA-well-matched unrelated donors (URD), 45%; and partially/mismatched URD, 21%. Risk stratification according to Dynamic International Prognostic Scoring System (DIPSS): low, 12%; intermediate-1, 49%; intermediate-2, 37%; and high, 1%. The probability of survival at 5-years was 47% (95% CI 40–53). In a multivariate analysis, donor type was the only independent factor associated with survival. Adjusted probabilities of survival at 5-years for MSD, well matched URD and partially matched/mismatched URD were 56% (95% CI 44–67), 48% (95% CI 37–58), and 34% (95% CI 21–47), respectively (p=0.002). Relative risks (RR) for NRM for well-matched URD and partially matched/mismatched URD were 3.92 (p=0.006) and 9.37 (p<0.0001), respectively. A trend towards increased NRM (RR 1.7, p=0.07) and inferior survival (RR 1.37, p=0.10) was observed in DIPSS-intermediate-2/high-risk patients compared to DIPSS-low/intermediate-1 risk patients. RIC HCT is a potentially curative option for patients with MF, and donor type is the most important factor influencing survival in these patients. PMID:24161923

  3. Impact of Human Leukocyte Antigen Allele Mismatch in Unrelated Bone Marrow Transplantation with Reduced-Intensity Conditioning Regimen.

    PubMed

    Yokoyama, Hisayuki; Kanda, Junya; Fuji, Shigeo; Kim, Sung-Won; Fukuda, Takahiro; Najima, Yuho; Ohno, Hitoshi; Uchida, Naoyuki; Ueda, Yasunori; Eto, Tetsuya; Iwato, Koji; Kobayashi, Hikaru; Ozawa, Yukiyasu; Kondo, Tadakazu; Ichinohe, Tatsuo; Atsuta, Yoshiko; Kanda, Yoshinobu

    2017-02-01

    The impact of HLA mismatch in hematopoietic stem cell transplantation with reduced-intensity conditioning (RIC) has not been fully examined. We analyzed a total of 1130 cases to examine the effects of HLA allele mismatch in unrelated bone marrow transplantation (BMT) with RIC in the Japan Marrow Donor Program registry cohort. Compared with HLA 8/8-allele match (n = 720, 8/8 match), both 1 (n = 295, 7/8 match) and 2 allele mismatches (n = 115, 6/8 match) were associated with significant reduction of overall survival (OS) (hazard ratio [HR],  1.34; P = .0024 and HR, 1.33; P = .035 for 7/8 and 6/8 match, respectively). The incidence of grades 2 to 4 acute graft-versus-host disease (aGVHD) increased with increasing number of mismatched alleles (HR, 1.36 and HR, 2.08 for 7/8 and 6/8 match, respectively). Nonrelapse mortality showed a similar tendency to aGVHD (HR, 1.35 for 7/8 and HR, 1.63 for 6/8). One-allele mismatches at the HLA-A or -B and HLA-C loci were significantly associated with inferior OS compared with 8/8 match (HR, 1.64 for A or B mismatch and HR, 1.41 for C mismatch), whereas HLA-DRB1 allele mismatch was not (HR, 1.16; P = .30). However, the effect of HLA-A or -B and -C mismatch on OS was not observed in those who received RIC BMT since 2010, in contrast to recipients before 2010. These results suggested that in unrelated RIC BMT, 1-allele mismatch is associated with poorer outcome, and the impact of HLA mismatch may differ depending on the HLA locus, although these HLA mismatch effects may be different in recent cases.

  4. Bone marrow transplant

    MedlinePlus

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; ...

  5. Risk adopted allogeneic hematopoietic stem cell transplantation using a reduced intensity regimen for children with thalassemia major.

    PubMed

    Hussein, Ayad Ahmed; Al-Zaben, Abdulhadi; Ghatasheh, Lubna; Natsheh, Abeer; Hammada, Tuka; Abdel-Rahman, Fawzi; Abu-Jazar, Husam; Sharma, Shanta; Najjar, Rula; Frangoul, Haydar

    2013-08-01

    Patients with thalassemia in developing countries have limited access to safe transfusions, regular medical care and chelation therapy. Although allogeneic hematopoietic stem cell transplantation (HSCT) can offer a curative approach, there are limited data on the use of this procedure in developing countries. Forty-four patients underwent a risk adopted HSCT from matched related family donor in Jordan. Thirty-one patients (7 Class 1 and 24 Class 2) underwent myeloablative conditioning (MAC) with busulfan (16 mg/kg), cyclophosphamide (200 mg/kg) and antithymocyte globulin (ATG). Thirteen patients all with Class 3, seven with hepatitis C received reduced intensity conditioning (RIC) with busulfan (8 mg/kg), fludarabine (175 mg/m(2)), total lymphoid irradiation (500 cGy) and ATG. All patients had initial neutrophil and platelet engraftment. Secondary graft failure was observed in 2 (6%) patients receiving myeloablative HSCT and 3 (23%) patients receiving RIC. At a median follow up of 64 months (13-108), 43 of 44 patients are alive. The 5-year probability of overall survival (OS) was 97.8% for all patients, 96.8% for patients received MAC and 100% for patients received RIC. The 5-year probability of thalassemia-free survival was 86.4% for all patients, 90.3% and 77% for patients who received MAC and RIC, respectively. Implementing a risk-adopted therapy in patient with thalassemia in Jordan can result in an excellent thalassemia free and OS, especially in those at highest risk. Copyright © 2013 Wiley Periodicals, Inc.

  6. Histology and Time to Progression Predict Survival for Lymphoma Recurring after Reduced Intensity Conditioning and Allogeneic Hematopoietic Cell Transplantation

    PubMed Central

    Ram, Ron; Gooley, Ted A.; Maloney, David G.; Press, Oliver W.; Pagel, John M.; Petersdorf, Stephen H.; Shustov, Andrei R.; Flowers, Mary E.D.; O’Donnell, Paul; Sandmaier, Brenda M.; Storb, Rainer F.; Gopal, Ajay K.

    2011-01-01

    Reduced-intensity-conditioning (RIC) prior to allogeneic hematopoietic cell transplantation (HCT) is increasingly employed as a potentially curative option for patients with advanced lymphoma; however relapse remains a major challenge. Unfortunately, little data exist on the outcomes, predictors of survival, and results of specific management strategies of such individuals. One-hundred-one consecutive relapses occurred and were evaluated in 280 lymphoma patients following RIC-HCT. Characteristics included: aggressive non-Hodgkin lymphoma (NHL) (n=42), indolent NHL (n=33) and Hodgkin’s Lymphoma (HL) (n=26). Median time to relapse was 90 (range 3 - 1275) days and graft-versus-host-disease at relapse was present in 56 (55%) patients. Interventions following relapse included no therapy (n=14), withdrawal of immunosuppression alone (n=11), chemoradiotherapy (n=60), and donor lymphocyte infusion/second HCT (n=16). Overall survival (OS) at 3 and 5 years following relapse was 33% (95%CI 23-44%) and 23% (95%CI 13-34%), respectively. Aggressive NHL (vs indolent disease, HR=2.29, p=.008) and relapse <1 month after HCT (vs >6 months HR=3.17 p=.004) were each associated with increased mortality. Estimated 3-year OS after relapse for aggressive, indolent and HL was 16% (95%CI 5-32%), 40% (95%CI 19-61%) and 47% (95%CI 29-64%), respectively. The 1-year survival for patients relapsing within 1 month of HCT was 24% as compared to 52%, 74%, and 77%, for those relapsing at 1-3 months, 3-6 months, and >6 months after HCT. We conclude that despite relapse of lymphoma after RIC-HCT, some patients can experience prolonged survival with better post-relapse outcomes occurring in patients with indolent NHL, HL or late relapse. PMID:21536145

  7. An intermediate alemtuzumab schedule reduces the incidence of mixed chimerism following reduced-intensity conditioning hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis.

    PubMed

    Marsh, Rebecca A; Kim, Mi-Ok; Liu, Chunyan; Bellman, Denise; Hart, Laura; Grimley, Michael; Kumar, Ashish; Jodele, Sonata; Myers, Kasiani C; Chandra, Sharat; Leemhuis, Tom; Mehta, Parinda A; Bleesing, Jack J; Davies, Stella M; Jordan, Michael B; Filipovich, Alexandra H

    2013-11-01

    Reduced-intensity conditioning (RIC) improves the outcomes of hematopoietic cell transplantation (HCT) in patients with hemophagocytic lymphohistiocytosis (HLH). Proximal (ie, close to graft infusion) dosing of alemtuzumab is associated with a high incidence of mixed chimerism, whereas distal (ie, distant from graft infusion) dosing is associated with less mixed chimerism but more acute graft-versus-host disease (GVHD). The alemtuzumab dose per kilogram of body weight also influences these outcomes. We hypothesized that an intermediate alemtuzumab dosing schedule would reduce mixed chimerism and maintain a low incidence of acute GVHD. In this study, 24 consecutive HCTs were performed in patients with HLH or a related disorder using a novel intermediate alemtuzumab schedule of 1 mg/kg starting on day -14. The cumulative incidences (CIs) of mixed chimerism, upfront acute GVHD grades II-IV, and receipt of additional hematopoietic cell products after HCT were compared in patients treated with a distal alemtuzumab schedule (n = 15) and those treated with a proximal alemtuzumab schedule (n = 33). All patients received fludarabine and melphalan. The CI of mixed chimerism was 31% in the intermediate group, 72% in the proximal group (P < .01), and 75% in the distal group patients who received ≥2 mg/kg alemtuzumab (P = .03). The CI of acute GVHD grades II-IV before the development of mixed chimerism was 4% in the intermediate group, 0% in the proximal group, and 13% in the distal group (P = .04, proximal versus distal). The 1-year CI of administration of additional hematopoietic cell products for mixed chimerism (donor lymphocyte infusion ± hematopoietic stem cell boost ± repeat HCT) was 14% in the intermediate group, 53% in the proximal group (P = .01), and 38% in the distal ≥2 mg/kg alemtuzumab group (P = .02). Our findings indicate that intermediate RIC reduces the incidence of mixed chimerism, is associated with a low incidence of upfront acute

  8. Quality of life assessment in patients undergoing reduced intensity conditioning allogeneic as compared to autologous transplantation: results of a prospective study.

    PubMed

    Díez-Campelo, M; Pérez-Simón, J A; González-Porras, J R; García-Cecilia, J M; Salinero, M; Caballero, M D; Cañizo, M C; Ocio, E M; Miguel, J F San

    2004-10-01

    The aim was to analyze quality-of-life (QOL) during the first year post transplant in 47 patients undergoing reduced-intensity conditioning (RIC) allotransplantation, and to compare these with a similar subgroup of patients receiving autologous stem cell transplantation (ASCT). We used self-reported questionnaires. Each answer scored from 0 (not at all) to 4 (very much), with higher scores indicating worse functioning. Mean value of physical categories among RIC transplants ranged between 1.23 and 0.77 indicating that patients scored very low for physical symptoms. Patients undergoing ASCT had higher scores in questionnaires performed early after transplant and then gradually improved (P < 0.001). Overall, when we compared physical functioning scores, allo-RIC did significantly better (P = 0.049). Nevertheless, while allo-RIC scores were significantly better for the first three questionnaires, ASCT patients did better in the last two questionnaires. These findings are in accordance with the toxicities observed in both subgroups which are lower in the RIC group early after transplant. No significant differences were observed between either subgroup for any of the functional, social/ family, psychological distress and satisfaction with doctor/nurse relationship items. We have observed similar QOL among patients undergoing RIC-allo as compared to ASCT although GVHD remains an important 'event' in QOL.

  9. An Intermediate Alemtuzumab Schedule Reduces the Incidence of Mixed Chimerism Following Reduced-Intensity Conditioning Hematopoietic Cell Transplantation for Hemophagocytic Lymphohistiocytosis

    PubMed Central

    Marsh, Rebecca A.; Kim, Mi-Ok; Liu, Chunyan; Bellman, Denise; Hart, Laura; Grimley, Michael; Kumar, Ashish; Jodele, Sonata; Myers, Kasiani C.; Chandra, Sharat; Leemhuis, Tom; Mehta, Parinda A.; Bleesing, Jack J.; Davies, Stella M.; Jordan, Michael B.; Filipovich, Alexandra H.

    2014-01-01

    Reduced-intensity conditioning (RIC) improves the outcomes of hematopoietic cell transplantation (HCT) in patients with hemophagocytic lymphohistiocytosis (HLH). Proximal (ie, close to graft infusion) dosing of alemtuzumab is associated with a high incidence of mixed chimerism, whereas distal (ie, distant from graft infusion) dosing is associated with less mixed chimerism but more acute graft-versus-host disease (GVHD). The alemtuzumab dose per kilogram of body weight also influences these outcomes. We hypothesized that an intermediate alemtuzumab dosing schedule would reduce mixed chimerism and maintain a low incidence of acute GVHD. In this study, 24 consecutive HCTs were performed in patients with HLH or a related disorder using a novel intermediate alemtuzumab schedule of 1 mg/kg starting on day -14. The cumulative incidences (CIs) of mixed chimerism, upfront acute GVHD grades II-IV, and receipt of additional hematopoietic cell products after HCT were compared in patients treated with a distal alemtuzumab schedule (n = 15) and those treated with a proximal alemtuzumab schedule (n = 33). All patients received fludarabine and melphalan. The CI of mixed chimerism was 31% in the intermediate group, 72% in the proximal group (P < .01), and 75% in the distal group patients who received ≥2 mg/kg alemtuzumab (P = .03). The CI of acute GVHD grades II-IV before the development of mixed chimerism was 4% in the intermediate group, 0% in the proximal group, and 13% in the distal group (P = .04, proximal versus distal). The 1-year CI of administration of additional hematopoietic cell products for mixed chimerism (donor lymphocyte infusion ± hematopoietic stem cell boost ± repeat HCT) was 14% in the intermediate group, 53% in the proximal group (P = .01), and 38% in the distal ≥2 mg/kg alemtuzumab group (P = .02). Our findings indicate that intermediate RIC reduces the incidence of mixed chimerism, is associated with a low incidence of upfront acute GVHD, and decreases

  10. Role of reduced intensity conditioning in T-cell and B-cell immune reconstitution after HLA-identical bone marrow transplantation in ADA-SCID.

    PubMed

    Cancrini, Caterina; Ferrua, Francesca; Scarselli, Alessia; Brigida, Immacolata; Romiti, Maria Luisa; Barera, Graziano; Finocchi, Andrea; Roncarolo, Maria Grazia; Caniglia, Maurizio; Aiuti, Alessandro

    2010-10-01

    The treatment of choice for severe combined immunodeficiency is bone marrow transplantation from an HLA-identical donor sibling without conditioning. However, this may result in low donor stem cell chimerism, leading to reduced long-term immune reconstitution. We compared engraftment, metabolic, and T-cell and B-cell immune reconstitution of HLA-identical sibling bone marrow transplantation performed in 2 severe combined immunodeficiency infants with adenosine deaminase deficiency from the same family treated with or without a reduced intensity conditioning regimen (busulfan/fludarabine). Only the patient who received conditioning showed a stable mixed chimerism in all lineages, including bone marrow myeloid and B cells. The use of conditioning resulted in higher thymus-derived naïve T cells and T-cell receptor excision circles, normalization of the T-cell repertoire, and faster and complete B-cell and metabolic reconstitution. These results suggest the utility of exploring the use of reduced intensity conditioning in bone marrow transplantation from HLA-identical donor in severe combined immunodeficiency to improve long-term immune reconstitution.

  11. Outcome of Allogeneic Stem Cell Transplantation Following Reduced-Intensity Conditioninig Regimen in Patients With Idiopathic Myelofibrosis: the G.I.T.M.O. Experience

    PubMed Central

    Patriarca, Francesca; Bacigalupo, Andrea; Sperotto, Alessandra; Isola, Miriam; Bruno, Barbara; van Lint, Maria Teresa; Iori, Anna Paola; Di Bartolomeo, Paolo; Musso, Maurizio; Pioltelli, Pietro; Visani, Giuseppe; Iacopino, Pasquale; Fanin, Renato; Bosi., Alberto

    2010-01-01

    Background: Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for myelofibrosis (MI), though limited by a high rate of transplant-related mortality (TRM). In the present study we evaluate the outcome of MI patients undergoing an allogenic SCT after reduced intensity conditioning (RIC) regimens, and the impact of prognostic factors. Design and methods: Fifty two patients were transplanted in 26 Italian centres between 1998 and 2006. We analyzed the influence of patient and disease clinical features before SCT and of transplant procedures on TRM and overall survival (OS) by means of univariate and multivariate analyses. Results: At SCT, median age was 52,5 years (32–68) and 89% of the patients had an intermediate or high Dupriez score. Conditioning regimens were based on fludarabine plus busulphan in 27% of patients, thiotepa plus cyclophosphamide in 46% and miscellaneous drug combinations in the other 27% of cases. Stem cells came from matched sibling donors for 75% of the patients and mismatched sibling or unrelated donors for the remaining 25%. The cumulative incidence of engraftment at day 90 after transplant was 83% (95% CI, 0.87–0.97). The estimated 1-year TRM was 30%. The estimated 3-year event-free-survival (EFS) and OS after hematopoietic SCT was 44% and 38% respectively. In multivariate analysis, an higher leukocyte count and circulating blasts in the peripheral blood before SCT significantly reduced EFS and OS respectively. Interpretation and conclusions: We conclude that the extension of the disease before transplantation based on the presence of circulating blasts and high leukocyte counts significantly affected the outcome after HSCT PMID:21415963

  12. Long-term survival outcomes of reduced-intensity allogeneic or autologous transplantation in relapsed grade 3 follicular lymphoma

    PubMed Central

    Klyuchnikov, Evgeny; Bacher, Ulrike; Ahn, Kwang Woo; Carreras, Jeanette; Kröger, Nicolaus M.; Hari, Parameswaran N.; Ku, Grace H.; Ayala, Ernesto; Chen, Andy I.; Chen, Yi-Bin; Cohen, Jonathon B.; Freytes, César O.; Gale, Robert Peter; Kamble, Rammurti T.; Kharfan-Dabaja, Mohamed A.; Lazarus, Hillard M.; Martino, Rodrigo; Mussetti, Alberto; Savani, Bipin N.; Schouten, Harry C.; Usmani, Saad Z.; Wiernik, Peter H.; Wirk, Baldeep; Smith, Sonali M.; Sureda, Anna; Hamadani, Mehdi

    2015-01-01

    Grade-3 follicular lymphoma (FL) has aggressive clinical behavior. To evaluate the optimal first transplantation approach in relapsed/refractory grade-3 FL patients, we compared the long-term outcomes after allogeneic (allo-) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era. A total of 197 patients undergoing first RIC allo-HCT or first auto-HCT during 2000-2012 were included. Rituximab-naïve patients were excluded. Allo-HCT recipients were younger; more heavily pretreated, and had a longer interval between diagnosis and HCT. The 5-year probabilities of non-relapse mortality (NRM), relapse/progression, progression-free survival (PFS) and overall survival (OS) for auto-HCT vs. allo-HCT groups were 4% vs. 27% (p<0.001); 61% vs. 20% (p<0.001); 36% vs. 51% (p=0.07) and 59% vs. 54% (p=0.7), respectively. On multivariate analysis auto-HCT was associated with reduced risk of NRM (RR=0.20; p=0.001). Within the first 11months post-HCT auto- and allo-HCT had similar risks of relapse/progression and PFS. Beyond 11months, auto-HCT was associated with higher risk of relapse/progression (RR=21.3; p=0.003) and inferior PFS (RR=3.2; p=0.005). In the first 24 months post-HCT, auto-HCT was associated with improved OS (RR=0.42; p=0.005), but in long-time survivors (beyond 24 months) it was associated with inferior OS (RR=3.6; p=0.04). RIC allo-HCT as the first transplant approach can provide improved PFS and OS, in long-term survivors. PMID:26437062

  13. Reduced-intensity conditioning for unrelated donor progenitor cell transplantation: long-term follow-up of the first 285 reported to the national marrow donor program.

    PubMed

    Giralt, Sergio; Logan, Brent; Rizzo, Douglas; Zhang, Mei-Jie; Ballen, Karen; Emmanouilides, Christos; Nath, Rajneesh; Parker, Pablo; Porter, David; Sandmaier, Brenda; Waller, Edmund K; Barker, Juliet; Pavletic, Steven; Weisdorf, Daniel

    2007-07-01

    To determine the long-term outcome of patients undergoing unrelated donor transplantation (URD) after a reduced intensity conditioning (RIC) regimen, we performed a retrospective analysis of the transplant outcomes of the first 5 years of RIC experience as reported to the National Marrow Donor Program (NMDP). Patients were included if they were older than 18 years and had undergone a URD transplant procured through the NMDP from January 1, 1996 until May 31, 2001, with an RIC regimen for a hematologic malignancy. The number of URDs performed using an RIC increased from 59 during 1996 to 1999, to 149 in the year 2000. RIC recipients were older (53 vs. 33 years) and had a higher likelihood of having advanced disease (81% vs. 51%) when compared to patients undergoing a myeloablative conditioning regimen during the same time period. The 5-year survival rate is 23% (95% confidence interval [CI]; 18, 28), whereas the 5 year incidence of progression/relapse is 43.4% (95% CI; 37,49). Prognostic factors for better overall survival on multivariate analysis were earlier disease stage, longer time to transplant from diagnosis, better HLA match, >or=90% performance score, and use of peripheral blood stem cells. This analysis demonstrates that long-term survival and disease control can be obtained with URD progenitor cell transplantation after RIC conditioning. However, only prospective trials will define the optimal role of this therapy in patients with hematologic malignancies. Therefore, URD transplantation with RIC should continue to be explored in the context of clinical trials.

  14. Initial fluconazole prophylaxis may not be required in adults with acute leukemia or myelodysplastic/myeloproliferative disorders after reduced intensity conditioning peripheral blood stem cell allogeneic transplantation.

    PubMed

    Brissot, Eolia; Cahu, Xavier; Guillaume, Thierry; Delaunay, Jacques; Ayari, Sameh; Peterlin, Pierre; Le Bourgeois, Amandine; Harousseau, Jean-Luc; Milpied, Noel; Bene, Marie-Christine; Moreau, Philippe; Mohty, Mohamad; Chevallier, Patrice

    2015-04-01

    In the myeloablative transplant setting, the early use of fluconazole prophylaxis provides a benefit in overall survival. Recent changes in transplantation practices, including the use of peripheral blood stem cells (PBSC) and/or reduced intensity conditioning (RIC) regimen may have favorably impacted the epidemiology of invasive fungal infections (IFI) after allogeneic stem cell transplantation (allo-SCT). Yet, the impact of removing fluconazole prophylaxis after RIC PBSC allotransplant is ill known. Here, a retrospective analysis was performed comparing patients who received fluconazole as antifungal prophylaxis (n = 53) or not (n = 56) after allo-SCT for acute leukemia or myelodysplastic/myeloproliferative syndrome. Sixteen IFI were documented (14 %) at a median time of 103 days after transplantation, including eight before day +100, at a similar rate, whether the patients received fluconazole prophylaxis (13 %) or not (16 %). IFI were due mainly to Aspergillus species (87 %), and only two Candida-related IFI (13 %) were documented in the non-fluconazole group before day +100. The incidences of IFI (overall, before or after day +100) as well as 3-year overall and disease-free survival, non-relapse mortality, or acute and chronic graft-versus-host disease (GVHD) were similar between both groups. In conclusion, this study suggests that fluconazole may not be required at the initial phase of RIC allo-SCT using PBSC. This result has to be confirmed prospectively while Aspergillus prophylaxis should be discussed in this particular setting.

  15. Fractionated gemtuzumab ozogamicin combined with intermediate-dose cytarabine and daunorubicin as salvage therapy in very high-risk AML patients: a bridge to reduced intensity conditioning transplant?

    PubMed

    Paubelle, Etienne; Ducastelle-Leprêtre, Sophie; Labussière-Wallet, Hélène; Nicolini, Franck Emmanuel; Barraco, Fiorenza; Plesa, Adriana; Salles, Gilles; Wattel, Eric; Thomas, Xavier

    2017-03-01

    Outcome of patients with primary refractory/relapsed (R/R) acute myeloid leukemia (AML) remains dismal. Herein, we present a retrospective monocentric study of 24 very high-risk AML patients who received a combination of fractionated gemtuzumab ozogamicin (GO) with intermediate-dose cytarabine and daunorubicin as salvage therapy. Median age was 55.3 years. Diagnostic was secondary AML for 33% of them. Seven patients had favorable risk, 8 had intermediate-1 or intermediate-2, and 6 had unfavorable risk of AML according to the European LeukemiaNet prognostic index. Complete remission was achieved in 50% of cases (46% in refractory and 55% in relapsed AML) without excessive toxicity. Thirteen patients could be referred for transplant. Only allogeneic hematopoietic stem cell transplantation provided a benefit in this patient cohort with a 1-year overall survival of 50.7 versus 18.1% in the absence of transplantation. Patients treated with reduced intensity conditioning (RIC) showed a longer survival as compared to those undergoing myeloablative conditioning regimen mainly because of decreased toxicity.Our data suggest that salvage therapy with fractionated GO combined with intermediate-dose cytarabine and daunorubicin in very high-risk patients may serve as a potential bridge therapy to RIC transplant.

  16. Bone marrow transplant - discharge

    MedlinePlus

    Transplant - bone marrow - discharge; Stem cell transplant - discharge; Hematopoietic stem cell transplant - discharge; Reduced intensity; Non-myeloablative transplant - discharge; Mini transplant - discharge; Allogenic bone marrow transplant - ...

  17. The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome–negative acute lymphoblastic leukemia in first and second complete remission

    PubMed Central

    Marks, David I.; Wang, Tao; Pérez, Waleska S.; Antin, Joseph H.; Copelan, Edward; Gale, Robert Peter; George, Biju; Gupta, Vikas; Halter, Joerg; Khoury, H. Jean; Klumpp, Thomas R.; Lazarus, Hillard M.; Lewis, Victor A.; McCarthy, Philip; Rizzieri, David A.; Sabloff, Mitchell; Szer, Jeff; Tallman, Martin S.

    2010-01-01

    We examined the efficacy of reduced-intensity conditioning (RIC) and compared outcomes of 93 patients older than 16 years after RIC with 1428 patients receiving full-intensity conditioning for allografts using sibling and unrelated donors for Philadelphia-negative acute lymphoblastic leukemia (ALL) in first or second complete remission. RIC conditioning included busulfan 9 mg/kg or less (27), melphalan 150 mg/m2 or less (23), low-dose total body irradiation (TBI; 36), and others (7). The RIC group was older (median 45 vs 28 years, P < .001) and more received peripheral blood grafts (73% vs 43%, P < .001) but had similar other prognostic factors. The RIC versus full-intensity conditioning groups had slightly, but not significantly, less acute grade II-IV graft-versus-host disease (39% vs 46%) and chronic graft-versus-host disease (34% vs 42%), yet similar transplantation-related mortality. RIC led to slightly more relapse (35% vs 26%, P = .08) yet similar age-adjusted survival (38% vs 43%, P = .39). Multivariate analysis showed that conditioning intensity did not affect transplantation-related mortality (P = .92) or relapse risk (P = .14). Multivariate analysis demonstrated significantly improved overall survival with: Karnofsky performance status more than 80, first complete remission, lower white blood count, well-matched unrelated or sibling donors, transplantation since 2001, age younger than 30 years, and conditioning with TBI, but no independent impact of conditioning intensity. RIC merits further investigation in prospective trials of adult ALL. PMID:20404137

  18. Decreased serum albumin as a biomarker for severe acute graft-vs.-host disease after reduced-intensity allogeneic hematopoietic cell transplantation

    PubMed Central

    Rezvani, Andrew R.; Storer, Barry E.; Storb, Rainer F.; Mielcarek, Marco; Maloney, David G.; Sandmaier, Brenda M.; Martin, Paul J.; McDonald, George B.

    2011-01-01

    Biomarkers capable of predicting the onset and severity of acute graft-vs.-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) would enable pre-emptive and risk-stratified therapy. Severe acute GVHD leads to gastrointestinal protein loss, resulting in hypoalbuminemia. We hypothesized that decreases in serum albumin at onset of acute GVHD would predict the risk of progression to severe acute GVHD. We identified 401 patients who developed acute GVHD grades II–IV after reduced-intensity allogeneic HCT and reviewed all available serum albumin values from 30 days before HCT to 45 days after initiation of treatment for acute GVHD. A ≥0.5 g/dL decrease in serum albumin concentration from pre-transplant baseline to the onset of treatment for acute GVHD predicted the subsequent development of grade III/IV acute GVHD (vs. grade II acute GVHD) with a sensitivity of 69% and a specificity of 73%. Overall mortality at 6 months after initiation of acute GVHD treatment was 36% vs. 17% for patients with and without ≥0.5 g/dL decreases in serum albumin, respectively (p=0.0009). We conclude that change in serum albumin concentration from baseline to initiation of acute GVHD treatment is an inexpensive, readily available, and predictive biomarker of GVHD severity and mortality after reduced-intensity allogeneic HCT. PMID:21806949

  19. Impact of disease status and stem cell source on the results of reduced intensity conditioning transplant for Hodgkin’s lymphoma: a retrospective study from the French Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)

    PubMed Central

    Marcais, Ambroise; Porcher, Raphael; Robin, Marie; Mohty, Mohamad; Michalet, Mauricette; Blaise, Didier; Tabrizi, Reza; Clement, Laurence; Ceballos, Patrice; Daguindau, Etienne; Bilger, Karin; Dhedin, Nathalie; Lapusan, Simona; Bay, Jacques-Olivier; Pautas, Cécile; Garban, Frederic; Ifrah, Norbert; Guillerm, Gaelle; Contentin, Nathalie; Bourhis, Jean-Henri; Agha, Ibrahim Yakoub; Bernard, Marc; Cornillon, Jérôme; Milpied, Noel

    2013-01-01

    The role of reduced intensity allogeneic stem cell transplantation for the treatment of relapsed/refractory Hodgkin’s lymphoma remains controversial. We retrospectively analyzed 191 patients who underwent reduced intensity allogeneic stem cell transplantation between 1998 and 2008 for relapsed or refractory Hodgkin’s lymphoma and whose data were reported to the French registry. The median follow-up was 36 months. The estimated 3-year overall survival rate, progression-free survival rate, cumulative incidence of relapse and cumulative incidence of non-relapse mortality were 63%, 39%, 46%, and 16%, respectively. There was no difference in outcome between patients in complete response and in partial response at the time of transplantation with regards to overall survival (70% versus 74%, no significant difference) and progression-free survival (51% versus 42%, no significant difference). Patients with chemoresistant disease had a shorter overall survival (39% at 3 years; P=0.0003) and progression-free survival (18% at 3 years; P=0.001) than patients in complete remission. The use of umbilical cord blood as the source of stem cells was associated with a poor outcome with an increased risk of death with a hazard ratio of 3.49 (95% confidence interval: 1.26 to 9.63; P=0.016). The use of peripheral blood was associated with a better outcome for patients who where alive 1 year after transplantation with a hazard ratio of 0.38 (95% confidence interval: 0.17 to 0.83; P=0.016). Disease status at transplantation remains the most important risk factor for outcome. Our data suggest that the use of peripheral blood should be preferred whereas umbilical cord blood should be used with caution. PMID:23539540

  20. Impact of disease status and stem cell source on the results of reduced intensity conditioning transplant for Hodgkin's lymphoma: a retrospective study from the French Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC).

    PubMed

    Marcais, Ambroise; Porcher, Raphael; Robin, Marie; Mohty, Mohamad; Michalet, Mauricette; Blaise, Didier; Tabrizi, Reza; Clement, Laurence; Ceballos, Patrice; Daguindau, Etienne; Bilger, Karin; Dhedin, Nathalie; Lapusan, Simona; Bay, Jacques-Olivier; Pautas, Cécile; Garban, Frederic; Ifrah, Norbert; Guillerm, Gaelle; Contentin, Nathalie; Bourhis, Jean-Henri; Yakoub Agha, Ibrahim; Bernard, Marc; Cornillon, Jérôme; Milpied, Noel

    2013-09-01

    The role of reduced intensity allogeneic stem cell transplantation for the treatment of relapsed/refractory Hodgkin's lymphoma remains controversial. We retrospectively analyzed 191 patients who underwent reduced intensity allogeneic stem cell transplantation between 1998 and 2008 for relapsed or refractory Hodgkin's lymphoma and whose data were reported to the French registry. The median follow-up was 36 months. The estimated 3-year overall survival rate, progression-free survival rate, cumulative incidence of relapse and cumulative incidence of non-relapse mortality were 63%, 39%, 46%, and 16%, respectively. There was no difference in outcome between patients in complete response and in partial response at the time of transplantation with regards to overall survival (70% versus 74%, no significant difference) and progression-free survival (51% versus 42%, no significant difference). Patients with chemoresistant disease had a shorter overall survival (39% at 3 years; P=0.0003) and progression-free survival (18% at 3 years; P=0.001) than patients in complete remission. The use of umbilical cord blood as the source of stem cells was associated with a poor outcome with an increased risk of death with a hazard ratio of 3.49 (95% confidence interval: 1.26 to 9.63; P=0.016). The use of peripheral blood was associated with a better outcome for patients who where alive 1 year after transplantation with a hazard ratio of 0.38 (95% confidence interval: 0.17 to 0.83; P=0.016). Disease status at transplantation remains the most important risk factor for outcome. Our data suggest that the use of peripheral blood should be preferred whereas umbilical cord blood should be used with caution.

  1. The combination of sirolimus plus tacrolimus improves outcome after reduced-intensity conditioning, unrelated donor hematopoietic stem cell transplantation compared with cyclosporine plus mycofenolate

    PubMed Central

    Perez-Simón, Jose Antonio; Martino, Rodrigo; Parody, Rocío; Cabrero, Mónica; Lopez-Corral, Lucía; Valcarcel, David; Martinez, Carmen; Solano, Carlos; Vazquez, Lourdes; Márquez-Malaver, Francisco J.; Sierra, Jordi; Caballero, Dolores

    2013-01-01

    Different types of graft-versus-host disease prophylaxis have been proposed in the setting of reduced intensity and non-myeloablative allogeneic stem cell transplantation. An alternative combination with sirolimus and tacrolimus has recently been tested although comparative studies against the classical combination of a calcineurin inhibitor and mycophenolate mofetil or methotrexate are lacking. We describe the results of a prospective, multicenter trial using sirolimus + tacrolimus as immunoprophylaxis, and compare this approach with our previous experience using cyclosporine + mycophenolate in the setting of unrelated donor transplantation setting after reduced-intensity conditioning. Forty-five patients received cyclosporine + mycophenolate between 2002 and mid-2007, while the subsequent 50 patients, who were transplanted from late 2007, were given sirolimus + tacrolimus. No significant differences were observed in terms of hematopoietic recovery or acute graft-versus-host disease overall, although gastrointestinal acute graft-versus-host disease grade ≥2 was more common in the cyclosporine + mycophenolate group (55% versus 21%, respectively, P=0.003). The 1-year cumulative incidence of chronic graft-versus-host disease was 50% versus 90% for the patients treated with the sirolimus- versus cyclosporine-based regimen, respectively (P<0.001), while the incidence of extensive chronic disease was 27% versus 49%, respectively (P=0.043). The 2-year non-relapse mortality rate was 18% versus 38% for patients receiving the sirolimus- versus the cyclosporine-based regimen, respectively (P=0.02). The event-free survival and overall survival at 2 years were 53% versus 29% (P=0.028) and 70% versus 45% (P=0.018) among patients receiving the sirolimus- versus the cyclosporine-based regimen, respectively. In conclusion, in the setting of reduced intensity transplantation from an unrelated donor, promising results can be achieved with the combination of sirolimus + tacrolimus

  2. Long-term outcomes of autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis: physician's and patient's perspectives.

    PubMed

    Shevchenko, Jury L; Kuznetsov, Alexey N; Ionova, Tatyana I; Melnichenko, Vladimir Y; Fedorenko, Denis A; Kurbatova, Kira A; Gorodokin, Gary I; Novik, Andrei A

    2015-07-01

    High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (AHSCT) is a promising approach to treatment of multiple sclerosis (MS) patients. In this paper, we present the long-term outcomes of a prospective single-center study with the analysis of the safety and efficacy of HDIT + AHSCT with reduced-intensity BEAM-like conditioning regimen in 99 MS patients: mean age-35 years old; male/female-39/60; median Expanded Disability Status Scale (EDSS) = 3.5; 43 relapsing/remitting MS, 56 progressive MS. No transplant-related deaths were observed. The mobilization and transplantation procedures were well tolerated. At 6 months post-transplant, neurological improvement or stabilization was observed in all the patients except one. Cumulative incidence of disease progression was 16.7 % at 8 years after HDIT + AHSCT. Estimated event-free survival at median follow-up of 48.9 months was 80 %: 83.3 % in relapsing/remitting MS vs 75.5 % in progressive MS. Sixty-four patients who did not progress during the first 3 years post-transplant and were monitored for more than 3 years were included in long-term outcome analysis. At the median long-term follow-up of 62 months, 47 % of patients improved by at least 0.5 points on the EDSS scale as compared to baseline and exhibited improvement during the entire period of follow-up; 45 % of patients were stable. No active, new, or enlarging lesions on magnetic resonance imaging were registered in patients without disease progression. AHSCT was accompanied by a significant improvement in patient's quality of life. Due to the fact that patient selection was quite different to the other studies and that the information about disease activity prior in the disease course and its treatment was inhomogeneous, comparison with the results in the literature should be done with caution. Thus, the risk/benefit ratio of HDIT + AHSCT with reduced-intensity BEAM-like conditioning regimen in our population

  3. Low CD34 dose is associated with poor survival after reduced-intensity conditioning allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndrome.

    PubMed

    Törlén, Johan; Ringdén, Olle; Le Rademacher, Jennifer; Batiwalla, Minoo; Chen, Junfang; Erkers, Tom; Ho, Vincent; Kebriaei, Partow; Keever-Taylor, Carolyn; Kindwall-Keller, Tamila; Lazarus, Hillard M; Laughlin, Mary J; Lill, Michael; O'Brien, Tracey; Perales, Miguel-Angel; Rocha, Vanderson; Savani, Bipin N; Szwajcer, David; Valcarcel, David; Eapen, Mary

    2014-09-01

    Reduced-intensity conditioning/nonmyeloablative conditioning regimens are increasingly used in allogeneic hematopoietic cell transplantation (HCT). Reports have shown CD34(+) dose to be important for transplantation outcome using myeloablative conditioning. The role of CD34(+) dose of peripheral blood progenitor cells (PBPC) has not been previously analyzed in a large population undergoing reduced-intensity conditioning/nonmyeloablative HCT. We studied 1054 patients, ages 45 to 75 years, with acute myeloid leukemia or myelodysplastic syndrome who underwent transplantation between 2002 and 2011. Results of multivariate analysis showed that PBPC from HLA-matched siblings containing <4 × 10(6) CD34(+)/kg was associated with higher nonrelapse mortality (hazard ratio [HR], 2.03; P = .001), overall mortality (HR, 1.48; P = .008), and lower neutrophil (odds ratio [OR], .76; P = .03) and platelet (OR, .76; P = .03) recovery. PBPC from unrelated donors with CD34(+) dose < 6 × 10(6) CD34(+)/kg was also associated with higher nonrelapse (HR, 1.38; P = .02) and overall mortality (HR, 1.20; P = .05). In contrast to reports after myeloablative HCT, CD34(+) dose did not affect relapse or graft-versus-host disease with either donor type. An upper cell dose limit was not associated with adverse outcomes. These data suggest that PBPC CD34(+) doses >4 × 10(6) CD34(+)/kg and >6 × 10(6) CD34(+)/kg are optimal for HLA-matched sibling and unrelated donor HCT, respectively.

  4. Increased bacterial infections after transfusion of leukoreduced non-irradiated blood products in recipients of allogeneic stem cell transplants after reduced-intensity conditioning.

    PubMed

    Jaime-Pérez, José C; Villarreal-Villarreal, César D; Salazar-Riojas, Rosario; Méndez-Ramírez, Nereida; Vázquez-Garza, Eduardo; Gómez-Almaguer, David

    2015-03-01

    Blood components transfused to hematopoietic stem cell transplant (HSCT) recipients are irradiated to prevent transfusion-associated graft-versus-host disease (TA-GVHD). The effect of transfusing non-irradiated blood products in HSCT outcome, including incidence of transplant complications, bacterial infections, acute and chronic GVHD presentation, and characteristics, has not been documented. Clinical records as well as blood bank and electronic databases of HSCT patients grafted after reduced-intensity conditioning who received irradiated versus non-irradiated blood products, after blood irradiation became unavailable at our center, were scrutinized for transplant outcome, clinical evolution, engraftment characteristics including days to neutrophil and platelet recovery, acute and chronic GVHD, rate and type of infections, and additional transplant-related comorbidities. All transfused blood products were leukoreduced. A total of 156 HSCT recipients was studied, 73 received irradiated and 83 non-irradiated blood components. Bacterial infections were significantly more frequent in patients transfused with non-irradiated blood products, P = .04. Clinically relevant increased rates of fever and neutropenia and mucositis were also documented in these patients. No cases of TA-GVHD occurred. Classical GVHD developed in 37 patients (50.7%) who received irradiated blood products and 36 (43.9%) who received non-irradiated blood products, P = .42. Acute GVHD developed in 28 patients (38.4%) in the blood-irradiated and 33 patients (39.8%) in the non-irradiation group, P = .87. The 2-year GVHD-free survival rate was 40% in the irradiated versus 40.6% in the non-irradiation group, P = .071. Increased bacterial infections were found in HSCT recipients transfused with non-irradiated blood products, which ideally must always be irradiated.

  5. Acute GVHD is a strong predictor of full donor CD3+ T cell chimerism after reduced intensity conditioning allogeneic stem cell transplantation.

    PubMed

    El-Cheikh, Jean; Vazquez, Alberto; Crocchiolo, Roberto; Furst, Sabine; Calmels, Boris; Castagna, Luca; Lemarie, Claude; Granata, Angela; Ladaique, Patrick; Oudin, Claire; Faucher, Catherine; Chabannon, Christian; Blaise, Didier

    2012-12-01

    The monitoring of chimerism is a standard procedure to assess engraftment and achievement of full donor lymphoid cells after reduced intensity conditioning (RIC) stem cell transplantation (Allo-SCT). However, there is no consensus on when and how often to monitor post-transplant chimerism. We retrospectively analyzed our experience regarding the impact of acute graft versus host disease (GVHD) for the prediction of allograft chimerism. One-hundred-and-fifteen patients transplanted between 2001 and 2010 were identified. This group included 57 females and 58 males with a median age of 50 years (range: 26-68). Patients evaluated in this study were adult patients with hematologic malignancies, who received transplants from an HLA-matched sibling donor or matched unrelated donor (MUD) at allele level so-called 10/10, and received the RIC regimen including fludarabine/busulfan and anti-thymoglobulin (ATG). Mixed T-cell chimerism was defined as between 5 and 94% recipient cells, and full chimerism was defined as the presence of more than 95% donor T-cell chimerism (TCC). Full donor TCC was achieved in 93 patients (81%) at a median of 77 days (range: 30-120) post-transplant. The cumulative incidence of Grade 2-4 GVHD in our population was 25% (95% CI 17-34). The analysis of the population of patients with acute GVHD grade ≥2 showed that at day 120 after Allo-SCT they all had a total full donor TCC. On the other hand, 78 (68%) patients without acute GVHD grade ≥2 presented with mixed chimerism (p = 0.002) on day 120 post-transplant. Interestingly, patients who received ATG 5 mg/kg obtained a higher probability of complete chimerism compared with those receiving 2.5 mg/kg (p = 0.03). In conclusion, our study demonstrates that acute GVHD was predictive of full donor TCC after RIC Allo-SCT. Therefore, our data may challenge the concept of the frequent or close monitoring of donor chimerism in some patients with ongoing acute GVHD. However, chimerism testing could represent

  6. Reduced-intensity conditioning for allogeneic haematopoietic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: impact of alemtuzumab and donor lymphocyte infusions on long-term outcomes.

    PubMed

    Peggs, Karl S; Sureda, Anna; Qian, Wendi; Caballero, Dolores; Hunter, Ann; Urbano-Ispizua, Alvaro; Cavet, James; Ribera, Josep M; Parker, Anne; Canales, Miguel; Mahendra, Premini; Garcia-Conde, Javier; Milligan, Donald; Sanz, Guillermo; Thomson, Kirsty; Arranz, Reyes; Goldstone, Anthony H; Alvarez, Ivan; Linch, David C; Sierra, Jorge; Mackinnon, Stephen

    2007-10-01

    The introduction of reduced-intensity conditioning (RIC) has enabled the role of allogeneic transplantation to be re-evaluated in Hodgkin lymphoma (HL). While T-cell depletion reduces graft-versus-host disease (GvHD), it potentially abrogates graft-versus-tumour activity and increases infective complications. We compared the results in 67 sibling donor transplantations following RIC in multiply relapsed patients from two national phase II studies conditioned with fludarabine/melphalan. One used cyclosporine/alemtuzumab (MF-A, n = 31), the other used cyclosporine/methotrexate (MF, n = 36) as GvHD prophylaxis. There was a small excess of chemorefractory cases in the MF cohort (P = NS). MF-A resulted in significantly lower incidences of non-relapse mortality, acute and chronic GvHD, but no significant excess of relapse/progression. Post donor lymphocyte infusion (DLI) disease responses occurred in 8/14 (57%) and 6/11 (55%) patients in the MF-A and MF groups, respectively. Current progression-free survival (CPFS) was superior with MF-A (univariate analysis), with durable responses to DLI contributing to the favourable outcome (43% vs. 25%, P = 0.0356). Disease status at transplantation significantly influenced overall survival (P = 0.0038) and CPFS (P = 0.0014), retaining significance in multivariate analyses, which demonstrated a trend towards improved CPFS with T-cell depletion (P = 0.0939). These data suggest that alemtuzumab significantly reduced GvHD without resulting in a deleterious impact on survival outcomes following RIC in HL, and that durable responses to DLI may be more common following the inclusion of alemtuzumab in the conditioning protocol.

  7. Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation for Patients with Hematologic Malignancies Who Relapse following Autologous Transplantation: A Multi-Institutional Prospective Study from the Cancer and Leukemia Group B (CALGB trial 100002)

    PubMed Central

    Bashey, Asad; Owzar, Kouros; Johnson, Jeffrey L.; Edwards, Peggy S.; Kelly, Michael; Baxter-Lowe, Lee-Ann; Devine, Steven; Farag, Sherif; Hurd, David; Ball, Edward; McCarthy, Philip; Lister, John; Shea, Thomas C.; Linker, Charles

    2013-01-01

    We prospectively treated 80 patients with relapse of malignancy or secondary myelodysplasia after autologous hematopoietic cell transplantation (AHCT) with allogeneic hematopoietic cell transplantation (allo-HCT) using a reduced-intensity conditioning (RIC) regimen of fludarabine 150 mg/m2 plus intravenous busulfan 6.4 mg/kg. Both sibling (MSD) and unrelated donors (MUD) were allowed. Patients transplanted from MUD donors received more intensive graft-versus-host disease (GVHD) prophylaxis, including rabbit anti-thymocyte globulin 10 mg/kg, mycophenolate mofetil, and an extended schedule of tacrolimus. With a median follow-up of 3.1 years (0.9 to 5.8), TRM at 6 months and 2 years was 8% and 23% respectively. Neither TRM nor the rates of acute GVHD were different in those with sibling or MUD donors. Donor CD3 cell chimerism > 90% at day +30 was achieved more often in patients with MUD than with MSD donors, 70% versus 23% (p<0.0001). Median EFS was higher in patients who achieved early full donor chimerism (14.2 versus 8 mo, p = 0.0395). Allo-HCT using this RIC regimen can be performed with low TRM in patients who have received a prior AHCT. Efforts to improve early donor CD3 chimerism may improve EFS. PMID:20674758

  8. Evidence for a graft-versus-leukemia effect after allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning in acute myelogenous leukemia and myelodysplastic syndromes.

    PubMed

    Martino, Rodrigo; Caballero, María Dolores; Pérez-Simón, José Antonio; Simón, José Antonio Pérez; Canals, Carmen; Solano, Carlos; Urbano-Ispízua, Alvaro; Bargay, Joan; Léon, Angel; Sarrá, Josep; Sanz, Guillermo F; Moraleda, José María; Brunet, Salut; San Miguel, Jesús; Sierra, Jorge

    2002-09-15

    We report the results of a prospective study of a reduced-intensity conditioning (RIC) regimen followed by allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA-identical sibling in 37 patients with acute myeloid leukemia (AML; n = 17) or myelodysplastic syndrome (MDS; n = 20). The median age was 57 years, and 22 (59%) were beyond the early phase of their disease. The incidence of grade II to IV acute graft-versus-host disease (GVHD) was 19% (5% grade III-IV), and the 1-year incidence of chronic extensive GVHD was 46%. With a median follow-up of 297 days (355 days in 24 survivors), the 1-year probability of transplant-related mortality was 5%, and the 1-year progression-free survival was 66%. The 1-year incidence of disease progression in patients with and without GVHD was 13% (95% CI, 4%-34%) and 58% (95% CI, 36%-96%), respectively (P =.008). These results suggest that a graft-versus-leukemia effect plays a crucial role in reducing the risk of relapse after a RIC allograft in AML and MDS.

  9. Radiolabeled Anti-CD45 Antibody with Reduced-Intensity Conditioning and Allogeneic Transplantation for Younger Patients with Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

    PubMed Central

    Mawad, Raya; Gooley, Ted A.; Rajendran, Joseph G.; Fisher, Darrell R.; Gopal, Ajay K.; Shields, Andrew T.; Sandmaier, Brenda M.; Sorror, Mohamed L.; Deeg, H. Joachim; Storb, Rainer; Green, Damian J.; Maloney, David G.; Appelbaum, Frederick R.; Press, Oliver W.; Pagel, John M.

    2014-01-01

    We treated patients under age 50 years with 131I-anti-CD45 antibody combined with fludarabine and 2 Gy total body irradiation to create an improved hematopoietic cell transplantation (HCT) strategy for advanced acute myeloid leukemia or high-risk myelodysplastic syndrome patients. Fifteen patients received 332–1,561 mCi of 131I, delivering an average of 27 Gy to bone marrow, 84 Gy to spleen, and 21 Gy to liver. Although a maximum dose of 28 Gy was delivered to the liver, no dose-limiting toxicity was observed. Marrow doses were arbitrarily capped at 43 Gy to avoid radiation-induced stromal damage; however no graft failure or evidence of stromal damage was observed. Twelve patients (80%) developed Grade II graft-versus-host disease (GVHD), one patient developed Grade III GVHD, and no patients developed Grade IV GVHD during the first 100 days after HCT. Of the 12 patients with chronic GVHD data, 10 developed chronic GVHD, generally involving the skin and mouth. Six patients (40%) are surviving after a median of 5.0 years (range, 4.2 to 8.3 years). The estimated survival at 1 year was 73% among the 15 treated patients. Eight patients relapsed, 7 of whom subsequently died. The median time to relapse among these 8 patients was 54 days (range, 26 to 1364 days). No cases of non-relapse mortality were observed in the first year after transplant. However, two patients died in remission from complications of chronic GVHD and cardiomyopathy, at 18 months and 14 months after transplant, respectively. This study suggests that patients may tolerate myeloablative doses >28 Gy delivered to the liver using 131I-anti-CD45 antibody in addition to standard reduced intensity conditioning. Moreover, the arbitrary limit of 43 Gy to the marrow may be unnecessarily conservative, and continued escalation of targeted radioimmunotherapy doses may be feasible to further reduce relapse. PMID:24858425

  10. Comparison of Triple GVHD Prophylaxis Regimens for Nonmyeloablative or Reduced Intensity Conditioning Unrelated Mobilized Blood Cell Transplantation

    ClinicalTrials.gov

    2017-08-21

    Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Diffuse Large B-Cell Lymphoma; Hematopoietic Cell Transplantation Recipient; Loss of Chromosome 17p; Mantle Cell Lymphoma; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Hodgkin Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Recurrent Waldenstrom Macroglobulinemia; T-Cell Chronic Lymphocytic Leukemia

  11. Therapeutic potential of a reduced-intensity preparative regimen for allogeneic transplantation with cladribine, busulfan, and antithymocyte globulin against advanced/refractory acute leukemia/lymphoma.

    PubMed

    Saito, Takeshi; Kanda, Yoshinobu; Kami, Masahiro; Kato, Kazunori; Shoji, Nahoko; Kanai, Sachiyo; Ohnishi, Toshihiro; Kawano, Yoshifumi; Nakai, Kunihisa; Ogasawara, Toshie; Matsubara, Hiroshi; Makimoto, Atsushi; Tanosaki, Ryuji; Tobinai, Kensei; Wakasugi, Hiro; Takaue, Yoichi; Mineishi, Shin

    2002-04-01

    Cladribine (2-CdA) is a purine analogue that exhibits activity against a variety of hematological malignancies and has a potent immunosuppressive effect. We therefore performed a pilot study to evaluate the feasibility of a novel 2-CdA-based reduced-intensity stem cell transplantation (RIST) regimen. A total of 16 scheduled patients with hematological malignancies were enrolled for comparison of their data with conventional stem cell transplantation (n = 19). The regimen for RIST consisted of 2-CdA (0.11 mg/kg/day for 6 days), busulfan (4 mg/kg/day for 2 days), and rabbit antithymocyte globulin (2.5 mg/kg/day for 4, 2, or 0 days). The underlying diseases included acute myelogenous leukemia (n = 6), chronic myelogenous leukemia (n = 2), myelodysplastic syndrome (n = 6), and non-Hodgkin's lymphoma (n = 2). After RIST, four patients died before day 100 as a result of acute graft-versus-host disease (n = 1), bacteremia (n = 1), disseminated candidasis (n = 1) and congestive heart failure (n = 1). Another patient died of cerebral infarction on day 140. Thus, acute-phase regimen-related toxicities >grade III were observed in only one patient. Engraftment and complete donor chimerism were achieved by day 28 in 14 evaluable patients, and 6 of them (43%) experienced grade II-IV acute graft-versus-host disease. With a median follow-up of 328 days (range, 231-633 days), the actuarial 1-year overall and disease-free survival rates were 69% and 50%, respectively. Notably, among seven high-risk patients (five patients had been in complete remission two or more times and two not in complete remission with refractory disease at transplant), only two patients developed leukemia relapse after RIST. Although the recovery of CD4+ cells was significantly slower (P = 0.02) in RIST than in conventional stem cell transplantation, the incidence of clinically documented infections was not significantly different between the two groups. The results suggest that this novel regimen containing

  12. Optimal initial dose of oral cyclosporine in relation to its toxicities for graft-versus-host disease prophylaxis following reduced-intensity stem cell transplantation in Japanese patients.

    PubMed

    Kishi, Y; Murashige, N; Kami, M; Miyakoshi, S; Shibagaki, Y; Hamaki, T; Takaue, Y; Taniguchi, S

    2005-06-01

    Since the introduction of reduced-intensity stem-cell transplantation (RIST), allogeneic stem-cell transplantation has become available for elderly patients. While pharmacokinetics of cyclosporine might differ according to age or other factors, cyclosporine is uniformly started at an oral dose of 6 mg/kg/day. We retrospectively reviewed medical records of 35 patients aged between 32 and 65 (median 52) years who had undergone RIST. Doses of cyclosporine were adjusted to the target blood trough level of 150-250 ng/ml. Cyclosporine dosages were changed in 33 patients (94%). Dose reduction was required in 32 patients because of high blood levels (n=25), renal dysfunction (n=3), hepatic dysfunction (n=2), and hypertension (n=2). Cyclosporine doses were increased in one because of the suboptimal level. The median of the achieved stable doses was 3.1 mg/kg/day (range, 1.0-7.4). Five patients sustained Grade III toxicities according to NCI-CTC version 2.0: renal dysfunction (n=4), hyperbilirubinemia (n=2), and hypertension (n=2). No patients developed grade IV toxicity. There was no statistically significant difference in the frequency and severity of cyclosporine toxicities between patients aged 50 years and above and those below 50 years. The initial oral cyclosporine dose of 6 mg/kg/day was unnecessarily high irrespective of age. The possible overdose of cyclosporine might have aggravated regimen-related toxicities.

  13. Reduced-intensity allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using fludarabine, busulphan, and alemtuzumab (FBC) conditioning.

    PubMed

    Ho, Aloysius Y L; Pagliuca, Antonio; Kenyon, Michelle; Parker, Jane E; Mijovic, Aleksandar; Devereux, Stephen; Mufti, Ghulam J

    2004-09-15

    Reduced-intensity conditioned (RIC) hematopoietic stem cell transplantation (HSCT) has improved the accessibility of transplantation in patients previously ineligible. We report the results of allografting following conditioning with fludarabine, busulphan, and alemtuzumab in 62 patients with myelodysplastic syndromes (MDSs) (matched sibling donors [24] or volunteer unrelated donors [VUDs, 38]). The median age for sibling recipients was 56 years (range, 41-70 years) and for VUD recipients, 52 years (range, 22-65 years), with a median follow-up (survivors) of 524 days (range, 93-1392 days) and 420 days (range, 53-1495 days), respectively. The nonrelapse mortality (NRM) at days 100, 200, and 360 was 0%, 5%, and 5%, respectively, for siblings and 11%, 17%, and 21%, respectively, for VUD. The overall survival at one year was 73% for siblings and 71% for VUDs, with a disease-free survival (DFS) of 61% and 59%, respectively. The prognostic significance of the International Prognostic Scoring System (IPSS) was preserved. Of recipients, 86% achieved full-donor chimerism. The cumulative incidence at day 100 of grades III to IV graft-versus-host disease (GVHD) for VUD recipients was 9% and for sibling recipients, 0%. There were 26 patients (16 sibling and 10 VUD) who received donor lymphocyte infusion (DLI) at a median of 273 days (range, 126-1323 days). RIC allogeneic HSCT using this protocol appears to be safe and permits durable donor engraftment. Longer follow-up is required to confirm any potential survival advantage.

  14. Ovarian Function after Hematopoietic Cell Transplantation: A Descriptive Study Following the Use of GnRH Agonists for Myeloablative Conditioning and Observation Only for Reduced-Intensity Conditioning

    PubMed Central

    Phelan, Rachel; Mann, Elizabeth; Napurski, Char; DeFor, Todd E; Petryk, Anna; Miller, Weston P; Wagner, John E; Verneris, Michael R; Smith, Angela R

    2017-01-01

    Gonadal failure is a health and quality of life concern in hematopoietic cell transplant (HCT) survivors. While ovarian dysfunction is nearly universal following myeloablative (MA) conditioning, risk is unclear after reduced-intensity conditioning (RIC). Gonadotropin-releasing hormone agonists decrease ovarian failure rates following conventional chemotherapy but little is known about its effectiveness with HCT. We investigated the impact of leuprolide on ovarian function after MA conditioning and monitored ovarian function after RIC in this descriptive pilot study. Post-menarchal females <50 years undergoing HCT with adequate baseline ovarian function (FSH level <40 mIU/mL and normal menstruation) were eligible. Prior to MA conditioning, leuprolide was administered. Those undergoing RIC were observed. FSH was measured at various time points. Seventeen women aged 12–45 years were evaluated (7 in the intervention group and 10 observation group). Compared to the historical high rate of ovarian failure after MA conditioning, 3 of 7 evaluable Lupron recipients had ovarian failure at a median of 703 days post-transplant. Ovarian failure occurred in 1 of 10 recipients of RIC at median follow-up of 901 days. In conclusion, leuprolide may protect ovarian function after MA conditioning. Additionally, RIC with cyclophosphamide, fludarabine and low-dose TBI has a low risk of ovarian failure. PMID:27272448

  15. Allogeneic stem cell transplantation after reduced-intensity conditioning for acute myeloid leukaemia: impact of chronic graft-versus-host disease.

    PubMed

    Valcárcel, David; Martino, Rodrigo; Piñana, Jose L; Sierra, Jorge

    2009-06-01

    The antineoplastic effect of allogeneic stem cell transplantation after reduced-intensity conditioning (RIC) relies on the graft-versus-tumour (GvT) reaction. GvT is closely linked to the development of graft-versus-host disease (GvHD). The incidence of acute GvHD after RIC seems lower than after myeloablative conditioning (MAC), whereas the incidence of chronic GvHD after RIC seems similar to after MAC. The results of RIC for acute myeloid leukaemia show a non-relapse mortality of approximately 15% at one year, a relapse incidence of approximately 40% after a median of 4-6 months, translating into overall and disease-free survival rates of 40-60%. The factors associated with improved outcome in most studies are the stage of the disease at transplantation, age and the development of chronic GvHD (and thus GvT). In a recent report, chronic GvHD was the most important factor associated with prolonged survival. Future efforts should be directed at aiming to decrease relapse rates. For this purpose, an adequate identification of high-risk patients, close monitoring of minimal residual disease after the procedure, and the use of antineoplastic drugs or immunotherapy may be of help.

  16. Effect of acute and chronic graft-versus-host disease on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma

    PubMed Central

    Ringdén, Olle; Shrestha, Smriti; da Silva, Gisela Tunes; Zhang, Mei-Jie; Dispenzieri, Angela; Remberger, Mats; Kamble, Rammurti; Freytes, Cesar O.; Gale, Robert Peter; Gibson, John; Gupta, Vikas; Holmberg, Leona; Lazarus, Hillard; McCarthy, Philip; Meehan, Kenneth; Schouten, Harry; Milone, Gustavo A.; Lonial, Sagar; Hari, Parameswaran N

    2011-01-01

    We evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on relapse and survival after allogeneic haematopoietic stem cell transplantation (HSCT) for multiple myeloma (MM) using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177 HLA-identical sibling HSCT recipients between 1997 and 2005 following NMA (n=98) or RIC (n=79) were analyzed. In 105 patients, autografting was followed by planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a time-dependent covariate using Cox models. The incidence of acute GVHD (grades I–IV) was 42% (95% confidence interval (CI) 35 – 49%) and of chronic GVHD at five years was 59% (95% CI 49 – 69%), with 70% developing extensive chronic GVHD. In multivariate analysis, acute GVHD (≥ grade I) was associated with an increased risk of TRM (relative risk (RR)=2.42; p=0.016), whereas limited chronic GVHD significantly decreased the risk of myeloma relapse (RR=0.35, p=0.035) and was associated with superior event-free survival (RR=0.40, p=0.027). Acute GVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR=3.52; p=0.001). The reduction in relapse risk associated with chronic GVHD is consistent with a beneficial graft-versus-myeloma effect, but this did not translate into a survival advantage. PMID:21946381

  17. A Prospective Study of an Alemtuzumab Containing Reduced-intensity Allogeneic Stem Cell Transplantation Program in Patients with Poor-Risk and Advanced Lymphoid Malignancies

    PubMed Central

    Sauter, Craig S.; Chou, Joanne F.; Papadopoulos, Esperanza B.; Perales, Miguel-Angel; Jakubowski, Ann A.; Young, James W.; Scordo, Michael; Giralt, Sergio; Castro-Malaspina, Hugo

    2015-01-01

    Reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT) have used alemtuzumab to abrogate the risk of graft-versus-host disease (GVHD). Thirty-eight advanced lymphoma patients underwent a prospective phase II study of melphalan, fludarabine and alemtuzumab containing RIC allo-SCT from 20 matched related and 18 unrelated donors with cyclosporin-A as GVHD prophylaxis. The cumulative incidence of grade II-IV acute GVHD at 3 months was 10.5% and three evaluable patients experienced chronic GVHD. Progression-free (PFS) and overall (OS) survival at 5 years is 25% (95% CI: 13-40) and 44% (95% CI: 28-59%) respectively. Previous high-dose therapy and autologous stem cell transplantation (HDT-ASCT) and elevated LDH at the time of allo-SCT resulted in inferior OS. Within this cohort of high-risk lymphoma patients, alemtuzumab containing RIC resulted in a low risk of GVHD and a high incidence of POD, especially in those with poor-risk features defined by elevated LDH pre-allo-SCT and previous HDT-ASCT. PMID:24528216

  18. Second reduced intensity conditioning allogeneic transplant as a rescue strategy for acute leukaemia patients who relapse after an initial RIC allogeneic transplantation: analysis of risk factors and treatment outcomes.

    PubMed

    Vrhovac, R; Labopin, M; Ciceri, F; Finke, J; Holler, E; Tischer, J; Lioure, B; Gribben, J; Kanz, L; Blaise, D; Dreger, P; Held, G; Arnold, R; Nagler, A; Mohty, M

    2016-02-01

    Limited therapeutic options are available after relapse of acute leukaemia following first reduced intensity conditioning haematopoietic stem cell transplantation (RIC1). A retrospective study on European Society for Blood and Marrow Transplantation (EBMT) registry data was performed on 234 adult patients with acute leukaemia who received a second RIC transplantation (RIC2) from 2000 to 2012 as a salvage treatment for relapse following RIC1. At the time of RIC2, 167 patients (71.4%) had relapsed or refractory disease, 49 (20.9%) were in second CR and 18 (7.7%) in third or higher CR. With a median follow-up of 21 (1.5-79) months after RIC2, 51 patients are still alive. At 2 years, the cumulative incidence of non-relapse mortality (NRM), relapse incidence (RI), leukaemia-free survival (LFS) and overall survival (OS) were 22.4% (95% confidence interval (CI): 17-28.4), 63.9% (56.7-70.1), 14.6% (8.8-18.5) and 20.5% (14.9-26.1), respectively. In patients with acute myelogenous, biphenotypic and undifferentiated leukaemia (representing 89.8% of all patients), duration of remission following RIC1 >225 days, presence of CR at RIC2, patient's Karnofsky performance status >80 at RIC2 and non-myeloablative conditioning were found to be the strongest predictors of patients' favourable outcome.

  19. Sequential myeloablative autologous stem cell transplantation and reduced intensity allogeneic hematopoietic cell transplantation is safe and feasible in children, adolescents and young adults with poor-risk refractory or recurrent Hodgkin and non-Hodgkin lymphoma.

    PubMed

    Satwani, P; Jin, Z; Martin, P L; Bhatia, M; Garvin, J H; George, D; Chaudhury, S; Talano, J; Morris, E; Harrison, L; Sosna, J; Peterson, M; Militano, O; Foley, S; Kurtzberg, J; Cairo, M S

    2015-02-01

    The outcome of children, adolescents and young adults (CAYA) with poor-risk recurrent/refractory lymphoma is dismal (⩽30%). To overcome this poor prognosis, we designed an approach to maximize an allogeneic graft vs lymphoma effect in the setting of low disease burden. We conducted a multi-center prospective study of myeloablative conditioning (MAC) and autologous stem cell transplantation (AutoSCT), followed by a reduced intensity conditioning (RIC) and allogeneic hematopoietic cell transplantation (AlloHCT) in CAYA, with poor-risk refractory or recurrent lymphoma. Conditioning for MAC AutoSCT consisted of carmustine/etoposide/cyclophosphamide, RIC consisted of busulfan/fludarabine. Thirty patients, 16 Hodgkin lymphoma (HL) and 14 non-Hodgkin lymphoma (NHL), with a median age of 16 years and median follow-up of 5years, were enrolled. Twenty-three patients completed both MAC AutoSCT and RIC AlloHCT. Allogeneic donor sources included unrelated cord blood (n=9), unrelated donor (n=8) and matched siblings (n=6). The incidence of transplant-related mortality following RIC AlloHCT was only 12%. In patients with HL and NHL, 10 year EFS was 59.8% and 70% (P=0.613), respectively. In summary, this approach is safe, and long-term EFS with this approach is encouraging considering the poor-risk patient characteristics and the use of unrelated donors for RIC AlloHCT in the majority of cases.

  20. Reduced-intensity and non-myeloablative allogeneic stem cell transplantation from alternative HLA-mismatched donors for Hodgkin lymphoma: a study by the French Society of Bone Marrow Transplantation and Cellular Therapy.

    PubMed

    Gauthier, J; Castagna, L; Garnier, F; Guillaume, T; Socié, G; Maury, S; Maillard, N; Tabrizi, R; Marchand, T; Malfuson, J; Gac, A; Gyan, E; Mercier, M; Béguin, Y; Delage, J; Turlure, P; Marçais, A; Nguyen, S; Dulery, R; Bay, J; Huynh, A; Daguindau, E; Cornillon, J; Régny, C; Michallet, M; Peffault de Latour, R; Yakoub-Agha, I; Blaise, D

    2017-05-01

    Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB. Ninety-eight patients were included. Median follow-up was 31 months for the whole cohort. All patients in the HAPLO group (N=34) received a T-cell replete allo-SCT after a NMA (FLU-CY-TBI, N=31, 91%) or a RIC (N=3, 9%) followed by post-transplant cyclophosphamide. After adjustment for significant covariates, MMUD and CB were associated with significantly lower GvHD-free relapse-free survival (GRFS; hazard ratio (HR)=2.02, P=0.03 and HR=2.43, P=0.009, respectively) compared with HAPLO donors. In conclusion, higher GRFS was observed in Hodgkin lymphoma patients receiving a RIC or NMA allo-SCT with post-transplant cyclophosphamide from HAPLO donors. Our findings suggest they should be favoured over MMUD and CB in this setting.

  1. Influence of Stem Cell Source on Outcomes of Allogeneic Reduced-Intensity Conditioning Therapy Transplants Using Haploidentical Related Donors.

    PubMed

    Bradstock, Kenneth; Bilmon, Ian; Kwan, John; Blyth, Emily; Micklethwaite, Kenneth; Huang, Gillian; Deren, Stephanie; Byth, Karen; Gottlieb, David

    2015-09-01

    We compared outcomes for 2 retrospective cohorts of patients undergoing reduced-intensity conditioning (RIC) therapy transplants using haploidentical related donors and post-transplant prophylaxis against graft-versus-host disease (GVHD) with high-dose cyclophosphamide, tacrolimus, and mycophenolate. The first cohort of 13 was transplanted with bone marrow (BM) as the stem cell source, whereas the second cohort of 23 used peripheral blood stem cells (PBSCs) mobilized with granulocyte colony-stimulating factor. The BM cohort received a single 60-mg/kg dose of cyclophosphamide on day +3, whereas the PBSC cohort received 2 doses on days +3 and +4. Patients in the first cohort were slightly older and had a higher proportion of acute myeloid leukemia, but there were no differences in the distribution of Disease Risk Index scores between the 2 groups. Patients in the PBSC group received double the number of CD34(+) cells in the stem cell graft. Times to neutrophil and platelet recovery were not different between the 2 groups. Three patients, all in the PBSC group, failed to engraft but recovered with autologous hemopoiesis and survived. The 6-month cumulative incidences of acute GVHD were 55.1% for BM and 48.5% for PBSCs (P = .651), whereas 24-month cumulative rates for chronic GHVD were 28.6% for BM and 32.3% for PBSCs (P = .685). Only 2 patients, both in the BM group, died of nonrelapse causes, both of second cancers. The 2-year cumulative incidences of relapse were 43.9% for BM and 23.5% for PBSCs (P = .286). Overall survival at 2 years was significantly better for PBSC patients (P = .028), at 83.4% versus 52.7% for BM. Relapse-free and event-free survival did not differ significantly between BM and PBSC groups. In this retrospective analysis, we conclude that the use of PBSCs for haploidentical RIC transplants is a feasible strategy, with equivalent rates of acute and chronic GVHD and risk of relapse and low nonrelapse mortality compared with BM.

  2. Reduced Intensity Allogeneic Transplant In Patients Older Than 55 Years: Unrelated Umbilical Cord Blood Is Safe And Effective For Patients Without A Matched Related Donor

    PubMed Central

    Majhail, Navneet S; Brunstein, Claudio G; Tomblyn, Marcie; Thomas, Avis J; Miller, Jeffrey S; Arora, Mukta; Kaufman, Dan S; Burns, Linda J; Slungaard, Arne; McGlave, Philip B; Wagner, John E; Weisdorf, Daniel J

    2009-01-01

    The lower morbidity and mortality of reduced-intensity conditioning (RIC) regimens have allowed allogeneic hematopoietic cell transplantation (HCT) in older patients. Unrelated umbilical cord blood (UCB) has been investigated as an alternative stem cell source to suitably HLA matched related (MRD) and adult volunteer unrelated donors. We hypothesized that RIC HCT using UCB would be safe and efficacious in older patients and compared the transplant related mortality (TRM) and overall survival of RIC HCT in patients older than 55 years using either MRD (n=47) or, in patients with no 5/6 or 6/6 HLA compatible related donors, UCB (n=43). RIC regimen consisted of total-body irradiation (200 cGy) and either cyclophosphamide and fludarabine (n=69), or busulfan and fludarabine (n=16) or busulfan and cladribine (n=5). The median age of MRD and UCB cohorts was 58 (range, 55-70) and 59 (range, 55-69) years, respectively. AML/MDS (50%) was the most common diagnosis. All MRD grafts were 6 of 6 HLA matched to the recipient. Among patients undergoing UCB HCT, 88% received two UCB units to optimize cell dose and 93% received 1-2 HLA mismatched grafts. The median followup for survivors was 27 (range, 12-61) months. The 3-year probabilities of progression-free survival (30% vs. 34%, p=0.98) and overall survival (43% vs. 34%, p=0.57) were similar for recipients of MRD and UCB. The cumulative incidence of grade 2-4 acute graft-versus-host disease (42% vs. 49%, p=0.20) and TRM at 180-days (23% vs. 28%, p=0.36) were comparable. However, UCB recipients had a lower incidence of chronic graft-versus-host disease at 1-year (40% vs. 17%, p=0.02). On multivariate analysis, graft type had no impact on TRM or survival and HCT comorbidity index score was the only factor independently predictive for these endpoints. Our study supports the use of HLA mismatched UCB as an alternative graft source for older patients who need a transplant but do not have a MRD. The use of RIC and UCB extends the

  3. JC Virus Leuko-Encephalopathy in Reduced Intensity Conditioning Cord Blood Transplant Recipient with a Review of the Literature.

    PubMed

    El-Cheikh, Jean; Fürst, Sabine; Casalonga, Francois; Crocchiolo, Roberto; Castagna, Luca; Granata, Angela; Oudin, Claire; Faucher, Catherine; Berger, Pierre; Sarran, Anthony; Blaise, Didier

    2012-01-01

    We report here the case of progressive multifocal leukoencephalopathy (PML) related to human polyomavirus JC (JCV) infection after an allogeneic transplantation with umbilical cord blood cells in 59-year-old woman with follicular Non Hodgkin lymphoma. She presented with dysphagia and weakness; magnetic resonance imaging demonstrated marked signal abnormality in the sub-cortical white matter of the left frontal lobe and in the posterior limb of the right internal capsule. Polymerase chain reaction (PCR) analysis of the cerebrospinal fluid (CSF) was positive for John Cunningham (JC) virus. JC viral DNA in the CSF was positive, establishing the diagnosis of PML. Brain biopsy was not done. Extensive investigations for other viral infections seen in immuno-compromised patients were negative. The patient's neurologic deficits rapidly increased throughout her hospital stay, and she died one month after the diagnosis. These findings could have practical implications and demonstrate that in patients presenting neurological symptoms and radiological signs after UCBT, the JCV encephalitis must be early suspected.

  4. Similar Survival for Patients Undergoing Reduced-Intensity Total Body Irradiation (TBI) Versus Myeloablative TBI as Conditioning for Allogeneic Transplant in Acute Leukemia

    SciTech Connect

    Mikell, John L.; Waller, Edmund K.; Switchenko, Jeffrey M.; Rangaraju, Sravanti; Ali, Zahir; Graiser, Michael; Hall, William A.; Langston, Amelia A.; Esiashvili, Natia; Khoury, H. Jean; Khan, Mohammad K.

    2014-06-01

    Purpose: Hematopoietic stem cell transplantation (HSCT) is the mainstay of treatment for adults with acute leukemia. Total body irradiation (TBI) remains an important part of the conditioning regimen for HCST. For those patients unable to tolerate myeloablative TBI (mTBI), reduced intensity TBI (riTBI) is commonly used. In this study we compared outcomes of patients undergoing mTBI with those of patients undergoing riTBI in our institution. Methods and Materials: We performed a retrospective review of all patients with acute leukemia who underwent TBI-based conditioning, using a prospectively acquired database of HSCT patients treated at our institution. Patient data including details of the transplantation procedure, disease status, Karnofsky performance status (KPS), response rates, toxicity, survival time, and time to progression were extracted. Patient outcomes for various radiation therapy regimens were examined. Descriptive statistical analysis was performed. Results: Between June 1985 and July 2012, 226 patients with acute leukemia underwent TBI as conditioning for HSCT. Of those patients, 180 had full radiation therapy data available; 83 had acute lymphoblastic leukemia and 94 had acute myelogenous leukemia; 45 patients received riTBI, and 135 received mTBI. Median overall survival (OS) was 13.7 months. Median relapse-free survival (RFS) for all patients was 10.2 months. Controlling for age, sex, KPS, disease status, and diagnosis, there were no significant differences in OS or RFS between patients who underwent riTBI and those who underwent mTBI (P=.402, P=.499, respectively). Median length of hospital stay was shorter for patients who received riTBI than for those who received mTBI (16 days vs 23 days, respectively; P<.001), and intensive care unit admissions were less frequent following riTBI than mTBI (2.22% vs 12.69%, respectively, P=.043). Nonrelapse survival rates were also similar (P=.186). Conclusions: No differences in OS or RFS were seen between

  5. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study.

    PubMed

    Güngör, Tayfun; Teira, Pierre; Slatter, Mary; Stussi, Georg; Stepensky, Polina; Moshous, Despina; Vermont, Clementien; Ahmad, Imran; Shaw, Peter J; Telles da Cunha, José Marcos; Schlegel, Paul G; Hough, Rachel; Fasth, Anders; Kentouche, Karim; Gruhn, Bernd; Fernandes, Juliana F; Lachance, Silvy; Bredius, Robbert; Resnick, Igor B; Belohradsky, Bernd H; Gennery, Andrew; Fischer, Alain; Gaspar, H Bobby; Schanz, Urs; Seger, Reinhard; Rentsch, Katharina; Veys, Paul; Haddad, Elie; Albert, Michael H; Hassan, Moustapha

    2014-02-01

    In chronic granulomatous disease allogeneic haemopoietic stem-cell transplantation (HSCT) in adolescents and young adults and patients with high-risk disease is complicated by graft-failure, graft-versus-host disease (GVHD), and transplant-related mortality. We examined the effect of a reduced-intensity conditioning regimen designed to enhance myeloid engraftment and reduce organ toxicity in these patients. This prospective study was done at 16 centres in ten countries worldwide. Patients aged 0-40 years with chronic granulomatous disease were assessed and enrolled at the discretion of individual centres. Reduced-intensity conditioning consisted of high-dose fludarabine (30 mg/m(2) [infants <9 kg 1·2 mg/kg]; one dose per day on days -8 to -3), serotherapy (anti-thymocyte globulin [10 mg/kg, one dose per day on days -4 to -1; or thymoglobuline 2·5 mg/kg, one dose per day on days -5 to -3]; or low-dose alemtuzumab [<1 mg/kg on days -8 to -6]), and low-dose (50-72% of myeloablative dose) or targeted busulfan administration (recommended cumulative area under the curve: 45-65 mg/L × h). Busulfan was administered mainly intravenously and exceptionally orally from days -5 to -3. Intravenous busulfan was dosed according to weight-based recommendations and was administered in most centres (ten) twice daily over 4 h. Unmanipulated bone marrow or peripheral blood stem cells from HLA-matched related-donors or HLA-9/10 or HLA-10/10 matched unrelated-donors were infused. The primary endpoints were overall survival and event-free survival (EFS), probabilities of overall survival and EFS at 2 years, incidence of acute and chronic GVHD, achievement of at least 90% myeloid donor chimerism, and incidence of graft failure after at least 6 months of follow-up. 56 patients (median age 12·7 years; IQR 6·8-17·3) with chronic granulomatous disease were enrolled from June 15, 2003, to Dec 15, 2012. 42 patients (75%) had high-risk features (ie, intractable infections and

  6. Radiolabeled anti-CD45 antibody with reduced-intensity conditioning and allogeneic transplantation for younger patients with advanced acute myeloid leukemia or myelodysplastic syndrome.

    PubMed

    Mawad, Raya; Gooley, Ted A; Rajendran, Joseph G; Fisher, Darrell R; Gopal, Ajay K; Shields, Andrew T; Sandmaier, Brenda M; Sorror, Mohamed L; Deeg, Hans Joachim; Storb, Rainer; Green, Damian J; Maloney, David G; Appelbaum, Frederick R; Press, Oliver W; Pagel, John M

    2014-09-01

    We treated patients under age 50 years with iodine-131 ((131)I)-anti-CD45 antibody combined with fludarabine and 2 Gy total body irradiation to create an improved hematopoietic cell transplantation (HCT) strategy for advanced acute myeloid leukemia or high-risk myelodysplastic syndrome patients. Fifteen patients received 332 to 1561 mCi of (131)I, delivering an average of 27 Gy to bone marrow, 84 Gy to spleen, and 21 Gy to liver. Although a maximum dose of 28 Gy was delivered to the liver, no dose-limiting toxicity was observed. Marrow doses were arbitrarily capped at 43 Gy to avoid radiation-induced stromal damage; however, no graft failure or evidence of stromal damage was observed. Twelve patients (80%) developed grade II graft-versus-host disease (GVHD), 1 patient developed grade III GVHD, and no patients developed grade IV GVHD during the first 100 days after HCT. Of the 12 patients with chronic GVHD data, 10 developed chronic GVHD, generally involving the skin and mouth. Six patients (40%) are surviving after a median of 5.0 years (range, 4.2 to 8.3 years). The estimated survival at 1 year was 73% among the 15 treated patients. Eight patients relapsed, 7 of whom subsequently died. The median time to relapse among these 8 patients was 54 days (range, 26 to 1364 days). No cases of nonrelapse mortality were observed in the first year after transplantation. However, 2 patients died in remission from complications of chronic GVHD and cardiomyopathy, at 18 months and 14 months after transplantation, respectively. This study suggests that patients may tolerate myeloablative doses >28 Gy delivered to the liver using (131)I-anti-CD45 antibody in addition to standard reduced-intensity conditioning. Moreover, the arbitrary limit of 43 Gy to the marrow may be unnecessarily conservative, and continued escalation of targeted radioimmunotherapy doses may be feasible to further reduce relapse.

  7. Pharmacokinetic modelling and development of Bayesian estimators for therapeutic drug monitoring of mycophenolate mofetil in reduced-intensity haematopoietic stem cell transplantation

    PubMed Central

    Saint-Marcoux, Franck; Royer, Bernard; Debord, Jean; Larosa, Fabrice; Legrand, Faezeh; Deconinck, Eric; Kantelip, Jean-Pierre; Marquet, Pierre

    2009-01-01

    Background Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is used during nonmyeloablative and reduced-intensity conditioning haematopoetic cell transplantation (HCT) to improve engraftment and reduce graft versus host disease (GVHD). However, information about MPA pharmacokinetics is sparse in this context and its use is still empirical. Objectives To perform a pilot pharmacokinetic study and to develop maximum a posteriori Bayesian estimators (MAP-BEs) for the estimation of MPA exposure in HCT. Patients and methods Fourteen patients given orally MMF 15 mg/kg 3 times daily were included. Two consecutive 8-hour PK profiles were performed the same day respectively three days before and 4 days after the HCT. One 8-hour PK profile was performed on day 27 after transplantation. For these 8-hours pharmacokinetic profiles, blood samples were collected pre-dose and 20, 40, 60, 90 min, 2, 4, 6 and 8 h post-dose after administration of the drug. Using the iterative two-stage method (ITS), two different one-compartment open PK models with first-order elimination were developed to describe the data: one with two gamma laws and one with three gamma laws to describe the absorption phase. For each PK profile, the Akaike criterion was calculated to evaluate model fitting. On the basis of the population PK parameters, MAP-BEs were developed for the estimation of MPA pharmacokinetics and area under the concentration-time curves (AUC0-8h) at the different studied periods using a limited sampling strategy (LSS). These MAP-BEs were then validated using a data-splitting method. Results The ITS approach allowed the development of MAP-BEs based either on “double-gamma” or “triple-gamma” models, the combination of which allowed correct estimation of MPA pharmacokinetics and AUC on the basis of a C20min-C90min-C240min sampling schedule. The mean bias of the Bayesian versus reference (trapezoidal) AUCs was <5% with less than 16% of the patients with absolute bias

  8. Clofarabine versus fludarabine-based reduced-intensity conditioning regimen prior to allogeneic transplantation in adults with AML/MDS.

    PubMed

    Chevallier, Patrice; Labopin, Myriam; de La Tour, Regis Peffault; Lioure, Bruno; Bulabois, Claude-Eric; Huynh, Anne; Blaise, Didier; Turlure, Pascal; Daguindau, Etienne; Maillard, Natacha; Yakoub-Agha, Ibrahim; Guillerm, Gaelle; Delage, Jeremy; Contentin, Nathalie; Bay, Jacques-Olivier; Beckerich, Florence; Bourhis, Jean-Henri; Detrait, Marie; Vigouroux, Stéphane; François, Sylvie; Legrand, Faezeh; Guillaume, Thierry; Mohty, Mohamad

    2016-11-01

    We have retrospectively compared survivals between acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients who received either a clofarabine/busulfan (CloB2A2) or a fludarabine/busulfan (FB2A2) RIC regimen for allogeneic stem cell transplantation. Between 2009 and 2014, 355 allotransplanted cases were identified from the SFGM-TC registry as having received either the FB2A2 (n = 316, 56% males, median age: 59.2 years, AML 78.5%, first complete remission [CR1] 72%, median follow-up: 20 months) or the CloB2A2 (n = 39, 62% males, median age: 60.8 years, AML 62%, CR1 69%, median follow-up: 22.4 months) RIC regimen. In multivariate analysis, FB2A2 was associated with significant lower overall survival (OS, HR: 2.14; 95%CI: 1.05-4.35, P = 0.04) and higher relapse incidence (RI, HR: 2.17; 95%CI: 1.02-4.61, P = 0.04) and a trend for lower leukemia-free survival (LFS, HR: 1.75; 95%CI: 0.94-3.26, P = 0.08). These results were confirmed using a propensity score-matching strategy. However, when considering AML and MDS patients separately, the benefit of the CLOB2A2 regimen was restricted to AML patients (2-year OS FB2A2: 38% [14.5-61.6] vs. CloB2A2: 79.2% [62.9-95.4], P = 0.01; 2-year LFS FB2A2: 38% [16-59.9] vs. CloB2A2: 70.8% [52.6-89], P = 0.03). The better survivals were due to the lower risk of relapse in this CloB2A2 AML subgroup (2-year RI FB2A2: 41.2% [19-62.4] vs. CloB2A2: 16.7% [5-34.2], P = 0.05). This retrospective comparison suggests that the CloB2A2 RIC regimen can likely provide longer survival than that awarded by a FB2A2 RIC regimen and may become a new standard of care RIC regimen for allotransplanted AML patients. A prospective phase 3 randomized study is warranted.

  9. Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

    ClinicalTrials.gov

    2016-10-19

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non

  10. Health-Related Quality of Life in leukemia Survivors of Allogeneic Hematopoietic Stem Cell Transplantation Employing the Mexican Reduced-Intensity Conditioning.

    PubMed

    González-Ramírez, Mónica P; Miravete-Lagunes, Karla; Gómez-de-León, Andrés; Ponce-de-León, Sergio; Tenorio-Rojo, Andrea P; Martagón-Herrera, Nora A; Hernández-Reyes, Jesús A; García-Villasenor, Arturo; Burguette, Esteban; Vallejo-Villalobos, María Fernanda; Ruiz-Delgado, Guillermo J; Gómez-Almaguer, David; Ruiz-Argüelles, Guillermo J

    2015-01-01

    Quality of life (QOL) is an important consideration in the counseling, implementation, and post-treatment management of arduous treatments for life-threatening conditions such as allogeneic hematopoietic cell transplantation (allo-HCT). To analyze the QOL of leukemia patients allografted with the Mexican reduced-intensity conditioning regimen in two Mexican academic medical centers. By means of the quality metric short form 36 version 2 to measure generic health concepts, relevant QOL was analyzed in leukemia patients who underwent allo-HCT using reduced-intensity conditioning on an outpatient basis at either the Centro de Hematología y Medicina Interna de Puebla of the Clínica Ruiz or the Hematology Service of the Internal Medicine Department of the Hospital "Dr. José Eleuterio González" of the Universidad Autónoma de Nuevo León, and who had survived more than 12 months after the allograft, who could be approached, who were in a continued complete remission (with or without graft-versus-host disease), and who were willing to respond to the questionnaire. Thirty-five patients fulfilling these requirements were included, and a sex- and age-matched group of 35 reference subjects was also studied. Allografted patients were found to have a slightly better mental component summary than the reference subjects (53.23 vs. 48.66 points; p = 0.01), whereas the physical component summary did not show a difference (54.53 vs. 52.05 points; p = 0.59). Most of the differences between allografted individuals and reference subject controls were not significant. Despite several sources of bias, these data suggest that allografted individuals employing the Mexican reduced-intensity conditioning regimen enjoy a health-related QOL life similar to that of reference subjects, adding another advantage of this method of conducting stem cell allografts. However, more work needs to be done to elucidate the impact of reduced-intensity conditioning on post allo-HCT QOL.

  11. Outcomes of patients with acute leukaemia who relapsed after reduced-intensity stem cell transplantation from HLA-identical or one antigen-mismatched related donors.

    PubMed

    Kobayashi, Kazuhiko; Kami, Masahiro; Murashige, Naoko; Kusumi, Eiji; Kishi, Yukiko; Hamaki, Tamae; Hori, Akiko; Matsumura, Tomoko; Yuji, Koichiro; Masuo, Shigeru; Mori, Shinichiro; Miyakoshi, Shigesaburo; Tanosaki, Ryuji; Mitamura, Tadayuki; Takaue, Yoichi; Taniguchi, Shuichi

    2005-06-01

    The characteristics of relapse following reduced-intensity stem-cell transplantation (RIST) remain to be clarified. We reviewed the medical records of 19 patients with acute leukaemia [acute myeloid leukaemia (AML), 16; acute lymphoblastic leukaemia (ALL), 3] who relapsed after RIST from related donors using purine-analogue-based regimens. Their median age was 55 years (range, 29-65 years). Median interval between RIST and relapse was 4.9 months (range, 1.8-24.9 months). Three chose not to receive interventions. The remaining 16 patients received withdrawal of immunosuppression (n = 3), chemotherapy (n = 2), donor lymphocyte infusion (n = 10) and second transplantation (n = 7), alone (n = 9) or in combination (n = 7). Four are alive with a median follow-up of 27.6 months (range, 16.0-28.9 months); three in remission and one in relapse. The 2-year overall survival after relapse was 28.9%. Causes of death in 15 patients included progressive disease (n = 7), graft-versus-host disease (n = 5) and infections (n = 3). Cumulative incidences of relapse-related and non-relapse-related deaths at 2 years after relapse were 37% and 32% respectively. Two prognostic factors were identified on univariate analysis: age [P = 0.017; hazard ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.32], and ALL as underlying disease (P = 0.011; HR, 10.4; 95% CI, 1.73-62.4). Some AML patients who relapse after RIST achieve durable remission with allogeneic immunotherapy-based interventions; however they carry a significant risk of non-relapse mortality.

  12. Poor Growth, Thyroid Dysfunction and Vitamin D Deficiency Remain Prevalent Despite Reduced Intensity Chemotherapy for Hematopoietic Stem Cell Transplantation in Children and Young Adults

    PubMed Central

    Myers, Kasiani C; Howell, Jonathan C.; Wallace, Gregory; Dandoy, Christopher; El-Bietar, Javier; Lane, Adam; Davies, Stella M.; Jodele, Sonata; Rose, Susan R.

    2016-01-01

    Myeloablative conditioning regimens for hematopoietic stem cell transplant (HSCT) are known to affect endocrine function, but little is known regarding reduced intensity conditioning (RIC) regimens. We retrospectively reviewed 114 children and young adults after single RIC HSCT. Analysis was grouped by age (<2y and ≥2y), and diagnosis (HLH/XLP, other immune disorders, metabolic/genetic disorders). All groups displayed short stature by mean height adjusted Z-score (HAZ) before −1.29 and after HSCT (HAZ −1.38, p=0.47). After HSCT, younger children with HLH/XLP grew better (HAZ −3.41 vs −1.65, p= 0.006), while older subjects had worsening (HAZ −0.8 vs −1.01, p= 0.06). Those with steroid therapy beyond standard GVHD prophylaxis were shorter than those without (p 0.04). After HSCT, older subjects with HLH/XLP became thinner with mean BMI Z-score of 1.20 vs. 0.64, p=0.02, likewise in metabolic/genetic disorders (BMI-Z= 0.59 vs. −0.99, p<0.001). BMI increased among younger children in these same groups. Thyroid function was abnormal in 24% (18/76). 25-OH vitamin D levels, were insufficient in 73% (49/65), with low bone mineral density in 8 of 19 evaluable subjects. Despite RIC, children and young adults still have significant late endocrine effects. Further research is required to compare post-transplant endocrine effects after RIC to standard chemotherapy protocols. PMID:26974276

  13. Decreased nonrelapse mortality after unrelated cord blood transplantation for acute myeloid leukemia using reduced-intensity conditioning: a prospective phase II multicenter trial.

    PubMed

    Rio, Bernard; Chevret, Sylvie; Vigouroux, Stéphane; Chevallier, Patrice; Fürst, Sabine; Sirvent, Anne; Bay, Jacques-Olivier; Socié, Gérard; Ceballos, Patrice; Huynh, Anne; Cornillon, Jérôme; Françoise, Sylvie; Legrand, Faezeh; Yakoub-Agha, Ibrahim; Michel, Gérard; Maillard, Natacha; Margueritte, Geneviève; Maury, Sébastien; Uzunov, Madalina; Bulabois, Claude Eric; Michallet, Mauricette; Clement, Laurence; Dauriac, Charles; Bilger, Karin; Gluckman, Eliane; Ruggeri, Annalisa; Buzyn, Agnès; Nguyen, Stéphanie; Simon, Tabassome; Milpied, Nöel; Rocha, Vanderson

    2015-03-01

    A prospective phase II multicenter trial was performed with the aim to obtain less than 25% nonrelapse mortality (NRM) after unrelated cord blood transplantation (UCBT) for adults with acute myeloid leukemia (AML) using a reduced-intensity conditioning regimen (RIC) consisting of total body irradiation (2 Gy), cyclophosphamide (50 mg/kg), and fludarabine (200 mg/m(2)). From 2007 to 2009, 79 UCBT recipients were enrolled. Patients who underwent transplantation in first complete remission (CR1) (n = 48) had a higher frequency of unfavorable cytogenetics and secondary AML and required more induction courses of chemotherapy to achieve CR1 compared with the others. The median infused total nucleated cells (TNC) was 3.4 × 10(7)/kg, 60% received double UCBT, 77% were HLA mismatched (4/6), and 40% had major ABO incompatibility. Cumulative incidence of neutrophil recovery at day 60 was 87% and the cumulative incidence of 100-day acute graft-versus-host disease (II to IV) was 50%. At 2 years, the cumulative incidence of NRM and relapse was 20% and 46%, respectively. In multivariate analysis, major ABO incompatibility (P = .001) and TNC (<3.4 × 10(7)/kg; P = .001) were associated with increased NRM, and use of 2 or more induction courses to obtain CR1 was associated with increased relapse incidence (P = .04). Leukemia-free survival (LFS) at 2 years was 35%, and the only factor associated with decreased LFS was secondary AML (P = .04). In conclusion, despite the decreased NRM observed, other RIC regimens with higher myelosuppression should be evaluated to decrease relapse in high-risk AML. (EUDRACT 2006-005901-67).

  14. Ph+ ALL patients in first complete remission have similar survival after reduced intensity and myeloablative allogeneic transplantation: impact of tyrosine kinase inhibitor and minimal residual disease.

    PubMed

    Bachanova, V; Marks, D I; Zhang, M-J; Wang, H; de Lima, M; Aljurf, M D; Arellano, M; Artz, A S; Bacher, U; Cahn, J-Y; Chen, Y-B; Copelan, E A; Drobyski, W R; Gale, R P; Greer, J P; Gupta, V; Hale, G A; Kebriaei, P; Lazarus, H M; Lewis, I D; Lewis, V A; Liesveld, J L; Litzow, M R; Loren, A W; Miller, A M; Norkin, M; Oran, B; Pidala, J; Rowe, J M; Savani, B N; Saber, W; Vij, R; Waller, E K; Wiernik, P H; Weisdorf, D J

    2014-03-01

    The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKIs), mostly imatinib; 39% (RIC) and 49% (MAC) were minimal residual disease (MRD)(neg) pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%; P=0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC (P=0.058). Overall survival (OS) was similar (RIC 39% (95% confidence interval (CI) 27-52) vs 35% (95% CI 27-44); P=0.62). Patients MRD(pos) pre-HCT had higher risk of relapse with RIC vs MAC (hazard ratio (HR) 1.97; P=0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared with a similar MRD population after MAC (33%; P=0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; P=0.057), but absence of pre-HCT TKI (HR 1.88; P=0.018), RIC (HR 1.891; P=0.054) and pre-HCT MRD(pos) (HR 1.6; P=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD(neg) status is preferred pre-HCT.

  15. Ph+ ALL patients in first complete remission have similar survival after reduced intensity and myeloablative allogeneic transplantation: Impact of tyrosine kinase inhibitor and minimal residual disease

    PubMed Central

    Bachanova, Veronika; Marks, David I.; Zhang, Mei-Jie; Wang, Hailin; de Lima, Marcos; Aljurf, Mahmoud D.; Arellano, Martha; Artz, Andrew S.; Bacher, Ulrike; Cahn, Jean-Yves; Chen, Yi-Bin; Copelan, Edward A.; Drobyski, William R.; Gale, Robert Peter; Greer, John P; Gupta, Vikas; Hale, Gregory A.; Kebriaei, Partow; Lazarus, Hillard M.; Lewis, Ian D.; Lewis, Victor A.; Liesveld, Jane L.; Litzow, Mark R.; Loren, Alison W.; Miller, Alan M.; Norkin, Maxim; Oran, Betul; Pidala, Joseph; Rowe, Jacob M.; Savani, Bipin N.; Saber, Wael; Vij, Ravi; Waller, Edmund K.; Wiernik, Peter H.; Weisdorf, Daniel J.

    2014-01-01

    The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Ph+ acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type, and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKI), mostly imatinib; 39% (RIC) and 49% (MAC) were MRDneg pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%;p=0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC (p=0.058). Overall survival was similar (RIC 39% [95% CI:27–52] vs. 35% [95% CI:270–44];p=0.62). Patients MRDpos pre-HCT had higher risk of relapse with RIC versus MAC (HR 1.97;p=0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared to a similar MRDneg population after MAC (33%; p=0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; p=0.057), but absence of pre-HCT TKI (HR 1.88;p=0.018), RIC (HR 1.891;p=0.054) and pre-HCT MRDpos (HR 1.6; p=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRDneg status is preferred pre-HCT. PMID:23989431

  16. Cost utility analysis of reduced intensity hematopoietic stem cell transplantation in adolescence and young adult with severe thalassemia compared to hypertransfusion and iron chelation program

    PubMed Central

    2013-01-01

    Background Hematopoieticic stem cell transplantation is the only therapeutic option that can cure thalassemia disease. Reduced intensity hematopoietic stem cell transplantation (RI-HSCT) has demonstrated a high cure rate with minimal complications compared to other options. Because RI-HSCT is very costly, economic justification for its value is needed. This study aimed to estimate the cost-utility of RI-HSCT compared with blood transfusions combined with iron chelating therapy (BT-ICT) for adolescent and young adult with severe thalassemia in Thailand. Methods A Markov model was used to estimate the relevant costs and health outcomes over the patients’ lifetimes using a societal perspective. All future costs and outcomes were discounted at a rate of 3% per annum. The efficacy of RI-HSCT was based a clinical trial including a total of 18 thalassemia patients. Utility values were derived directly from all patients using EQ-5D and SF-6D. Primary outcomes of interest were lifetime costs, quality adjusted life-years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) in US ($) per QALY gained. One-way and probabilistic sensitivity analyses (PSA) were conducted to investigate the effect of parameter uncertainty. Results In base case analysis, the RI-HSCT group had a better clinical outcomes and higher lifetime costs. The incremental cost per QALY gained was US $ 3,236 per QALY. The acceptability curve showed that the probability of RI-HSCT being cost-effective was 71% at the willingness to pay of 1 time of Thai Gross domestic product per capita (GDP per capita), approximately US $ 4,210 per QALY gained. The most sensitive parameter was utility of severe thalassemia patients without cardiac complication patients. Conclusion At a societal willingness to pay of 1 GDP per capita, RI-HSCT was a cost-effective treatment for adolescent and young adult with severe thalassemia in Thailand compared to BT-ICT. PMID:23379888

  17. Dose-Adjusted EPOCH-Rituximab Combined With Fludarabine Provides an Effective Bridge to Reduced-Intensity Allogeneic Hematopoietic Stem-Cell Transplantation in Patients With Lymphoid Malignancies

    PubMed Central

    Salit, Rachel B.; Fowler, Daniel H.; Wilson, Wyndham H.; Dean, Robert M.; Pavletic, Steven Z.; Dunleavy, Kieron; Hakim, Frances; Fry, Terry J.; Steinberg, Seth M.; Hughes, Thomas E.; Odom, Jeanne; Bryant, Kelly; Gress, Ronald E.; Bishop, Michael R.

    2012-01-01

    Purpose There is currently no standard chemotherapy regimen for patients with lymphoid malignancies being considered for reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation (RIC-alloHSCT). The ideal regimen would provide disease control and result in lymphocyte depletion to facilitate engraftment. To this end, we developed a novel regimen by adding fludarabine to dose-adjusted continuous-infusion etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus with or without rituximab (DA-EPOCH-F/R). Patients and Methods One hundred forty-seven patients with lymphoid malignancy (median age, 50 years) who had heavily pretreated (median prior regimens, three) and chemo-refractory (47%) disease were treated with DA-EPOCH-F/R before RIC-alloHSCT. Patients received one to three consecutive cycles until achieving lymphocyte depletion (CD4+ count < 200/μL) or progressive disease. Results Overall response rate was 41%; 39% of patients had stable disease. Toxicity included grade 4 neutropenia in 65% and thrombocytopenia in 25% of patients. DA-EPOCH-F/R resulted in lymphocyte depletion (P < .001), which was inversely associated with serum interleukin (IL) 7 and IL-15 levels. Of 147 patients, 143 patients proceeded to RIC-alloHSCT. Patients with lower CD3+ (P < .001), CD4+ (P < .001), and CD8+ (P < .001) T-cell counts after DA-EPOCH-F/R were more likely to achieve full donor lymphoid chimerism by day +14 after transplant. Relative to nonresponders to DA-EPOCH-F/R, patients with complete and partial response had increased event-free survival (77.4 v 4.8 months; P < .001) and overall survival (98.5 v 16.2 months; P < .001). Conclusion DA-EPOCH-F/R safely provides tumor cytoreduction and lymphocyte depletion, thereby offering a bridge to RIC-alloHSCT in patients with aggressive lymphoid malignancies. PMID:22312100

  18. Graft-versus-host disease following allogeneic transplantation from HLA-identical sibling with antithymocyte globulin-based reduced-intensity preparative regimen.

    PubMed

    Mohty, Mohamad; Bay, Jacques-Olivier; Faucher, Catherine; Choufi, Bachra; Bilger, Karin; Tournilhac, Olivier; Vey, Norbert; Stoppa, Anne-Marie; Coso, Diane; Chabannon, Christian; Viens, Patrice; Maraninchi, Dominique; Blaise, Didier

    2003-07-15

    Reduced-intensity conditioning (RIC) regimens are increasingly used for allogeneic stem cell transplantation (allo-SCT). RIC has been shown to allow engraftment with minimal early transplantation-related mortality (TRM). However, in the context of RIC, predictive factors for acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) and their effect on outcome remain unknown. In this report, we analyzed the outcome of 101 high-risk patients (70 hematologic and 31 nonhematologic malignancies) who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan, and antithymocyte globulin (ATG). The cumulative incidence of grade II-IV aGVHD was 36% (95% confidence interval [CI], 27%-45%), whereas the cumulative incidence of cGVHD at 2 years was 43% (95% CI, 33%-53%). In multivariate analysis, the incidence of aGVHD was significantly associated with the ATG dose infused during conditioning (P =.0005), whereas peripheral blood as stem cell source was the only predictive factor for the development of cGVHD (P =.0007). The 1-year cumulative incidences of disease progression or relapse in patients with (n = 69) and without (n = 31) GVHD (whatever its form or grade) were 30% (95% CI, 19%-41%) and 55% (95% CI, 37%-72%), respectively (P =.02), suggesting that a potent graft-versus-tumor (GVT) effect can be achieved in high-risk patients following RIC. Moreover, the GVT effect was closely associated with GVHD without an increased risk of TRM (cumulative incidence of TRM, 18% [95% CI, 10%-25%]). Collectively, these results provide a framework for the refinement of RIC approaches designed to enhance the GVT effect with an acceptable risk of GVHD.

  19. Reduced-intensity allogeneic transplant in patients older than 55 years: unrelated umbilical cord blood is safe and effective for patients without a matched related donor.

    PubMed

    Majhail, Navneet S; Brunstein, Claudio G; Tomblyn, Marcie; Thomas, Avis J; Miller, Jeffrey S; Arora, Mukta; Kaufman, Dan S; Burns, Linda J; Slungaard, Arne; McGlave, Philip B; Wagner, John E; Weisdorf, Daniel J

    2008-03-01

    The lower morbidity and mortality of reduced-intensity conditioning (RIC) regimens have allowed allogeneic hematopoietic cell transplantation (HCT) in older patients. Unrelated umbilical cord blood (UCB) has been investigated as an alternative stem cell source to suitably HLA matched related (MRD) and adult volunteer unrelated donors. We hypothesized that RIC HCT using UCB would be safe and efficacious in older patients, and compared the treatment-related mortality (TRM) and overall survival (OS) of RIC HCT in patients older than 55 years using either MRD (n = 47) or, in patients with no 5 of 6 or 6 of 6 HLA compatible related donors, UCB (n = 43). RIC regimen consisted of total-body irradiation (TBI; 200 cGy) and either cyclophosphamide and fludarabine (n = 69), or busulfan and fludarabine (n = 16) or busulfan and cladribine (n = 5). The median age of MRD and UCB cohorts was 58 (range, 55-70) and 59 (range, 55-69) years, respectively. acute myelogenous leukemia/myelodysplastic syndrome (AML/MDS) (50%) was the most common diagnosis. All MRD grafts were 6 of 6 HLA matched to the recipient. Among patients undergoing UCB HCT, 88% received 2 UCB units to optimize cell dose and 93% received 1-2 HLA mismatched grafts. The median follow-up for survivors was 27 (range: 12-61) months. The 3-year probabilities of progression-free survival (PFS; 30% versus 34%, P = .98) and OS (43% versus 34%, P = .57) were similar for recipients of MRD and UCB. The cumulative incidence of grade II-IV acute graft-versus-host (aGVHD) disease (42% versus 49%, P = .20) and TRM at 180-days (23% versus 28%, P = .36) were comparable. However, UCB recipients had a lower incidence of chronic graft-versus-host disease (cGVHD) at 1 year (40% versus 17%, P = .02). On multivariate analysis, graft type had no impact on TRM or survival, and the HCT comorbidity index score was the only factor independently predictive for these endpoints. Our study supports the use of HLA mismatched UCB as an alternative

  20. Results of a phase I/II British Society of Bone Marrow Transplantation study on PCR-based pre-emptive therapy with valganciclovir or ganciclovir for active CMV infection following alemtuzumab-based reduced intensity allogeneic stem cell transplantation.

    PubMed

    Lim, Z Y; Cook, G; Johnson, P R; Parker, Anne; Zuckerman, M; Marks, D; Wiltshire, H; Mufti, G J; Pagliuca, A

    2009-02-01

    This multi-centre randomized study assessed the bioavailability of ganciclovir in patients undergoing alemtuzumab-based reduced intensity conditioning (RIC) haematopoietic stem cell transplantation (HSCT) after oral administration of valganciclovir. Patients were randomized to 2 groups receiving either oral valganciclovir (900 mg twice daily) or intravenous ganciclovir (5mg/kg twice daily) for 14 days. Twenty-seven patients were recruited and 18 patients (67%) completed allocated treatment resulting in clearance of cytomegolovirus (CMV) DNA load at a median of 14 days. The bioavailability of ganciclovir from valganciclovir was 73% (95% CI: 34-112%). The average exposure in the valganciclovir group (36.9+/-14.9 microg h/ml) was higher than the ganciclovir cohort (27.9+/-7.5 microg h/ml). When compared with intravenous ganciclovir, oral valganciclovir had high bioavailability in patients undergoing alemtuzumab-based RIC HSCT.

  1. The addition of sirolimus to the graft-versus-host disease prophylaxis regimen in reduced intensity allogeneic stem cell transplantation for lymphoma: a multicentre randomized trial.

    PubMed

    Armand, Philippe; Kim, Haesook T; Sainvil, Marie-Michele; Lange, Paulina B; Giardino, Angela A; Bachanova, Veronika; Devine, Steven M; Waller, Edmund K; Jagirdar, Neera; Herrera, Alex F; Cutler, Corey; Ho, Vincent T; Koreth, John; Alyea, Edwin P; McAfee, Steven L; Soiffer, Robert J; Chen, Yi-Bin; Antin, Joseph H

    2016-04-01

    Inhibition of the mechanistic target of rapamycin (mTOR) pathway has clinical activity in lymphoma. The mTOR inhibitor sirolimus has been used in the prevention and treatment of graft-versus-host disease (GVHD) after allogeneic haematopoietic stem cell transplantation (HSCT). A retrospective study suggested that patients with lymphoma undergoing reduced intensity conditioning (RIC) HSCT who received sirolimus as part of their GVHD prophylaxis regimen had a lower rate of relapse. We therefore performed a multicentre randomized trial comparing tacrolimus, sirolimus and methotrexate to standard regimens in adult patients undergoing RIC HSCT for lymphoma in order to assess the possible benefit of sirolimus on HSCT outcome. 139 patients were randomized. There was no difference overall in 2-year overall survival, progression-free survival, relapse, non-relapse mortality or chronic GVHD. However, the sirolimus-containing arm had a significantly lower incidence of grade II-IV acute GVHD (9% vs. 25%, P = 0·015), which was more marked for unrelated donor grafts. In conclusion, the addition of sirolimus for GVHD prophylaxis in RIC HSCT is associated with no increased overall toxicity and a lower risk of acute GVHD, although it does not improve survival; this regimen is an acceptable option for GVHD prevention in RIC HSCT. This trial is registered at clinicaltrials.gov (NCT00928018).

  2. Comparison of cyclosporine and tacrolimus combined with mycophenolate mofetil in prophylaxis for graft-versus-host disease after reduced-intensity umbilical cord blood transplantation.

    PubMed

    Miyamoto, Toshihiro; Takashima, Shuichiro; Kato, Koji; Takase, Ken; Yoshimoto, Goichi; Yoshida, Shuro; Henzan, Hideho; Osaki, Koichi; Kamimura, Tomohiko; Iwasaki, Hiromi; Eto, Tetsuya; Teshima, Takanori; Nagafuji, Koji; Akashi, Koichi

    2017-01-01

    Umbilical cord blood transplantation with a reduced-intensity conditioning regimen (RIC-UCBT) is used increasingly in patients who have comorbid organ functions and lack human leukocyte antigen-identical donors. We compared the outcomes in 35 patients who received mycophenolate mofetil plus cyclosporine (MMF/CSP, n = 17) or MMF plus tacrolimus (MMF/TAC, n = 18) for graft-versus-host disease (GVHD) prophylaxis after RIC-UCBT. Cumulative incidence of neutrophil engraftment was 94 and 89 % in MMF/CSP and MMF/TAC groups, respectively (p = 0.34). The incidence of pre-engraftment immune reaction did not differ between the MMF/CSP (41 %) and MMF/TAC (39 %, p = 1.00) groups; however, patients in the MMF/TAC group tended to have a lower incidence of grade II-IV acute GVHD than those in MMF/CSP group (28 vs 53 %, p = 0.11). Overall survival (OS) at 1 year was 43 and 60 % in MMF/CSP and MMF/TAC groups, respectively (p = 0.39). Progression-free survival, non-relapse mortality, and relapse rate were comparable between the two groups (p = 0.76, 0.59, and 0.88, respectively). In multivariate analyses, MMF/TAC GVHD prophylaxis was closely associated with improved OS, but not with incidence of engraftment and acute GVHD. These results suggest that more intensive GVHD prophylaxis with MMF/TAC decreased acute GVHD without affecting other clinical outcomes, resulting in improved OS after RIC-UCBT.

  3. Frequency and Risk Factors Associated with Cord Graft Failure after Transplant with Single-Unit Umbilical Cord Cells Supplemented by Haploidentical Cells with Reduced-Intensity Conditioning

    PubMed Central

    Tsai, Stephanie B.; Liu, Hongtao; Shore, Tsiporah; Fan, Yun; Bishop, Michael; Cushing, Melissa M.; Gergis, Usama; Godley, Lucy; Kline, Justin; Larson, Richard A.; Martinez, Guadalupe; Mayer, Sebastian; Odenike, Olatoyosi; Stock, Wendy; Wickrema, Amittha; van Besien, Koen; Artz, Andrew S.

    2016-01-01

    Delayed engraftment and cord graft failure (CGF) are serious complications after unrelated cord blood (UCB) hematopoietic stem cell transplantation (HSCT), particularly when using low-cell-dose UCB units. The haplo-cord HSCT approach allows the use of a lower dose single UCB unit by co-infusion of a CD34+ selected haploidentical graft, which provides early transient engraftment while awaiting durable UCB engraftment. We describe the frequency, complications, and risk factors of CGF after reduced-intensity conditioning haplo-cord HSCT. Among 107 patients who underwent haplo-cord HSCT, 94 were assessable for CGF, defined as <5% cord blood chimerism at day 60 in the myeloid and CD3 compartments, irrespective of neutrophil and platelet counts. CGF occurred in 14 of 94 assessable patients (15%). Median survival after CGF was 12.7 months with haploidentical or mixed haploidentical–autologous hematopoiesis persisting in the 7 surviving. Median progression-free survival after CGF was 7.7 months and was not statistically different from those without CGF (10.47 months; P = .18). In univariate analyses, no UCB factors were associated with CGF, including cell dose, cell viability, recipient major ABO mismatch against the UCB unit, or degree of HLA match. We also found no association of CGF with recipient cytomegalovirus serostatus, haploidentical donor age, or day 30 haploidentical chimerism. However, higher haploidentical total nucleated and CD34+ cell doses and day 30 UCB chimerism < 5% in either the myeloid or CD3 compartments were associated with greater risk of CGF. We conclude that assessing chimerism at day 30 may foretell impending CGF, and avoidance of high haploidentical cell doses may reduce risk of CGF after haplo-cord HSCT. However, long-term survival is possible after CGF because of predominant haploidentical or mixed chimerism and hematopoietic function. PMID:26912055

  4. Frequency and Risk Factors Associated with Cord Graft Failure after Transplant with Single-Unit Umbilical Cord Cells Supplemented by Haploidentical Cells with Reduced-Intensity Conditioning.

    PubMed

    Tsai, Stephanie B; Liu, Hongtao; Shore, Tsiporah; Fan, Yun; Bishop, Michael; Cushing, Melissa M; Gergis, Usama; Godley, Lucy; Kline, Justin; Larson, Richard A; Martinez, Guadalupe; Mayer, Sebastian; Odenike, Olatoyosi; Stock, Wendy; Wickrema, Amittha; van Besien, Koen; Artz, Andrew S

    2016-06-01

    Delayed engraftment and cord graft failure (CGF) are serious complications after unrelated cord blood (UCB) hematopoietic stem cell transplantation (HSCT), particularly when using low-cell-dose UCB units. The haplo-cord HSCT approach allows the use of a lower dose single UCB unit by co-infusion of a CD34(+) selected haploidentical graft, which provides early transient engraftment while awaiting durable UCB engraftment. We describe the frequency, complications, and risk factors of CGF after reduced-intensity conditioning haplo-cord HSCT. Among 107 patients who underwent haplo-cord HSCT, 94 were assessable for CGF, defined as <5% cord blood chimerism at day 60 in the myeloid and CD3 compartments, irrespective of neutrophil and platelet counts. CGF occurred in 14 of 94 assessable patients (15%). Median survival after CGF was 12.7 months with haploidentical or mixed haploidentical-autologous hematopoiesis persisting in the 7 surviving. Median progression-free survival after CGF was 7.7 months and was not statistically different from those without CGF (10.47 months; P = .18). In univariate analyses, no UCB factors were associated with CGF, including cell dose, cell viability, recipient major ABO mismatch against the UCB unit, or degree of HLA match. We also found no association of CGF with recipient cytomegalovirus serostatus, haploidentical donor age, or day 30 haploidentical chimerism. However, higher haploidentical total nucleated and CD34(+) cell doses and day 30 UCB chimerism < 5% in either the myeloid or CD3 compartments were associated with greater risk of CGF. We conclude that assessing chimerism at day 30 may foretell impending CGF, and avoidance of high haploidentical cell doses may reduce risk of CGF after haplo-cord HSCT. However, long-term survival is possible after CGF because of predominant haploidentical or mixed chimerism and hematopoietic function.

  5. Reduced-intensity allografting as first transplantation approach in relapsed/refractory grade 1-2 follicular lymphoma provides improved outcomes in long-term survivors

    PubMed Central

    Klyuchnikov, Evgeny; Bacher, Ulrike; Kröger, Nicolaus M.; Hari, Parameswaran N.; Ahn, Kwang Woo; Carreras, Jeanette; Bachanova, Veronika; Bashey, Asad; Cohen, Jonathon B.; D'Souza, Anita; Freytes, César O.; Gale, Robert Peter; Ganguly, Siddhartha; Hertzberg, Mark S.; Holmberg, Leona A.; Kharfan-Dabaja, Mohamed A.; Klein, Andreas; Ku, Grace H.; Laport, Ginna G.; Lazarus, Hillard M.; Miller, Alan M.; Mussetti, Alberto; Olsson, Richard F.; Slavin, Shimon; Usmani, Saad Z.; Vij, Ravi; Wood, William A.; Maloney, David G.; Sureda, Anna M.; Smith, Sonali M.; Hamadani, Mehdi

    2015-01-01

    Purpose Comparison of long-term outcomes in patients with refractory/relapsed grade 1-2 follicular lymphoma (FL) after allogeneic (allo-HCT) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era. Methods Adult patients with relapsed/refractory grade 1-2 FL undergoing 1st reduced-intensity allo-HCT or 1st autograft during 2000-2012 were evaluated. Results A total of 518 rituximab-treated patients were included. Allo-HCT patients were younger; more heavily pretreated, and more patients had advanced stage and chemoresistant disease. The 5-year adjusted probabilities, comparing auto- vs. allo-HCT groups for non-relapse mortality (NRM) were 5% vs. 26% (p<0.0001); relapse/progression: 54% vs. 20% (p<0.0001); progression-free survival (PFS): 41% vs. 58% (p<0.001) and overall survival (OS): 74% vs. 66% (p=0.05). Auto-HCT was associated with a higher risk of relapse/progression beyond 5 months post-HCT (RR=4.4; p<0.0001), and worse PFS (RR=2.9; p<0.0001) beyond 11 months post HCT. In the first 24 months post HCT, auto-HCT was associated with improved OS (RR=0.41; p<0.0001), but beyond 24 months with inferior OS (RR=2.2; p=0.006). A landmark analysis of patients alive and progression-free at 2-years post-HCT confirmed these observations, showing no difference in further NRM between both groups, but significantly higher risk of relapse/progression (RR=7.3; p<0.0001) and inferior PFS (RR=3.2; p<0.0001) and OS (RR=2.1; p=0.04) following auto-HCT. The 10-year cumulative incidence of second hematological malignancies following allo- and auto-HCT was 0% and 7%, respectively. Conclusion Auto- and RIC-allo-HCT as 1st transplantation approach can provide durable disease control in grade 1-2 FL patients. Continued disease relapse-risk following auto-HCT translates into improved PFS and OS following allo-HCT, in long-term survivors. PMID:26253007

  6. Unrelated donor allogeneic hematopoietic stem cell transplantation for patients with hemoglobinopathies using a reduced-intensity conditioning regimen and third-party mesenchymal stromal cells.

    PubMed

    Kharbanda, Sandhya; Smith, Angela R; Hutchinson, Stephanie K; McKenna, David H; Ball, James B; Lamb, Lawrence S; Agarwal, Rajni; Weinberg, Kenneth I; Wagner, John E

    2014-04-01

    Allogeneic hematopoietic stem cell transplantation for patients with a hemoglobinopathy can be curative but is limited by donor availability. Although positive results are frequently observed in those with an HLA-matched sibling donor, use of unrelated donors has been complicated by poor engraftment, excessive regimen-related toxicity, and graft-versus-host disease (GVHD). As a potential strategy to address these obstacles, a pilot study was designed that incorporated both a reduced-intensity conditioning and mesenchymal stromal cells (MSCs). Six patients were enrolled, including 4 with high-risk sickle cell disease (SCD) and 2 with transfusion-dependent thalassemia major. Conditioning consisted of fludarabine (150 mg/m(2)), melphalan (140 mg/m(2)), and alemtuzumab (60 mg for patients weighing > 30 kg and .9 mg/kg for patients weighing <30 kg). Two patients received HLA 7/8 allele matched bone marrow and 4 received 4-5/6 HLA matched umbilical cord blood as the source of HSCs. MSCs were of bone marrow origin and derived from a parent in 1 patient and from an unrelated third-party donor in the remaining 5 patients. GVHD prophylaxis consisted of cyclosporine A and mycophenolate mofetil. One patient had neutropenic graft failure, 2 had autologous hematopoietic recovery, and 3 had hematopoietic recovery with complete chimerism. The 2 SCD patients with autologous hematopoietic recovery are alive. The remaining 4 died either from opportunistic infection, GVHD, or intracranial hemorrhage. Although no infusion-related toxicity was seen, the cotransplantation of MSCs was not sufficient for reliable engraftment in patients with advanced hemoglobinopathy. Although poor engraftment has been observed in nearly all such trials to date in this patient population, there was no evidence to suggest that MSCs had any positive impact on engraftment. Because of the lack of improved engraftment and unacceptably high transplant-related mortality, the study was prematurely terminated

  7. Reduced-intensity conditioning hematopoietic cell transplantation is an effective treatment for patients with SLAM-associated protein deficiency/X-linked lymphoproliferative disease type 1.

    PubMed

    Marsh, Rebecca A; Bleesing, Jack J; Chandrakasan, Shanmuganathan; Jordan, Michael B; Davies, Stella M; Filipovich, Alexandra H

    2014-10-01

    X-linked lymphoproliferative disease type 1 (XLP1) is a rare immune deficiency caused by mutations in SH2D1A. Allogeneic hematopoietic cell transplantation (HCT) is often performed because of the morbidity and mortality associated with XLP1. There is limited experience using reduced-intensity conditioning (RIC) regimens for these patients. Here we report our 8-year single-center experience. Sixteen consecutive patients diagnosed with XLP1 underwent allogeneic HCT between 2006 and 2013 after a RIC regimen consisting of alemtuzumab, fludarabine, and melphalan. Patient phenotypes included hemophagocytic lymphohistiocytosis (HLH) after Epstein-Barr virus (n = 5) or human herpesvirus 6 (n = 1), macrophage activation syndrome (n = 1), interstitial pneumonitis and encephalitis (n = 1), B cell lymphoma (n = 8), and hypogammaglobulinemia (n = 2). One patient was asymptomatic. Fourteen of 16 patients received 8/8 HLA-matched unrelated or related bone marrow grafts, whereas 2 patients received mismatched unrelated grafts. Acute graft-versus-host disease (GVHD) prophylaxis consisted of methylprednisolone and cyclosporine in all but 1 patient, who additionally received methotrexate. All patients had hematopoietic recovery. There were no cases of hepatic veno-occlusive disease or pulmonary hemorrhage. One patient (6%) developed acute GVHD and later also developed chronic GVHD (6%). Five patients (31%) developed mixed chimerism. Only 1 patient with mixed chimerism (6%) experienced a decline of donor chimerism to less than 50% but returned to full donor chimerism after infusion of donor lymphocytes and a CD34(+) selected stem cell boost. Infectious complications were frequent, particularly viral reactivation. One-year survival estimated by Kaplan-Meier analysis was 80%, with long-term survival estimated at 71%. Survival was similar for patients with or without a history of HLH (86% versus 75%, respectively, P = .70). There were no occurrences of lymphoma or HLH

  8. Characterization of acute graft-versus-host disease following reduced-intensity stem-cell transplantation from an HLA-identical related donor.

    PubMed

    Murashige, Naoko; Kami, Masahiro; Mori, Shin-ichiro; Katayama, Yuta; Kobayashi, Kazuhiko; Onishi, Yasushi; Hori, Akiko; Kishi, Yukiko; Hamaki, Tamae; Tajima, Kinuko; Kanda, Yoshinobu; Tanosaki, Ryuji; Takaue, Yoichi

    2008-08-01

    To investigate clinical features of acute graft-versus-host disease (GVHD) following reduced intensity stem-cell transplantation (RIST), we retrospectively investigated medical records of 65 patients with hematologic malignancies who underwent RIST from a matched related donor. Preparative regimen comprised fludarabine 30 mg/m(2) (n = 53) or cladribine 0.11 mg/kg (n = 12) for 6 days plus busulfan 4 mg/kg for 2 days. Twelve patients received rabbit antithymocyte globulin 2.5 mg/kg/day for 2-4 consecutive days. Grade II to IV acute GVHD was diagnosed in 36 patients (55%). Its median onset was day 58 (range, 17-109), while it was bimodal, peaking day 15-29 (early-onset GVHD, n = 18) and day 75-89 days (late-onset GVHD, n = 18). Variables that were more common in early-onset GVHD than late-onset GVHD included skin rash (89% vs. 61%) and noninfectious fevers (33% vs. 11%). Desaturation, pulmonary infiltrates and hyperbilirubinemia (>2.0 mg/dL) were more common in late-onset GVHD (6% vs. 22%, 0% vs. 17%, and 6% vs. 33%, respectively). All of the patients with early-onset GVHD given corticosteroid responded to it, while 5 of the 18 patients with late-onset GVHD failed to respond it. Patients with either early-onset or late-onset GVHD tended to have better progression-free survival (PFS) than those without it; however, there was no significant difference in PFS between patients with early-onset GVHD and those with late-onset GVHD. This study suggests that several etiologies might have contributed to the development of acute GVHD following RIST.

  9. Methotrexate dose delivery is more important than ciclosporin level in graft-versus-host disease prophylaxis following T-replete reduced-intensity sibling allogeneic stem cell transplant.

    PubMed

    Medd, Patrick; Monk, Ian; Danby, Robert; Malladi, Ram; Clifford, Ruth; Ellis, Amanda; Roberts, David; Hatton, Chris; Vyas, Paresh; Littlewood, Tim; Peniket, Andy

    2011-09-01

    We investigated the contributions of methotrexate (MTX) and ciclosporin (CsA) prophylaxis to acute/chronic graft-versus-host disease (a/cGvHD) prevention following reduced-intensity conditioned allogeneic haematopoietic stem cell transplant (HSCT). Ninety-two fludarabine-melphalan sibling allo-SCT received CsA. Nine, 30 and 47 patients received no MTX, 2-3 doses and 4 doses, respectively. Cumulative CsA blood level to day 21 (CsA(21)) was calculated. Grades II-IV aGvHD incidence was 37.2%. In multivariate analysis, MTX omission and increasing donor age significantly associated with aGvHD incidence whilst MTX reduction and CsA(21) did not. Median duration of first immunosuppressive therapy (IST) for aGvHD was 68 days; duration of first IST was significantly longer in older patients but was not associated with MTX or CsA(21). Extensive cGvHD incidence was 60.6% at 1 year. Reduction of MTX to 2-3 doses, but not MTX omission or CsA(21), was associated with greater incidence of cGvHD affecting ≥3 organs. Median IST duration was 22 months; neither MTX nor CsA(21) influenced this. IST duration was significantly greater in patients receiving a CD34 dose below median. Neither MTX nor CsA(21) altered survival or relapse outcomes. MTX influences GvHD following T-replete RIC sibling HSCT.

  10. Feasible outcomes of T cell-replete haploidentical stem cell transplantation with reduced-intensity conditioning in patients with myelodysplastic syndrome.

    PubMed

    Shin, Seung-Hwan; Kim, Jung-Ho; Jeon, Young-Woo; Yoon, Jae-Ho; Yahng, Seung-Ah; Lee, Sung-Eun; Choi, Yun-Suk; Kim, Dae-Young; Lee, Jung-Hee; Lee, Seok; Kim, Hee-Je; Min, Chang-Ki; Lee, Jong-Wook; Lee, Kyoo-Hyung; Min, Woo-Sung; Kim, Yoo-Jin; Lee, Je-Hwan

    2015-02-01

    Even with the recent optimization of haploidentical stem cell transplantation (SCT), its role for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia evolving from MDS (sAML) should be validated. We analyzed the outcomes of consecutive 60 patients with MDS or sAML who received T cell-replete haploidentical SCT after reduced-intensity conditioning with fludarabine, busulfan, and rabbit antithymocyte globuline ± 800 cGy total body irradiation. Patients achieved a rapid neutrophil engraftment after a median of 12 days (range, 8 to 23) and an early immune reconstitution without high incidences of acute graft-versus-host disease (GVHD) II to IV and chronic GVHD (36.7% and 48.3%, respectively). After a median follow-up of 4 years, incidence of relapse and nonrelapse mortality and rate of overall survival and disease-free survival was 34.8%, 23.3%, 46.8%, and 41.9%, respectively. In multivariate analysis, the disease status at peak was a significant predictor for relapse (lower-risk MDS versus higher-risk MDS or sAML; hazard ratio [HR], 5.69; 95% confidence interval [CI], 1.45 to 22.29; P = .013) and disease-free survival (HR, 4.44; 95% CI, 1.14 to 17.34; P = .032). Chronic GVHD was an additional significant predictor for relapse (no versus yes; HR, 2.87; 95% CI, 1.03 to 7.51; P = .043). Our T cell-replete haploidentical SCT may be a feasible option for patients with MDS and sAML without conventional donors.

  11. Impact of Cyclosporine Levels on the Development of Acute Graft versus Host Disease after Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation

    PubMed Central

    García Cadenas, Irene; Valcarcel, David; Martino, Rodrigo; Piñana, J. L.; Barba, Pere; Novelli, Silvana; Esquirol, Albert; Garrido, Ana; Saavedra, Silvana; Granell, Miquel; Moreno, Carol; Briones, Javier; Brunet, Salut; Sierra, Jorge

    2014-01-01

    We analyze the impact of cyclosporine (CsA) levels in the development of acute graft-versus-host disease (aGVHD) after reduced intensity conditioning allogeneic hematopoietic transplantation (allo-RIC). We retrospectively evaluated 156 consecutive patients who underwent HLA-identical sibling allo-RIC at our institution. CsA median blood levels in the 1st, 2nd, 3rd and 4th weeks after allo-RIC were 134 (range: 10–444), 219 (54–656), 253 (53–910) and 224 (30–699) ng/mL; 60%, 16%, 11% and 17% of the patients had median CsA blood levels below 150 ng/mL during these weeks. 53 patients developed grade 2–4 aGVHD for a cumulative incidence of 45% (95% CI 34–50%) at a median of 42 days. Low CsA levels on the 3rd week and sex-mismatch were associated with the development of GVHD. Risk factors for 1-year NRM and OS were advanced disease status (HR: 2.2, P = 0.02) and development of grade 2–4 aGVHD (HR: 2.5, P < 0.01), while there was a trend for higher NRM in patients with a low median CsA concentration on the 3rd week (P = 0.06). These results emphasize the relevance of sustaining adequate levels of blood CsA by close monitoring and dose adjustments, particularly when engraftment becomes evident. CsA adequate management will impact on long-term outcomes in the allo-RIC setting. PMID:24623962

  12. Outcome of lower-intensity allogeneic transplantation in non-Hodgkin lymphoma after autologous transplantation failure.

    PubMed

    Freytes, César O; Zhang, Mei-Jie; Carreras, Jeanette; Burns, Linda J; Gale, Robert Peter; Isola, Luis; Perales, Miguel-Angel; Seftel, Matthew; Vose, Julie M; Miller, Alan M; Gibson, John; Gross, Thomas G; Rowlings, Philip A; Inwards, David J; Pavlovsky, Santiago; Martino, Rodrigo; Marks, David I; Hale, Gregory A; Smith, Sonali M; Schouten, Harry C; Slavin, Simon; Klumpp, Thomas R; Lazarus, Hillard M; van Besien, Koen; Hari, Parameswaran N

    2012-08-01

    We studied the outcome of allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning regimens (reduced-intensity conditioning and nonmyeloablative) in patients with non-Hodgkin lymphoma who relapsed after autologous hematopoietic stem cell transplantation. Nonrelapse mortality, lymphoma progression/relapse, progression-free survival (PFS), and overall survival were analyzed in 263 patients with non-Hodgkin lymphoma. All 263 patients had relapsed after a previous autologous hematopoietic stem cell transplantation and then had undergone allogeneic hematopoietic stem cell transplantation from a related (n = 26) or unrelated (n = 237) donor after reduced-intensity conditioning (n = 128) or nonmyeloablative (n = 135) and were reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2006. The median follow-up of survivors was 68 months (range, 3-111 months). Three-year nonrelapse mortality was 44% (95% confidence interval [CI], 37%-50%). Lymphoma progression/relapse at 3 years was 35% (95% CI, 29%-41%). Three-year probabilities of PFS and overall survival were 21% (95% CI, 16%-27%) and 32% (95% CI, 27%-38%), respectively. Superior Karnofsky Performance Score, longer interval between transplantations, total body irradiation-based conditioning regimen, and lymphoma remission at transplantation were correlated with improved PFS. Allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning is associated with significant nonrelapse mortality but can result in long-term PFS. We describe a quantitative risk model based on pretransplantation risk factors to identify those patients likely to benefit from this approach.

  13. Regimen-related toxicity following reduced-intensity stem-cell transplantation (RIST): comparison between Seattle criteria and National Cancer Center Common Toxicity Criteria (NCI-CTC) version 2.0.

    PubMed

    Sakiyama, M; Kami, M; Hori, A; Imataki, O; Hamaki, T; Murashige, N; Kobayashi, K; Kishi, Y; Kojima, R; Kim, S-W; Kusumi, E; Yuji, K; Miyakoshi, S; Mori, S; Tanosaki, R; Taniguchi, S; Takaue, Y

    2004-11-01

    Acute regimen-related toxicity (RRT) is minimal in reduced-intensity stem-cell transplantation (RIST). However, the Seattle RRT grading (Bearman et al), developed in the context of conventional-intensity transplantation, is frequently applied to RIST. We compared the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0 with the Seattle criteria after RIST in 86 patients. RRT within 30 days of transplant graded by both sets of criteria were significantly associated with the outcome confirming the predictive value of both the systems. A total of 15 patients died of disease progression, and 12 of transplant-related mortality: RRT (n = 2), graft-versus-host disease (GVHD) (n = 7), infection (n = 1), and others (n = 2). GVHD-related deaths primarily resulted from infections after steroid treatment (n = 6) and bronchiolitis obliterans (n = 1). This study shows that NCI-CTC is appropriate in toxicity evaluation of RIST, and that its application to RIST enables a toxicity comparison between RIST and other types of cancer treatments. Since GVHD is a significant problem in RIST, modifications are required to evaluate immunological complications following RIST.

  14. Comparison of Reduced-Intensity and Myeloablative Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia: A Meta-Analysis

    PubMed Central

    Ismail, Nor-Azimah; Mohd-Idris, Mohd-Razif; Jamaluddin, Fariza Wan; Tumian, NorRafeah; Sze-Wei, Ernie Yap; Muhammad, Norasiah; Nai, Ming Lai

    2014-01-01

    Currently, the indications to perform reduced-intensity conditioning allogeneic hematopoietic stem cell transplant (RIC-HCT) are based on data derived mainly from large registry and single-centre retrospective studies. Thus, at the present time, there is limited direct evidence supporting the current practice in selecting patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) for RIC versus myeloablative conditioning (MAC) transplants. To determine the relationship between dose intensity of conditioning regimen and survival outcomes after allografting in AML/ALL patients, we performed a meta-analysis of 23 clinical trials reported between 1990 and 2013 involving 15,258 adult patients that compare survival outcomes after RIC-HCT versus MAC-HCT. RIC-HCT resulted in comparable <2-year and 2–6 year overall survival (OS) rates post-transplantation even though the RIC-HCT recipients were older and had more active disease than MAC-HCT recipients. The 2–6 year progression-free survival (PFS), nonrelapse mortality, acute graft-versus-host disease (GvHD) and chronic GvHD rates were reduced after RIC-HCT, but relapse rate was increased. Similar outcomes were observed regardless of disease type and status at transplantation. Odds ratio for all outcomes remained comparable with or without performing separate analyses for the year of HCT and for retrospective versus prospective studies. Among RIC-HCT recipients, survival rates were superior if patients were in CR at transplantation. Significant inter-study heterogeneity for aGvHD data and publication bias for PFS data were observed. This meta-analysis showed no OS benefit of MAC-HCT over RIC-HCT across the entire cohort of patients suggesting that RIC-HCT could be an effective therapeutic option for AML/ALL patients who are ineligible for MAC-HCT and CR status is preferred before RIC-HCT. PMID:25072307

  15. Intensive care outcomes in adult hematopoietic stem cell transplantation patients.

    PubMed

    Bayraktar, Ulas D; Nates, Joseph L

    2016-02-10

    Although outcomes of intensive care for patients undergoing hematopoietic stem cell transplantation (HSCT) have improved in the last two decades, the short-term mortality still remains above 50% among allogeneic HSCT patients. Better selection of HSCT patients for intensive care, and consequently reduction of non-beneficial care, may reduce financial costs and alleviate patient suffering. We reviewed the studies on intensive care outcomes of patients undergoing HSCT published since 2000. The risk factors for intensive care unit (ICU) admission identified in this report were primarily patient and transplant related: HSCT type (autologous vs allogeneic), conditioning intensity, HLA mismatch, and graft-versus-host disease (GVHD). At the same time, most of the factors associated with ICU outcomes reported were related to the patients' functional status upon development of critical illness and interventions in ICU. Among the many possible interventions, the initiation of mechanical ventilation was the most consistently reported factor affecting ICU survival. As a consequence, our current ability to assess the benefit or futility of intensive care is limited. Until better ICU or hospital mortality prediction models are available, based on the available evidence, we recommend practitioners to base their ICU admission decisions on: Patient pre-transplant comorbidities, underlying disease status, GVHD diagnosis/grade, and patients' functional status at the time of critical illness.

  16. Rapid improvement of disseminated intravascular coagulation by donor leukocyte infusions in a patient with promyelocytic crisis of chronic myelogenous leukemia after reduced-intensity stem cell transplantation from an HLA 2-antigen-mismatched mother.

    PubMed

    Matsue, Kosei; Yamada, Konagi; Takeuchi, Masami; Tabayashi, Takayuki

    2003-05-01

    Donor leukocyte infusion (DLI) is recognized as effective therapy for relapse after stem cell transplantation in patients with chronic myelogenous leukemia (CML). However, the clinical efficacy of DLI in the advanced phase of CML or other types of leukemia has not been clearly defined because of its varying degree of success. We describe a 22-year-old male patient with promyelocytic crisis of CML who had a relapse after peripheral blood stem cell transplantation, under reduced-intensity conditioning, from his HLA 2-antigen-mismatched mother. Complete hematologic remission was obtained after transplantation. However, a relapse that occurred on day 66 posttransplantion was characterized by an increase in number of leukemic promyelocytes with simultaneous exacerbation of disseminated intravascular coagulation (DIC). The patient received DLI containing 1 x 10(7)/kg CD3+ cells on day 73. Because rapid improvement of DIC paralleled the decrease in leukemic cells and because it was observed soon after DLI and before the development of acute graft-versus-host disease (GVHD), we hypothesized that leukemia-specific cells other than natural killer cells or cytotoxic T-cells unrelated to GVHD played a role in the graft-versus-leukemia effect observed in our patient. In addition, this may be the first report of effective correction of DIC by DLI after stem cell transplantation.

  17. Role of minimal residual disease and chimerism after reduced-intensity and myeloablative allo-transplantation in acute myeloid leukemia and high-risk myelodysplastic syndrome.

    PubMed

    Bernal, Teresa; Diez-Campelo, María; Godoy, Vicky; Rojas, Silvia; Colado, Enrique; Alcoceba, Miguel; González, Marcos; Vidriales, Belén; Sánchez-Guijo, Fermín M; López-Corral, Lucía; Luño, Elisa; del Cañizo, Consuelo

    2014-05-01

    We evaluated the impact of detection of minimal residual disease by flow cytometry (FCMRD) and CD3 chimerism in relapse in a cohort of 87 patients with acute myeloid leukemia or myelodysplastic syndrome undergoing stem cell transplantation. Patients with a positive FCMRD at day +100 after transplantation showed higher relapse rates and worse overall survival. In multivariate analysis, a positive FCMRD after transplantation was a significant predictor of relapse. Mixed chimerism showed a trend to statistical signification. We conclude that FCMRD at day 100 after SCT is the best predictor of relapse after SCT in patients with aggressive myeloid malignancies.

  18. High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

    ClinicalTrials.gov

    2017-01-04

    Post-Transplant Lymphoproliferative Disorder; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

  19. Incidence and risk factors for moderate-to-severe veno-occlusive disease of the liver after allogeneic stem cell transplantation using a reduced intensity conditioning regimen.

    PubMed

    Tsirigotis, P D; Resnick, I B; Avni, B; Grisariu, S; Stepensky, P; Or, R; Shapira, M Y

    2014-11-01

    The incidence and outcome of moderate-to-severe veno-occlusive (VOD) disease was analyzed in 271 consecutive patients with hematological malignancies who underwent allogeneic SCT (allo-SCT) using the same reduced intensity regimen (RIC). RIC consisted of fludarabine, BU and antithymocyte globulin (ATG). Twenty-four out of 271 patients (8.8%) developed VOD, which was severe in only 4 (1.4%) out of 24 cases. All four patients with severe VOD finally succumbed to their disease. In multivariate analysis, i.v. administration of BU was associated with significant reduced incidence of VOD as compared with per os administration. In conclusion, VOD remains a serious complication of allo-SCT using RIC regimens containing BU. Although the incidence of severe VOD is very low, the overall mortality rate in the group of patients with severe VOD remains extremely high and therefore novel treatment approaches are needed.

  20. Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplant to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Intermediate-2 and High Risk Myelodysplastic Syndrome Blood and Marrow Transplant Clinical Trials Network #1102 Study Rationale, Design and Methods

    PubMed Central

    Saber, Wael; Le Rademacher, Jennifer; Sekeres, Mikkael; Logan, Brent; Lewis, Moira; Mendizabal, Adam; Leifer, Eric; Appelbaum, Frederick R.; Horowitz, Mary M; Nakamura, Ryotaro; Cutler, Corey S.

    2014-01-01

    The introduction of reduced intensity conditioning regimens (RIC) made it possible to offer allogeneic hematopoietic cell transplantation (alloHCT) to older patients with myelodysplastic syndromes (MDS). However, the relative risks and benefits of alloHCT compared to novel non-transplant therapies continue to be the source of considerable uncertainty. We will perform a prospective biologic assignment trial to compare RIC alloHCT to non-transplant therapies based on donor availability. Primary outcome is 3-year overall survival. Secondary outcomes include leukemia-free survival, quality of life, and cost-effectiveness. Four hundred patients will be enrolled over roughly 3 years. Planned subgroup analyses will evaluate key biologic questions, such as the impact of age & response to hypomethylating agents on treatment effects. Findings from this study potentially may set a new standard of care for older MDS patients who are considered candidates for alloHCT. PMID:24972249

  1. The long-term outcome of reduced-intensity allogeneic stem cell transplantation from a matched related or unrelated donor, or haploidentical family donor in patients with leukemia: a retrospective analysis of data from the China RIC Cooperative Group.

    PubMed

    Yu, Chang-Lin; Zheng-Dong; Qiao, Zhen-Hua; Wang, Jian-Min; Huang-He; Liang, Ying-Min; Wu, De-Pei; Chen, Bao-An; Bai-Hai; Shi, Bao-Fu; Sun, Wan-Jun; Qiao, Jun-Xiao; Guo, Mei; Qiao, Jian-Hui; Sun, Qi-Yun; Hu, Kai-Xun; Huang, Ya-Jing; Zuo, Hong-Li; Huang, Xiao-Jun; Ai, Hui-Sheng

    2017-02-01

    This study compared 6-year follow-up data from patients undergoing reduced-intensity conditioning (RIC) transplantation with an HLA-matched related donor (MRD), an HLA-matched unrelated donor (MUD), or an HLA-haploidentical donor (HID) for leukemia. Four hundred and twenty-seven patients from the China RIC Cooperative Group were enrolled, including 301 in the MRD, 79 in the HID, and 47 in the MUD groups. The conditioning regimen involved fludarabine combined with anti-lymphocyte globulin and cyclophosphamide. Graft-versus-host disease (GVHD) prophylaxis was administered using cyclosporin A (CsA) and mycophenolate mofetil (MMF). Four hundred and nineteen patients achieved stable donor chimerism. The incidence of stage II-IV acute GVHD in the HID group was 44.3 %, significantly higher than that in the MRD (23.6 %) and MUD (19.1 %) groups. The 1-year transplantation-related mortality (TRM) rates were 44.3, 17.6, and 21.3, respectively. Event-free survival (EFS) at 6 years in the HID group was 36.7 %, significantly lower than that of the MRD and MUD groups (59.1 and 66.0 %, P < 0.001 and P = 0.001, respectively). For advanced leukemia, the relapse rate of the HID group was 18.5 %, lower than that of the MRD group (37.5 %, P = 0.05), but the EFS at 6 years was 31.7 and 30.4 % (P > 0.05), respectively. RIC transplantation with MRD and MUD had similar outcome in leukemia which is better than that with HID. RIC transplantation with HID had lower relapsed with higher TRM and GVHD rate, particularly in advanced leukemias. RIC transplantation with MRD and MUD had similar outcomes in leukemia and they were better than those with HID. RIC transplantation with HID had a lower relapse rate but higher TRM and GVHD rates, particularly in cases of advanced leukemia.

  2. Reduced-Intensity Conditioning Combined with (188)Rhenium Radioimmunotherapy before Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia: The Role of In Vivo T Cell Depletion.

    PubMed

    Schneider, Sebastian; Strumpf, Annette; Schetelig, Johannes; Wunderlich, Gerd; Ehninger, Gerhard; Kotzerke, Jörg; Bornhäuser, Martin

    2015-10-01

    The combination of reduced-intensity conditioning, (188)rhenium anti-CD66 radioimmunotherapy, and in vivo T cell depletion was successfully applied in elderly patients with acute myeloid leukemia or myelodysplastic syndrome. Within a prospective phase II protocol, we investigated whether a dose reduction of alemtuzumab (from 75 mg to 50 mg MabCampath) would improve leukemia-free survival by reducing the incidence of relapse. Fifty-eight patients (median age, 67 years; range, 54 to 76) received radioimmunotherapy followed by fludarabine 150 mg/m(2) and busulfan 8 mg/kg combined with either 75 mg (n = 26) or 50 mg (n = 32) alemtuzumab. Although we observed a trend towards a shorter duration of neutropenia in the 50 mg group (median, 19 versus 21 days; P = .07), the time from transplantation to neutrophil and platelet engraftment as well as the overall incidence of engraftment did not differ. The incidence of severe acute graft-versus-host disease tended to be higher after the lower alemtuzumab dose (17% versus 4%; P = .15). No significant differences in the cumulative incidences of relapse (38% versus 35%; P = .81) or nonrelapse mortality (46% versus 27%; P = .31) were observed. Accordingly, disease-free and overall survival were not significantly different between groups. Although the feasibility of radioimmunotherapy plus reduced-intensity conditioning could be demonstrated in elderly patients, the dose reduction of alemtuzumab had no positive impact on overall outcome. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  3. Prognostic impact of immune status and hematopoietic recovery before and after fludarabine, IV busulfan, and antithymocyte globulins (FB2 regimen) reduced-intensity conditioning regimen (RIC) allogeneic stem cell transplantation (allo-SCT).

    PubMed

    Le Bourgeois, Amandine; Lestang, Elsa; Guillaume, Thierry; Delaunay, Jacques; Ayari, Sameh; Blin, Nicolas; Clavert, Aline; Tessoulin, Benoit; Dubruille, Viviane; Mahe, Beatrice; Roland, Virginie; Gastinne, Thomas; Le Gouill, Steven; Moreau, Philippe; Mohty, Mohamad; Planche, Lucie; Chevallier, Patrice

    2013-03-01

    This retrospective analysis aimed to assess hematopoietic and immune recovery in a cohort of 53 patients [males: n = 33; median age: 59 yr (range: 22-70)] who received a FB2 (fludarabine 120-150 mg/m² + IV busulfan 6.4 mg/kg + antithymocyte globulin thymoglobulin 5 mg/kg) reduced-intensity conditioning (RIC) allo-stem cells transplantations (SCT). With a median follow-up of 19 months (range: 2-53), the 2-yr overall survival, disease-free survival (DFS), relapse incidence, and non-relapse mortality were 63%, 59.5%, 35%, and 6%, respectively. In univariate analysis, the factors correlated with a significantly higher 2-yr OS and DFS were a higher total circulating lymphocytes count at transplant (>730/mm(3) ; OS: 81% vs. 43%, P = 0.02; DFS: 73% vs. 45.5%, P = 0.03) and a higher recovery of leukocytes (>5300/mm(3) ) (2-yr OS: 81% vs. 44%, P = 0.007; 2-yr DFS: 72% vs. 46%, P = 0.08), neutrophils (>3200/mm(3) ) (2-yr OS: 76% vs. 50%, P = 0.03; 2-yr DFS: 67% vs. 52.0%, P = 0.1), and monocytes (>590/mm(3) ; 2-yr OS: 80% vs. 45%, P = 0.004; 2-yr DFS: 76% vs. 42%, P = 0.01) at day +30 post-transplant. In multivariate analysis, the only independent factors associated with a significantly higher OS and DFS were a better immune status at transplant (lymphocytes count >730/mm(3) ) and a higher monocytes count (>590/mm(3) ) at day +30 post-transplant. These results suggest that immune status and hematopoietic recovery before and after FB2 RIC allo-SCT can be significant predictors of outcome. This paves the way for future studies aiming to closely monitor the kinetics of immune recovery after RIC allo-SCT and to evaluate the impact of growth factors and other immunostimulatory cytokines in the setting of RIC allo-SCT.

  4. Cytoreductive treatment with clofarabine/ara-C combined with reduced-intensity conditioning and allogeneic stem cell transplantation in patients with high-risk, relapsed, or refractory acute myeloid leukemia and advanced myelodysplastic syndrome.

    PubMed

    Buchholz, Stefanie; Dammann, Elke; Stadler, Michael; Krauter, Juergen; Beutel, Gernot; Trummer, Arne; Eder, Matthias; Ganser, Arnold

    2012-01-01

    The combination of cytoreductive chemotherapy with reduced-intensity conditioning (RIC) is a highly effective antileukemic therapy. Purpose of this retrospective analysis was to evaluate the antileukemic efficacy and toxicity of clofarabine-based chemotherapy followed by RIC and allogeneic stem cell transplantation (SCT) for high-risk, relapsed, or refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). From May 2007 until October 2009, a total of 27 patients underwent allogeneic SCT after treatment with clofarabine and ara-C for 5d and RIC (4Gy TBI/cyclophosphamide/ATG). Prophylaxis of graft-versus-host disease (GvHD) consisted of cyclosporine and mycophenolate mofetil. Unmanipulated G-CSF mobilized PBSC (n=26) or bone marrow cells (n=1) were transplanted from unrelated (n=21) or matched related (n=6) donors. Non-hematological toxicities of this regimen mainly affected liver and skin and were all reversible. Seven patients relapsed within a median time of 5.7 months. The overall survival (OS) and relapse-free survival rates were 56% and 52% at 2 yr, respectively. In this cohort of patients, cytoreduction with clofarabine/ara-C (ClAraC) followed by RIC allogeneic SCT was well tolerated and showed good antileukemic efficacy even in patients with high-risk AML or MDS, with engraftment and GvHD-incidence comparable to other RIC regimens.

  5. Phase II Study of Yttrium-90-Ibritumomab Tiuxetan as Part of Reduced-Intensity Conditioning (with Melphalan, Fludarabine ± Thiotepa) for Allogeneic Transplantation in Relapsed or Refractory Aggressive B Cell Lymphoma: A GELTAMO Trial.

    PubMed

    Cabrero, Monica; Martin, Alejandro; Briones, Javier; Gayoso, Jorge; Jarque, Isidro; López, Javier; Grande, Carlos; Heras, Inmaculada; Arranz, Reyes; Bernal, Teresa; Perez-Lopez, Estefania; López-Godino, Oriana; Conde, Eulogio; Caballero, Dolores

    2017-01-01

    We designed a phase II clinical trial including Y-90 ibritumomab-tiuxetan as part of a reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (Clinical Trials Identifier: NCT00644371). Eligible patients had high-risk relapsed/refractory aggressive lymphoma. The conditioning regimen consisted of rituximab 250 mg (days -21 and -14), Y-90 ibritumomab IV (.4 m Ci/kg, day -14), fludarabine 30 mg/m(2) i.v. (days -3 and -2) plus melphalan 70 mg/m(2) i.v. (days -3 and -2) or 1 dose of melphalan and thiotepa 5 mg/kg (day -8). Donors were related. Eighteen patients were evaluable. At the time of transplantation, responses were complete remission (CR) (n = 7, 39%), partial remission (n = 6, 33%) or refractory disease (n = 4, 28%). Y-90-ibritumomab infusions were well tolerated, with no adverse reactions. Nonrelapse mortality at 1 year was 28%. Median follow-up was 46 (range, 39 to 55) months. Estimated 1-year progression-free survival (PFS) was 50%, and 4-year overall survival (OS) and PFS were both 44.4%. CR at the moment of AlloSCT had significant impact on PFS (71% versus 27%, P = .046) and OS (71% versus 27%, P = .047). Our results show that Y-90-ibritumomab-tiuxetan as a component of RIC for AlloSCT is feasible in patients with high-risk B cell lymphoma. Development of phase III clinical trials is needed to clarify the contribution of radioimmunotherapy to RIC AlloSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2014-09-01

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

  7. High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia — an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

    PubMed Central

    Czerw, Tomasz; Labopin, Myriam; Schmid, Christoph; Cornelissen, Jan J.; Chevallier, Patrice; Blaise, Didier; Kuball, Jürgen; Vigouroux, Stephane; Garban, Frédéric; Lioure, Bruno; Fegueux, Nathalie; Clement, Laurence; Sandstedt, Anna; Maertens, Johan; Guillerm, Gaëlle; Bordessoule, Dominique

    2016-01-01

    Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, >347 × 10^6/kg and >8.25 × 10^6 /kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes. PMID:27036034

  8. Experience with Alemtuzumab, Fludarabine, and Melphalan Reduced-Intensity Conditioning Hematopoietic Cell Transplantation in Patients with Nonmalignant Diseases Reveals Good Outcomes and That the Risk of Mixed Chimerism Depends on Underlying Disease, Stem Cell Source, and Alemtuzumab Regimen.

    PubMed

    Marsh, Rebecca A; Rao, Marepalli B; Gefen, Aharon; Bellman, Denise; Mehta, Parinda A; Khandelwal, Pooja; Chandra, Sharat; Jodele, Sonata; Myers, Kasiani C; Grimley, Michael; Dandoy, Christopher; El-Bietar, Javier; Kumar, Ashish R; Leemhuis, Tom; Zhang, Kejian; Bleesing, Jack J; Jordan, Michael B; Filipovich, Alexandra H; Davies, Stella M

    2015-08-01

    Alemtuzumab, fludarabine, and melphalan reduced-intensity conditioning (RIC) regimens are increasingly used for the hematopoietic cell transplantation (HCT) of pediatric and young adult patients with nonmalignant diseases. Early experience suggests that these regimens are associated with good survival but a high incidence of mixed chimerism, which we have previously shown to be influenced by the alemtuzumab schedule. We hypothesized that the underlying diagnosis and donor graft source would also affect the development of mixed chimerism and that the majority of patients would survive RIC HCT without graft loss. To examine this, we conducted a retrospective study of 206 patients with metabolic diseases, non-Fanconi anemia marrow failure disorders, and primary immune deficiencies who underwent 210 consecutive RIC HCT procedures at Cincinnati Children's Hospital. Ninety-seven percent of the patients engrafted. Mixed donor and recipient chimerism developed in 46% of patients. Patients with marrow failure had a low risk of mixed chimerism (hazard ratio [HR], .208; 95% confidence interval [CI], .061 to .709; P = .012). The risk of mixed chimerism was high in patients who received a cord blood graft (HR, 3.122; 95% CI, 1.236 to 7.888; P = .016). As expected, patients who received a proximal or higher dose per kilogram of alemtuzumab schedule also experienced higher rates of mixed chimerism (all HR > 2, all P < .05). At the time of last follow-up (median, 654 days; range, 13 to 3337), over 75% of patients had greater than 90% whole blood donor chimerism. A second transplantation was performed in 5% of patients. Three-year survival without retransplantation was 84% (95% CI, 71% to 98%) for patients who underwent transplantation with an HLA-matched sibling donor. Survival without retransplantation was negatively affected by lack of a matched related donor, increasing age, and development of grades III and IV acute graft-versus-host disease. We conclude that alemtuzumab

  9. Comparison of Tacrolimus and Sirolimus (Tac/Sir) versus Tacrolimus, Sirolimus, and mini-methotrexate (Tac/Sir/MTX) as acute graft-versus-host disease prophylaxis after reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation.

    PubMed

    Ho, Vincent T; Aldridge, Julie; Kim, Haesook T; Cutler, Corey; Koreth, John; Armand, Philippe; Antin, Joseph H; Soiffer, Robert J; Alyea, Edwin P

    2009-07-01

    Previous studies have shown that adding sirolimus to a tacrolimus/mini-methotrexate regimen (Tac/Sir/MTX) as graft-versus-host disease (GVHD) prophylaxis produces low rates of acute GVHD (aGVHD) after reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). To assess whether posttransplantation methotrexate MTX can be safely eliminated altogether, we conducted a prospective clinical trial testing the combination of T and Sir alone (tac/sir) as GVHD prophylaxis after RIC SCT from matched related donors. We compared the results with patients who received (Tac/Sir/MTX) as GVHD prophylaxis after RIC SCT from matched related donors in a previous prospective study. Patients in both groups received i.v. fludarabine (Flu) 30 mg/m(2)/day and i.v. busulfan (Bu) 0.8 mg/kg/day on days -5 to -2 as conditioning, followed by transplantation of unmanipulated filgrastim-mobilized peripheral blood stem cells (PBSCS). After transplantation, patients in both groups received Tac and Sir orally starting on day -3, with doses adjusted to achieve trough serum levels of 5 to 10 ng/mL and 3 to 12 ng/mL, respectively. The patients in the Tac/Sir/MTX group also received mini-MTX therapy (5 mg/m(2) i.v.) on days +1, +3, and +6. Filgrastim 5 microg/kg/day s.c. was started on day +1 and continued until neutrophil engraftment. Twenty-nine patients received the Tac/Sir regimen, and 46 patients received the Tac/Sir/MTX regimen. The 2 groups were balanced in terms of age, sex, and disease characteristics. Engraftment was brisk and donor chimerism after transplantation robust in both groups. The cumulative incidence of grade II-IV aGVHD was similar in the 2 groups (17% for Tac/Sir versus 11% for Tac/Sir/MTX; P = .46). There also were no differences between the 2 groups in cumulative incidence of extensive chronic GVHD (cGVHD), treatment-related mortality (TRM), disease relapse, or survival. The Tac/Sir combination for GVHD prophylaxis is well tolerated and associated with a

  10. Sequential chemotherapy followed by reduced-intensity conditioning and allogeneic haematopoietic stem cell transplantation in adult patients with relapse or refractory acute myeloid leukaemia: a survey from the Acute Leukaemia Working Party of EBMT.

    PubMed

    Ringdén, Olle; Labopin, Myriam; Schmid, Christoph; Sadeghi, Behnam; Polge, Emmanuelle; Tischer, Johanna; Ganser, Arnold; Michallet, Mauricette; Kanz, Lothar; Schwerdtfeger, Rainer; Nagler, Arnon; Mohty, Mohamad

    2017-02-01

    This study analysed the outcome of 267 patients with relapse/refractory acute myeloid leukaemia (AML) who received sequential chemotherapy including fludarabine, cytarabine and amsacrine followed by reduced-intensity conditioning (RIC) and allogeneic haematopoietic stem cell transplantation (HSCT). The transplants in 77 patients were from matched sibling donors (MSDs) and those in 190 patients were from matched unrelated donors. Most patients (94·3%) were given anti-T-cell antibodies. The incidence of acute graft-versus-host disease (GVHD) of grades II-IV was 32·1% and that of chronic GVHD was 30·2%. The 3-year probability of non-relapse mortality (NRM) was 25·9%, that of relapse was 48·5%, that of GVHD-free and relapse-free survival (GRFS) was 17·8% and that of leukaemia-free survival (LFS) was 25·6%. In multivariate analysis, unrelated donor recipients more frequently had acute GVHD of grades II-IV [hazard ratio (HR) = 1·98, P = 0·017] and suffered less relapses (HR = 0·62, P = 0·01) than MSD recipients. Treatment with anti-T-cell antibodies reduced NRM (HR = 0·35, P = 0·01) and improved survival (HR = 0·49, P = 0·01), GRFS (HR = 0·37, P = 0·0004) and LFS (HR = 0·46, P = 0·005). Thus, sequential chemotherapy followed by RIC HSCT and use of anti-T-cell antibodies seems promising in patients with refractory AML. © 2016 John Wiley & Sons Ltd.

  11. Reducing transfusion requirements in liver transplantation

    PubMed Central

    Donohue, Ciara I; Mallett, Susan V

    2015-01-01

    Liver transplantation (LT) was historically associated with massive blood loss and transfusion. Over the past two decades transfusion requirements have reduced dramatically and increasingly transfusion-free transplantation is a reality. Both bleeding and transfusion are associated with adverse outcomes in LT. Minimising bleeding and reducing unnecessary transfusions are therefore key goals in the perioperative period. As the understanding of the causes of bleeding has evolved so too have techniques to minimize or reduce the impact of blood loss. Surgical “piggyback” techniques, anaesthetic low central venous pressure and haemodilution strategies and the use of autologous cell salvage, point of care monitoring and targeted correction of coagulopathy, particularly through use of factor concentrates, have all contributed to declining reliance on allogenic blood products. Pre-emptive management of preoperative anaemia and adoption of more restrictive transfusion thresholds is increasingly common as patient blood management (PBM) gains momentum. Despite progress, increasing use of marginal grafts and transplantation of sicker recipients will continue to present new challenges in bleeding and transfusion management. Variation in practice across different centres and within the literature demonstrates the current lack of clear transfusion guidance. In this article we summarise the causes and predictors of bleeding and present the evidence for a variety of PBM strategies in LT. PMID:26722645

  12. Phase II Trial of Reduced-Intensity Busulfan/Clofarabine Conditioning with Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia, Myelodysplastic Syndromes, and Acute Lymphoid Leukemia.

    PubMed

    El-Jawahri, Areej; Li, Shuli; Ballen, Karen K; Cutler, Corey; Dey, Bimalangshu R; Driscoll, Jessica; Hunnewell, Chrisa; Ho, Vincent T; McAfee, Steven L; Poliquin, Cathleen; Saylor, Meredith; Soiffer, Robert J; Spitzer, Thomas R; Alyea, Edwin; Chen, Yi-Bin

    2016-01-01

    Clofarabine has potent antileukemia activity and its inclusion in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia could potentially improve outcomes. We conducted a phase II study of busulfan (.8 mg/kg i.v. twice daily on days -5, -4, -3, and -2) with clofarabine (40 mg/m(2) i.v. daily on days -5, -4, -3, and -2) conditioning before allogeneic 8/8 HLA-matched related or unrelated HSCT. The primary endpoint was donor neutrophil engraftment by day +40. Secondary endpoints included nonrelapse mortality (NRM), acute and chronic graft-versus-host disease (GVHD), progression-free survival (PFS), and overall survival (OS). Thirty-four patients (acute myeloid leukemia [AML], n = 25; myelodysplastic syndromes, n = 5; and acute lymphoid leukemia, n = 4) were enrolled. Day 40+ engraftment with donor chimerism was achieved in 33 of 34 patients with 1 patient dying before count recovery. Day 100 and 1-year NRM were 5.9% (95% confidence interval [CI], 1.0 to 17.4) and 24% (95% CI, 11 to 39), respectively. The 2-year relapse rate was 26% (95% CI, 13 to 42). Cumulative incidences of acute and chronic GVHD were 21% and 44%, respectively. The 2-year PFS was 50% (95% CI, 32 to 65) and OS was 56% (95% CI, 38 to 71). For patients with AML in first complete remission, 2-year PFS and OS were both 82% (95% CI, 55 to 94). RIC with busulfan and clofarabine leads to successful engraftment with acceptable rates of NRM and GVHD. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  13. Experience with Alemtuzumab, Fludarabine, and Melphalan Reduced-Intensity Conditioning Hematopoietic Cell Transplantation in Patients with Nonmalignant Diseases Reveals Good Outcomes and That the Risk of Mixed Chimerism Depends on Underlying Disease, Stem Cell Source, and Alemtuzumab Regimen

    PubMed Central

    Marsh, Rebecca A.; Rao, Marepalli B.; Gefen, Aharon; Bellman, Denise; Mehta, Parinda A.; Khandelwal, Pooja; Chandra, Sharat; Jodele, Sonata; Myers, Kasiani C.; Grimley, Michael; Dandoy, Christopher; El-Bietar, Javier; Kumar, Ashish R.; Leemhuis, Tom; Zhang, Kejian; Bleesing, Jack J.; Jordan, Michael B.; Filipovich, Alexandra H.; Davies, Stella M.

    2015-01-01

    Alemtuzumab, fludarabine, and melphalan reduced-intensity conditioning (RIC) regimens are increasingly used for the hematopoietic cell transplantation (HCT) of pediatric and young adult patients with nonmalignant diseases. Early experience suggests that these regimens are associated with good survival but a high incidence of mixed chimerism, which we have previously shown to be influenced by the alemtuzumab schedule. We hypothesized that the underlying diagnosis and donor graft source would also affect the development of mixed chimerism and that the majority of patients would survive RIC HCT without graft loss. To examine this, we conducted a retrospective study of 206 patients with metabolic diseases, non-Fanconi anemia marrow failure disorders, and primary immune deficiencies who underwent 210 consecutive RIC HCT procedures at Cincinnati Children’s Hospital. Ninety-seven percent of the patients engrafted. Mixed donor and recipient chimerism developed in 46% of patients. Patients with marrow failure had a low risk of mixed chimerism (hazard ratio [HR], .208; 95% confidence interval [CI], .061 to .709; P = .012). The risk of mixed chimerism was high in patients who received a cord blood graft (HR, 3.122; 95% CI, 1.236 to 7.888; P = .016). As expected, patients who received a proximal or higher dose per kilogram of alemtuzumab schedule also experienced higher rates of mixed chimerism (all HR > 2, all P < .05). At the time of last follow-up (median, 654 days; range, 13 to 3337), over 75% of patients had greater than 90% whole blood donor chimerism. A second transplantation was performed in 5% of patients. Three-year survival without retransplantation was 84% (95% CI, 71% to 98%) for patients who underwent transplantation with an HLA-matched sibling donor. Survival without retransplantation was negatively affected by lack of a matched related donor, increasing age, and development of grades III and IV acute graft-versus-host disease. We conclude that alemtuzumab

  14. 'A post-transplant person': Narratives of heart or lung transplantation and intensive care unit delirium.

    PubMed

    Flynn, Katy; Daiches, Anna; Malpus, Zoey; Yonan, Nizar; Sanchez, Melissa

    2014-07-01

    Exploring patients' narratives can lead to new understandings about perceived illness states. Intensive Care Unit delirium is when people experience transitory hallucinations, delusions or paranoia in the Intensive Care Unit and little is known about how this experience affects individuals who have had a heart or lung transplant. A total of 11 participants were recruited from two heart and lung transplant services and were invited to tell their story of transplant and Intensive Care Unit delirium. A narrative analysis was conducted and the findings were presented as a shared story. This shared story begins with death becoming prominent before the transplant: 'you live all the time with Mr Death on your shoulder'. Following the operation, death permeates all aspects of dream worlds, as dreams in intensive care 'tunes into the subconscious of your fears'. The next part of the shared story offers hope of restitution; however, this does not last as reality creeps in: 'I thought it was going to be like a miracle cure'. Finally, the restitution narrative is found to be insufficient and individuals differ in the extent to which they can achieve resolution. The societal discourse of a transplant being a 'gift', which gives life, leads to internalised responsibility for the 'success' or 'failure' of the transplant. Participants describe how their experiences impact their sense of self: 'a post-transplant person'. The clinical implications of these findings are discussed.

  15. Outcomes of Cord Blood Transplantation Using Reduced-Intensity Conditioning for Chronic Lymphocytic Leukemia: A Study on Behalf of Eurocord and Cord Blood Committee of Cellular Therapy and Immunobiology Working Party, Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation, and the Societé Française de Greffe de Moelle et Therapie Cellulaire.

    PubMed

    Xavier, Erick; Cornillon, Jérôme; Ruggeri, Annalisa; Chevallier, Patrice; Cornelissen, Jan J; Andersen, Niels S; Maillard, Natacha; Nguyen, Stephanie; Blaise, Didier; Deconinck, Eric; Veelken, Hendrik; Milpied, Noel; Van Gelder, Michel; Peffault de Latour, Regis; Gluckman, Eliane; Kröger, Nicolaus; Schetelig, Johannes; Rocha, Vanderson

    2015-08-01

    Outcomes after umbilical cord blood transplantation (UCBT) for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are unknown. We analyzed outcomes of 68 patients with poor-risk CLL/SLL who underwent reduced-intensity (RIC) UCBT from 2004 to 2012. The median age was 57 years and median follow-up 36 months; 17 patients had del 17p/p53mutation, 19 patients had fludarabine-refractory disease, 11 relapsed after autologous stem cell transplantation, 8 had diagnosis of prolymphocytic leukemia, 4 had Richter syndrome, and 8 underwent transplantation with progressive or refractory disease. The most common RIC used was cyclophosphamide, fludarabine, and total body irradiation (TBI) in 82%; 15 patients received antithymocyte globulin. Most of the cord blood grafts were HLA mismatched and 76% received a double UCBT. Median total nucleated cells collected was 4.7 × 10(7)/kg. The cumulative incidences (CI) of neutrophil and platelet engraftment were 84% and 72% at 60 and 180 days respectively; day 100 graft-versus-host disease (GVHD) (grade II to IV) was 43% and 3-year chronic GVHD was 32%. The CI of relapse, nonrelapse mortality, overall survival, and progression-free survival (PFS) at 3 years were 16%, 39%, 54%, and 45%, respectively. Fludarabine-sensitive disease at transplantation and use of low-dose TBI regimens were associated with acceptable PFS. In conclusion, use of RIC-UCBT seems to be feasible in patients with poor-risk CLL/SLL and improved outcomes were observed in patients with fludarabine-sensitive disease who received low-dose TBI regimens.

  16. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin’s lymphoma. Results of the HDR-ALLO study – a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation

    PubMed Central

    Sureda, Anna; Canals, Carme; Arranz, Reyes; Caballero, Dolores; Ribera, Josep Maria; Brune, Mats; Passweg, Jacob; Martino, Rodrigo; Valcárcel, David; Besalduch, Joan; Duarte, Rafael; León, Angel; Pascual, Maria Jesus; García-Noblejas, Ana; Corral, Lucia López; Xicoy, Bianca; Sierra, Jordi; Schmitz, Norbert

    2012-01-01

    Background Although Hodgkin’s lymphoma is a highly curable disease with modern chemotherapy protocols, some patients are primary refractory or relapse after first-line chemotherapy or even after high-dose therapy and autologous stem cell transplantation. We investigated the potential role of allogeneic stem cell transplantation in this setting. Design and Methods In this phase II study 92 patients with relapsed Hodgkin’s lymphoma and an HLA-identical sibling, a matched unrelated donor or a one antigen mismatched, unrelated donor were treated with salvage chemotherapy followed by reduced intensity allogeneic transplantation. Fourteen patients showed refractory disease and died from progressive lymphoma with a median overall survival after trial entry of 10 months (range, 6–17). Seventy-eight patients proceeded to allograft (unrelated donors, n=23). Fifty were allografted in complete or partial remission and 28 in stable disease. Fludarabine (150 mg/m2 iv) and melphalan (140 mg/m2 iv) were used as the conditioning regimen. Anti-thymocyte globulin was additionally used as graft-versus-host-disease prophylaxis for recipients of grafts from unrelated donors. Results The non-relapse mortality rate was 8% at 100 days and 15% at 1 year. Relapse was the major cause of failure. The progression-free survival rate was 47% at 1 year and 18% at 4 years from trial entry. For the allografted population, the progression-free survival rate was 48% at 1 year and 24% at 4 years. Chronic graft-versus-host disease was associated with a lower incidence of relapse. Patients allografted in complete remission had a significantly better outcome. The overall survival rate was 71% at 1 year and 43% at 4 years. Conclusions Allogeneic stem cell transplantation can result in long-term progression-free survival in heavily pre-treated patients with Hodgkin’s lymphoma. The reduced intensity conditioning approach significantly reduced non-relapse mortality; the high relapse rate represents

  17. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin's lymphoma. Results of the HDR-ALLO study - a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.

    PubMed

    Sureda, Anna; Canals, Carme; Arranz, Reyes; Caballero, Dolores; Ribera, Josep Maria; Brune, Mats; Passweg, Jacob; Martino, Rodrigo; Valcárcel, David; Besalduch, Joan; Duarte, Rafael; León, Angel; Pascual, Maria Jesus; García-Noblejas, Ana; López Corral, Lucia; Xicoy, Bianca; Sierra, Jordi; Schmitz, Norbert

    2012-02-01

    Although Hodgkin's lymphoma is a highly curable disease with modern chemotherapy protocols, some patients are primary refractory or relapse after first-line chemotherapy or even after high-dose therapy and autologous stem cell transplantation. We investigated the potential role of allogeneic stem cell transplantation in this setting. In this phase II study 92 patients with relapsed Hodgkin's lymphoma and an HLA-identical sibling, a matched unrelated donor or a one antigen mismatched, unrelated donor were treated with salvage chemotherapy followed by reduced intensity allogeneic transplantation. Fourteen patients showed refractory disease and died from progressive lymphoma with a median overall survival after trial entry of 10 months (range, 6-17). Seventy-eight patients proceeded to allograft (unrelated donors, n=23). Fifty were allografted in complete or partial remission and 28 in stable disease. Fludarabine (150 mg/m(2) iv) and melphalan (140 mg/m(2) iv) were used as the conditioning regimen. Anti-thymocyte globulin was additionally used as graft-versus-host-disease prophylaxis for recipients of grafts from unrelated donors. The non-relapse mortality rate was 8% at 100 days and 15% at 1 year. Relapse was the major cause of failure. The progression-free survival rate was 47% at 1 year and 18% at 4 years from trial entry. For the allografted population, the progression-free survival rate was 48% at 1 year and 24% at 4 years. Chronic graft-versus-host disease was associated with a lower incidence of relapse. Patients allografted in complete remission had a significantly better outcome. The overall survival rate was 71% at 1 year and 43% at 4 years. Allogeneic stem cell transplantation can result in long-term progression-free survival in heavily pre-treated patients with Hodgkin's lymphoma. The reduced intensity conditioning approach significantly reduced non-relapse mortality; the high relapse rate represents the major remaining challenge in this setting. The HDR

  18. Readmission to the intensive care unit after liver transplantation.

    PubMed

    Levy, M F; Greene, L; Ramsay, M A; Jennings, L W; Ramsay, K J; Meng, J; Hein, H A; Goldstein, R M; Husberg, B S; Gonwa, T A; Klintmalm, G B

    2001-01-01

    We undertook this study to understand the factors at our transplant center that contribute to patients' return to the ICU after their liver transplant and their initial discharge from that unit. Patients who, after liver transplantation, fail discharge from the Intensive Care Unit (ICU) and must be readmitted to that unit may well utilize many more resources than those patients who are well enough to stay out of the ICU. A retrospective review of a prospectively maintained liver transplant research database followed by a retrospective review of (a subgroup) patient charts and contemporaneous controls. A large metropolitan tertiary care center and adult liver transplant center. A total of 1,197 consecutive adult patients who underwent their initial liver transplantation from 1984 to 1996. Readmission to the intensive care unit after adult liver transplantation and discharge from that unit. Only recipient age, pretransplant synthetic function labs (protime and albumin), bilirubin levels, and intraoperative blood product requirements could be statistically linked to the group requiring ICU readmission. The primary etiology for ICU readmission was cardiopulmonary deterioration. Readmission was associated with significantly lower patient and graft survivals. A detailed review of 23 patients transplanted from October 1994 to June 1996 was made, with special emphasis on cardiopulmonary status (hemodynamics, respiratory variables, and chest radiograph findings). This subgroup was compared with 30 temporally matched controls who were not readmitted to the ICU. Intravascular fluid overload and lower inspiratory capacity were significant factors related to ICU readmission. Readmitted patients had a longer hospitalization with higher hospital charges than the control group. We conclude that the most important means of preventing ICU readmission in liver transplantation patients is to optimize cardiopulmonary function and status. Close monitoring of fluid balance to avoid

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

    PubMed

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

    2016-04-01

    Myeloablative conditioning and allogeneic hematopoietic stem cell transplant (alloHSCT) in children with acute myeloid leukemia (AML) in first complete remission (CR1) may be associated with significant acute toxicity and late effects. Reduced-intensity conditioning (RIC) and alloHSCT in children is safe, feasible, and may be associated with less adverse effects. Gemtuzumab ozogamicin (GO) induces a response in 30% of patients with CD33+ relapsed/refractory AML. The dose of GO is significantly lower when combined with chemotherapy. We examined the feasibility and toxicity of RIC alloHSCT followed by GO targeted immunotherapy in children with CD33+ AML in CR1/CR2. Conditioning consisted of fludarabine 30 mg/m2 × 6 days, busulfan 3.2 to 4 mg/kg × 2 days ± rabbit antithymocyte globulin 2 mg/kg × 4 days followed by alloHSCT from matched related/unrelated donors. GO was administered ≥60 days after alloHSCT in 2 doses (8 weeks apart), following a dose-escalation design (4.5, 6, 7.5, and 9 mg/m2). Fourteen patients with average risk AML received RIC alloHSCT and post-GO consolidation: median age 13.5 years at transplant (range, 1 to 21), male-to-female 8:6, and disease status at alloHSCT 11 CR1 and 3 CR2. Eleven patients received alloHSCT from 5-6/6 HLA-matched family donors: 8 received peripheral blood stem cells, 2 received bone marrow, and 1 received related cord blood transplantation. Three patients received an unrelated allograft (two 4-5/6 and one 9/10) from unrelated cord blood unit and bone marrow, respectively. Neutrophil and platelet engraftment was observed in all assessable patients (100%), achieved at median 15.5 days (range, 7 to 31) and 21 days (range, 10 to 52), respectively. Three patients received GO at dose level 1 (4.5 mg/m2 per dose), 5 at dose level 2 (6 mg/m2 per dose), 3 at dose level 3 (7.5 mg/m2 per dose), and 3 at dose level 4 (9 mg/m2 per dose). Three of 14 patients received only 1 dose of GO after alloHSCT. One patient experienced grade

  20. Low nonrelapse mortality and prolonged long-term survival after reduced-intensity allogeneic stem cell transplantation for relapsed or refractory diffuse large B cell lymphoma: report of the Société Française de Greffe de Moelle et de Thérapie Cellulaire.

    PubMed

    Sirvent, Anne; Dhedin, Nathalie; Michallet, Mauricette; Mounier, Nicolas; Faucher, Catherine; Yakoub-Agha, Ibrahim; Mohty, Mohamad; Robin, Marie; Tabrizi, Reza; Clement, Laurence; Bilger, Karin; Larosa, Fabrice; Contentin, Nathalie; Huyn, Anne; François, Sylvie; Bulabois, Claude-Eric; Ceballos, Patrice; Bourrhis, Jean-Henri; Buzyn, Agnès; Cornillon, Jérôme; Guillerm, Gaelle; de Revel, Thierry; Bay, Jacques-Olivier; Guilhot, François; Milpied, Noël

    2010-01-01

    Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have a very poor prognosis. However, they may achieve long-term survival by undergoing allogeneic stem cell transplantation (SCT). The purpose of this study was to assess the outcome of all adult patients with DLBCL whose treatment included a reduced-intensity conditioning (RIC) regimen for allogeneic SCT and whose data were reported in the French Society of Marrow Transplantation and Cellular Therapy registry. Sixty-eight patients (median age: 48 years) were transplanted from October 1998 to January 2007. They had received a median of 2 regimens of therapy prior to allogeneic SCT, and 54 (79%) had already undergone SCT. Prior to transplantation, 32 patients (47%) were in complete remission (CR). For all patients but 1, conditioning regimens were based on fludarabine (Flu), which was combined with other chemotherapy drugs in 50 cases (74%) and with total body irradiation (TBI) in 17 (25%). For 56 patients (82%), the donor was an HLA-matched sibling, and peripheral blood was the most widely used source of stem cells (57 patients, 84%). With a median follow-up of 49 months, estimated 2-year overall survival (OS), progression-free survival (PFS), and the cumulative incidence of relapse were 49%, 44%, and 41%, respectively. The 1-year cumulative incidence of nonrelapse mortality (NRM) was 23%. According to multivariate analysis, the patients in CR before transplantation had a significantly longer PFS and a lower CI of relapse than patients transplanted during partial remission or stable or progressive disease. These results suggest that reduced-intensity allergenic transplantation is an attractive therapeutic option for patients with high-risk DLBCL.

  1. Impact of donor-specific anti-HLA antibodies on graft failure and survival after reduced intensity conditioning-unrelated cord blood transplantation: a Eurocord, Société Francophone d'Histocompatibilité et d'Immunogénétique (SFHI) and Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) analysis.

    PubMed

    Ruggeri, Annalisa; Rocha, Vanderson; Masson, Emeline; Labopin, Myriam; Cunha, Renato; Absi, Lena; Boudifa, Ali; Coeffic, Brigitte; Devys, Anne; De Matteis, Muriel; Dubois, Valérie; Hanau, Daniel; Hau, Françoise; Jollet, Isabelle; Masson, Dominique; Pedron, Beatrice; Perrier, Pascale; Picard, Christophe; Ramouneau-Pigot, Annie; Volt, Fernanda; Charron, Dominique; Gluckman, Eliane; Loiseau, Pascale

    2013-07-01

    Graft failure is a major complication after unrelated cord blood transplantation. Presence of HLA-antibodies before cord blood transplantation may impact graft failure. To analyze the effect of anti-HLA antibodies on unrelated cord blood transplantation outcomes, we analyzed 294 unrelated cord blood transplant recipients after reduced intensity conditioning regimen. The majority of the patients (82%) were transplanted for malignancies, 60% with double-unrelated cord blood transplant, 63% were HLA mismatched. Retrospectively, pre-unrelated cord blood transplant serum was tested for HLA-Ab using Luminex™ platform. Results were interpreted as mean fluorescence intensity (MFI) against donor-specific mismatch. Among 62 recipients (23%) who had anti-HLA antibodies before unrelated cord blood transplant, 14 patients had donor specific anti-HLA antibodies (DSA) (7 were donor-specific anti-HLA antibodies for single unrelated cord blood transplant and 7 for double unrelated cord blood transplant). Donor specific anti-HLA antibodies threshold ranged from 1620-17629 of mean fluorescence intensity (MFI). Cumulative incidence of Day-60 neutrophil engraftment was 76%: 44% for recipients with donor specific anti-HLA antibodies and 81% in those without donor specific anti-HLA antibodies (P=0.006). The cumulative incidence of 1-year transplant related mortality was 46% in patients with donor specific anti-HLA antibodies and 32% in those without antibodies (P=0.06). The presence of donor specific anti-HLA antibodies was associated with a trend for decreased survival rate (42% vs. 29%; P=0.07). Donor specific anti-HLA antibody in recipients of unrelated cord blood transplant is associated with graft failure and decreased survival. Patient's screening for donor specific anti-HLA antibodies before unrelated cord blood transplantation is recommended before choosing an HLA mismatched cord blood unit. Whenever possible it is important to avoid selecting a unit for which the patient has

  2. Impact of donor-specific anti-HLA antibodies on graft failure and survival after reduced intensity conditioning-unrelated cord blood transplantation: a Eurocord, Société Francophone d’Histocompatibilité et d’Immunogénétique (SFHI) and Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) analysis

    PubMed Central

    Ruggeri, Annalisa; Rocha, Vanderson; Masson, Emeline; Labopin, Myriam; Cunha, Renato; Absi, Lena; Boudifa, Ali; Coeffic, Brigitte; Devys, Anne; De Matteis, Muriel; Dubois, Valérie; Hanau, Daniel; Hau, Françoise; Jollet, Isabelle; Masson, Dominique; Pedron, Beatrice; Perrier, Pascale; Picard, Christophe; Ramouneau-Pigot, Annie; Volt, Fernanda; Charron, Dominique; Gluckman, Eliane; Loiseau, Pascale

    2013-01-01

    Graft failure is a major complication after unrelated cord blood transplantation. Presence of HLA-antibodies before cord blood transplantation may impact graft failure. To analyze the effect of anti-HLA antibodies on unrelated cord blood transplantation outcomes, we analyzed 294 unrelated cord blood transplant recipients after reduced intensity conditioning regimen. The majority of the patients (82%) were transplanted for malignancies, 60% with double-unrelated cord blood transplant, 63% were HLA mismatched. Retrospectively, pre-unrelated cord blood transplant serum was tested for HLA-Ab using Luminex™ platform. Results were interpreted as mean fluorescence intensity (MFI) against donor-specific mismatch. Among 62 recipients (23%) who had anti-HLA antibodies before unrelated cord blood transplant, 14 patients had donor specific anti-HLA antibodies (DSA) (7 were donor-specific anti-HLA antibodies for single unrelated cord blood transplant and 7 for double unrelated cord blood transplant). Donor specific anti-HLA antibodies threshold ranged from 1620–17629 of mean fluorescence intensity (MFI). Cumulative incidence of Day-60 neutrophil engraftment was 76%: 44% for recipients with donor specific anti-HLA antibodies and 81% in those without donor specific anti-HLA antibodies (P=0.006). The cumulative incidence of 1-year transplant related mortality was 46% in patients with donor specific anti-HLA antibodies and 32% in those without antibodies (P=0.06). The presence of donor specific anti-HLA antibodies was associated with a trend for decreased survival rate (42% vs. 29%; P=0.07). Donor specific anti-HLA antibody in recipients of unrelated cord blood transplant is associated with graft failure and decreased survival. Patient’s screening for donor specific anti-HLA antibodies before unrelated cord blood transplantation is recommended before choosing an HLA mismatched cord blood unit. Whenever possible it is important to avoid selecting a unit for which the patient

  3. Predictive factors for outcomes after reduced intensity conditioning hematopoietic stem cell transplantation for hematological malignancies: a 10-year retrospective analysis from the Société Française de Greffe de Moelle et de Thérapie Cellulaire.

    PubMed

    Michallet, Mauricette; Le, Quoc-Hung; Mohty, Mohamad; Prébet, Thomas; Nicolini, Franck; Boiron, Jean Michel; Esperou, Hélène; Attal, Michel; Milpied, Noel; Lioure, Bruno; Bordigoni, Pierre; Yakoub-Agha, Ibrahim; Bourhis, Jean-Henri; Rio, Bernard; Deconinck, Eric; Renaud, Marc; Chir, Zina; Blaise, Didier

    2008-05-01

    This retrospective study analyzed the impact of demographic and transplantation variables on outcomes of 1108 patients who have undergone allogeneic hematopoietic stem cell transplantation after reduced intensity conditioning (RIC HSCT) for hematological malignancies and were reported to the Société Française de Greffe de Moelle et de Thérapie Cellulaire registry between November 1994 and December 2004. Only 442 patients (40%) were in complete remission (CR) at time of transplantation. Peripheral blood stem cells were used in the majority of patients (n = 878; 79%), 255 patients received fludarabine and low-dose total body irradiation, while 465 patients (42%) fludarabine and busulfan with rabbit anti-thymocyte globulins (ATG). The impact of demographic and transplant variables was studied on overall (OS) and event-free survival (EFS) in univariate and multivariate analysis. With a median follow-up of 21 months, 3-year probability of OS and EFS was 42% and 30%, respectively, and treatment-related mortality was 15% at 2 years. The multivariate analysis showed a significant negative impact on OS and EFS of the absence of CR status before transplantation; conditioning regimen, including >10 mg/kg ATG; and minor ABO incompatibility. In conclusion, this study highlights the major impact on RIC HSCT outcome of disease status before transplantation, ATG dose and ABO incompatibility.

  4. Strategies to reduce hepatitis C virus recurrence after liver transplantation

    PubMed Central

    Ciria, Ruben; Pleguezuelo, María; Khorsandi, Shirin Elizabeth; Davila, Diego; Suddle, Abid; Vilca-Melendez, Hector; Rufian, Sebastian; de la Mata, Manuel; Briceño, Javier; Cillero, Pedro López; Heaton, Nigel

    2013-01-01

    Hepatitis C virus (HCV) is a major health problem that leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma, being the most frequent indication for liver transplantation in several countries. Unfortunately, HCV re-infects the liver graft almost invariably following reperfusion, with an accelerated history of recurrence, leading to 10%-30% of patients progressing to cirrhosis within 5 years of transplantation. In this sense, some groups have even advocated for not re-transplanting this patients, as lower patient and graft outcomes have been reported. However, the management of HCV recurrence is being optimized and several strategies to reduce post-transplant recurrence could improve outcomes, decrease the rate of re-transplantation and optimize the use of available grafts. Three moments may be the focus of potential actions in order to decrease the impact of viral recurrence: the pre-transplant moment, the transplant environment and the post-transplant management. In the pre-transplant setting, it is not well established if reducing the pre transplant viral load affects the risk for HCV progression after transplant. Obviously, antiviral treatment can render the patient HCV RNA negative post transplant but the long-term benefit has not yet been fully established to justify the cost and clinical risk. In the transplant moment, factors as donor age, cold ischemia time, graft steatosis and ischemia/reperfusion injury may lead to a higher and more aggressive viral recurrence. After the transplant, discussion about immunosuppression and the moment to start the treatment (prophylactic, pre-emptive or once-confirmed) together with new antiviral drugs are of interest. This review aims to help clinicians have a global overview of post-transplant HCV recurrence and strategies to reduce its impact on our patients. PMID:23717735

  5. A Time-to-Event Model for Acute Kidney Injury after Reduced Intensity Conditioning Stem Cell Transplantation Using a Tacrolimus and Sirolimus-Based Graft-Versus-Host Disease Prophylaxis.

    PubMed

    Piñana, Jose Luis; Perez-Pitarch, Alejandro; Garcia-Cadenas, Irene; Barba, Pere; Hernandez-Boluda, Juan Carlos; Esquirol, Albert; Fox, María Laura; Terol, María José; Queraltó, Josep M; Vima, Jaume; Valcarcel, David; Ferriols-Lisart, Rafael; Sierra, Jorge; Solano, Carlos; Martino, Rodrigo

    2017-04-07

    There is a paucity of data evaluating acute kidney injury (AKI) incidence and its relationship with the tacrolimus-sirolimus (Tac-Sir) concentrations in the setting of reduced intensity conditioning after allogeneic stem cell transplantation (RIC-allo-HSCT). This multicenter retrospective study evaluated risk factors of AKI defined by two classification systems (KDIGO score and "Grade 0-3 staging") in 186 consecutive RIC-allo-HSCT recipients with Tac-Sir as graft-versus-host disease prophylaxis. Conditioning regimens consisted of fludarabine and busulfan (n=53), or melphalan (n=83), or a combination of thiotepa, fludarabine and busulfan (n=50). A parametric model, with detailed Tac-Sir consecutive blood levels, describing time to AKI was developed using the NONMEM software version 7.4. Overall, 81 (44%) out of 186 RIC-allo-HSCT recipients developed AKI with a cumulative incidence of 42% at a median follow-up of 25 months. Time to AKI was best described using a piecewise-function. AKI-predicting factors were: melphalan-based conditioning regimen (HR=1.96, p<0.01), unrelated donor (HR 1.79, p=0.04) and tacrolimus concentration: the risk of AKI increased 2.3% per each 1 ng/ml increase in tacrolimus whole blood concentration (p<0.01). In multivariate analysis, AKI grade 2 and 3 according to KDIGO staging were independent risk factors for 2-year non-relapse mortality (HR 2.8, p=0.05 and HR 6.6, p<0.0001, respectively). According to the KDIGO score, overall survival decreased with the increase in severity of AKI; 78% for patients without AKI versus 68%, 50% and 30% for grade 1, 2 and 3, respectively (p< 0.0001). In conclusion, AKI is frequent after Tac-Sir based RIC-allo-HSCT and has a negative impact on outcome. This study presents the first predictive model describing time to AKI as a function of tacrolimus drug concentration.

  6. [Health education in transplant patients and their families in an intensive care unit].

    PubMed

    Pueyo-Garrigues, M; San Martín Loyola, Á; Caparrós Leal, M C; Jiménez Muñoz, C

    2016-01-01

    Health Education (HE) is extremely important in transplant patients and their families in order to promote suitable self-care in this new stage of life. Intensive Care Units offer various opportunities by nurses in order to improve their Health Education. This process could start in this unit where the interaction between nurse and family is constant. The HE of transplant patient includes three dimensions: Knowledge: information about self-care in order to have a healthy way of life, and getting some information on how to reduce anxiety in patients and their families; Skills: as regards the abilities to properly apply the Health Education, where the families are really important; and finally Attitudes: ambivalent attitudes that are experienced by transplant patients. The objective is to describe the level of development of HE for critical transplant patients and their families from Intensive Care Units. A non-systematic literature review was performed in Pubmed and CINHAL data bases. In conclusion, it is emphasised that the skill of the HE nurse in an Intensive Care Units is important to promote lifestyles appropriate to the cognitive, affective, and psychomotor needs of transplant patients. Its implementation entails positive effects on clinical outcomes of the patient, decreased morbidity and mortality, costs, and health resources.

  7. Survival Advantage and Comparable Toxicity in Reduced-Toxicity Treosulfan-Based versus Reduced-Intensity Busulfan-Based Conditioning Regimen in Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients after Allogeneic Hematopoietic Cell Transplantation.

    PubMed

    Sakellari, Ioanna; Mallouri, Despina; Gavriilaki, Eleni; Batsis, Ioannis; Kaliou, Maria; Constantinou, Varnavas; Papalexandri, Apostolia; Lalayanni, Chrysavgi; Vadikolia, Chrysanthi; Athanasiadou, Anastasia; Yannaki, Evangelia; Sotiropoulos, Damianos; Smias, Christos; Anagnostopoulos, Achilles

    2017-03-01

    Treosulfan has been incorporated in conditioning regimens for sustained remission without substantial toxicity and treatment-related mortality (TRM). We aimed to analyze the safety and efficacy of a fludarabine 150 mg/m(2) and treosulfan 42 g/m(2) (FluTreo) conditioning regimen in medically infirm patients. Outcomes were compared with those of a similar historical group treated with fludarabine 150 mg/m(2) to 180 mg/m(2), busulfan 6.4 mg/kg, and antithymocyte globulin (ATG) 5 mg/kg to 7.5 mg/kg (FluBuATG). Thirty-one consecutive patients with acute myeloid leukemia (AML; n = 21), myelodysplastic syndrome (MDS; n = 6), or treatment-related AML (n = 4) received FluTreo conditioning. The historical group consisted of 26 consecutive patients treated with FluBuATG. In the FluTreo group, engraftment was prompt in all patients and 74% achieved >99% donor chimerism by day +30. No grades III or IV organ toxicities were noted. One-year cumulative incidences (CI) of acute and chronic graft-versus-host disease (GVHD) were 19.4% and 58.4%. The groups were similar for age, disease risk, lines of treatment, hematopoietic cell transplantation-specific comorbidity index, and acute or chronic GVHD incidence, except that there were more matched unrelated donor recipients in the FluTreo group (P < .001). With 20 (range, 2 to 36) months follow-up for FluTreo and 14 (range, 2 to 136) for FluBuATG, the 1-year cumulative overall survival (OS) probability was 76% versus 57%, respectively (P = .026); 1-year disease-free survival (DFS) was 79% versus 38% (P < .001). In multivariate analysis, the only significantly favorable factor for OS and DFS was FluTreo (P = .010 and P = .012). The CI of relapse mortality was markedly decreased in FluTreo versus FluBuATG (7.4% versus 42.3%, P < .001). In conclusion, the treosulfan-based regimen resulted in favorable OS and DFS with acceptable toxicity and low relapse rates compared with busulfan-based conditioning.

  8. Intensive agriculture reduces soil biodiversity across Europe.

    PubMed

    Tsiafouli, Maria A; Thébault, Elisa; Sgardelis, Stefanos P; de Ruiter, Peter C; van der Putten, Wim H; Birkhofer, Klaus; Hemerik, Lia; de Vries, Franciska T; Bardgett, Richard D; Brady, Mark Vincent; Bjornlund, Lisa; Jørgensen, Helene Bracht; Christensen, Sören; Hertefeldt, Tina D'; Hotes, Stefan; Gera Hol, W H; Frouz, Jan; Liiri, Mira; Mortimer, Simon R; Setälä, Heikki; Tzanopoulos, Joseph; Uteseny, Karoline; Pižl, Václav; Stary, Josef; Wolters, Volkmar; Hedlund, Katarina

    2015-02-01

    Soil biodiversity plays a key role in regulating the processes that underpin the delivery of ecosystem goods and services in terrestrial ecosystems. Agricultural intensification is known to change the diversity of individual groups of soil biota, but less is known about how intensification affects biodiversity of the soil food web as a whole, and whether or not these effects may be generalized across regions. We examined biodiversity in soil food webs from grasslands, extensive, and intensive rotations in four agricultural regions across Europe: in Sweden, the UK, the Czech Republic and Greece. Effects of land-use intensity were quantified based on structure and diversity among functional groups in the soil food web, as well as on community-weighted mean body mass of soil fauna. We also elucidate land-use intensity effects on diversity of taxonomic units within taxonomic groups of soil fauna. We found that between regions soil food web diversity measures were variable, but that increasing land-use intensity caused highly consistent responses. In particular, land-use intensification reduced the complexity in the soil food webs, as well as the community-weighted mean body mass of soil fauna. In all regions across Europe, species richness of earthworms, Collembolans, and oribatid mites was negatively affected by increased land-use intensity. The taxonomic distinctness, which is a measure of taxonomic relatedness of species in a community that is independent of species richness, was also reduced by land-use intensification. We conclude that intensive agriculture reduces soil biodiversity, making soil food webs less diverse and composed of smaller bodied organisms. Land-use intensification results in fewer functional groups of soil biota with fewer and taxonomically more closely related species. We discuss how these changes in soil biodiversity due to land-use intensification may threaten the functioning of soil in agricultural production systems.

  9. Clinical impact of NK-cell reconstitution after reduced intensity conditioned unrelated cord blood transplantation in patients with acute myeloid leukemia: analysis of a prospective phase II multicenter trial on behalf of the Société Française de Greffe de Moelle Osseuse et Thérapie Cellulaire and Eurocord.

    PubMed

    Nguyen, S; Achour, A; Souchet, L; Vigouroux, S; Chevallier, P; Furst, S; Sirvent, A; Bay, J-O; Socié, G; Ceballos, P; Huynh, A; Cornillon, J; Francois, S; Legrand, F; Yakoub-Agha, I; Michel, G; Maillard, N; Margueritte, G; Maury, S; Uzunov, M; Bulabois, C-E; Michallet, M; Clement, L; Dauriac, C; Bilger, K; Lejeune, J; Béziat, V; Rocha, V; Rio, B; Chevret, S; Vieillard, V

    2017-06-26

    Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.Bone Marrow Transplantation advance online publication, 26 June 2017; doi:10.1038/bmt.2017.122.

  10. Intensive Early Rehabilitation in the Intensive Care Unit for Liver Transplant Recipients: A Randomized Controlled Trial.

    PubMed

    Maffei, Pierre; Wiramus, Sandrine; Bensoussan, Laurent; Bienvenu, Laurence; Haddad, Eric; Morange, Sophie; Fathallah, Mohamed; Hardwigsen, Jean; Viton, Jean-Michel; Le Treut, Y Patrice; Albanese, Jacques; Gregoire, Emilie

    2017-08-01

    To validate the feasibility and tolerance of an intensive rehabilitation protocol initiated during the postoperative period in an intensive care unit (ICU) in liver transplant recipients. Prospective randomized study. ICU. Liver transplant recipients over a period of 1 year (N=40). The "usual treatment group" (n=20), which benefited from the usual treatment applied in the ICU (based on physician prescription for the physiotherapist, with one session a day), and the experimental group (n=20), which followed a protocol of early and intensive rehabilitation (based on a written protocol validated by physicians and an evaluation by physiotherapist, with 2 sessions a day), were compared. Our primary aims were tolerance, assessed from the number of adverse events during rehabilitation sessions, and feasibility, assessed from the number of sessions discontinued. The results revealed a small percentage of adverse events (1.5% in the usual treatment group vs 1.06% in the experimental group) that were considered to be of low intensity. Patients in the experimental group sat on the edge of their beds sooner (2.6 vs 9.7d; P=.048) and their intestinal transit resumed earlier (5.6 vs 3.7d; P=.015) than patients in the usual treatment group. There was no significant difference between the 2 arms regarding length of stay (LOS), despite a decrease in duration in the experimental group. The introduction of an intensive early rehabilitation program for liver transplant recipients was well tolerated and feasible in the ICU. We noted that the different activities proposed were introduced sooner in the experimental group. Moreover, there is a tendency to decreased LOS in the ICU for the experimental group. These results now need to be confirmed by studies on a larger scale. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  11. Intense Physical Exercise Reduces Overt Attentional Capture.

    PubMed

    Llorens, Francesc; Sanabria, Daniel; Huertas, Florentino; Molina, Enrique; Bennett, Simon

    2015-10-01

    The abrupt onset of a visual stimulus typically results in overt attentional capture, which can be quantified by saccadic eye movements. Here, we tested whether attentional capture following onset of task-irrelevant visual stimuli (new object) is reduced after a bout of intense physical exercise. A group of participants performed a visual search task in two different activity conditions: rest, without any prior effort, and effort, immediately after an acute bout of intense exercise. The results showed that participants exhibited (1) slower reaction time of the first saccade toward the target when a new object was simultaneously presented in the visual field, but only in the rest activity condition, and (2) more saccades to the new object in the rest activity condition than in the effort activity condition. We suggest that immediately after an acute bout of effort, participants improved their ability to inhibit irrelevant (distracting) stimuli.

  12. Intrastriatal chromospheres' transplant reduces nociception in hemiparkinsonian rats.

    PubMed

    Gómez-Paz, Alejandra; Drucker-Colín, René; Milán-Aldaco, Diana; Palomero-Rivero, Marcela; Ambriz-Tututi, Mónica

    2017-09-08

    The present study evaluates the possible antinociceptive effect of chromosphere transplants in rats injected with 6-hydroxydopamine (6-OHDA), a model of Parkinson's disease. Male adult Wistar rats received 40μg/0.5μl of 6-OHDA or 0.5μl of vehicle into the left substantia nigra (SNc). Rats were evaluated for mechanical allodynia, cold allodynia, thermal hyperalgesia and formalin. Rats with altered nociceptive threshold were transplanted with chromospheres. After transplant, rats were evaluated every week. Our results confirm that 6-OHDA injection into rat's SNc reduces mechanical, thermal, and chemical thresholds. Interestingly, chromospheres' transplant reverted 6-OHDA-induced allodynia and hyperalgesia. The antinociceptive effect induced by chromospheres was dopamine D2- and opioid-receptor dependent since sulpiride or naltrexone reverted its effect. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Reduced-intensity conditioning followed by allogeneic transplantation in pediatric malignancies: a report from the Société Française des Cancers de l'Enfant and the Société Française de Greffe de Moelle et de Thérapie Cellulaire.

    PubMed

    Paillard, C; Rochette, E; Lutz, P; Bertrand, Y; Michel, G; Bordigoni, P; Dalle, J H; Rohrlich, P; Vannier, J P; Perel, Y; Plantaz, D; Leverger, G; Sirvent, A; Dore, E; Isfan, F; Merlin, E; Pereira, B; Halle, P; Rabiau, N; Kanold, J; Deméocq, F

    2013-11-01

    We report French prospective experience with reduced-intensity conditioning-allo-SCT in 46 patients (median age: 15.5 years, 4.8-20.2) presenting high-risk AL (n=11), Hodgkin's lymphoma (n=15) or solid tumors (n=20). Graft sources were BM (n=21), PBSC (n=20) and cord blood (CB; n=5) from related (n=20) or unrelated (n=26) donors. For CB grafts, only one patient out of five achieved sustained engraftment. For PBSC/BM grafts, engraftment rate was 95%, hematopoietic recovery times were not significantly different between BM, PBSC, sibling or unrelated grafts, day+100. Full donor chimerism was achieved in 94% of patients, and incidences of primary acute GVHD and chronic GVHD were 49% and 14%, respectively. Underlying disease was fatal in 39% of patients. TRM was 6.9%. Three-year OS was 49.15%. OS and EFS were not significantly different between patients transplanted with different grafts and with or without primary GVHD. Patients with solid tumor or measurable disease at transplant had poorer outcomes. Three-year EFS: 33.3% for ALL, 75.0% for AML, 51.8% for Hodgkin's lymphoma, 28.6% for neuroblastoma and 22.2% for sarcoma patients. This multicentre study concluded that Bu/fludarabine/anti-thymocyte globulin conditioning with PB or BM, related or unrelated grafts in patients with various malignancies at high-risk for transplantation toxicity results in high engraftment rates, low TRM and acceptable survival.

  14. The effect of intensive nutrition interventions on weight gain after kidney transplantation: protocol of a randomised controlled trial.

    PubMed

    Ryan, Kristin J; Casas, Jessie M Segedin; Mash, Laura E; McLellan, Sandra L; Lloyd, Lyn E; Stinear, James W; Plank, Lindsay D; Collins, Michael G

    2014-09-09

    Weight gain and obesity are common after kidney transplantation, particularly during the first year. Obesity is a risk factor for the development of new-onset diabetes after transplantation, and is associated with reduced graft survival. There is a lack of evidence for effective interventions to prevent weight gain after kidney transplantation. The effect of INTEnsive Nutrition interventions on weight gain after kidney Transplantation (INTENT) trial is a single-blind (outcomes assessor), randomised controlled trial to assess the effect of intensive nutrition interventions, including exercise advice, on weight gain and metabolic parameters in the first year after transplantation. Participants will be randomised during the first post-transplant month to either standard care (four visits with a renal dietitian over twelve months) or intensive nutrition intervention (eight visits with a renal dietitian over the first six months, four visits over the second six months, and three visits over the first six months with an exercise physiologist). In the intensive intervention group, nutrition counselling will be provided using motivational interviewing techniques to encourage quality engagement. Collaborative goal setting will be used to develop personalised nutrition care plans. Individualised advice regarding physical activity will be provided by an exercise physiologist. The primary outcome of the study is weight at six months after transplant, adjusted for baseline (one month post-transplant) weight, obesity and gender. Secondary outcomes will include changes in weight and other anthropometric measures over 12 months, body composition (in vivo neutron activation analysis, total body potassium, dual-energy X-ray absorptiometry, and bioelectrical impedance), biochemistry (fasting glucose, lipids, haemoglobin A1c and insulin), dietary intake and nutritional status, quality of life, and physical function. There are currently few randomised clinical trials of nutrition

  15. Triacontanol Reduces Transplanting Shock in Machine-Transplanted Rice by Improving the Growth and Antioxidant Systems.

    PubMed

    Li, Xiaochun; Zhong, Qiuyi; Li, Yuxiang; Li, Ganghua; Ding, Yanfeng; Wang, Shaohua; Liu, Zhenghui; Tang, She; Ding, Chengqiang; Chen, Lin

    2016-01-01

    Machine transplantation results in serious transplant shock in seedlings and results in a longer recover stage, which negatively impacts the growth of low-position tillers and the yield of machine-transplanted rice. A barrel experiment was conducted to examine the effect of the foliar application of triacontanol (TRIA) on machine-transplanted rice during the recovery stage. TRIA (0, 1, 5, and 10 μM) was sprayed over leaves 2 days before transplanting. The chlorophyll content, sucrose content, oxidative damage, antioxidant enzyme levels, glutathione (GSH), and ascorbate (ASA) redox states, tiller dynamics and yield components of the plants were investigated. The results show that foliar-applied TRIA significantly alleviates the growth inhibition and oxidative damage caused by transplant shock. Furthermore, the application of TRIA increased the chlorophyll and sucrose contents of the plants. Importantly, TRIA not only significantly improved the activity of catalase (CAT) and guaiacol peroxidase (POD), demonstrating that POD can play an important role in scavenging H2O2 during the recovery stage, but it also enhanced the redox states of ASA and GSH by regulating the activities of enzymes involved in the ASA-GSH cycle, such as ascorbate peroxidase (APX) and glutathione reductase (GR). A dose of 10 μM TRIA was the most efficient in reducing the negative effects of transplant shock, increasing the panicles, grain filling, and grain yield per hill by 17.80, 5.86, and 16.49%, respectively. These results suggest that TRIA acts to reduce transplant shock in association with the regulation of the redox states of ASA and GSH and antioxidant enzymes and serves as an effective antioxidant to maintain photosynthetic capacity and promote the occurrence of low tillers.

  16. Triacontanol Reduces Transplanting Shock in Machine-Transplanted Rice by Improving the Growth and Antioxidant Systems

    PubMed Central

    Li, Xiaochun; Zhong, Qiuyi; Li, Yuxiang; Li, Ganghua; Ding, Yanfeng; Wang, Shaohua; Liu, Zhenghui; Tang, She; Ding, Chengqiang; Chen, Lin

    2016-01-01

    Machine transplantation results in serious transplant shock in seedlings and results in a longer recover stage, which negatively impacts the growth of low-position tillers and the yield of machine-transplanted rice. A barrel experiment was conducted to examine the effect of the foliar application of triacontanol (TRIA) on machine-transplanted rice during the recovery stage. TRIA (0, 1, 5, and 10 μM) was sprayed over leaves 2 days before transplanting. The chlorophyll content, sucrose content, oxidative damage, antioxidant enzyme levels, glutathione (GSH), and ascorbate (ASA) redox states, tiller dynamics and yield components of the plants were investigated. The results show that foliar-applied TRIA significantly alleviates the growth inhibition and oxidative damage caused by transplant shock. Furthermore, the application of TRIA increased the chlorophyll and sucrose contents of the plants. Importantly, TRIA not only significantly improved the activity of catalase (CAT) and guaiacol peroxidase (POD), demonstrating that POD can play an important role in scavenging H2O2 during the recovery stage, but it also enhanced the redox states of ASA and GSH by regulating the activities of enzymes involved in the ASA–GSH cycle, such as ascorbate peroxidase (APX) and glutathione reductase (GR). A dose of 10 μM TRIA was the most efficient in reducing the negative effects of transplant shock, increasing the panicles, grain filling, and grain yield per hill by 17.80, 5.86, and 16.49%, respectively. These results suggest that TRIA acts to reduce transplant shock in association with the regulation of the redox states of ASA and GSH and antioxidant enzymes and serves as an effective antioxidant to maintain photosynthetic capacity and promote the occurrence of low tillers. PMID:27379149

  17. Protocol of the KTFT-TALK study to reduce racial disparities in kidney transplant evaluation and living donor kidney transplantation.

    PubMed

    Bornemann, Kellee; Croswell, Emilee; Abaye, Menna; Bryce, Cindy L; Chang, Chung-Chou H; Good, Deborah S; Freehling Heiles, Cathleen A; Dew, Mary Amanda; Boulware, L Ebony; Tevar, Amit D; Myaskovsky, Larissa

    2017-02-01

    Living donor kidney transplantation (LDKT) is the optimal treatment for end-stage kidney disease (ESKD). The evaluation process for a kidney transplant is complex, time consuming, and burdensome to the ESKD patient. Also, race disparities exist in rates of transplant evaluation completion, transplantation, and LDKT. In December 2012 our transplant center implemented a streamlined, one-day evaluation process, dubbed Kidney Transplant Fast Track (KTFT). This paper describes the protocol of a two-part study to evaluate the effectiveness of KTFT at increasing transplant rates (compared to historical controls) and the TALK intervention (Talking About Live Kidney Donation) at increasing LDKT during KTFT. All participants will receive the KTFT evaluation as part of their usual care. Participants will be randomly assigned to TALK versus no-TALK conditions. Patients will undergo interviews at pre-transplant work-up and transplant evaluation. Transplant status will be tracked via medical records. Our aims are to: (1) test the efficacy and cost effectiveness of the KTFT in reducing time to complete kidney transplant evaluation, and increasing kidney transplant rates relative to standard evaluation practices; (2) test whether TALK increases rates of LDKT during KTFT; and (3) determine whether engaging in a streamlined and coordinated-care evaluation experience within the transplant center reduces negative perceptions of the healthcare system. The results of this two-pronged approach will help pave the way for other transplant centers to implement a fast-track system at their sites, improve quality of care by transplanting a larger number of vulnerable patients, and address stark race/ethnic disparities in rates of LDKT.

  18. Serum thymus and activation-regulated chemokine level monitoring may predict disease relapse detected by PET scan after reduced-intensity allogeneic stem cell transplantation in patients with Hodgkin lymphoma.

    PubMed

    Farina, Lucia; Rezzonico, Francesca; Spina, Francesco; Dodero, Anna; Mazzocchi, Arabella; Crippa, Flavio; Alessi, Alessandra; Dalto, Serena; Viviani, Simonetta; Corradini, Paolo

    2014-12-01

    Patients with relapsed and refractory Hodgkin lymphoma (HL) may experience long-term survival after allogeneic stem cell transplantation (alloSCT), but disease recurrence represents the main cause of treatment failure. Positron-emission tomography (PET)-positive patients after alloSCT have a dismal outcome. Serum thymus and activation-regulated chemokine (TARC) is produced by Reed-Sternberg cells and may be a marker of disease. Our study aimed at assessing whether TARC levels after alloSCT correlated with disease status and whether TARC monitoring could increase the ability to predict relapse. Twenty-four patients were evaluated in a prospective observational study. TARC serum level and PET were assessed before and after alloSCT during the follow-up (median, 30 months; range, 2 to 54). Before alloSCT, the median TARC level was 721 pg/mL (range, 209 to 1332) in PET-negative patients and 2542 pg/mL (range, 94 to 13,870) in PET-positive patients. After alloSCT, TARC was 620 pg/mL (range, 12 to 4333) in persistently PET-negative patients compared with 22,397 pg/mL (range, 602 to 106,578) in PET-positive patients (P < .0001). In 7 patients who relapsed after alloSCT, TARC level increased progressively even before PET became positive, with a median fold increase of 3.19 (range, 1.66 to 7.11) at relapse. The cut-off value of 1726 pg/mL had a sensitivity of 100% and a specificity of 71% for PET positivity. Patients with at least 1 TARC value above 1726 pg/mL during the first year after alloSCT had a worse progression-free survival (P = .031). In conclusion, TARC was correlated with disease status and its monitoring may be able to predict PET positivity after alloSCT, thus potentially allowing an early immune manipulation.

  19. Kidney Transplantation and the Intensity of Poverty in the Contiguous United States

    PubMed Central

    Mohan, Sumit; Mutell, Richard; Patzer, Rachel E.; Holt, James; Cohen, David; McClellan, William

    2014-01-01

    Background Geographic variation in kidney transplantation rates in the United States has been described previously but remains unexplained by age, race, sex, or socioeconomic status differences. Geographic variations in the concentration of poverty appear to impact end-stage renal disease care and potentially access to transplantation. Methods We studied the impact of how spatial topography of poverty across geographical regions in the contiguous United States is associated with kidney transplantation in the 48 contiguous U.S. states. Results We found considerable geographic variation in transplantation rates across the country that persisted across quartiles of county-level median household income and percentage minority population. Higher transplant rates were seen with increasing median household income and decreasing minority populations but were not influenced by education level. Transplantation rates in counties with poverty rates above the national average had low transplant rates, but these rates were influenced by the poverty level in the surrounding counties. Similarly, wealthy counties had higher transplant rates but were lowered in counties of relative wealth that were surrounded by less wealthy counties. Conclusions Our results underline the geographical heterogeneity of kidney transplantation in the United States and identify regions of the country most likely to benefit from interventions that may reduce disparities in transplantation. PMID:24809750

  20. Kidney transplantation and the intensity of poverty in the contiguous United States.

    PubMed

    Mohan, Sumit; Mutell, Richard; Patzer, Rachel E; Holt, James; Cohen, David; McClellan, William

    2014-09-27

    Geographic variation in kidney transplantation rates in the United States has been described previously but remains unexplained by age, race, sex, or socioeconomic status differences. Geographic variations in the concentration of poverty appear to impact end-stage renal disease care and potentially access to transplantation. We studied the impact of how spatial topography of poverty across geographical regions in the contiguous United States is associated with kidney transplantation in the 48 contiguous U.S. states. We found considerable geographic variation in transplantation rates across the country that persisted across quartiles of county-level median household income and percentage minority population. Higher transplant rates were seen with increasing median household income and decreasing minority populations but were not influenced by education level. Transplantation rates in counties with poverty rates above the national average had low transplant rates, but these rates were influenced by the poverty level in the surrounding counties. Similarly, wealthy counties had higher transplant rates but were lowered in counties of relative wealth that were surrounded by less wealthy counties. Our results underline the geographical heterogeneity of kidney transplantation in the United States and identify regions of the country most likely to benefit from interventions that may reduce disparities in transplantation.

  1. Prothrombin Complex Concentrate Reduces Blood Product Utilization in Heart Transplantation.

    PubMed

    Enter, Daniel H; Zaki, Anthony L; Marsh, Megan; Cool, Nikki; Kruse, Jane; Li, Zhi; Andrei, Adin-Cristian; Iddriss, Adam; McCarthy, Patrick M; Malaisrie, S Chris; Anderson, Allen; Rich, Jonathan D; Pham, Duc Thinh

    2017-08-22

    Current practices for the reversal of warfarin prior to cardiac surgery include the use of vitamin K and fresh frozen plasma (FFP) to reduce the risk of bleeding. Although the 2010 International Society of Heart and Lung Transplantation guidelines acknowledge the use of PCC (Prothrombin Complex Concentrate), there is no clear consensus on its efficacy. The objective of this study was to assess the efficacy of 4-factor Prothrombin Complex Concentrate (4-F PCC) administration in patients requiring warfarin reversal prior to heart transplantation by determining blood product utilization perioperatively. Twenty-one patients who received 4-F PCC for warfarin reversal prior to heart transplantation were compared to a similar cohort of 39 patients who did not receive 4-F PCC from January 2011 to July 2015. Blood product utilization was collected retrospectively for the 24-hour preoperative, intraoperative, and 48-hour postoperative periods. Patients receiving 4-F PCC required fewer blood products in all 3 time periods. In the 24-hour preoperative period, 22 patients (56%) in the control group and 2 patients (10%) in the 4-F PCC groups received blood products (p<0.001). Intraoperatively, all patients received blood products. The 4-F PCC group required fewer units of packed red blood cells (median 3 vs. 7 units, p<0.001) and FFP (median 4 vs. 9 units, p<0.001). In the 48-hour postoperative period, 20 patients (51%) in the control group and 5 patients (24%) in the 4-F PCC group received blood products (p=0.04). 4-F PCC is associated with reduced blood product utilization 24 hours preoperatively and intraoperatively. Historically, the majority of patients require FFP for warfarin reversal preoperatively. In this single-center study, a significant reduction in the need for FFP was demonstrated with the use of 4-F PCC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Acute Respiratory Failure in Renal Transplant Recipients: A Single Intensive Care Unit Experience.

    PubMed

    Ulas, Aydin; Kaplan, Serife; Zeyneloglu, Pinar; Torgay, Adnan; Pirat, Arash; Haberal, Mehmet

    2015-11-01

    Frequency of pulmonary complications after renal transplant has been reported to range from 3% to 17%. The objective of this study was to evaluate renal transplant recipients admitted to an intensive care unit to identify incidence and cause of acute respiratory failure in the postoperative period and compare clinical features and outcomes between those with and without acute respiratory failure. We retrospectively screened the data of 540 consecutive adult renal transplant recipients who received their grafts at a single transplant center and included those patients admitted to an intensive care unit during this period for this study. Acute respiratory failure was defined as severe dyspnea, respiratory distress, decreased oxygen saturation, hypoxemia or hypercapnia on room air, or requirement of noninvasive or invasive mechanical ventilation. Among the 540 adult renal transplant recipients, 55 (10.7%) were admitted to an intensive care unit, including 26 (47.3%) admitted for acute respiratory failure. Median time from transplant to intensive care unit admission was 10 months (range, 0-67 mo). The leading causes of acute respiratory failure were bacterial pneumonia (56%) and cardiogenic pulmonary edema (44%). Mean partial pressure of arterial oxygen to fractional inspired oxygen ratio was 174 ± 59, invasive mechanical ventilation was used in 13 patients (50%), and noninvasive mechanical ventilation was used in 8 patients (31%). The overall mortality was 16.4%. Acute respiratory failure was the reason for intensive care unit admission in almost half of our renal transplant recipients. Main causes of acute respiratory failure were bacterial pneumonia and cardiogenic pulmonary edema. Mortality of patients admitted for acute respiratory failure was similar to those without acute respiratory failure.

  3. Correction of Postkidney Transplant Anemia Reduces Progression of Allograft Nephropathy

    PubMed Central

    Kamar, Nassim; Dussol, Bertrand; Etienne, Isabelle; Cassuto-Viguier, Elisabeth; Toupance, Olivier; Glowacki, François; Moulin, Bruno; Lebranchu, Yvon; Touchard, Guy; Jaureguy, Maïté; Pallet, Nicolas; Le Meur, Yannick; Rostaing, Lionel; Martinez, Frank

    2012-01-01

    Retrospective studies suggest that chronic allograft nephropathy might progress more rapidly in patients with post-transplant anemia, but whether correction of anemia improves renal outcomes is unknown. An open-label, multicenter, randomized controlled trial investigated the effect of epoetin-β to normalize hemoglobin values (13.0–15.0 g/dl, n=63) compared with partial correction of anemia (10.5–11.5 g/dl, n=62) on progression of nephropathy in transplant recipients with hemoglobin <11.5 g/dl and an estimated creatinine clearance (eCrCl) <50 ml/min per 1.73 m2. After 2 years, the mean hemoglobin was 12.9 and 11.3 g/dl in the normalization and partial correction groups, respectively (P<0.001). From baseline to year 2, the eCrCl decreased by a mean 2.4 ml/min per 1.73 m2 in the normalization group compared with 5.9 ml/min per 1.73 m2 in the partial correction group (P=0.03). Furthermore, fewer patients in the normalization group progressed to ESRD (3 versus 13, P<0.01). Cumulative death-censored graft survival was 95% and 80% in the normalization and partial correction groups, respectively (P<0.01). Complete correction was associated with a significant improvement in quality of life at 6 and 12 months. The number of cardiovascular events was low and similar between groups. In conclusion, this prospective study suggests that targeting hemoglobin values ≥13 g/dl reduces progression of chronic allograft nephropathy in kidney transplant recipients. PMID:22193388

  4. New Solutions to Reduce Discard of Kidneys Donated for Transplantation.

    PubMed

    Reese, Peter P; Harhay, Meera N; Abt, Peter L; Levine, Matthew H; Halpern, Scott D

    2016-04-01

    Kidney transplantation is a cost-saving treatment that extends the lives of patients with ESRD. Unfortunately, the kidney transplant waiting list has ballooned to over 100,000 Americans. Across large areas of the United States, many kidney transplant candidates spend over 5 years waiting and often die before undergoing transplantation. However, more than 2500 kidneys (>17% of the total recovered from deceased donors) were discarded in 2013, despite evidence that many of these kidneys would provide a survival benefit to wait-listed patients. Transplant leaders have focused attention on transplant center report cards as a likely cause for this discard problem, although that focus is too narrow. In this review, we examine the risks associated with accepting various categories of donated kidneys, including discarded kidneys, compared with the risk of remaining on dialysis. With the goal of improving access to kidney transplant, we describe feasible proposals to increase acceptance of currently discarded organs.

  5. Reduced Intensity Preparative Regimen Followed by Stem Cell Transplant (FAB)

    ClinicalTrials.gov

    2016-03-29

    Myelodysplastic and Myeloproliferative Disorders; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia; Multiple Myeloma; Plasma Cell Dyscrasia; Lymphoproliferative Disorders; Hematologic Diseases

  6. Effect of graft source on unrelated donor hemopoietic stem cell transplantation in adults with acute myeloid leukemia after reduced-intensity or nonmyeloablative conditioning: a study from the Société Francaise de Greffe de Moelle et de Thérapie Cellulaire.

    PubMed

    Malard, Florent; Milpied, Noel; Blaise, Didier; Chevallier, Patrice; Michallet, Mauricette; Lioure, Bruno; Clément, Laurence; Hicheri, Yosr; Cordonnier, Catherine; Huynh, Anne; Yakoub-Agha, Ibrahim; Peffault de Latour, Regis; Mohty, Mohamad

    2015-06-01

    This retrospective report compared the 4-year outcomes of allogeneic stem cell transplantation (allo-SCT) in 651 adult patients with acute myeloid leukemia receiving a reduced-intensity (RIC) or nonmyeloablative conditioning (NMA) regimen according to the type of unrelated donors. These were either umbilical cord blood (UCB, n = 205), a 9/10 mismatched unrelated donor (MisMUD, n = 99), or a 10/10 matched unrelated donor (MUD, n = 347) graft. Neutrophil recovery was slower in UCB (74.5% by day 42) compared with MisMUD (94.8%) and MUD (95.6%) (P < .001). There was no significant difference in nonrelapse mortality between UCB and both MUD (hazard ratio [HR], 1.05; 95% confidence interval [CI], .62 to 1.78; P = .85) and MisMUD (HR, 1.58; 95% CI, .88 to 2.83; P = .13) The relapse/progression was similar between UCB and MisMUD (HR, .62; 95% CI, .37 to 1.03; P = .07), but was significantly lower in MUD compared with UCB (HR, .60; 95% CI, .39 to .92; P = .02). The rate of extensive chronic graft-versus-host disease (GVHD) was similar between UCB and both MUD (HR, 2.15; 95% CI, .93 to 4.97; P = .08) and MisMUD (HR, 1.84; 95% CI, .68 to 4.95; P = .23). The rate of severe grade III and IV acute GVHD was significantly increased in MisMUD compared with UCB (HR, 2.61; 95% CI, 1.30 to 5.23; P = .007). There was no significant difference in overall survival between UCB and both MisMUD (HR, .98; 95% CI, .66 to 1.45; P = .92) and MUD (HR, .74; 95% CI, .52 to 1.03; P = .08). These data suggest that in the setting of RIC/NMA, allo-SCT UCB is a valid alternative graft source, with significantly less chronic GVHD, compared with MisMUD, when there is no MUD available or when urgent transplantation is needed.

  7. Intensive care outcomes in bone marrow transplant recipients: a population-based cohort analysis

    PubMed Central

    Scales, Damon C; Thiruchelvam, Deva; Kiss, Alexander; Sibbald, William J; Redelmeier, Donald A

    2008-01-01

    Introduction Intensive care unit (ICU) admission for bone marrow transplant recipients immediately following transplantation is an ominous event, yet the survival of these patients with subsequent ICU admissions is unknown. Our objective was to determine the long-term outcome of bone marrow transplant recipients admitted to an ICU during subsequent hospitalizations. Methods We conducted a population-based cohort analysis of all adult bone marrow transplant recipients who received subsequent ICU care in Ontario, Canada from 1 January 1992 to 31 March 2002. The primary endpoint was mortality at 1 year. Results A total of 2,653 patients received bone marrow transplantation; 504 of which received ICU care during a subsequent hospitalization. Patients receiving any major procedure during their ICU stay had higher 1-year mortality than those patients who received no ICU procedure (87% versus 44%, P < 0.0001). Death rates at 1 year were highest for those receiving mechanical ventilation (87%), pulmonary artery catheterization (91%), or hemodialysis (94%). In combination, the strongest independent predictors of death at 1 year were mechanical ventilation (odds ratio, 7.4; 95% confidence interval, 4.8 to 11.4) and hemodialysis (odds ratio, 8.7; 95% confidence interval, 2.1 to 36.7), yet no combination of procedures uniformly predicted 100% mortality. Conclusion The prognosis of bone marrow transplant recipients receiving ICU care during subsequent hospitalizations is very poor but should not be considered futile. PMID:18547422

  8. Reducing luminance intensity can improve motion perception in noise

    PubMed Central

    Allard, Rémy; Arleo, Angelo

    2017-01-01

    Visual perception generally improves under brighter environments. For instance, motion sensitivity is known to improve with luminance intensity especially at high temporal frequencies. However, the current study counter-intuitively shows that increasing luminance intensity can impair motion sensitivity in noise. Motion sensitivity was measured with and without noise added to a drifting Gabor patch as a function of the temporal frequency and luminance intensity. As expected, motion sensitivity in absence of noise reached a ceiling performance at a relatively low luminance intensity (about 35 td) for low temporal frequencies and improved with luminance intensity up to the highest luminance intensity tested (353 td) for high temporal frequencies. In noise, reducing mean luminance intensity facilitated motion sensitivity (up to a factor of about 1.7) for temporal frequencies up to 7.5 Hz and impaired sensitivity at higher temporal frequencies (15 and 30 Hz). We conclude that reducing luminance intensity is effectively equivalent to applying a low-pass filter, which can improve motion sensitivity in noise to low and middle temporal frequencies. This counterintuitive facilitation effect can be explained by two known properties of the visual system: decreasing luminance intensity impairs the visibility of high temporal frequencies (equivalent to a low-pass filter) and motion detectors are broadly tuned. PMID:28220883

  9. Impact of conditioning intensity and TBI on acute GVHD after hematopoietic cell transplantation.

    PubMed

    Nakasone, H; Fukuda, T; Kanda, J; Mori, T; Yano, S; Kobayashi, T; Miyamura, K; Eto, T; Kanamori, H; Iwato, K; Uchida, N; Mori, S; Nagamura-Inoue, T; Ichinohe, T; Atsuta, Y; Teshima, T; Murata, M

    2015-04-01

    The impact of the conditioning intensity and TBI on acute GVHD (aGVHD) is still a matter of debate. We analyzed 6848 adult recipients who received allogeneic hematopoietic cell transplants (HCT) between 2006 and 2011 in Japan. The subjects were divided into groups who had received myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC), either with or without TBI. There was a significant difference in the incidence of aGVHD 2-4 among the different conditioning types: 39% in TBI-MAC, 35% in TBI-RIC and 32% in both no-TBI MAC and no-TBI-RIC (P<0.001). In a multivariate analysis, TBI-MAC, but not no-TBI MAC, was significantly associated with an increased risk of aGVHD 2-4 (hazard ratio (HR) 1.33, P<0.01), whereas TBI-RIC was associated with an increased risk of GVHD 3-4 (HR 1.36, P=0.048). TBI-MAC and TBI-RIC were significantly associated with skin and gastrointestinal aGVHD. Subgroup analyses demonstrated that not only TBI-MAC, but also TBI-RIC, was significantly associated with aGVHD 2-4 in older patients. Furthermore, high-dose TBI only had an adverse impact on aGVHD 2-4 in HLA-matched HCT. Impacts of intensity and TBI on aGVHD differ by patient backgrounds, and this difference should be considered to establish a risk-adapted strategy for the prevention of aGVHD.

  10. Novel strategies for improving hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation or intensive chemotherapy.

    PubMed

    Baron, Frédéric; Nagler, Arnon

    2017-02-01

    High-dose conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT) as well as intensive poly-chemotherapy for acute myeloid leukemia (AML) induce prolonged periods of neutropenia. The duration of the neutropenia is particularly long following umbilical cord blood transplantation (UCBT). Areas covered: After briefly reviewing the impact of hematopoietic growth factors administration to hasten hematologic reconstitution after allo-HCT or intensive AML chemotherapy, this article summarizes recent approaches that have been investigated to prompt hematologic reconstruction after UCBT or intensive AML chemotherapy. Expert opinion: In the allo-HCT setting, administration of G-CSF or GM-CSF shortened the duration of the neutropenia but failed to decrease infection-related mortality or to improve survival. Novel approaches to hasten hematological reconstruction after UCBT such as double UCBT with expansion of one of the 2 UCB units with Notch ligand, mesenchymal stromal cells, nicotinamide, or StemRegenin 1, co-transplanting a single UCB unit with HLA-haploidentical CD34+ cells, or increasing UCB HSC homing to marrow niches via direct intra bone UCB administration, pulse treatment with dmPGE2 or enforced fucosylation are promising and deserve further investigations in prospective phase III studies. In the AML setting, G-CSF or GM-CSF administration after intensive chemotherapy decreased the duration of the neutropenia without improving survival.

  11. Attitudes of intensive care nurses towards brain death and organ transplantation: instrument development and testing.

    PubMed

    Kim, Jung Ran; Fisher, Murray John; Elliott, Doug

    2006-03-01

    This paper reports the development and testing of an instrument assessing attitudes of Korean intensive care unit nurses. Reluctance by healthcare professionals to identify brain-dead patients as a potential donor is one reason for a shortfall in transplantable organs in all countries. Organ donation from brain-dead patients is a particularly contentious issue in Korea, following recent legal recognition of brain death within the cultural context of Confucian beliefs. A 38-item instrument was developed from the literature and key informant interviews, and validated by an expert panel and a pilot study. A survey was conducted with Korean intensive care unit nurses (n = 520) from October 2003 to January 2004. Principal component analysis with varimax rotation was used to determine construct validity. Item-to-total correlations and Cronbach's coefficient alpha were used to determine the scale's internal consistency and unidimensionality. The scale demonstrated high internal consistency (alpha = 0.88). Principal component analysis yielded a four-component structure: Discomfort, Enhancing quality of life, Willingness to be a donor and Rewarding experience. Overall, Korean intensive care unit nurses showed positive attitudes towards organ transplantation, despite some mixed feelings. The attitude scale was reliable and valid for this cohort. Areas were identified where professional development may enhance positive attitudes towards organ transplantation from brain-dead donors. Effective education for intensive care unit nurses is necessary to increase the organ donor pool in Korea. Further research could test the instrument with other populations.

  12. Replacing craving imagery with alternative pleasant imagery reduces craving intensity.

    PubMed

    Knäuper, Bärbel; Pillay, Rowena; Lacaille, Julien; McCollam, Amanda; Kelso, Evan

    2011-08-01

    Laboratory studies have shown that asking people to engage in imagery reduces the intensity of laboratory-induced food cravings. This study examined whether the intensity of naturally occurring cravings can be reduced by replacing the craving-related imagery with alternative, pleasant imagery. Participants were instructed to vividly imagine engaging in their favorite activity. They had to apply this imagery technique over a period of four days whenever they felt a craving arising and were asked to keep applying this technique until the craving passed. Compared to baseline, craving intensity and vividness of craving-related imagery were both significantly reduced. Vividness of craving-related imagery fully mediated the effect of the alternative imagery on craving intensity. No effects were found for control conditions in which participants (1) just formed the goal intention to reduce their cravings, (2) formed implementation intentions to reduce their cravings, and (3) engaged in a cognitive task (reciting the alphabet backwards). The findings suggest that vividly imagining a pleasant element can be an effective technique to curb cravings in everyday life.

  13. Combination of clopidogrel and everolimus dramatically reduced the development of transplant arteriosclerosis in murine aortic allografts.

    PubMed

    Eckl, Sebastian; Heim, Christian; Abele-Ohl, Silke; Hoffmann, Julia; Ramsperger-Gleixner, Martina; Weyand, Michael; Ensminger, Stephan M

    2010-09-01

    Our group has shown that platelet inhibition with clopidogrel, an antagonist of the P2Y12 adenosine diphosphate receptor on platelets, reduced the formation of transplant arteriosclerosis. The aim of this study was to investigate whether a combination of cyclosporin or everolimus with clopidogrel has a beneficial effect on the development of transplant arteriosclerosis. Fully MHC mismatched C57Bl/6 (H2(b)) donor aortas were transplanted into CBA.J (H2(k)) recipients and mice received either clopidogrel alone (1 mg/kg/day) or in combination with cyclosporin (2 mg/kg/day) or everolimus (0.05 mg/kg/day). Grafts were analysed by histology and morphometry on day 30 after transplantation. In mice treated with clopidogrel alone, transplant arteriosclerosis was significantly reduced [intima proliferation 56 +/- 11% vs. 81 +/- 7% (control)/n = 7]. Daily application of everolimus reduced the development of transplant arteriosclerosis compared with untreated controls [intima proliferation of 29 +/- 9% vs. 81 +/- 7% (control)/n = 7]. Strikingly, combination of clopidogrel and everolimus almost abolished the formation of transplant arteriosclerosis [intima proliferation: 11 +/- 8% vs. 81 +/- 7% (control)/n = 7]. By contrast, combination of cyclosporin and clopidogrel compared with clopidogrel alone showed no additive effect. These results demonstrate that combination of platelet- and mammalian target of Rapamycin-inhibition can dramatically reduce the development of transplant arteriosclerosis.

  14. Feeling close: emotional intensity reduces perceived psychological distance.

    PubMed

    Van Boven, Leaf; Kane, Joanne; McGraw, A Peter; Dale, Jeannette

    2010-06-01

    The results of 6 experiments indicate that emotional intensity reduces perceived psychological distance. People who described events emotionally rather than neutrally perceived those events as less psychologically distant, including embarrassing autobiographical events (Experiment 1), past and future dentist visits (Experiment 2), positive and negative events (Experiment 3), and a national tragedy (Experiment 6). People also perceived an event (dancing in front of an audience) as less psychologically distant when they were in a more emotionally arousing social role (of performer) than in a less emotionally arousing social role (of observer; Experiment 4). Two findings bolster the causal role of emotional intensity in reducing perceived psychological distance. First, reported emotional intensity was negatively correlated with perceived psychological distance and statistically mediated the effect of being in an emotionally arousing social role on perceived psychological distance (Experiment 4). Second, providing people with an alternative interpretation of their emotions (emotionally ambiguous whale songs) significantly reduced, even reversed, the negative correlation between self-reported emotional intensity and perceived psychological distance (Experiment 5). These findings about emotional intensity are consistent with the broader idea that perceived psychological distance is grounded in and influenced by the phenomenology of objective distance. Implications for theories of psychological distance, emotionality, and choice are discussed. (c) 2010 APA, all rights reserved).

  15. Haemodynamic effects of physiotherapy programme in intensive care unit after liver transplantation.

    PubMed

    Senduran, Meric; Yurdalan, Saadet Ufuk; Karadibak, Didem; Gunerli, Ali

    2010-01-01

    To determine the haemodynamic effects of intensive care physiotherapy after liver transplantation. Thirteen patients were included in the study after liver transplantation. The following physiotherapy programme were applied to the patients in intensive care unit: Respiratory physiotherapy, active joint movements, sitting in bed (first task), sitting at the edge of bed (second task), standing (third task), sitting out of bed (fourth task) and walking (fifth task). Heart rate (HR), mean, systolic and diastolic blood pressures (MBP, SBP, DBP), peripheral oxygen saturation (SpO(2)), respiration rate (RR) were recorded before treatment, after each task, after treatment and at the fifth minute of recovery. Pain level was assessed with Visual Analogue Scale (0-10). When compared with supine position before treatment, all of the parameters except RR increased after the first task whereas HR, SBP, MBP and pain increased after the second task. After the third task only HR and pain increased. There was no significant difference between the fourth task and pre-treatment values while HR, DBP and pain increased after the fifth task. When measurements of pre-treatment, immediately after treatment and the fifth minute of recovery were compared HR, MBP and pain increased after treatment whereas HR, RR and pain decreased after recovery. There was no significant difference between pre-treatment values and fifth minute of recovery measurements. Returning to initial values after a 5-min period shows that cardiopulmonary changes caused by intensive care physiotherapy after liver transplantation are responded at physiological limits.

  16. Impact of ABO blood group mismatch in alemtuzumab-based reduced-intensity conditioned haematopoietic SCT.

    PubMed

    Brierley, C K; Littlewood, T J; Peniket, A J; Gregg, R; Ward, J; Clark, A; Parker, A; Malladi, R; Medd, P

    2015-07-01

    The impact of ABO incompatibility on clinical outcomes following haematopoietic SCT (HSCT) remains controversial. This retrospective study assessed the effect of ABO mismatch on transplant outcomes and transfusion requirements in 594 patients undergoing reduced-intensity conditioned (RIC) HSCT with alemtuzumab in three UK transplant centres. We found no significant effects of minor, major or bidirectional ABO mismatch on overall survival, relapse-free survival, nonrelapse mortality or relapse incidence. Although the rate of acute GVHD was unaffected by ABO mismatch, the incidence of extensive chronic GVHD was higher in patients with minor and major mismatch compared with those who were ABO matched (hazard ratio (HR) 1.74, P=0.032 for minor, HR 1.69 P=0.0036 for major mismatch). Red cell and platelet transfusion requirements in the first 100 days post transplant did not differ by ABO mismatch. In this large UK series, ABO mismatch in RIC HSCT has no clinically significant effect on survival outcomes but appears to modify susceptibility to extensive chronic GVHD.

  17. Nursing intensity and costs of nurse staffing demonstrated by the RAFAELA system: liver vs. kidney transplant recipients.

    PubMed

    Andersen, Marit Helen; Lønning, Kjersti; Bjørnelv, Gudrun Maria Waaler; Fagerström, Lisbeth

    2016-09-01

    To compare nursing intensity and nurse staffing costs for liver transplant (LTx) vs. kidney transplant (KTx) patients through the use of the RAFAELA system (the OPCq instrument). High-quality patient care correlates with the correct allocation of nursing staff. Valid systems for obtaining data on nursing intensity, in relation to actual patient care needs, are needed to ensure correct staffing. A prospective, comparative study of 85 liver and 85 kidney transplant patients. Nursing intensity was calculated using the Oulu Patient Classification (OPCq) instrument. The cost per nursing intensity point was calculated by dividing annual total nursing wage costs with annual total nursing intensity points. The results showed significantly higher nursing intensity per day for liver transplant patients compared to kidney transplant patients. The length of stay was the most important variable in relation to nursing intensity points per day. The study demonstrated differences in nursing intensity and nurse staffing costs between the two patient groups. When defending nurse staffing decisions, it is essential that nurse managers have evidence-based knowledge of nursing intensity and nurse staffing costs. © 2016 The Authors. Journal of Nursing Management Published by John Wiley & Sons Ltd.

  18. IVIg Treatment Reduces Catalytic Antibody Titers of Renal Transplanted Patients

    PubMed Central

    Mahendra, Ankit; Peyron, Ivan; Dollinger, Cécile; Gilardin, Laurent; Sharma, Meenu; Wootla, Bharath; Padiolleau-Lefevre, Séverine; Friboulet, Alain; Boquet, Didier; Legendre, Christophe; Kaveri, Srinivas V.

    2013-01-01

    Catalytic antibodies are immunoglobulins endowed with enzymatic activity. Catalytic IgG has been reported in several human autoimmune and inflammatory diseases. In particular, low levels of catalytic IgG have been proposed as a prognostic marker for chronic allograft rejection in patients undergoing kidney transplant. Kidney allograft is a treatment of choice for patients with end-stage renal failure. Intravenous immunoglobulins, a therapeutic pool of human IgG, is used in patients with donor-specific antibodies, alone or in conjunction with other immunosuppressive treatments, to desensitize the patients and prevent the development of acute graft rejection. Here, we followed for a period of 24 months the levels of catalytic IgG towards the synthetic peptide Pro-Phe-Arg-methylcoumarinimide in a large cohort of patients undergoing kidney transplantation. Twenty-four percent of the patients received IVIg at the time of transplantation. Our results demonstrate a marked reduction in levels of catalytic antibodies in all patients three months following kidney transplant. The decrease was significantly pronounced in patients receiving adjunct IVIg therapy. The results suggests that prevention of acute graft rejection using intravenous immunoglobulins induces a transient reduction in the levels of catalytic IgG, thus potentially jeopardizing the use of levels of catalytic antibodies as a prognosis marker for chronic allograft nephropathy. PMID:23967092

  19. How can we reduce hepatic veno-occlusive disease-related deaths after allogeneic stem cell transplantation?

    PubMed

    Johnson, Douglas B; Savani, Bipin N

    2012-07-01

    Hepatic veno-occlusive disease (VOD) is a common and potentially devastating complication of hematopoietic stem cell transplantation. Confirmative diagnosis of this disorder can prove difficult early post hematopoietic stem cell transplantation, as a broad differential diagnosis exists and no definitive diagnostic test is available. Incidence of VOD has decreased in recent years, with especially dramatic declines in severe and fatal VOD. This improvement is attributed to less toxic and reduced-intensity conditioning regimens, and more appropriate patient selection. When severe VOD does occur, current treatments have been largely ineffective. Prevention remains the primary tool in the clinician's arsenal for managing VOD. Our institution pursues aggressive preventative measures for VOD, including appropriate conditioning regimen selection, avoiding hepatotoxic drugs, early prophylactic use of ursodiol, and aggressive fluid management. With appropriate management steps, we believe the incidence of VOD and related deaths can be further decreased.

  20. Faecal microbiota transplantation for severe Clostridium difficile infection in the intensive care unit.

    PubMed

    Trubiano, Jason A; Gardiner, Bradley; Kwong, Jason C; Ward, Peter; Testro, Adam G; Charles, Patrick G P

    2013-02-01

    We describe a case of faecal microbiota transplantation (FMT) used for severe binary toxin-positive Clostridium difficile infection in an intensive care setting. The patient was admitted to the ICU of a tertiary hospital and failed traditional maximal pharmacological management. Adjunctive therapy with FMT given through gastroscopy resulted in resolution of the C. difficile-related symptoms. Although there is a growing experience with FMT for recurrent C. difficile infection, published evidence in severe disease is very limited. In a landscape of increasingly severe C. difficile infection, adjunctive FMT may be considered a useful early treatment option.

  1. Reducing hospital acquired pressure ulcers in intensive care

    PubMed Central

    Cullen Gill, Emma

    2015-01-01

    Pressure ulcers are a definite problem in our health care system and are growing in numbers. Unfortunately, it is usually the most weak and vulnerable of our culture that faces these complications, causing the patient and their families discomfort, anguish, and economic hardship due to their expensive treatment. Data collected by the tissue viability department showed high incidence of hospital acquire pressure ulcers in the intensive care unit in March 2013. An action plan was initiated and implemented by the tissue viability team, senior nursing management, pressure ulcer prevention (PUP) team and respiratory therapists (RT's) within the ICU. Our objective was to reduce hospital acquired pressure ulcers in the intensive care unit using the plan, do, check, act quality improvement process. PMID:26734370

  2. Reconstitution of natural killer cells in HLA-matched HSCT after reduced-intensity conditioning: impact on clinical outcome.

    PubMed

    Pical-Izard, Caroline; Crocchiolo, Roberto; Granjeaud, Samuel; Kochbati, Eloise; Just-Landi, Sylvaine; Chabannon, Christian; Frassati, Coralie; Picard, Christophe; Blaise, Didier; Olive, Daniel; Fauriat, Cyril

    2015-03-01

    Recent advances in the development of reduced-intensity conditioning (RIC) have allowed a broader range of patients to access allogeneic hematopoietic stem cell transplantation (HSCT). Reconstitution of an effective immune system post-transplant, including natural killer (NK) cells, is critical for both tumor control and infectious disease control or prevention. The development and functions of NK cells in such settings remain elusive. Here we analyzed NK cell development in HLA-matched HSCT from related or unrelated donors, after RIC that included antithymocyte globulin (N = 45 patients). Our data reveal that NK cells quickly recover after RIC-HSCT, irrespective of donor type. Rapidly re-emerging NK cells, however, remain immature for more than 6 months. Effector functions resemble that of immature NK cells because they poorly produce IFN-γ and TNF-α in response to target cell stimulation, despite a rapid acquisition of degranulation ability and MIP-1β production. Strikingly, rapid reconstitution of cytokine production correlates with a lower relapse incidence (P = .01) and a better survival rate (P < .0001) at 1 year post-transplant, whereas degranulation capacity was associated with less relapse (P = .05). Our study demonstrates rapid quantitative reconstitution of the NK cell compartment despite administration of potent immune suppressive drugs as part of the conditioning regimen and after transplantation. However, there is a prolonged persistence of functional defects, the correction of which positively correlates with clinical outcome. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  3. Evaluation of engraftment and immunological tolerance after reduced intensity conditioning in a rhesus hematopoietic stem cell gene therapy model.

    PubMed

    Uchida, N; Weitzel, R P; Evans, M E; Green, R; Bonifacino, A C; Krouse, A E; Metzger, M E; Hsieh, M M; Donahue, R E; Tisdale, J F

    2014-02-01

    Reduced intensity conditioning (RIC) is desirable for hematopoietic stem cell (HSC) targeted gene therapy; however, RIC may be insufficient for efficient engraftment and inducing immunological tolerance to transgenes. We previously established long-term gene marking in our rhesus macaque autologous HSC transplantation model following 10 Gy total body irradiation (TBI). In this study, we evaluated RIC transplantation with 4 Gy TBI in two rhesus macaques that received equal parts of CD34(+) cells transduced with green fluorescent protein (GFP)-expressing lentiviral vector and empty vector not expressing transgenes. In both animals, equivalently low gene marking between GFP and empty vectors was observed 6 months post-transplantation, even with efficient transduction of CD34(+) cells in vitro. Autologous lymphocyte infusion with GFP marking resulted in an increase of gene marking in lymphocytes in a control animal with GFP tolerance, but not in the two RIC-transplanted animals. In vitro assays revealed strong cellular and humoral immune responses to GFP protein in the two RIC-transplanted animals, but this was not observed in controls. In summary, 4 Gy TBI is insufficient to permit engraftment of genetically modified HSCs and induce immunological tolerance to transgenes. Our findings should help in the design of conditioning regimens in gene therapy trials.

  4. A Peptide to Reduce Pulmonary Edema in a Rat Model of Lung Transplantation

    PubMed Central

    Finsterwalder, Richard; Friedl, Heinz P.; Rauscher, Sabine; Gröger, Marion; Kocher, Alfred; Wagner, Christine; Wagner, Stephan N.; Fischer, Gottfried; Schultz, Marcus J.; Wiedemann, Dominik; Petzelbauer, Peter

    2015-01-01

    Background Despite significant advances in organ preservation, surgical techniques and perioperative care, primary graft dysfunction is a serious medical problem in transplantation medicine in general and a specific problem in patients undergoing lung transplantation. As a result, patients develop lung edema, causing reduced tissue oxygenation capacity, reduced lung compliance and increased requirements for mechanical ventilatory support. Yet, there is no effective strategy available to protect the grafted organ from stress reactions induced by ischemia/reperfusion and by the surgical procedure itself. Methods We assessed the effect of a cingulin-derived peptide, XIB13 or a random peptide in an established rat model of allogeneic lung transplantation. Donor lungs and recipients received therapeutic peptide at the time of transplantation and outcome was analyzed 100min and 28 days post grafting. Results XIB13 improved blood oxygenation and reduced vascular leak 100min post grafting. Even after 28 days, lung edema was significantly reduced by XIB13 and lungs had reduced fibrotic or necrotic zones. Moreover, the induction of an allogeneic T cell response was delayed indicating a reduced antigen exchange between the donor and the host. Conclusions In summary, we provide a new tool to strengthen endothelial barrier function thereby improving outcomes in lung transplantation. PMID:26536466

  5. A stringent preemptive protocol reduces cytomegalovirus disease in the first 6 months after kidney transplantation.

    PubMed

    Greiner, M; Cusini, A; Ruesch, M; Schiesser, M; Ledergerber, B; Fehr, T; Mueller, N J

    2012-12-01

    The optimal strategy to prevent cytomegalovirus (CMV) disease after kidney transplantation continues to be open to debate. The preemptive approach requires regular determination of CMV viremia and prompt initiation of therapy. We retrospectively compared the incidence of CMV disease during two periods at our center: A first phase (P1, n = 84 kidney recipients), during which time the intensity of surveillance was determined by the responsible physician, was compared to a second phase (P2, n = 74), when a stringent protocol of CMV surveillance was required for all patients. The preemptive approach was applied for all CMV risk groups; prophylaxis was optional in the case of treatment for rejection or delayed graft function in the intermediate- and high-risk group. Follow-up was truncated at 6 months after transplant surgery. CMV syndrome was differentiated from asymptomatic replication by the presence of at least one systemic symptom, while diagnosis of CMV end-organ disease required histological confirmation. Immunosuppression was similar in the two periods. CMV prophylaxis was used equally (26 %) in both periods. The probability for asymptomatic viremia episodes was not different for patients in P1 and P2 regardless of the prevention strategy. For patients following the preemptive strategy, the probability for CMV disease was increased during P1 (p = 0.016), despite fewer PCR assays being performed in phase 2. Protocol violations were only observed during P1. The probability of CMV disease episodes (CMV syndrome and CMV end-organ disease) was substantially reduced using a very stringent protocol. This study highlights the crucial importance of a stringent protocol with optimal adherence by all caregivers if the preemptive strategy is to be successful.

  6. Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation.

    PubMed

    Rivinius, Rasmus; Helmschrott, Matthias; Ruhparwar, Arjang; Schmack, Bastian; Erbel, Christian; Gleissner, Christian A; Akhavanpoor, Mohammadreza; Frankenstein, Lutz; Darche, Fabrice F; Schweizer, Patrick A; Thomas, Dierk; Ehlermann, Philipp; Bruckner, Tom; Katus, Hugo A; Doesch, Andreas O

    2016-01-01

    Amiodarone is a frequently used antiarrhythmic drug in patients with end-stage heart failure. Given its long half-life, pre-transplant use of amiodarone has been controversially discussed, with divergent results regarding morbidity and mortality after heart transplantation (HTX). The aim of this study was to investigate the effects of long-term use of amiodarone before HTX on early post-transplant atrial fibrillation (AF) and mortality after HTX. Five hundred and thirty patients (age ≥18 years) receiving HTX between June 1989 and December 2012 were included in this retrospective single-center study. Patients with long-term use of amiodarone before HTX (≥1 year) were compared to those without long-term use (none or <1 year of amiodarone). Primary outcomes were early post-transplant AF and mortality after HTX. The Kaplan-Meier estimator using log-rank tests was applied for freedom from early post-transplant AF and survival. Of the 530 patients, 74 (14.0%) received long-term amiodarone therapy, with a mean duration of 32.3±26.3 months. Mean daily dose was 223.0±75.0 mg. Indications included AF, Wolff-Parkinson-White syndrome, ventricular tachycardia, and ventricular fibrillation. Patients with long-term use of amiodarone before HTX had significantly lower rates of early post-transplant AF (P=0.0105). Further, Kaplan-Meier analysis of freedom from early post-transplant AF showed significantly lower rates of AF in this group (P=0.0123). There was no statistically significant difference between patients with and without long-term use of amiodarone prior to HTX in 1-year (P=0.8596), 2-year (P=0.8620), 5-year (P=0.2737), or overall follow-up mortality after HTX (P=0.1049). Moreover, Kaplan-Meier survival analysis showed no statistically significant difference in overall survival (P=0.1786). Long-term use of amiodarone in patients before HTX significantly reduces early post-transplant AF and is not associated with increased mortality after HTX.

  7. Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation

    PubMed Central

    Rivinius, Rasmus; Helmschrott, Matthias; Ruhparwar, Arjang; Schmack, Bastian; Erbel, Christian; Gleissner, Christian A; Akhavanpoor, Mohammadreza; Frankenstein, Lutz; Darche, Fabrice F; Schweizer, Patrick A; Thomas, Dierk; Ehlermann, Philipp; Bruckner, Tom; Katus, Hugo A; Doesch, Andreas O

    2016-01-01

    Background Amiodarone is a frequently used antiarrhythmic drug in patients with end-stage heart failure. Given its long half-life, pre-transplant use of amiodarone has been controversially discussed, with divergent results regarding morbidity and mortality after heart transplantation (HTX). Aim The aim of this study was to investigate the effects of long-term use of amiodarone before HTX on early post-transplant atrial fibrillation (AF) and mortality after HTX. Methods Five hundred and thirty patients (age ≥18 years) receiving HTX between June 1989 and December 2012 were included in this retrospective single-center study. Patients with long-term use of amiodarone before HTX (≥1 year) were compared to those without long-term use (none or <1 year of amiodarone). Primary outcomes were early post-transplant AF and mortality after HTX. The Kaplan–Meier estimator using log-rank tests was applied for freedom from early post-transplant AF and survival. Results Of the 530 patients, 74 (14.0%) received long-term amiodarone therapy, with a mean duration of 32.3±26.3 months. Mean daily dose was 223.0±75.0 mg. Indications included AF, Wolff–Parkinson–White syndrome, ventricular tachycardia, and ventricular fibrillation. Patients with long-term use of amiodarone before HTX had significantly lower rates of early post-transplant AF (P=0.0105). Further, Kaplan–Meier analysis of freedom from early post-transplant AF showed significantly lower rates of AF in this group (P=0.0123). There was no statistically significant difference between patients with and without long-term use of amiodarone prior to HTX in 1-year (P=0.8596), 2-year (P=0.8620), 5-year (P=0.2737), or overall follow-up mortality after HTX (P=0.1049). Moreover, Kaplan–Meier survival analysis showed no statistically significant difference in overall survival (P=0.1786). Conclusion Long-term use of amiodarone in patients before HTX significantly reduces early post-transplant AF and is not associated with

  8. The reduced left lateral segment in pediatric liver transplantation: an alternative to the monosegment graft.

    PubMed

    Attia, M S; Stringer, M D; McClean, P; Prasad, K R

    2008-09-01

    Tailoring graft size to small paediatric recipients is a challenge. We have developed a reduced left lateral segment as an alternative to monosegment transplantation for small size recipients. Since November 2000, 89 children have been transplanted with 100 deceased donor liver grafts in our unit. Our median patient and graft survival is 89% and 88% respectively. Four of these cases were performed using a new technique of creating a small donor graft by reducing the left lateral segment. The median weight of the reduced liver graft was 264 g (range: 165-390 g). The median blood transfusion requirement was 101 mL/kg body weight (range 69-167 mL/kg). The median values of peak ALT were 1473 IU/L, INR 2.2 and bilirubin 293 micromol/L in the first two wk following surgery. One neonatal recipient died five days after transplantation from a massive intracranial haemorrhage despite satisfactory graft function. Another recipient with excellent graft function died 10 months later from primary pulmonary hypertension and secondary cardiac failure. Hepatic artery thrombosis occurred in one patient with successful revascularization but he was retransplanted three months later for chronic rejection. No biliary or venous outflow complications occurred in this group. This technique of reduced left lateral segment liver transplantation is an alternative to the monosegment graft and allows small recipients to be successfully transplanted with few technical complications related to graft preparation.

  9. [Transfer of allogeneic stem cell transplant recipients to the intensive care unit: Guidelines from the Francophone society of marrow transplantation and cellular therapy (SFGM-TC)].

    PubMed

    Moreau, Anne-Sophie; Bourhis, Jean-Henri; Contentin, Nathalie; Couturier, Marie-Anne; Delage, Jeremy; Dumesnil, Cécile; Gandemer, Virginie; Hichri, Yosr; Jost, Edgar; Platon, Laura; Jourdain, Mercé; Pène, Frédéric; Yakoub-Agha, Ibrahim

    2016-11-01

    Transferring a patient undergoing an allogeneic stem cell transplantation to the intensive care unit (ICU) is always a challenging situation on a medical and psychological point of view for the patient and his relatives as well as for the medical staff. Despite the progress in hematology and intensive care during the last decade, the prognosis of these patients admitted to the ICU remains poor and mortality is around 50 %. The harmonization working party of the SFGM-TC assembled hematologists and intensive care specialist in order to improve conditions and modalities of the transfer of a patient after allogeneic stem cell transplantation to the ICU. We propose a structured medical form comprising all essential information necessary for optimal medical care on ICU. Copyright © 2016. Published by Elsevier Masson SAS.

  10. Alternatives, and adjuncts, to prophylactic platelet transfusion for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation.

    PubMed

    Desborough, Michael; Estcourt, Lise J; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Stanworth, Simon J; Murphy, Michael F

    2016-08-22

    review included 10 trials in eight references with 554 participants. Six trials (336 participants) only included participants with acute myeloid leukaemia undergoing intensive chemotherapy, two trials (38 participants) included participants with lymphoma undergoing intensive chemotherapy and two trials (180 participants) reported participants undergoing allogeneic stem cell transplantation. Men and women were equally well represented in the trials. The age range of participants included in the trials was from 16 years to 81 years. All trials took place in high-income countries. The manufacturers of the agent sponsored eight trials that were under investigation, and two trials did not report their source of funding.No trials assessed artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII or desmopressin.Nine trials compared a TPO mimetic to placebo or standard care; seven of these used pegylated recombinant human megakaryocyte growth and differentiation factor (PEG-rHuMGDF) and two used recombinant human thrombopoietin (rhTPO).One trial compared platelet-poor plasma to platelet transfusion.We considered that all the trials included in this review were at high risk of bias and meta-analysis was not possible in seven trials due to problems with the way data were reported.We are very uncertain whether TPO mimetics reduce the number of participants with any bleeding episode (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.10 to 1.62, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce the risk of a life-threatening bleed after 30 days (OR 1.46, 95% CI 0.06 to 33.14, three trials, 209 participants, very low quality evidence); or after 90 days (OR 1.00, 95% CI 0.06 to 16.37, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce platelet transfusion requirements after 30 days (mean difference -3.00 units, 95% CI -5.39 to -0.61, one

  11. Alternatives, and adjuncts, to prophylactic platelet transfusion for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation

    PubMed Central

    Desborough, Michael; Estcourt, Lise J; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Stanworth, Simon J; Murphy, Michael F

    2016-01-01

    not yet been published (trial completion dates: April 2012 to February 2017). Therefore, the review included 10 trials in eight references with 554 participants. Six trials (336 participants) only included participants with acute myeloid leukaemia undergoing intensive chemotherapy, two trials (38 participants) included participants with lymphoma undergoing intensive chemotherapy and two trials (180 participants) reported participants undergoing allogeneic stem cell transplantation. Men and women were equally well represented in the trials. The age range of participants included in the trials was from 16 years to 81 years. All trials took place in high-income countries. The manufacturers of the agent sponsored eight trials that were under investigation, and two trials did not report their source of funding. No trials assessed artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII or desmopressin. Nine trials compared a TPO mimetic to placebo or standard care; seven of these used pegylated recombinant human megakaryocyte growth and differentiation factor (PEG-rHuMGDF) and two used recombinant human thrombopoietin (rhTPO). One trial compared platelet-poor plasma to platelet transfusion. We considered that all the trials included in this review were at high risk of bias and meta-analysis was not possible in seven trials due to problems with the way data were reported. We are very uncertain whether TPO mimetics reduce the number of participants with any bleeding episode (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.10 to 1.62, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce the risk of a life-threatening bleed after 30 days (OR 1.46, 95% CI 0.06 to 33.14, three trials, 209 participants, very low quality evidence); or after 90 days (OR 1.00, 95% CI 0.06 to 16.37, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce

  12. Post-transplant bendamustine reduces GvHD while preserving GvL in experimental haploidentical bone marrow transplantation.

    PubMed

    Stokes, Jessica; Hoffman, Emely A; Zeng, Yi; Larmonier, Nicolas; Katsanis, Emmanuel

    2016-07-01

    Advances in haploidentical bone marrow transplantation (h-BMT) have drastically broadened the treatment options for patients requiring BMT. The possibility of significantly reducing the complications resulting from graft-versus-host disease (GvHD) with the administration of post-transplant cyclophosphamide (PT-CY) has substantially improved the efficacy and applicability of T cell-replete h-BMT. However, higher frequency of disease recurrence remains a major challenge in h-BMT with PT-CY. There is a critical need to identify novel strategies to prevent GvHD while sparing the graft-versus-leukaemia (GvL) effect in h-BMT. To this end, we evaluated the impact of bendamustine (BEN), given post-transplant, on GvHD and GvL using clinically relevant murine h-BMT models. We provide results indicating that post-transplant bendamustine (PT-BEN) alleviates GvHD, significantly improving survival, while preserving engraftment and GvL effects. We further document that PT-BEN can mitigate GvHD even in the absence of Treg. Our results also indicate that PT-BEN is less myelosuppressive than PT-CY, significantly increasing the number and proportion of CD11b(+) Gr-1(hi) cells, while decreasing lymphoid cells. In vitro we observed that BEN enhances the suppressive function of myeloid-derived suppressor cells (MDSCs) while impairing the proliferation of T- and B-cells. These results advocate for the consideration of PT-BEN as a new therapeutic platform for clinical implementation in h-BMT. © 2016 John Wiley & Sons Ltd.

  13. Living donor kidney transplantation preceding pancreas transplantation reduces mortality in type 1 diabetics with end-stage renal disease.

    PubMed

    Kaku, K; Kitada, H; Noguchi, H; Kurihara, K; Kawanami, S; Nakamura, U; Tanaka, M

    2015-04-01

    Simultaneous pancreas-kidney transplantation (SPK) is a definitive treatment for type 1 diabetics with end-stage renal disease (ESRD). Because of the shortage of deceased donors in Japan, the mortality rate during the waiting period is high. We evaluated mortality risk in patients with type 1 diabetes waiting for SPK, and the benefit of living-donor kidney transplantation (LDK) preceding pancreas transplantation, which may reduce mortality in patients awaiting SPK. This retrospective study included 71 patients with type 1 diabetes. Twenty-six patients underwent SPK, 15 underwent LDK, and 30 were waiting for SPK. Their cumulative patient and graft survival rates were retrospectively evaluated. Risk factors contributing to mortality in patients with type 1 diabetes awaiting SPK were evaluated with the use of a Cox proportional hazards model. The 5-year cumulative patient survival rates in the SPK and LDK groups were 100% and 93.3%, respectively (P = .19), and 5-year kidney graft survival rates were 95.7% and 100% (P = .46), respectively. The cumulative survival rate in patients awaiting SPK was 77.7% at 5 years after registration. Duration of dialysis was the only factor significantly associated with patient and graft survivals according to both univariate and multivariate analyses. Patient and graft survival rates were similar in the SPK and LDK groups, but the survival rate of patients awaiting SPK decreased over time. Duration of dialysis was an independent risk factor for patient and graft survival. LDK preceding pancreas transplantation may be an effective therapeutic option for patients with type 1 diabetes and ESRD. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Liver transplant quality and safety plan in anesthesia and intensive care medicine.

    PubMed

    Della Rocca, G; De Flaviis, A; Costa, M G; Chiarandini, P; Pompei, L; Venettoni, S

    2010-01-01

    Patients scheduled for orthotopic liver transplantation (OLT) may have coexisting diseases and more likely receive grafts of poorer quality than in the past. Perioperative mortality and morbidity are usually due to a combination of factors related to the patient, graft, surgery, anesthesia, and intensive care management. Anesthesia and intensive care are the areas with the highest frequency and severity of errors. Error and accident risks are always present in this context where a human component is unavoidable. The matter of medical errors is becoming noteworthy worldwide. Nevertheless, data concerning medical errors during OLT are not available in Italy. There are only hypothetical evaluations. The number of adverse events may be high, but so far no specific programs have been developed to increase patient safety. To improve patient safety, anesthesia and intensive care units must use a proactive approach dedicated to an OLT program. We have presented herein a prevention policy to detect errors before they happen through incident reporting, anonymous and voluntary reports of adverse events or near misses, operating room checklists (patient, drugs, devices, equipment), improved training, safer facilities, equipment function, and adequate drug supplies for an OLT program. Copyright 2010 Elsevier Inc. All rights reserved.

  15. Fecal Microbiota Transplant: Treatment Options for Clostridium difficile Infection in the Intensive Care Unit.

    PubMed

    Han, Samuel; Shannahan, Sarah; Pellish, Randall

    2016-10-01

    Clostridium difficile infection (CDI) has steadily increased in incidence since the 1990s, with an associated increase in recurrence and severity, which has in turn lead to more intensive care unit (ICU) admissions. The development of recurrent CDI, in particular, has been associated with increasing patient morbidity and mortality as well as an immense financial burden on the health care system. Recently, fecal microbiota transplantation (FMT) has received much publicity as an effective means of treatment for recurrent CDI. The goal of this review is to provide evidence-based recommendations for the diagnosis and management of CDI, with a particular focus on FMT and its utilization in the ICU. © The Author(s) 2015.

  16. Interventions to reduce medication errors in pediatric intensive care.

    PubMed

    Manias, Elizabeth; Kinney, Sharon; Cranswick, Noel; Williams, Allison; Borrott, Narelle

    2014-10-01

    To systematically examine the research literature to identify which interventions reduce medication errors in pediatric intensive care units. Databases were searched from inception to April 2014. Studies were included if they involved the conduct of an intervention with the intent of reducing medication errors. In all, 34 relevant articles were identified. Apart from 1 study, all involved single-arm, before-and-after designs without a comparative, concurrent control group. A total of 6 types of interventions were utilized: computerized physician order entry (CPOE), intravenous systems (ISs), modes of education (MEs), protocols and guidelines (PGs), pharmacist involvement (PI), and support systems for clinical decision making (SSCDs). Statistically significant reductions in medication errors were achieved in 7/8 studies for CPOE, 2/5 studies for ISs, 9/11 studies for MEs, 1/2 studies for PGs, 2/3 studies for PI, and 3/5 studies for SSCDs. The test for subgroup differences showed that there was no statistically significant difference among the 6 subgroups of interventions, χ(2)(5) = 1.88, P = 0.87. The following risk ratio results for meta-analysis were obtained: CPOE: 0.47 (95% CI = 0.28, 0.79); IS: 0.37 (95% CI = 0.19, 0.73); ME: 0.36 (95% CI = 0.22, 0.58); PG: 0.82 (95% CI = 0.21, 3.25); PI: 0.39 (95% CI = 0.10, 1.51), and SSCD: 0.49 (95% CI = 0.23, 1.03). Available evidence suggests some aspects of CPOE with decision support, ME, and IS may help in reducing medication errors. Good quality, prospective, observational studies are needed for institutions to determine the most effective interventions. © The Author(s) 2014.

  17. Predisposing risk factors for delirium in living donor liver transplantation patients in intensive care units.

    PubMed

    Wang, Szu-Han; Wang, Jiun-Yi; Lin, Ping-Yi; Lin, Kuo-Hua; Ko, Chih-Jan; Hsieh, Chia-En; Lin, Hui-Chuan; Chen, Yao-Li

    2014-01-01

    Delirium is one of the main causes of increased length of intensive care unit (ICU) stay among patients who have undergone living donor liver transplantation (LDLT). We aimed to evaluate risk factors for delirium after LDLT as well as to investigate whether delirium impacts the length of ICU and hospital stay. Seventy-eight patients who underwent LDLT during the period January 2010 to December 2012 at a single medical center were enrolled. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) scale was used to diagnose delirium. Preoperative, postoperative, and hematologic factors were included as potential risk factors for developing delirium. During the study period, delirium was diagnosed in 37 (47.4%) patients after LDLT. The mean onset of symptoms occurred 7.0±5.5 days after surgery and the mean duration of symptoms was 5.0±2.6 days. The length of stay in the ICU for patients with delirium (39.8±28.1 days) was significantly longer than that for patients without delirium (29.3±19.0 days) (p<0.05). Risk factors associated with delirium included history of alcohol abuse [odds ratio (OR) = 6.40, 95% confidence interval (CI): 1.85-22.06], preoperative hepatic encephalopathy (OR = 4.45, 95% CI: 1.36-14.51), APACHE II score ≥16 (OR = 1.73, 95% CI: 1.71-2.56), and duration of endotracheal intubation ≥5 days (OR = 1.81, 95% CI: 1.52-2.23). History of alcohol abuse, preoperative hepatic encephalopathy, APACHE II scores ≥16 and endotracheal intubation ≥5 days were predictive of developing delirium in the ICU following liver transplantation surgery and were associated with increased length of ICU and hospital stay.

  18. An intensive family intervention clinic for reducing childhood obesity.

    PubMed

    Endevelt, Ronit; Elkayam, Orit; Cohen, Rinat; Peled, Ronit; Tal-Pony, Limor; Michaelis Grunwald, Ruth; Valinsky, Liora; Porath, Avi; Heymann, Anthony David

    2014-01-01

    Childhood and adolescent obesity constitute a significant public health concern. Family health care settings with multidisciplinary teams provide an opportunity for weight loss treatment. The objective of this study was to examine the effect of intensive treatment designed to reduce weight using a parent-child lifestyle modification intervention in a family health care clinic for obese and overweight children who had failed previous treatment attempts. This was a practice-based 6-month intervention at Maccabi Health Care Services, an Israeli health maintenance organization, consisting of parental education, individual child consultation, and physical activity classes. We included in the intervention 100 obese or overweight children aged 5 to 14 years and their parents and 943 comparison children and their parents. Changes in body mass index z-scores, adjusted for socioeconomic status, were analyzed, with a follow-up at 14 months and a delayed follow-up at an average of 46.7 months. The mean z-score after the intervention was lower in the intervention group compared to the comparison group (1.74 and 1.95, respectively; P = .019). The intervention group sustained the reduction in z-score after an average of 46.7 months (P < .001). Of the overweight or obese children, 13% became normal weight after the intervention, compared with 4% of the comparison children. This multidisciplinary team treatment of children and their parents in family health care clinics positively affected measures of childhood obesity. Additional randomized trials are required to verify these findings.

  19. Reduced size liver transplantation from a donor supported by a Berlin Heart.

    PubMed

    Misra, M V; Smithers, C J; Krawczuk, L E; Jenkins, R L; Linden, B C; Weldon, C B; Kim, H B

    2009-11-01

    Patients on cardiac assist devices are often considered to be high-risk solid organ donors. We report the first case of a reduced size liver transplant performed using the left lateral segment of a pediatric donor whose cardiac function was supported by a Berlin Heart. The recipient was a 22-day-old boy with neonatal hemochromatosis who developed fulminant liver failure shortly after birth. The transplant was complicated by mild delayed graft function, which required delayed biliary reconstruction and abdominal wall closure, as well as a bile leak. However, the graft function improved quickly over the first week and the patient was discharged home with normal liver function 8 weeks after transplant. The presence of a cardiac assist device should not be considered an absolute contraindication for abdominal organ donation. Normal organ procurement procedures may require alteration due to the unusual technical obstacles that are encountered when the donor has a cardiac assist device.

  20. IGL-1 solution reduces endoplasmic reticulum stress and apoptosis in rat liver transplantation

    PubMed Central

    Mosbah, I B; Zaouali, M A; Martel, C; Bjaoui, M; Abdennebi, H B; Hotter, G; Brenner, C; Roselló-Catafau, J

    2012-01-01

    Injury due to cold ischemia reperfusion (I/R) is a major cause of primary graft non-function following liver transplantation. We postulated that I/R-induced cellular damage during liver transplantation might affect the secretory pathway, particularly at the endoplasmic reticulum (ER). We examined the involvement of ER stress in organ preservation, and compared cold storage in University of Wisconsin (UW) solution and in Institute Georges Lopez-1 (IGL-1) solution. In one group of rats, livers were preserved in UW solution for 8 h at 4 °C, and then orthotopic liver transplantation was performed according to Kamada's cuff technique. In another group, livers were preserved in IGL-1 solution. The effect of each preservation solution on the induction of ER stress, hepatic injury, mitochondrial damage and cell death was evaluated. As expected, we found increased ER stress after liver transplantation. IGL-1 solution significantly attenuated ER damage by reducing the activation of three pathways of unfolded protein response and their effector molecules caspase-12, C/EBP homologous protein-10, X-box-binding protein 1, tumor necrosis factor-associated factor 2 and eukaryotic translation initiation factor 2. This attenuation of ER stress was associated with a reduction in hepatic injury and cell death. Our results show that IGL-1 solution may be a useful means to circumvent excessive ER stress reactions associated with liver transplantation, and may optimize graft quality. PMID:22402603

  1. Changes in intensive care for allogeneic hematopoietic stem cell transplant recipients.

    PubMed

    Lengliné, E; Chevret, S; Moreau, A-S; Pène, F; Blot, F; Bourhis, J-H; Buzyn, A; Schlemmer, B; Socié, G; Azoulay, E

    2015-06-01

    Intensive care unit (ICU) admission is associated with high mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Whether mortality has decreased recently is unknown. The 497 adult allogeneic HSCT recipients admitted to three ICUs between 1997 and 2011 were evaluated retrospectively. Two hundred and nine patients admitted between 1997 and 2003 were compared with the 288 patients admitted from 2004 to 2011. Factors associated with 90-day mortality were identified. The recent cohort was characterized by older age, lower conditioning intensity, and greater use of peripheral blood or unrelated-donor graft. In the recent cohort, ICU was used more often for patients in hematological remission (67% vs 44%; P<0.0001) and without GVHD (73% vs 48%; P<0.0001) or invasive fungal infection (85% vs 73%; P=0.0003) despite a stable admission rate (21.7%). These changes were associated with significantly better 90-day survival (49% vs 31%). Independent predictors of hospital mortality were GVHD, mechanical ventilation (MV) and renal replacement therapy (RRT). Among patients who required MV or RRT, survival was 29% and 18%, respectively, but dropped to 18% and 6% in those with GVHD. The use of ICU admission has changed and translated into improved survival, but advanced life support in patients with GVHD usually provides no benefits.

  2. The RaDIANT community study protocol: community-based participatory research for reducing disparities in access to kidney transplantation.

    PubMed

    Patzer, Rachel E; Gander, Jennifer; Sauls, Leighann; Amamoo, M Ahinee; Krisher, Jenna; Mulloy, Laura L; Gibney, Eric; Browne, Teri; Plantinga, Laura; Pastan, Stephen O

    2014-10-28

    The Southeastern United States has the lowest kidney transplant rates in the nation, and racial disparities in kidney transplant access are concentrated in this region. The Southeastern Kidney Transplant Coalition (SEKTC) of Georgia, North Carolina, and South Carolina is an academic and community partnership that was formed with the mission to improve access to kidney transplantation and reduce disparities among African American (AA) end stage renal disease (ESRD) patients in the Southeastern United States. We describe the community-based participatory research (CBPR) process utilized in planning the Reducing Disparities In Access to kidNey Transplantation (RaDIANT) Community Study, a trial developed by the SEKTC to reduce health disparities in access to kidney transplantation among AA ESRD patients in Georgia, the state with the lowest kidney transplant rates in the nation. The SEKTC Coalition conducted a needs assessment of the ESRD population in the Southeast and used results to develop a multicomponent, dialysis facility-randomized, quality improvement intervention to improve transplant access among dialysis facilities in GA. A total of 134 dialysis facilities are randomized to receive either: (1) standard of care or "usual" transplant education, or (2) the multicomponent intervention consisting of transplant education and engagement activities targeting dialysis facility leadership, staff, and patients within dialysis facilities. The primary outcome is change in facility-level referral for kidney transplantation from baseline to 12 months; the secondary outcome is reduction in racial disparity in transplant referral. The RaDIANT Community Study aims to improve equity in access to kidney transplantation for ESRD patients in the Southeast. Clinicaltrials.gov number NCT02092727.

  3. The "House Calls" trial: a randomized controlled trial to reduce racial disparities in live donor kidney transplantation: rationale and design.

    PubMed

    Rodrigue, James R; Pavlakis, Martha; Egbuna, Ogo; Paek, Matthew; Waterman, Amy D; Mandelbrot, Didier A

    2012-07-01

    Despite a substantially lower rate of live donor kidney transplantation among Black Americans compared to White Americans, there are few systematic efforts to reduce this racial disparity. This paper describes the rationale and design of a randomized controlled trial evaluating the comparative effectiveness of three different educational interventions for increasing live donor kidney transplantation in Black Americans. This trial is a single-site, urn-randomized controlled trial with a planned enrollment of 180 Black Americans awaiting kidney transplantation. Patients are randomized to receive transplant education in one of three education conditions: through group education at their homes (e.g., House Calls), or through group (Group-Based) or individual education (Individual Counseling) in the transplant center. The primary outcome of the trial is the occurrence of a live donor kidney transplant, with secondary outcomes including living donor inquiries and evaluations as well as changes in patient live donor kidney transplantation readiness, willingness, knowledge, and concerns. Sex, age, dialysis status, and quality of life are evaluated as moderating factors. Findings from this clinical trial have the potential to inform strategies for reducing racial disparities in live donor kidney transplantation. Similar trials have been developed recently to broaden the evaluation of House Calls as an innovative disparity-reducing intervention in kidney transplantation. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Intervention to Reduce Transmission of Resistant Bacteria in Intensive Care

    PubMed Central

    Huskins, W. Charles; Huckabee, Charmaine M.; O’Grady, Naomi P.; Murray, Patrick; Kopetskie, Heather; Zimmer, Louise; Walker, Mary Ellen; Sinkowitz-Cochran, Ronda L.; Jernigan, John A.; Samore, Matthew; Wallace, Dennis; Goldmann, Donald A.

    2012-01-01

    BACKGROUND Intensive care units (ICUs) are high-risk settings for the transmission of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE). METHODS In a cluster-randomized trial, we evaluated the effect of surveillance for MRSA and VRE colonization and of the expanded use of barrier precautions (intervention) as compared with existing practice (control) on the incidence of MRSA or VRE colonization or infection in adult ICUs. Surveillance cultures were obtained from patients in all participating ICUs; the results were reported only to ICUs assigned to the intervention. In intervention ICUs, patients who were colonized or infected with MRSA or VRE were assigned to care with contact precautions; all the other patients were assigned to care with universal gloving until their discharge or until surveillance cultures obtained at admission were reported to be negative. RESULTS During a 6-month intervention period, there were 5434 admissions to 10 intervention ICUs, and 3705 admissions to 8 control ICUs. Patients who were colonized or infected with MRSA or VRE were assigned to barrier precautions more frequently in intervention ICUs than in control ICUs (a median of 92% of ICU days with either contact precautions or universal gloving [51% with contact precautions and 43% with universal gloving] in intervention ICUs vs. a median of 38% of ICU days with contact precautions in control ICUs, P<0.001). In intervention ICUs, health care providers used clean gloves, gowns, and hand hygiene less frequently than required for contacts with patients assigned to barrier precautions; when contact precautions were specified, gloves were used for a median of 82% of contacts, gowns for 77% of contacts, and hand hygiene after 69% of contacts, and when universal gloving was specified, gloves were used for a median of 72% of contacts and hand hygiene after 62% of contacts. The mean (±SE) ICU-level incidence of events of colonization or infection

  5. Reduced Toxicity Conditioning and Allogeneic Hematopoietic Progenitor Cell Transplantation for Recessive Dystrophic Epidermolysis Bullosa.

    PubMed

    Geyer, Mark B; Radhakrishnan, Kavita; Giller, Roger; Umegaki, Noriko; Harel, Sivan; Kiuru, Maija; Morel, Kimberly D; LeBoeuf, Nicole; Kandel, Jessica; Bruckner, Anna; Fabricatore, Sandra; Chen, Mei; Woodley, David; McGrath, John; Baxter-Lowe, LeeAnn; Uitto, Jouni; Christiano, Angela M; Cairo, Mitchell S

    2015-09-01

    Recessive dystrophic epidermolysis bullosa is a severe, incurable, inherited blistering disease caused by COL7A1 mutations. Emerging evidence suggests hematopoietic progenitor cells (HPCs) can be reprogrammed into skin; HPC-derived cells can restore COL7 expression in COL7-deficient mice. We report two children with recessive dystrophic epidermolysis bullosa treated with reduced-toxicity conditioning and HLA-matched HPC transplantation.

  6. Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia.

    PubMed

    Chalandon, Yves; Thomas, Xavier; Hayette, Sandrine; Cayuela, Jean-Michel; Abbal, Claire; Huguet, Françoise; Raffoux, Emmanuel; Leguay, Thibaut; Rousselot, Philippe; Lepretre, Stéphane; Escoffre-Barbe, Martine; Maury, Sébastien; Berthon, Céline; Tavernier, Emmanuelle; Lambert, Jean-François; Lafage-Pochitaloff, Marina; Lhéritier, Véronique; Chevret, Sylvie; Ifrah, Norbert; Dombret, Hervé

    2015-06-11

    In this study, we randomly compared high doses of the tyrosine kinase inhibitor imatinib combined with reduced-intensity chemotherapy (arm A) to standard imatinib/hyperCVAD (cyclophosphamide/vincristine/doxorubicin/dexamethasone) therapy (arm B) in 268 adults (median age, 47 years) with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). The primary objective was the major molecular response (MMolR) rate after cycle 2, patients being then eligible for allogeneic stem cell transplantation (SCT) if they had a donor, or autologous SCT if in MMolR and no donor. With fewer induction deaths, the complete remission (CR) rate was higher in arm A than in arm B (98% vs 91%; P = .006), whereas the MMolR rate was similar in both arms (66% vs 64%). With a median follow-up of 4.8 years, 5-year event-free survival and overall survival (OS) rates were estimated at 37.1% and 45.6%, respectively, without difference between the arms. Allogeneic transplantation was associated with a significant benefit in relapse-free survival (hazard ratio [HR], 0.69; P = .036) and OS (HR, 0.64; P = .02), with initial white blood cell count being the only factor significantly interacting with this SCT effect. In patients achieving MMolR, outcome was similar after autologous and allogeneic transplantation. This study validates an induction regimen combining reduced-intensity chemotherapy and imatinib in Ph+ ALL adult patients and suggests that SCT in first CR is still a good option for Ph+ ALL adult patients. This trial was registered at www.clinicaltrials.gov as #NCT00327678.

  7. Haploidentical hematopoietic transplantation from KIR ligand-mismatched donors with activating KIRs reduces nonrelapse mortality.

    PubMed

    Mancusi, Antonella; Ruggeri, Loredana; Urbani, Elena; Pierini, Antonio; Massei, Maria Speranza; Carotti, Alessandra; Terenzi, Adelmo; Falzetti, Franca; Tosti, Antonella; Topini, Fabiana; Bozza, Silvia; Romani, Luigina; Tognellini, Rita; Stern, Martin; Aversa, Franco; Martelli, Massimo F; Velardi, Andrea

    2015-05-14

    Because activating killer cell immunoglobulinlike receptors (KIRs) are heterogeneously expressed in the population, we investigated the role of donor activating KIRs in haploidentical hematopoietic transplants for acute leukemia. Transplants were grouped according to presence vs absence of KIR-ligand mismatches in the graft-vs-host direction (ie, of donor-vs-recipient natural killer [NK]-cell alloreactivity). In the absence of donor-vs-recipient NK-cell alloreactivity, donor activating KIRs had no effects on outcomes. In the 69 transplant pairs with donor-vs-recipient NK-cell alloreactivity, transplantation from donors with KIR2DS1 and/or KIR3DS1 was associated with reduced risk of nonrelapse mortality, largely infection related (KIR2DS1 present vs absent: hazard ratio [HR], 0.25; P = .01; KIR3DS1 present vs absent: HR, 0.18; P = .006), and better event-free survival (KIR2DS1 present vs absent: HR, 0.31; P = .011; KIR3DS1 present vs absent: HR, 0.30; P = .008). Transplantation from donors with KIR2DS1 and/or KIR3DS1 was also associated with a 50% reduction in infection rate (P = .003). In vitro analyses showed that KIR2DS1 binding to its HLA-C2 ligand upregulated inflammatory cytokine production by alloreactive NK cells in response to infectious challenges. Because ∼40% of donors able to exert donor-vs-recipient NK-cell alloreactivity carry KIR2DS1 and/or KIR3DS1, searching for them may become a feasible, additional criterion in donor selection. © 2015 by The American Society of Hematology.

  8. Impact of the intensity of the pretransplantation conditioning regimen in patients with prior invasive aspergillosis undergoing allogeneic hematopoietic stem cell transplantation: a retrospective survey of the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation

    PubMed Central

    Martino, Rodrigo; Parody, Rocio; Fukuda, Takahiro; Maertens, Johan; Theunissen, Koen; Ho, Aloysius; Mufti, Ghulam J.; Kroger, Nicolaus; Zander, Arnold R.; Heim, Dominik; Paluszewska, Monika; Selleslag, Dominik; Steinerova, Katerina; Ljungman, Per; Cesaro, Simone; Nihtinen, Anna; Cordonnier, Catherine; Vazquez, Lourdes; López-Duarte, Monica; Lopez, Javier; Cabrera, Rafael; Rovira, Montserrat; Neuburger, Stefan; Cornely, Oliver; Hunter, Ann E.; Marr, Kieren A.; Dornbusch, Hans Jürgen; Einsele, Hermann

    2006-01-01

    In this retrospective study, we analyzed the outcomes of 129 patients who underwent an allogeneic hematopoietic stem cell transplantation (allo-HSCT) and had a history of probable or proven invasive aspergillosis (IA), of whom 57 (44%) received a reduced-intensity conditioning (RIC). Overall, 27 patients with IA progressed after the allo-HSCT (cumulative incidence [CumInc] at 2 years, 22%). The variables that increased the 2-year CumInc of IA progression were (1) longer duration of neutropenia after transplantation; (2) advanced status of the underlying disease; and (3) less than 6 weeks from start of systemic anti-Aspergillus therapy and the allo-HSCT. In addition, (4) conventional myeloablative conditioning increased the risk of progression early after transplantation (before day 30) only, while 3 variables increased the risk beyond day 30 were (5) cytomegalovirus disease; (6) bone marrow or cord blood as source of stem cells; and (7) grades II to IV acute graft-versus-host disease (GVHD). A risk model for progression was generated, defined as low (0-1 risk factors, 6% incidence), intermediate (2-3 risk factors, 27% incidence), or high risk (≥ 3 risk factors, 72% incidence [P < .001]). These findings may help in the interpretation and design of future studies on secondary prophylaxis of IA after an allo-HSCT. PMID:16720833

  9. Impact of the intensity of the pretransplantation conditioning regimen in patients with prior invasive aspergillosis undergoing allogeneic hematopoietic stem cell transplantation: A retrospective survey of the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

    PubMed

    Martino, Rodrigo; Parody, Rocio; Fukuda, Takahiro; Maertens, Johan; Theunissen, Koen; Ho, Aloysius; Mufti, Ghulam J; Kroger, Nicolaus; Zander, Arnold R; Heim, Dominik; Paluszewska, Monika; Selleslag, Dominik; Steinerova, Katerina; Ljungman, Per; Cesaro, Simone; Nihtinen, Anna; Cordonnier, Catherine; Vazquez, Lourdes; López-Duarte, Monica; Lopez, Javier; Cabrera, Rafael; Rovira, Montserrat; Neuburger, Stefan; Cornely, Oliver; Hunter, Ann E; Marr, Kieren A; Dornbusch, Hans Jürgen; Einsele, Hermann

    2006-11-01

    In this retrospective study, we analyzed the outcomes of 129 patients who underwent an allogeneic hematopoietic stem cell transplantation (allo-HSCT) and had a history of probable or proven invasive aspergillosis (IA), of whom 57 (44%) received a reduced-intensity conditioning (RIC). Overall, 27 patients with IA progressed after the allo-HSCT (cumulative incidence [CumInc] at 2 years, 22%). The variables that increased the 2-year CumInc of IA progression were (1) longer duration of neutropenia after transplantation; (2) advanced status of the underlying disease; and (3) less than 6 weeks from start of systemic anti-Aspergillus therapy and the allo-HSCT. In addition, (4) conventional myeloablative conditioning increased the risk of progression early after transplantation (before day 30) only, while 3 variables increased the risk beyond day 30 were (5) cytomegalovirus disease; (6) bone marrow or cord blood as source of stem cells; and (7) grades II to IV acute graft-versus-host disease (GVHD). A risk model for progression was generated, defined as low (0-1 risk factors, 6% incidence), intermediate (2-3 risk factors, 27% incidence), or high risk (> or = 3 risk factors, 72% incidence [P < .001]). These findings may help in the interpretation and design of future studies on secondary prophylaxis of IA after an allo-HSCT.

  10. Erythropoietin reduces ischemia-reperfusion injury after liver transplantation in rats.

    PubMed

    Schmeding, Maximilian; Hunold, Gerhard; Ariyakhagorn, Veravoorn; Rademacher, Sebastian; Boas-Knoop, Sabine; Lippert, Steffen; Neuhaus, Peter; Neumann, Ulf P

    2009-07-01

    Human recombinant Erythropoietin (rHuEpo) has recently been shown to be a potent protector of ischemia- reperfusion injury in warm-liver ischemia. Significant enhancement of hepatic regeneration and survival after large volume partial hepatic resection has also been demonstrated. It was the aim of this study to evaluate the capacities of rHuEpo in the setting of rat liver transplantation. One-hundred-and-twenty Wistar rats were used: 60 recipients received liver transplantation following donor organ treatment (60 donors) with either 1000 IU rHuEpo or saline injection (controls) into portal veins (cold ischemia 18 h, University of Wisconsin (UW) solution). Recipients were allocated to two groups, which either received 1000 IU rHuEpo at reperfusion or an equal amount of saline (control). Animals were sacrificed at defined time-points (2, 4.5, 24, 48 h and 7 days postoperatively) for analysis of liver enzymes, histology [hematoxylin-eosin (HE) staining, periodic acid Schiff staining (PAS)], immunostaining [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Hypoxyprobe] and real-time polymerase chain reaction (RT-PCR) of cytokine mRNA (IL-1, IL-6). Lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) values were significantly reduced among the epo-treated animals 24 and 48 h after liver transplantation (LT). The TUNEL and Hypoxyprobe analyses as well as necrotic index evaluation displayed significant reduction of apoptosis and necrosis in rHuEpo-treated graft livers. Erythropoietin reduces ischemia-reperfusion injury after orthotopic liver transplantation in rats.

  11. Saccharomyces boulardii reduces infection intensity of mice with toxocariasis.

    PubMed

    de Avila, Luciana Farias da Costa; Conceição, Fabricio Rochedo; Telmo, Paula de Lima; Dutra, Gisele Ferreira; de los Santos, Diego Gil; Martins, Lourdes Helena Rodrigues; Berne, Maria Elisabeth Aires; da Silva, Pedro Eduardo Almeida; Scaini, Carlos James

    2012-06-08

    Several studies have shown the benefit of the use of probiotics in the prevention and treatment of diseases; however, few of them have investigated the effect of probiotics on parasitosis. In this study, the effect of Saccharomyces boulardii on the intensity of infection of mice with toxocariasis was evaluated. The animals were fed with a diet supplemented with S. boulardii for 15 days before inoculation with Toxocara canis eggs and for 2 or 60 days post-inoculation. S. boulardii promoted a reduction of approximately 36% in the average number of recovered T. canis larvae, suggesting that it can be used as an alternative to help control toxocariasis. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Pre-transplant Evaluation of Donor Urinary Biomarkers can Predict Reduced Graft Function After Deceased Donor Kidney Transplantation

    PubMed Central

    Koo, Tai Yeon; Jeong, Jong Cheol; Lee, Yonggu; Ko, Kwang-Pil; Lee, Kyoung-Bun; Lee, Sik; Park, Suk Joo; Park, Jae Berm; Han, Miyeon; Lim, Hye Jin; Ahn, Curie; Yang, Jaeseok

    2016-01-01

    Abstract Several recipient biomarkers are reported to predict graft dysfunction, but these are not useful in decision making for the acceptance or allocation of deceased donor kidneys; thus, it is necessary to develop donor biomarkers predictive of graft dysfunction. To address this issue, we prospectively enrolled 94 deceased donors and their 109 recipients who underwent transplantation between 2010 and 2013 at 4 Korean transplantation centers. We investigated the predictive values of donor urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and L-type fatty acid binding protein (L-FABP) for reduced graft function (RGF). We also developed a prediction model of RGF using these donor biomarkers. RGF was defined as delayed or slow graft function. Multiple logistic regression analysis was used to generate a prediction model, which was internally validated using a bootstrapping method. Multiple linear regression analysis was used to assess the association of biomarkers with 1-year graft function. Notably, donor urinary NGAL levels were associated with donor AKI (P = 0.014), and donor urinary NGAL and L-FABP were predictive for RGF, with area under the receiver-operating characteristic curves (AUROC) of 0.758 and 0.704 for NGAL and L-FABP, respectively. The best-fit model including donor urinary NGAL, L-FABP, and serum creatinine conveyed a better predictive value for RGF than donor serum creatinine alone (P = 0.02). In addition, we generated a scoring method to predict RGF based on donor urinary NGAL, L-FABP, and serum creatinine levels. Diagnostic performance of the RGF prediction score (AUROC 0.808) was significantly better than that of the DGF calculator (AUROC 0.627) and the kidney donor profile index (AUROC 0.606). Donor urinary L-FABP levels were also predictive of 1-year graft function (P = 0.005). Collectively, these findings suggest donor urinary NGAL and L-FABP to be useful biomarkers for RGF, and support

  13. Mindfulness meditation to reduce symptoms after organ transplant: a pilot study.

    PubMed

    Gross, Cynthia R; Kreitzer, Mary Jo; Russas, Valerie; Treesak, Charoen; Frazier, Patricia A; Hertz, Marshall I

    2004-01-01

    Solid organ transplant patients require life-long immune suppression that can produce distressing side effects and complications. To evaluate the potential of Mindfulness-Based Stress Reduction (MBSR) to reduce symptoms of depression, anxiety, and sleep disturbance and improve quality of life after solid organ transplantation. Longitudinal with evaluations at baseline, postcourse and 3-month follow-up. Kidney, lung, or pancreas transplant recipients (N=20), aged 35 to 59 years, living in the community. An MBSR class (2.5 hours weekly, for 8 weeks), modeled after the program of Jon Kabat-Zinn. Home practice (goal: 45 minutes, 5 days weekly) was monitored. Self-report scales for depression (CES-D), anxiety (STAI-Y1), and sleep dysfunction (PSQI). Nineteen participants completed the course. Findings suggest improvement from baseline symptom scores for depression (P=.006) and sleep (P=.011) at the completion of the MBSR program. At 3 months, improvement in sleep continued (P=.002), and a significant improvement in anxiety scores was seen (P=.043); scores for both symptoms demonstrated a linear trend and dose-response relationship with practice time. In contrast, depression scores showed a quadratic trend, and at 3 months were no longer different from baseline. A composite symptom measure was significantly improved at 3-month follow-up (P=.007). Global and health-related quality of life ratings were not improved. Effects of group support and instructor attention were not controlled, and sample size and follow-up time were limited. A randomized trial to overcome these shortcomings should be done, as symptom distress in transplant recipients appears responsive to MBSR.

  14. Mindfulness meditation to reduce symptoms after organ transplant: a pilot study.

    PubMed

    Gross, Cynthia R; Kreitzer, Mary Jo; Russas, Valerie; Treesak, Charoen; Frazier, Patricia A; Hertz, Marshall I

    2004-01-01

    Solid organ transplant patients require life-long immune suppression that can produce distressing side effects and complications. To evaluate the potential of Mindfulness-Based Stress Reduction (MBSR) to reduce symptoms of depression, anxiety, and sleep disturbance and improve quality of life after solid organ transplantation. Longitudinal with evaluations at baseline, postcourse and 3-month follow-up. Kidney, lung, or pancreas transplant recipients (N = 20), aged 35 to 59 years, living in the community. An MBSR class (2.5 hours weekly, for 8 weeks), modeled after the program of Jon Kabat-Zinn. Home practice (goal: 45 minutes, 5 days weekly) was monitored. Self-report scales for depression (CES-D), anxiety (STAI-Y1), and sleep dysfunction (PSQI). Nineteen participants completed the course. Findings suggest improvement from baseline symptom scores for depression (P = .006) and sleep (P = .011) at the completion of the MBSR program. At 3 months, improvement in sleep continued (P = .002), and a significant improvement in anxiety scores was seen (P = .043); scores for both symptoms demonstrated a linear trend and dose-response relationship with practice time. In contrast, depression scores showed a quadratic trend, and at 3 months were no longer different from baseline. A composite symptom measure was significantly improved at 3-month follow-up (P = .007). Global and health-related quality of life ratings were not improved. Effects of group support and instructor attention were not controlled, and sample size and follow-up time were limited. A randomized trial to overcome these shortcomings should be done, as symptom distress in transplant recipients appears responsive to MBSR.

  15. The ASCENT (Allocation System Changes for Equity in Kidney Transplantation) Study: a Randomized Effectiveness-Implementation Study to Improve Kidney Transplant Waitlisting and Reduce Racial Disparity.

    PubMed

    Patzer, Rachel E; Smith, Kayla; Basu, Mohua; Gander, Jennifer; Mohan, Sumit; Escoffery, Cam; Plantinga, Laura; Melanson, Taylor; Kalloo, Sean; Green, Gary; Berlin, Alex; Renville, Gary; Browne, Teri; Turgeon, Nicole; Caponi, Susan; Zhang, Rebecca; Pastan, Stephen

    2017-05-01

    The United Network for Organ Sharing (UNOS) implemented a new Kidney Allocation System (KAS) in December 2014 that is expected to substantially reduce racial disparities in kidney transplantation among waitlisted patients. However, not all dialysis facility clinical providers and end stage renal disease (ESRD) patients are aware of how the policy change could improve access to transplant. We describe the ASCENT (Allocation System Changes for Equity in KidNey Transplantation) study, a randomized controlled effectiveness-implementation study designed to test the effectiveness of a multicomponent intervention to improve access to the early steps of kidney transplantation among dialysis facilities across the United States. The multicomponent intervention consists of an educational webinar for dialysis medical directors, an educational video for patients and an educational video for dialysis staff, and a dialysis-facility specific transplant performance feedback report. Materials will be developed by a multidisciplinary dissemination advisory board and will undergo formative testing in dialysis facilities across the United States. This study is estimated to enroll ~600 U.S. dialysis facilities with low waitlisting in all 18 ESRD Networks. The co-primary outcomes include change in waitlisting, and waitlist disparity at 1 year; secondary outcomes include changes in facility medical director knowledge about KAS, staff training regarding KAS, patient education regarding transplant, and a medical director's intent to refer patients for transplant evaluation. The results from the ASCENT study will demonstrate the feasibility and effectiveness of a multicomponent intervention designed to increase access to the deceased-donor kidney waitlist and reduce racial disparities in waitlisting.

  16. Reducing Risk in DoD Software-Intensive Systems Development

    DTIC Science & Technology

    2016-03-01

    PROGRAM SPONSORED REPORT SERIES Reducing Risk in DoD Software -Intensive Systems Development March 2016 Brad Naegle, Senior Lecturer Graduate...both successful and unsuccessful software -intensive systems development, despite all of the considerable qualifications of the workforce and the...significant controls offered by the Defense Acquisition System (DAS). The unsuccessful software -intensive systems have suffered dramatic cost and

  17. Heparin-coated circuits reduce myocardial injury in heart or heart-lung transplantation: a prospective, randomized study.

    PubMed

    Wan, S; LeClerc, J L; Antoine, M; DeSmet, J M; Yim, A P; Vincent, J L

    1999-10-01

    The effects of heparin-coated (HC) circuits have been primarily investigated in routine cardiac operations with limited duration of cardiopulmonary bypass (CPB) and ischemia. Their benefits have not been conclusively proven but could be more significant when CPB and ischemic times are longer, such as during heart transplantation (HTx) or heart-lung transplantation (HLTx). In a 22-month period, 29 patients undergoing HTx and HLTx were randomly divided into two groups using HC (Duraflo II, n = 14, 10 HTx and 4 HLTx) or uncoated but identical circuits (NHC group, n = 15, 10 HTx and 5 HLTx). All patients received full systemic heparinization (3 mg/kg) during CPB. Plasma endotoxin, interleukin (IL)-6, IL-8, IL-10, IL-12, and cardiac troponin-I were measured before heparin administration, immediately after aortic cross-clamping, 5, 30, 60, 90, 120 minutes, and 12 and 24 hours after aortic declamping. The intensive care unit (ICU) staff and the laboratory technologists were blinded as to the use of HC circuits. No statistically significant differences between groups were found with respect to all baseline values, duration of CPB and aortic cross-clamping, graft ischemic time, doses of heparin, postoperative blood loss and transfusion, peak lactate and creatine kinase-MB isoenzyme values, duration of mechanical ventilation, or length of ICU stay. One patient in each group died during the hospital stay. Patients in the HC group needed more protamine sulfate after CPB. Although endotoxin levels were similar in the two groups, significantly lower IL-6, IL-8, and IL-10 levels were observed 1 hour after aortic declamping in the HC group. The release of cardiac troponin-I was also significantly reduced in the HC group 12 and 24 hours after reperfusion. The use of HC circuit limits both pro- and anti-inflammatory responses to CPB. It may also reduce myocardial injury after prolonged duration of CPB and ischemia.

  18. A PRELIMINARY STUDY OF THE REDUCING INTENSITY OF LUMINOUS BACTERIA

    PubMed Central

    Harvey, E. Newton

    1929-01-01

    The effect of a series of redox indicators and systems has been tested with a suspension of luminous bacteria (B. fischeri) in M/4 phosphate buffer of PH = 7.6. The indicators behave as expected from their position in the redox series, the most positive being reduced rapidly even in presence of air and before luminescence of the bacteria disappears, those of intermediate position at the time luminescence disappears, and the more negative only long after the luminescence had ceased, due to utilization of oxygen by the bacterial respiration. Indigo monosulphonate was the only indicator not reduced on long standing of a bacterial suspension. The aerobic redox potential may be placed at an RH = 18–20 and the anaerobic potential at an RH = 8–10. Ferricyanides do not affect luminescence and behave as if they could not penetrate the bacterial cell. Quinone and the napthoquinones cause progressive dimming of luminescence in any concentration which affects the light but it cannot be definitely stated that this is due to rapid oxidation of luciferin although it seems likely in the case of quinone. Some indophenols dim the luminescence at first, followed by return of brightness, which is interpreted to mean rapid oxidation of luciferin while the indophenol is unreduced, more luciferin production after reduction of indophenol. The more negative redox systems do not affect the luminescence. Investigation of indicator reduction and luminescence is being continued. PMID:19872505

  19. Admission of hematopoietic cell transplantation patients to the intensive care unit at the Pontificia Universidad Católica de Chile Hospital.

    PubMed

    Escobar, Karen; Rojas, Patricio; Ernst, Daniel; Bertin, Pablo; Nervi, Bruno; Jara, Veronica; Garcia, Maria Jose; Ocqueteau, Mauricio; Sarmiento, Mauricio; Ramirez, Pablo

    2015-01-01

    Patients undergoing hematopoietic cell transplantation (HCT) can have complications that require management in the intensive care unit (ICU). We conducted a retrospective study of patients undergoing HCT between 2007 and 2011 with admission to the ICU. We analyzed 97 patients, with an average age of 37 (range, 15 to 68). The main indications for HCT were hematologic malignancies (84%, n = 82). Ninety percent (n = 87) received myeloablative conditioning. Thirty-one percent were admitted (autologous transplant recipients 15%, allogeneic transplant recipients 34%, and umbilical cord blood [UCB] transplant recipients 48%) with an average length of stay of 19 days (range, 1 to 73 days). The average time between transplantation and transfer was 15 days. The main causes of admission were acute respiratory failure (63%) and septic shock (20%). ICU mortality was 20% for autologous transplantations and 64% for allogeneic transplantations (adult donor and UCB combined). On average, patients died 108 days after the transplantation (range, 4 to 320 days). One-year overall survival, comparing patients entering the ICU with those never admitted, was 16% versus 82% (P < .0001) for allogeneic transplantations (adult donor and UCB combined) and 80% versus 89% (P = not significant) for autologous transplantations. Acute graft-versus-host disease was significantly associated with death in ICU after UCB HCT. ICU support is satisfactory in about one half of patients admitted, characterized by a short and medium term prognosis not as unfavorable as has been previously reported.

  20. 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.

  1. Reduced sensations of intensity of breathlessness enhances maintenance of intense intermittent exercise.

    PubMed

    Tong, Tom K; Fu, Frank H; Quach, Binh; Lu, Kui

    2004-07-01

    To identify the effect of normal breathlessness sensation elicited during intense intermittent exercise at exhaustion on limitation of exercise maintenance (Ex), the contribution of the flow-resistive unloading effect of normoxic helium-oxygen breathing on the breathlessness sensation to the change in the Ex was examined. Seven men repeatedly performed 12-s exercise at 160% maximal aerobic power output followed by passive recovery for 18-s under normal (CON) and unloaded (UL) breathing conditions until exhaustion. In UL, Ex was enhanced [mean (SD) 127.2 (11.8)% CON] concomitantly with reduction in averaged peak inhaled mouth pressure (PPmi) of recorded breathing cycles that reflected approximate true inspiratory muscle force output. At the iso-time point of CON exhaustion, the reduction in PPmi to [75.7(10.2)% CON] in UL was concomitant with the reductions in the rating of perceived breathlessness (RPB) [87.5 (13.1)% CON] and in the slope of time course for RPB (RPB/2-min period) [82.1 (17.2)% CON]. It was also concomitant with increases in ventilation and total oxygen consumption. However, the augmented oxygen consumption did not result in lowering of subjects' metabolic stress that was indicated by accumulations of blood lactate and plasma ammonia and uric acid. Nevertheless, the reductions in the RPB and RPB/2-min period, which reflected the breathlessness intensity, were correlated to the CON Ex enhancement in UL (RPB r=-0.57, RPB/2-min period r=-0.83; P<0.05). These findings implied that the normal noxious breathlessness sensation elicited during intense intermittent exercise at exhaustion might contribute to the limitation of subjects' exercise maintenance.

  2. Warm HTK donor pretreatment reduces liver injury during static cold storage in experimental rat liver transplantation.

    PubMed

    Schoening, Wenzel; Ariyakhagorn, Veeravorn; Schubert, Thomas; Olschewski, Peter; Andreou, Andreas; Neuhaus, Peter; Pratschke, Johann; Puhl, Gero

    2015-12-01

    Organ shortage has led to an increased number of transplantations from extended criteria donors. These organs are more vulnerable to ischemia-reperfusion injury. Thus, improvement of organ preservation is needed. HTK is a widely used preservation solution for static cold storage in liver transplantation. The present study was to investigate the beneficial effect of warm HTK donor pretreatment on liver preservation. Male inbred Wistar rats (weighing 230-260 g) served as donors and recipients (n=6/group). Donors of treatment groups received i.v. 0.01 mL/g body weight (BW) warm (21 degree centigrade) HTK systemically 15 minutes prior to cold perfusion. Control groups received 0.01 mL/g BW warm (21 degree centigrade) NaCl 0.9%. Following pretreatment, donors were flushed with 4 degree centigrade cold HTK, livers were explanted and stored in 4 degree centigrade HTK for six hours. Thereafter orthotopic liver transplantation was performed. Recipients were harvested four hours, two and five days after reperfusion and blood and liver tissue samples were obtained. Blood samples were analyzed for AST, ALT, lactate dehydrogenase and bilirubin. Liver histological analysis as well as tissue analysis for pro-MMP2, MMP2 and pro-MMP9 using zymography was conducted. Treatment groups showed significantly lower ALT and lactate dehydrogenase levels as well as significantly lower activities of pro-MMP2, MMP2 and pro-MMP9. Histological analysis revealed only minor damage in all groups. The new concept of warm HTK pretreatment significantly reduced ischemia-reperfusion injury. The reduced ischemia-reperfusion injury was due to MMP inhibition. Warm HTK donor pretreatment is easy to handle and could further improve HTK's potency in liver preservation.

  3. The ability of winter grazing to reduce wildfire size, intensity ...

    EPA Pesticide Factsheets

    A recent study by Davies et al. sought to test whether winter grazing could reduce wildfire size, fire behavior metrics, and fire-induced plant mortality in shrub-grasslands. The authors concluded that ungrazed rangelands may experience more fire-induced mortality of native perennial bunchgrasses. The authors also presented several statements regarding the benefits of winter grazing on post-fire plant community responses. However, this commentary will show that the study by Davies et al. has underlying methodological flaws, lacks data necessary to support their conclusions, and does not provide an accurate discussion on the effect of grazing on rangeland ecosystems. Importantly, Davies et al. presented no data on the post-fire mortality of the perennial bunchgrasses or on the changes in plant community composition following their experimental fires. Rather, Davies et al. inferred these conclusions based off their observed fire behavior metrics of maximum temperature and a term described as the “heat load”. However, neither metric is appropriate for elucidating the heat flux impacts on plants. This lack of post-fire data, several methodological flaws, and the use of inadequate metrics describing heat cast doubts on the authors’ ability to support their stated conclusions. This article is a commentary highlights the scientific shortcomings in a forthcoming paper by Davies et al. in the International Journal of Wildland Fire. The study has methodological flaw

  4. The ability of winter grazing to reduce wildfire size, intensity ...

    EPA Pesticide Factsheets

    A recent study by Davies et al. sought to test whether winter grazing could reduce wildfire size, fire behavior metrics, and fire-induced plant mortality in shrub-grasslands. The authors concluded that ungrazed rangelands may experience more fire-induced mortality of native perennial bunchgrasses. The authors also presented several statements regarding the benefits of winter grazing on post-fire plant community responses. However, this commentary will show that the study by Davies et al. has underlying methodological flaws, lacks data necessary to support their conclusions, and does not provide an accurate discussion on the effect of grazing on rangeland ecosystems. Importantly, Davies et al. presented no data on the post-fire mortality of the perennial bunchgrasses or on the changes in plant community composition following their experimental fires. Rather, Davies et al. inferred these conclusions based off their observed fire behavior metrics of maximum temperature and a term described as the “heat load”. However, neither metric is appropriate for elucidating the heat flux impacts on plants. This lack of post-fire data, several methodological flaws, and the use of inadequate metrics describing heat cast doubts on the authors’ ability to support their stated conclusions. This article is a commentary highlights the scientific shortcomings in a forthcoming paper by Davies et al. in the International Journal of Wildland Fire. The study has methodological flaw

  5. Long-term results of placental blood allografting using reduced-intensity conditioning: multicenter experience in a developing country.

    PubMed

    Ruiz-Delgado, Guillermo J; Mancias-Guerra, Consuelo; Macias-Gallardo, Julio; Gonzalez-Llano, Oscar; Hernandez-Arizpe, Ana; Rodriguez-Romo, Laura Nelly; Martinez-Cabriales, Sylvia Aide; Gómez-Almaguer, David; Ruiz-Argüelles, Guillermo J

    2011-05-01

    Placental blood (PLB) hematopoietic stem cell transplantation has recently been explored in an increasing number of patients; the best conditioning regimen has not been established. In an eight-year period, 66 consecutive patients, both children and adults (40 males and 26 females), were grafted with allogeneic placental blood cells using a reduced-intensity conditioning regimen: 23 patients were grafted because of a non-malignant condition and 43 patients for a malignant disease. The median age was 7 years (range 5 months to 72 years). Median time to recover >0.5×10(9)/l granulocytes was 19 days, whereas median time to recover >20×10(9)/l platelets was 23 days. Thirty-eight individuals failed to engraft and they either recovered endogenous hematopoiesis or died. Patients have been followed for periods ranging from 0.5 to 66 months, median 9 months. The median overall post-transplant survival (OS) was 22 months and the 36-month OS was 32%; it was significantly better for individuals grafted with 6/6 matched cords (45%). The cumulative incidences of grade II-IV acute graft-versus-host disease (GVHD) and grade III-IV acute GVHD for the patients who engrafted were 33 and 10%, respectively. The low engraftment rate should be improved by selecting better cord blood units; additional studies are needed to define if non-myeloablative conditioning is preferable over conventional conditioning.

  6. Reduced Microbial Resilience after a 17-Year Climate Gradient Transplant Experiment

    NASA Astrophysics Data System (ADS)

    Bailey, V. L.; Fansler, S.; Bond-Lamberty, B. P.; Liu, C.; Smith, J. L.; Bolton, H.

    2012-12-01

    In 1994, a reciprocal soil transplant experiment was initiated between two elevations (310 m, warmer and drier, and 844 m, cooler and wetter) on Rattlesnake Mountain in southeastern Washington, USA. The original experiment sought to detect whether the microbial and biochemical dynamics developed under cool, moist conditions would be destabilized under hot, dry conditions. In March 2012 we resampled the original transplanted soils, control cores transplanted in situ, and native soils from each elevation, to study longer-term changes in microbial community composition, soil C and N dynamics, and soil physical structure. These resampled cores were randomly assigned to climate-control chambers simulating the diurnal conditions at either the lower or upper sites. We monitored respiration over 100 days, and couple these data with biogeochemical analyses conducted at time-zero, and at the end of the experiment, to examine the consequences of long-term climate change on microbial C cycling under new environmental stresses. All soil types incubated respired more C while in the simulated hotter, drier climate compared with the cooler, moister condition, except for those that had been transplanted from the lower elevation to the upper elevation in 1994, which actually respired less when returned to this, their original climate. These soils also exhibited almost no temperature sensitivity (Q10=1.07, 13-33 °C). Soils incubated in the cooler, moister chamber had greater N-acetylglucosaminidase and β-glucosidase potentials, suggesting that while loss of C as carbon dioxide respiration is reduced under these conditions, internal cycling of C may be enhanced. Ribosomal intergenic spacer analysis was used to fingerprint the bacterial community of all of these soils to identify possible high-level shifts in community composition in the 0-5, 5-10, and deeper depths in these soils. These results suggest that climate change has significantly altered the C dynamics in these soils, and

  7. Hypothermic machine preservation reduces molecular markers of ischemia/reperfusion injury in human liver transplantation.

    PubMed

    Henry, S D; Nachber, E; Tulipan, J; Stone, J; Bae, C; Reznik, L; Kato, T; Samstein, B; Emond, J C; Guarrera, J V

    2012-09-01

    Hypothermic machine perfusion (HMP) is in its infancy in clinical liver transplantation. Potential benefits include diminished preservation injury (PI) and improved graft function. Molecular data to date has been limited to extrapolation of animal studies. We analyzed liver tissue and serum collected during our Phase 1 trial of liver HMP. Grafts preserved with HMP were compared to static cold stored (SCS) transplant controls. Reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and transmission electron microscopy (TEM) were performed on liver biopsies. Expression of inflammatory cytokines, adhesion molecules and chemokines, oxidation markers, apoptosis and acute phase proteins and the levels of CD68 positive macrophages in tissue sections were evaluated. RT-PCR of reperfusion biopsy samples in the SCS group showed high expression of inflammatory cytokines, adhesion molecules and chemokines, oxidative markers and acute phase proteins. This upregulation was significantly attenuated in livers that were preserved by HMP. Immunofluorescence showed larger numbers of CD68 positive macrophages in the SCS group when compared to the HMP group. TEM samples also revealed ultrastructural damage in the SCS group that was not seen in the HMP group. HMP significantly reduced proinflammatory cytokine expression, relieving the downstream activation of adhesion molecules and migration of leukocytes, including neutrophils and macrophages when compared to SCS controls.

  8. High prevalence of cardiovascular and respiratory abnormalities in advanced, intensively treated (transplanted) myeloma: The case for 'late effects' screening and preventive strategies.

    PubMed

    Samuelson, Clare; O'Toole, Laurence; Boland, Elaine; Greenfield, Diana; Ezaydi, Yousef; Ahmedzai, Sam H; Snowden, John A

    2016-06-01

    Modern management of myeloma has significantly improved survival, with increasing numbers of patients living beyond a decade. However, little is known about the long-term cardiovascular and respiratory status of intensively treated and multiply relapsed survivors. We performed detailed cardiovascular and respiratory evaluations in patients with intensively treated, advanced but stable myeloma. All patients had received at least two lines of treatment, including at least one haematopoietic stem cell transplantation procedure, but had stable, controlled disease and were off active treatment at the time of evaluation. Thirty-two patients with a median duration of 6 years (range 2-12) from original diagnosis of myeloma and three lines (range 2-6) of treatment were evaluated. Despite normal physical examination in the majority, there was a high prevalence of sub-clinical cardiac and respiratory dysfunction, reflected by abnormalities of electrocardiography (45%), echocardiography (50%), serum N-terminal pro-B-type natriuretic peptide level (NT-pro-BNP, 50%), and pulmonary function testing (45%). NT-pro-BNP level correlated negatively with quality of life (P = 0.012) and positively with serum ferritin (P = 0.027). Dyspnoea score correlated with BMI (P = 0.001). Risk factors for cardiovascular disease (obesity, hypertension, hyperlipidaemia, and hyperinsulinaemia) were common. Even in the absence of overt clinical features, the majority of intensively treated long-term survivors of myeloma have established cardiovascular and/or respiratory dysfunction, above levels expected in the general population of a similar age. This study supports routine screening and lifestyle modification combined with primary and secondary preventive strategies to reduce cardiovascular and respiratory disease and to preserve quality of life in transplanted myeloma patients.

  9. High prevalence of cardiovascular and respiratory abnormalities in advanced, intensively treated (transplanted) myeloma: The case for ‘late effects’ screening and preventive strategies

    PubMed Central

    Samuelson, Clare; O'Toole, Laurence; Boland, Elaine; Greenfield, Diana; Ezaydi, Yousef; Ahmedzai, Sam H.; Snowden, John A.

    2016-01-01

    Objectives: Modern management of myeloma has significantly improved survival, with increasing numbers of patients living beyond a decade. However, little is known about the long-term cardiovascular and respiratory status of intensively treated and multiply relapsed survivors. Methods: We performed detailed cardiovascular and respiratory evaluations in patients with intensively treated, advanced but stable myeloma. All patients had received at least two lines of treatment, including at least one haematopoietic stem cell transplantation procedure, but had stable, controlled disease and were off active treatment at the time of evaluation. Results: Thirty-two patients with a median duration of 6 years (range 2–12) from original diagnosis of myeloma and three lines (range 2–6) of treatment were evaluated. Despite normal physical examination in the majority, there was a high prevalence of sub-clinical cardiac and respiratory dysfunction, reflected by abnormalities of electrocardiography (45%), echocardiography (50%), serum N-terminal pro-B-type natriuretic peptide level (NT-pro-BNP, 50%), and pulmonary function testing (45%). NT-pro-BNP level correlated negatively with quality of life (P = 0.012) and positively with serum ferritin (P = 0.027). Dyspnoea score correlated with BMI (P = 0.001). Risk factors for cardiovascular disease (obesity, hypertension, hyperlipidaemia, and hyperinsulinaemia) were common. Discussion: Even in the absence of overt clinical features, the majority of intensively treated long-term survivors of myeloma have established cardiovascular and/or respiratory dysfunction, above levels expected in the general population of a similar age. Conclusion: This study supports routine screening and lifestyle modification combined with primary and secondary preventive strategies to reduce cardiovascular and respiratory disease and to preserve quality of life in transplanted myeloma patients. PMID:27077780

  10. Reduced incidence of interstitial pneumonitis after allogeneic hematopoietic stem cell transplantation using a modified technique of total body irradiation

    PubMed Central

    Chiang, Yun; Tsai, Cheng-Hong; Kuo, Sung-Hsin; Liu, Chieh-Yu; Yao, Ming; Li, Chi-Cheng; Huang, Shang-Yi; Ko, Bor-Sheng; Lin, Chien-Ting; Hou, Hsin-An; Chou, Wen-Chien; Liu, Jia-Hau; Lin, Chien-Chin; Wu, Shang-Ju; Hsu, Szu-Chun; Chen, Yao-Chang; Lin, Kai-Hsin; Lin, Dong-Tsamn; Chou, Hsien-Tang; Lu, Meng-Yu; Yang, Yung-Li; Chang, Hsiu-Hao; Liu, Ming-Chih; Liao, Xiu-Wen; Wu, Jian-Kuen; Chou, Sheng-Chieh; Cheng, Chieh-Lung; Chen, Chien-Yuan; Tsay, Woei; Tien, Hwei-Fang; Tang, Jih-Luh; Chen, Yu-Hsuan

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. However, interstitial pneumonitis (IP) and other toxicities remain major concerns after total body irradiation (TBI). We have proposed using linear accelerators with rice-bag compensators for intensity modulation (IM-TBI), as an alternative to the traditional cobalt-60 teletherapy with lung-shielding technique (Co-TBI). Patients who received a TBI-based myeloablative conditioning regimen between 1995 and 2014 were recruited consecutively. Before March 2007, TBI was delivered using Co-TBI (n = 181); afterward, TBI was administered using IM-TBI (n = 126). Forty-four patients developed IP; of these cases, 19 were idiopathic. The IP-related mortality rate was 50% in the total IP cohort and 63% in the idiopathic subgroup. The 1-year cumulative incidences of IP and idiopathic IP were 16.5% and 7.4%, respectively; both rates were significantly higher in the Co-TBI group than in the IM-TBI group. Multivariate analysis revealed that Co-TBI was an independent prognostic factor for both total and idiopathic IP. In the acute myeloid leukemia subgroup, patients with different TBI techniques had similar outcomes for both overall and relapse-free survival. In conclusion, IM-TBI is an easy and effective TBI technique that could substantially reduce the complication rate of IP without compromising treatment efficacy. PMID:27830767

  11. Intensity of MRI gadolinium enhancement in cerebral adrenoleukodystrophy: a biomarker for inflammation and predictor of outcome following transplant in higher-risk patients

    PubMed Central

    Miller, Weston P.; Mantovani, Luiz F.; Muzic, John; Rykken, Jeffrey B.; Gawande, Rakhee S.; Lund, Troy C.; Shanley, Ryan M.; Raymond, Gerald V.; Orchard, Paul J.; Nascene, David R.

    2016-01-01

    BACKGROUND AND PURPOSE Outcomes following hematopoietic stem cell transplantation for higher-risk childhood-onset cerebral adrenoleukodystrophy are variable. We explored whether a brain MRI gadolinium intensity scoring system improves prediction of neurologic outcome. METHODS A four-point scale of gadolinium intensity relative to the choroid plexus was developed: 0 = no enhancement; 1 = hypo-intense; 2 = iso-intense; 3 = hyper-intense. The scale’s inter-observer concordance was assessed on 30 randomly chosen studies. Scores were generated for 64 evaluable patients and compared with cerebrospinal fluid chitotriosidase levels, a known inflammatory marker correlating with outcomes following transplant. For 25 evaluable higher-risk patients (Loes ≥ 10), the gadolinium intensity score was compared with longer-term post-transplant clinical change. RESULTS The gadolinium intensity scoring system showed good inter-observer reproducibility (kappa = 0.72). Of 64 evaluable boys, the score positively correlated with average concomitant cerebrospinal fluid chitotriosidase activity in ng/mL/hr: (0), 2,717, n=5; (1), 3,218, n=13; (2), 6,497, n=23; and (3), 12,030, n=23 (p < 0.01). For 25 evaluable higher-risk patients, more intense pre-transplant brain MRI gadolinium enhancement predicted greater average loss on the adrenoleukodystrophy neurologic function scale following transplant: (0/1), ΔNFS = 4.3, n = 7; (2/3), ΔNFS = 10.4, n = 18 (p = 0.05). CONCLUSION Gadolinium enhancement intensity on brain MRI can be scored simply and reproducibly for cerebral adrenoleukodystrophy. Enhancement score significantly correlates with chitotriosidase. In boys with higher-risk cerebral disease (Loes ≥ 10), enhancement score itself predicts neurologic outcome following treatment. Such data may help to guide treatment decisions for clinicians and families. PMID:26427835

  12. Reticulated platelets: a reliable measure to reduce prophylactic platelet transfusions after intensive chemotherapy.

    PubMed

    Chaoui, Driss; Chakroun, Tahar; Robert, Françoise; Rio, Bernard; Belhocine, Ramdane; Legrand, Ollivier; Salanoubat, Celia; Lecrubier, Chantal; Casadevall, Nicole; Marie, Jean-Pierre; Elalamy, Ismail

    2005-05-01

    Reticulated platelets (RPs) are the youngest circulating platelets (PLTs). The aim of our study was to predict PLT recovery with RP percentage (RP%) and therefore to identify PLT transfusions that could be avoided after autologous peripheral blood progenitor cell (PBPC) transplantation. With a whole-blood dual-labeling flow cytometric method, RP% was prospectively assessed in 47 patients who received myeloablative chemotherapy followed by autologous PBPC transplantation. Retrospective analysis of RP evolution identified three time points: nadir of the RP% (NRP), imminent PLT recovery (IPR) corresponding to an RP% of greater than 7 percent, and PLT transfusion autonomy (PTA). Median occurrences of NRP, IPR, and PTA were on Days +5, +8, and +12 after transplantation, respectively. The RP% value at NRP (4%) was significantly lower compared to the IPR (15%) and PTA (14%). Thirty patients (64%) achieved PTA within 4 days after IPR. On Day +8, if RP% was greater than 7 percent, positive and negative predictive values for PTA within 4 days, specificity, and sensitivity were 79, 63, 66, and 76 percent, respectively. Fever between IPR and PTA was the only factor found to negatively influence PLT recovery (p = 0.02). All patients required at least one PLT transfusion. Among patients with rapid PLT recovery (IPR-PTA interval < 4 days; n = 30), half of them received one PLT transfusion after RP increase, which could be avoided. These encouraging results may allow us to reduce the prophylactic PLT transfusion according to patients RP% increase.

  13. Elafin, a serine elastase inhibitor, attenuates post-cardiac transplant coronary arteriopathy and reduces myocardial necrosis in rabbits afer heterotopic cardiac transplantation.

    PubMed Central

    Cowan, B; Baron, O; Crack, J; Coulber, C; Wilson, G J; Rabinovitch, M

    1996-01-01

    We have related experimentally induced post-cardiac transplant coronary arteriopathy to increased elastolytic activity, IL-1beta, fibronectin-mediated inflammatory and smooth muscle cell (SMC) migration, and SMC proliferation. Since our in vitro studies show that a serine elastase releases SMC mitogens and facilitates IL-lbeta induction of fibronectin, we hypothesized that administration in vivo of the specific serine elastase inhibitor, elafin, would decrease the post-cardiac transplant coronary arteriopathy. Cholesterol-fed rabbits underwent a heterotopic cardiac transplant without immunosuppression and received elafin (1.79 mg/kg per d continuous infusion after a 9 mg bolus, n = 6) or vehicle (n = 6). 1 wk later, hearts were harvested for morphometric, immunohistochemical, and biochemical analyses. A > 70% decrease in the total number of coronary arteries with intimal thickening in elafin-treated compared to control donor hearts (P < 0.002) was associated with reduced vascular elastolytic activity judged by fewer breaks in the internal elastic lamina (P < 0.03), less accumulation of immunoreactive fibronectin (P < 0.02), and reduced cell proliferation quantified by proliferating cell nuclear antigen (P < 0.0001). Despite myocardial lymphocytic infiltration, wet weight of elafin-treated donor hearts was reduced by 50% compared to untreated controls (P < 0.002) and associated with relative preservation of myocyte integrity, instead of extensive myocardial necrosis (P < 0.004). This protective effect correlated with decreased myocardial elastolytic activity (P < 0.0001) and inflammatory cell proliferation (P < 0.0001) and with an elafin-inhibitable elastase in lymphocytes. Serine elastase activity thus appears an important therapeutic target for post-cardiac transplant coronary arteriopathy and myocardial necrosis induced by rejection. PMID:8647937

  14. Reducing liver transplant length of stay: a Lean Six Sigma approach.

    PubMed

    Toledo, Alexander H; Carroll, Tracy; Arnold, Emily; Tulu, Zeynep; Caffey, Tom; Kearns, Lauren E; Gerber, David A

    2013-12-01

    Organ transplant centers are under increasing scrutiny to maintain outcomes while controlling cost in a challenging population of patients. Throughout health care and transplant specifically, length of stay is used as a benchmark for both quality and resource utilization. To decrease our length of stay for liver transplant by using Lean Six Sigma methods. The Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) method was used to systematically analyze our process from transplant listing to hospital discharge after transplant, identifying many factors affecting length of stay. Adult, single-organ, primary liver transplant recipients between July 2008 and June 2012 were included in the study. Recipients with living donors or fulminant liver failure were excluded. Multiple interventions, including a clinical pathway and enhanced communication, were implemented. Length of stay after liver transplant and readmission after liver transplant.R ESULTS: Median length of stay decreased significantly from 11 days before the intervention to 8 days after the intervention. Readmission rate did not change throughout the study. The improved length of stay was maintained for 24 months after the study. Using a Lean Six Sigma approach, we were able to significantly decrease the length of stay of liver transplant patients. These results brought our center's outcomes in accordance with our goal and industry benchmark of 8 days. Clear expectations, improved teamwork, and a multidisciplinary clinical pathway were key elements in achieving and maintaining these gains.

  15. Postoperative delirium is associated with increased intensive care unit and hospital length of stays after liver transplantation.

    PubMed

    Bhattacharya, Bishwajit; Maung, Adrian; Barre, Kimberly; Maerz, Linda; Rodriguez-Davalos, Manuel I; Schilsky, Michael; Mulligan, David C; Davis, Kimberly A

    2017-01-01

    Delirium is increasingly recognized as a common and important postoperative complication that significantly hinders surgical recovery. However, there is a paucity of data examining the incidence and impact of delirium after liver transplantation. Retrospective case series in a tertiary care center examining all (n = 144) adult patients who underwent liver transplantation during a 6-y period. Delirium occurred in 25% of the patients with an average duration of 4.56 d. Patients who developed delirium were older (P = 0.007), had higher preoperative model for end-stage liver disease score (P = 0.019) and longer pretransplant hospital length of stay (LOS; P = 0.003). Patients with delirium were also more likely to have alcohol ingestion as an etiology of the liver failure (P = 0.033). Delirious patients had a trend toward increased ventilator days (P = 0.235) and significantly longer postoperative hospital (P = 0.001) and intensive care unit LOS (P = 0.001). Delirium was also associated with an increased frequency of hospital acquired infections including urinary tract infections (P = 0.005) and pneumonias (P = 0.001). Delirium is a common occurrence among liver transplant patients associated with increased complications and LOSs. Further prospective studies are needed to determine the specific risk factors in this complex population and to determine if delirium has an impact on long-term outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Risk Factors for Mortality in 272 Patients With Lung Transplant: A Multicenter Analysis of 7 Intensive Care Units.

    PubMed

    Rello, Jordi; Bello, Irene; de Vicente, Rosario; Hermira Anchuelo, Ana; Ballesteros, Maria Ángeles; Iranzo, Reyes; Rellán, Luzdivina; Riera, Jordi; Robles, Juan Carlos

    2017-08-01

    One-year survival in lung transplant is around 85%, but this figure has not increased in recent years, in spite of technical improvements. Retrospective, multicenter cohort study. Data from 272 eligible adults with lung transplant were recorded at 7 intensive care units (ICU) in Spain in 2013. The objective was to identify variables that might help to guide future clinical interventions in order to reducethe risk of death in the postoperative period. One patient (0.3%) died in the operating room and 27 (10%) within 90 days. Twenty (7.4%) died within 28 days, after a median of 14 ICU days. Grade 3 pulmonary graft dysfunction was documented in 108 patients, of whom 21 died, compared with 6 out of 163 without pulmonary graft dysfunction (P<.001). At ICU admission, non-survivors had significantly lower (P=.03) median PaO2/FiO2 (200mmHg vs 280mmHg), and the difference increased after 24hours (178 vs 297mmHg, P<.001). Thirteen required extracorporeal membrane oxygenation, and 7(53.8%) died. A logistic regression model identified pulmonary graft dysfunction (OR: 6.77), donor age>60yr (OR: 2.91) and SOFA>8 (OR: 2.53) as independent predictors of 90-day mortality. At ICU admission, higher median procalcitonin (1.6 vs 0.6) and lower median PaO2/FiO2 (200 vs 280mmHg) were significantly associated with mortality. Graft dysfunction remains a significant problem in lung transplant. Early ICU interventions in patients with severe hypoxemia or high procalcitonin are crucial in order to lower mortality. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final results of the CSTIBES02 trial.

    PubMed

    Ribera, Josep-Maria; Oriol, Albert; González, Marcos; Vidriales, Belén; Brunet, Salut; Esteve, Jordi; Del Potro, Eloy; Rivas, Concepción; Moreno, Maria-José; Tormo, Mar; Martín-Reina, Victoria; Sarrá, Josep; Parody, Ricardo; de Oteyza, Jaime Pérez; Bureo, Encarna; Bernal, Maria-Teresa

    2010-01-01

    Imatinib, given concurrently or alternating with chemotherapy, has improved the response and survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) but relapses are still frequent. The aim of this study was to evaluate the feasibility and results of giving imatinib concurrently with intensive chemotherapy, stem cell transplantation and post-transplant imatinib maintenance therapy in patients with newly diagnosed Ph(+) ALL. This was a phase II study of patients with newly diagnosed Ph(+) ALL given standard chemotherapy, together with imatinib (400 mg/day) until stem cell transplantation, followed by imatinib maintenance therapy for all patients regardless of the molecular status of the disease. Of the 30 patients included, 27 (90%) achieved complete remission, one was resistant to treatment and two died during induction therapy. The percentages of major and complete molecular responses were 86% and 21% after induction, and 81% and 65% after consolidation, respectively. Similar results were observed assessing minimal residual disease by flow cytometry. Of the 27 patients who achieved complete remission, 21 underwent stem cell transplantation (16 allogeneic, 5 autologous). Imatinib (400 mg/day) could be administered after transplantation for a median of 3.9 months in 12 patients, although it was interrupted in 10 patients (in 2 cases because of side effects of the drug). Nine patients relapsed, four before and five after stem cell transplantation and eight patients died of transplant-related causes. With a median follow-up of 4.1 years, the probabilities (95% CI) of disease-free and overall survival were 30% (15% to 45%) and 30% (16% to 45%), respectively. These results confirm that imatinib is an effective first-line treatment for adult Ph(+) ALL when given concurrently with chemotherapy, making stem cell transplantation feasible in a high proportion of patients. However, post-transplantation imatinib administration was

  18. Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final results of the CSTIBES02 trial

    PubMed Central

    Ribera, Josep-Maria; Oriol, Albert; González, Marcos; Vidriales, Belén; Brunet, Salut; Esteve, Jordi; del Potro, Eloy; Rivas, Concepción; Moreno, Maria-José; Tormo, Mar; Martín-Reina, Victoria; Sarrá, Josep; Parody, Ricardo; de Oteyza, Jaime Pérez; Bureo, Encarna; Bernal, Maria-Teresa

    2010-01-01

    Background Imatinib, given concurrently or alternating with chemotherapy, has improved the response and survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) but relapses are still frequent. The aim of this study was to evaluate the feasibility and results of giving imatinib concurrently with intensive chemotherapy, stem cell transplantation and post-transplant imatinib maintenance therapy in patients with newly diagnosed Ph+ ALL. Design and Methods This was a phase II study of patients with newly diagnosed Ph+ ALL given standard chemotherapy, together with imatinib (400 mg/day) until stem cell transplantation, followed by imatinib maintenance therapy for all patients regardless of the molecular status of the disease. Results Of the 30 patients included, 27 (90%) achieved complete remission, one was resistant to treatment and two died during induction therapy. The percentages of major and complete molecular responses were 86% and 21% after induction, and 81% and 65% after consolidation, respectively. Similar results were observed assessing minimal residual disease by flow cytometry. Of the 27 patients who achieved complete remission, 21 underwent stem cell transplantation (16 allogeneic, 5 autologous). Imatinib (400 mg/day) could be administered after transplantation for a median of 3.9 months in 12 patients, although it was interrupted in 10 patients (in 2 cases because of side effects of the drug). Nine patients relapsed, four before and five after stem cell transplantation and eight patients died of transplant-related causes. With a median follow-up of 4.1 years, the probabilities (95% CI) of disease-free and overall survival were 30% (15% to 45%) and 30% (16% to 45%), respectively. Conclusions These results confirm that imatinib is an effective first-line treatment for adult Ph+ ALL when given concurrently with chemotherapy, making stem cell transplantation feasible in a high proportion of patients. However, post-transplantation

  19. Point-of-care haemostasis monitoring during liver transplantation reduces transfusion requirements and improves patient outcome.

    PubMed

    Leon-Justel, Antonio; Noval-Padillo, Jose A; Alvarez-Rios, Ana I; Mellado, Patricia; Gomez-Bravo, Miguel A; Álamo, Jose M; Porras, Manuel; Barrero, Lydia; Hinojosa, Rafael; Carmona, Magdalena; Vilches-Arenas, Angel; Guerrero, Juan M

    2015-06-15

    Optimal haemostasis management can improve patient outcomes and reduce blood loss and transfusion volume in orthotopic-liver-transplant (OLT). We performed a prospective study including 200 consecutive OLTs. The first 100 patients were treated according to the clinic's standards and the next 100 patients were treated using the new point-of-care (POC)-based haemostasis management strategy. Transfusion parameters and other outcomes were compared between groups. Transfusion requirements were reduced in the POC group. The median and IQR of red-blood-cells (RBC) transfusion units were reduced from 5 [2-8] to 3 [0-5] (p < 0.001), plasma from 2 [0-4] to 0 (p < 0.001), and platelets from 1 [0-4] to 0 [0-1] (p < 0.001), into the POC group only four patients received tranexamic acid and fibrinogen transfusion rate was 1.13 ± 1.44 g (p = 0.001). We also improved the incidence of transfusion avoidance, 5% vs. 24% (p < 0.001) and reduced the incidence of massive transfusion (defined as the transfusion of more than 10 RBC units), 13% vs. 2% (p = 0.005). We also observed a relationship between RBC transfusion requirements and preoperative haemoglobin, and between platelet transfusion and preoperative fibrinogen levels. The incidence of postoperative complications, such as, reoperation for bleeding, acute-kidney-failure or haemodynamic instability was significantly lower (13.0% vs. 5%, p = 0.048, 17% vs. 2%, p < 0.001, and 29% vs. 16%, p = 0.028). Overall, blood product transfusion was associated with increased risk of postoperative complications. A haemostatic therapy algorithm based on POC monitoring reduced transfusion and improved outcome in OLT. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Outcome of Recipients of Hematopoietic Stem Cell Transplants Who Require Intensive Care Unit Support: A Single Institution Experience.

    PubMed

    Galindo-Becerra, Samantha; Labastida-Mercado, Nancy; Rosales-Padrón, Jaime; García-Chavez, Jessica; Soto-Vega, Elena; Rivadeneyra-Espinoza, Liliana; León-Peña, Andres A; Fernández-Lara, Danitza; Dominguez-Cid, Monica; Anthon-Méndez, Javier; Arizpe-Bravo, Daniel; Ruiz-Delgado, Guillermo J; Ruiz-Argüelles, Guillermo J

    2015-01-01

    Admission to the intensive care unit (ICU) of a patient who has been grafted with hematopoietic stem cells is a serious event, but the role of the ICU in this setting remains controversial. Data were analyzed from patients who underwent autologous or allogeneic bone marrow transplantation at the Centro de Hematología y Medicina Interna de Puebla, México, between May 1993 and October 2014. In total, 339 patients were grafted: 150 autografts and 189 allografts; 68 of the grafted patients (20%) were admitted to the ICU after transplantation: 27% of the allografted and 11% of the autografted patients (p = 0.2). Two of 17 autografted patients (12%) and 5 of 51 allografted patients (10%) survived. All patients who required insertion of an endotracheal tube died, whereas 7 of 11 patients without invasive mechanical ventilation survived (p = 0.001). Only 10% of the grafted patients survived their stay in the ICU; this figure is lower than those reported from other centers and may reflect several facts, varying from the quality of the ICU support to ICU admission criteria to the initial management of all the grafts in an outpatient setting, which could somehow delay the arrival of patients to the hospital.

  1. Postoperative complications in the intensive care unit following lung transplantation in adults: results in University Hospital Reina Sofia.

    PubMed

    Arango Tomás, E; Quero Ríos, M I; Robles Arista, J C; Algar Algar, F J; Wolf, J I; Alvarez Kindelan, A; Cerezo Madueño, F; Baamonde Laborda, C; Guerrero Pabon, R; Salvatierra Velazquez, A

    2012-11-01

    The postoperative period following lung transplantation remains critical because of several complications. Infection, primary graft failure, acute rejection, and surgical complications are risk factors for mortality and morbidity. The recognition and early treatment of these complications is important to optimize outcomes. This article provides an overview of postoperative complications observed in our center during the last year. We were particularly interested in the influence of variables, such as inotrope usage and Acute Physiology and Chronic Health Evaluation (APACHE II) score, a well-known, and validated mortality prediction model for general intensive care unit (ICU) patients only infrequently reported in the transplantation literature. High APACHE II scores were significantly associated with prolonged mechanical ventilation (P = 0.041) and a tracheostomy requirement (P = .035). The factors significantly associated with an early postoperative death were older donor age (P = .005), prolonged donor ICU period (P = .004), need for cardiopulmonary bypass (CB; P = .005), and high inotrope requirements in the ICU (P = .034). CB data were biased because we selected the worst case patients. Donor age and high inotrope requirements in the ICU have been reported previously to be prognostic factors for poor graft function. We believe that control of these variables may improve outcomes. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Early postoperative care of liver transplantation for infants with biliary atresia during pediatric intensive care unit stay.

    PubMed

    Guo, C-B; Li, Y-C; Zhang, M-M; Yan, L-N; Pu, C-L; Kang, Q; Jin, X-Q

    2010-06-01

    The aim of this study was to present our institutional experience with the pediatric intensive care unit (PICU) stays of liver recipients to understand prevention of complications. This retrospective review included 22 infants who weighed 8.8 kg or less and underwent 23 transplantations. No grafts were from executed prisoners. We summarized the diagnosis, evaluation, medicine usage, and therapeutic intervention associated with subjects experiencing complications of rejection episodes, surgery, or infection during their ICU stay. There was one perioperative death from primary graft nonfunction. The most common postoperative complications were infections, gastrointestinal bleeding, and vascular complications. Rejection episodes occurred among 25% of patients. The most common isolated pathogenic bacteria was Staphylococcus epidermidis. Median initial ICU stay was 10 days. Mean requirement for artificial ventilation was 37.6 hour. Mean times of use of dobutamine, prostaglandin E1, and dopamine was 3.3, 7.5, and 8.8 days, respectively. Parenteral nutrition was started at a mean of 12 hours and oral food intake at a mean of 72 hours. Although challenging, orthotopic liver transplantation (OLT) in small infants can be successfully performed with meticulous surgical technique and keen postoperative surveillance.

  3. Umbilical cord blood transplantation.

    PubMed

    Koo, Hong Hoe; Ahn, Hyo Seop

    2012-07-01

    Since the first umbilical cord blood transplantation (CBT) in 1998, cord blood (CB) has now become one of the most commonly used sources of hematopoietic stem cells for transplantation. CBT has advantages of easy procurement, no risk to donor, low risk of transmitting infections, immediate availability and immune tolerance allowing successful transplantation despite human leukocyte antigen disparity. Several studies have shown that the number of cells transplanted is the most important factor for engraftment in CBT, and it limits the wide use of CB in adult patients. New strategies for facilitating engraftment and reducing transplantation-related mortality are ongoing in the field of CBT and include the use of a reduced-intensity conditioning regimen, double-unit CBT, ex vivo expansion of CB, and co-transplantation of CB and mesenchymal stem cells. Recently, the results of two international studies with large sample sizes showed that CB is an acceptable alternative source of hematopoietic stem cells for adult recipients who lack human leukocyte antigen-matched adult donors. Along with the intensive researches, development in banking process of CB will amplify the use of CB and offer the chance for cure in more patients.

  4. Alpha-1-antitrypsin monotherapy reduces graft-versus-host disease after experimental allogeneic bone marrow transplantation

    PubMed Central

    Tawara, Isao; Sun, Yaping; Lewis, Eli C.; Toubai, Tomomi; Evers, Rebecca; Nieves, Evelyn; Azam, Tania; Dinarello, Charles A.; Reddy, Pavan

    2012-01-01

    Acute graft-versus-host disease (GvHD) is a major complication that prevents successful outcomes after allogeneic bone marrow transplantation (BMT), an effective therapy for hematological malignancies. Several studies demonstrate that donor T cells and host antigen-presenting cells along with several proinflammatory cytokines are required for the induction of GvHD and contribute to its severity. Increasing evidence demonstrates that human serum-derived αalpha-1- anti-trypsin (AAT) reduces production of proinflammatory cytokines, induces anti-inflammatory cytokines, and interferes with maturation of dendritic cells. Using well-characterized mouse models of BMT, we have studied the effects of AAT on GvHD severity. Administration of AAT early after BMT decreased mortality in three models of GvHD and reduced serum levels of proinflammatory cytokines in the allogeneic recipients compared with vehicle (albumin) treated animals. AAT treatment reduced the expansion of alloreactive T effector cells but enhanced the recovery of T regulatory T cells, (Tregs) thus altering the ratio of donor T effector to T regulatory cells in favor of reducing the pathological process. However, despite altering the ratio in vivo, AAT had no direct effects on either the donor T effector cells or T regulatory cells Tregs in vitro. In contrast, AAT suppressed LPS-induced in vitro secretion of proinflammatory cytokines such as TNF-α and IL-1β, enhanced the production of the anti-inflammatory cytokine IL-10, and impaired NF-κB translocation in the host dendritic cells. In light of its long history of safety in humans, these findings suggest that administration of AAT represents a novel unique and viable strategy to mitigate clinical GvHD. PMID:22203983

  5. Delayed olfactory ensheathing cell transplants reduce nociception after dorsal root injury.

    PubMed

    Wu, Ann; Lauschke, Jenny L; Gorrie, Catherine A; Cameron, Nicholas; Hayward, Ian; Mackay-Sim, Alan; Waite, Phil M E

    2011-05-01

    Injury to cervical dorsal roots mimics the deafferentation component of brachial plexus injury in humans, with intractable neuropathic pain in the deafferented limb being a common consequence. Such lesions are generally not amenable to surgical repair. The use of olfactory ensheathing cells (OECs) for dorsal root repair, via acute transplantation, has been successful in several studies. From a clinical point of view, delayed transplantation of OECs would provide a more realistic timeframe for repair. In this study we investigated the effect of delayed OEC transplantation on functional recovery of skilled forepaw movements and amelioration of neuropathic pain, using a C7 and C8 dorsal root injury rat model previously established in our lab. We found that OEC transplantation to the dorsal horn 1 week after root injury effectively attenuated neuropathic disturbances associated with dorsal root injury, including spontaneous pain behavior, tactile allodynia and thermal hyperalgesia. The sensory controls of complex, goal-oriented skilled reaching and ladder walking, however, were not improved by delayed OEC transplantation. We did not detect any significant influence of transplanted OECs on injury-induced central reorganisation and afferent sprouting. The anti-nociceptive effect mediated by OEC transplants may therefore be explained by alternative mechanisms such as modification of inflammation and astrogliosis. The significant effect of OEC transplants in mitigating neuropathic pain may be clinically useful in intractable pain syndromes arising from deafferentation. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.

  6. Altering Transplantation Time to Avoid Periods of High Temperature Can Efficiently Reduce Bacterial Wilt Disease Incidence with Tomato

    PubMed Central

    Wei, Zhong; Huang, Jian-Feng; Hu, Jie; Gu, Yi-An; Yang, Chun-Lan; Mei, Xin-Lan; Shen, Qi-Rong; Xu, Yang-Chun; Friman, Ville-Petri

    2015-01-01

    Tomato bacterial wilt caused by Ralstonia solanacearum bacterium is a severe problem in Southern China, where relatively high environmental temperatures commonly prevails during the crop seasons. Previous research has indicated that bacterial wilt disease incidence generally increases during the warm months of summer leading to reduced tomato yield. Moreover, the efficacy of bio-organic fertilizers (BOFs)–organic compost fortified with pathogen-suppressive bacteria—is often lost during the periods of high environmental temperatures. Here we studied if the disease incidence could be reduced and the BOF performance enhanced by simply preponing and postponing the traditional seedling transplantation times to avoid tomato plant development during periods of high environmental temperature. To this end, a continuous, two-year field experiment was conducted to evaluate the performance of BOF in two traditional (late-spring [LS] and early-autumn [EA]) and two alternative (early-spring [ES] and late-autumn [LA]) crop seasons. We found that changing the transplantation times reduced the mean disease incidence from 33.9% (LS) and 54.7% (EA) to 11.1% (ES) and 7.1% (LA), respectively. Reduction in disease incidence correlated with the reduction in R. Solanacearum pathogen density in the tomato plant rhizosphere and stem base. Applying BOF during alternative transplantation treatments improved biocontrol efficiency from 43.4% (LS) and 3.1% (EA) to 67.4% (ES) and 64.8% (LA). On average, the mean maximum air temperatures were positively correlated with the disease incidence, and negatively correlated with the BOF biocontrol efficacy over the crop seasons. Crucially, even though preponing the transplantation time reduced the tomato yield in general, it was still economically more profitable compared to LS season due to reduced crop losses and relatively higher market prices. Preponing and postponing traditional tomato transplantation times to cooler periods could thus offer

  7. Altering Transplantation Time to Avoid Periods of High Temperature Can Efficiently Reduce Bacterial Wilt Disease Incidence with Tomato.

    PubMed

    Wei, Zhong; Huang, Jian-Feng; Hu, Jie; Gu, Yi-An; Yang, Chun-Lan; Mei, Xin-Lan; Shen, Qi-Rong; Xu, Yang-Chun; Friman, Ville-Petri

    2015-01-01

    Tomato bacterial wilt caused by Ralstonia solanacearum bacterium is a severe problem in Southern China, where relatively high environmental temperatures commonly prevails during the crop seasons. Previous research has indicated that bacterial wilt disease incidence generally increases during the warm months of summer leading to reduced tomato yield. Moreover, the efficacy of bio-organic fertilizers (BOFs)-organic compost fortified with pathogen-suppressive bacteria-is often lost during the periods of high environmental temperatures. Here we studied if the disease incidence could be reduced and the BOF performance enhanced by simply preponing and postponing the traditional seedling transplantation times to avoid tomato plant development during periods of high environmental temperature. To this end, a continuous, two-year field experiment was conducted to evaluate the performance of BOF in two traditional (late-spring [LS] and early-autumn [EA]) and two alternative (early-spring [ES] and late-autumn [LA]) crop seasons. We found that changing the transplantation times reduced the mean disease incidence from 33.9% (LS) and 54.7% (EA) to 11.1% (ES) and 7.1% (LA), respectively. Reduction in disease incidence correlated with the reduction in R. Solanacearum pathogen density in the tomato plant rhizosphere and stem base. Applying BOF during alternative transplantation treatments improved biocontrol efficiency from 43.4% (LS) and 3.1% (EA) to 67.4% (ES) and 64.8% (LA). On average, the mean maximum air temperatures were positively correlated with the disease incidence, and negatively correlated with the BOF biocontrol efficacy over the crop seasons. Crucially, even though preponing the transplantation time reduced the tomato yield in general, it was still economically more profitable compared to LS season due to reduced crop losses and relatively higher market prices. Preponing and postponing traditional tomato transplantation times to cooler periods could thus offer simple

  8. 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.

  9. [Respiratory failure in cystic fibrosis: management in pediatric intensive care unit, lung transplantation recommendation].

    PubMed

    Pelluau, S; Oualha, M; Souilamas, R; Hubert, P H

    2012-05-01

    Admission to the ICU for respiratory failure of a child with cystic fibrosis is a telltale sign of the severity of the disease. Bronchopulmonary exacerbation, pneumothorax and hemoptysis are the primary causes, for which respiratory assistance is indispensable in these life-threatening situations. Non-invasive ventilation (NIV) has enabled significant progress in improving patient survival. The modalities of NIV must be tailored to both the patient and the cause of respiratory failure. Invasive ventilation, on the other hand, should be a treatment of last resort, because often associated with high mortality. It must be adapted to the therapeutic strategy involving an impending transplantation, including in critical situations where placement on a high emergency list is a possibility. Since admission to ICU is at times the reflection of the terminal evolution of the disease, ongoing treatment must hence be adapted to the comfort of the child.

  10. Non-melanoma skin cancer is reduced after switch of immunosuppression to mTOR-inhibitors in organ transplant recipients.

    PubMed

    Alter, Mareike; Satzger, Imke; Schrem, Harald; Kaltenborn, Alexander; Kapp, Alexander; Gutzmer, Ralf

    2014-06-01

    Organ transplant recipients are prone to the development of non-melanoma skin cancer. Organ transplant recipients often develop multiple non-melanoma skin cancers and the tumors show an aggressive growth pattern, therefore surgical therapy can be difficult. Switch of the immunosuppressive regimen to mTOR-inhibitors such as everolimus or sirolimus can have an antitumor effect. In a monocentric retrospective study we evaluated organ transplant recipients who presented with non-melanoma skin cancer in the years 2008-2010. Experience with patients who were switched to an mTOR-inhibitor due to non-melanoma skin cancer are reported in detail, and recent clinical studies are reviewed. 60 organ transplant recipients with non-melanoma skin cancer were evaluated. Due to the development of multiple non-melanoma skin cancer within a few years, the immunosuppressive regimen was switched to everolimus in 7 patients and to sirolimus in 5 patients. Eight patients were evaluable for the effect of mTOR-inhibitors on the development of non-melanoma skin cancer; 4 patients had to discontinue the medication with mTOR-inhibitors early due to various side effects. In the year before the switch to mTOR-inhibitors, 8 patients developed 16 squamous cell carcinomas, 3 Basal cell carcinomas and 22 cases of Bowen's disease. All tumors were histologically confirmed. In the year after switch of immunosuppression, the rate of squamous cell carcinomas (n = 2) and Bowen's disease (n = 3), but not of basal cell carcinomas (n = 2) was significantly reduced. Moreover, 5 prospective randomized trials recently have demonstrated a reduced number of non-melanoma skin cancers in organ transplant recipients after switch of the immunosuppressive regimen to mTOR-inhibitors. Switch of the immunosuppressive regimen to mTOR-inhibitors should be considered for organ transplant recipients suffering from multiple non-melanoma skin cancers. © 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley

  11. OUTCOME OF TRANSPLANTATION FOR MYELOFIBROSIS

    PubMed Central

    Ballen, Karen K.; Shrestha, Smriti; Sobocinski, Kathleen A; Zhang, Mei-Jie; Bashey, Asad; Bolwell, Brian J.; Cervantes, Francisco; Devine, Steven M.; Gale, Robert Peter; Gupta, Vikas; Hahn, Theresa E.; Hogan, William J.; Kröger, Nicolaus; Litzow, Mark R.; Marks, David I.; Maziarz, Richard T.; McCarthy, Philip L.; Schiller, Gary; Schouten, Harry C.; Roy, Vivek; Wiernik, Peter H.; Horowitz, Mary M.; Giralt, Sergio A.; Arora, Mukta

    2010-01-01

    Myelofibrosis is a myeloproliferative disorder incurable with conventional strategies. Several small series have reported long-term disease free survival after allogeneic hematopoietic cell transplantation. In this study, we analyze the outcomes of 289 patients receiving allogeneic transplantation for primary myelofibrosis between 1989 and 2002, from the database of the Center for International Bone Marrow Transplant Research (CIBMTR). The median age was 47 years (range 18-73 years). Donors were HLA identical siblings in 162 patients, unrelated individuals in 101 patients, and HLA non-identical family members in 26 patients. Patients were treated with a variety of conditioning regimens and graft versus host disease prophylaxis regimens. Splenectomy was performed in 65 patients prior to transplantation. The 100-day transplant related mortality was 18% for HLA identical sibling transplants, 35% for unrelated transplants, and 19% for transplants from alternative related donors. Corresponding 5 year overall survival rates were 37%, 30%, and 40% respectively. Disease-free survival rates were 33%, 27% and 22% respectively. Disease-free survival for patients receiving reduced intensity transplants was comparable, 39% for HLA identical sibling donors and 17% for unrelated donors at three years. In this large retrospective series, allogeneic transplantation for myelofibrosis resulted in long-term relapse-free survival in about one-third of patients. PMID:19879949

  12. Reduced bacteria on transplantable allograft skin after preparation with chlorhexidine gluconate, povidone-iodine, and isopropanol.

    PubMed

    May, S R; Roberts, D P; DeClement, F A; Still, J M

    1991-01-01

    A comparison was made of the residual microbiologic contamination on transplantable allograft skin for burn wound coverage taken from cadaver donors prepared by two different protocols. One group was prepared with povidone-iodine, detergent, and 70% isopropanol; the other was prepared with these agents and 4% chlorhexidine gluconate (CG). The skin from each of the donor bodies was removed from independently prepared body areas. Without CG, 13.7% of donor body areas were contaminated; with CG, only 5.6% were contaminated. The number of gram-positive bacterial species isolated from skin after CG preparation was dramatically reduced. The gram-positive bacterial contamination rate dropped from 12.1% to 2.2% of donor body areas, a drop of 82%. With CG, 12 of the 15 contaminant species were eliminated; and we saw a general reduction in the total number of contaminated body areas, a specific and pronounced reduction in gram-positive bacteria, and an increase from 86.3% to 94.4% in the amount of skin obtained from donor cadavers that tested negative for bacterial contamination.

  13. Mixed phenotype acute leukemia with t(9;22): success with nonacute myeloid leukemia-type intensive induction therapy and stem cell transplantation.

    PubMed

    Chan, Onyee; Jamil, Abdur Rehman; Millius, Rebecca; Kaur, Ramandeep; Anwer, Faiz

    2017-04-01

    Mixed phenotype acute leukemia with t(9;22) is a rare disease with poor prognosis, and information on optimal treatment is limited. We describe a case where our patient experienced positive outcome after nonacute myeloid leukemia-type intensive induction therapy followed by postremission therapy with stem cell transplant.

  14. Intensity dependent absorption/transparency of a reducing BaTiO3

    NASA Astrophysics Data System (ADS)

    Chang, J. Y.; Garrett, M. H.; Jenssen, H. P.; Warde, C.

    1993-12-01

    We report intensity dependent absorption and transparency as a function of wavelength for barium titanate. The BaTiO3 crystal examined has an as-grown, light-blue color due to an absorption centered at 690 nm, and when reduced in a partial pressure of 10-15 atm of oxygen it has a yellow-orange color due to an absorption centered at 470 nm. Both energy levels are active in the reduced sample as revealed in the spectrum of the intensity dependent changes in absorption.

  15. Bone Marrow Transplant Using a Reduced Intensity Regimen That is Given in Two Steps

    ClinicalTrials.gov

    2016-11-28

    Hematologic Malignancies; Acute Leukemia; Myelodysplastic Syndromes (MDS) Other Than RA or RARS Subtypes; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; Myeloma; Chronic Myelogenous (or Myeloid) Leukemia (CML) Resistant to STI Therapy

  16. A Two-Step Approach to Reduced Intensity Bone Marrow Transplant for Patients With Hematological Malignancies

    ClinicalTrials.gov

    2016-10-18

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Aplastic Anemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Essential Thrombocythemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Juvenile Myelomonocytic Leukemia; Mastocytosis; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Waldenström Macroglobulinemia

  17. Stromal Cells Act as Guardians for Endothelial Progenitors by Reducing Their Immunogenicity After Co-Transplantation.

    PubMed

    Souidi, Naima; Stolk, Meaghan; Rudeck, Juliane; Strunk, Dirk; Schallmoser, Katharina; Volk, Hans-Dieter; Seifert, Martina

    2017-05-01

    Regeneration of injured tissues requires effective therapeutic strategies supporting vasculogenesis. The lack of instantly available autologous cell sources and immunogenicity of allogeneic endothelial (progenitor) cells limits clinical progress. Based on the immunosuppressive potency of mesenchymal stem/progenitor cells (MSCs), we investigated whether crosstalk between endothelial colony-forming progenitor cells (ECFCs) and MSCs during vasculogenesis could lower allogeneic T cell responses against ECFCs allowing long-term engraftment in vivo. Immunodeficient mice received subcutaneous grafts containing human ECFCs alone, or pairs of human ECFCs/MSCs from the same umbilical cord (UC) to study vasculogenesis in the presence of human leukocyte antigen (HLA)-mismatched human peripheral blood mononuclear cells (PBMCs). In vitro, cell surface marker changes due to interferon gamma (IFNγ) stimulation during ECFC/MSC coculture were determined and further effects on allostimulated T cell proliferation and cytotoxic lysis were measured. IFNγ-induced HLA-DR expression on ECFCs and MSCs, but both cell types had significantly less HLA-DR in cocultures. ECFC-induced T cell proliferation was abolished after MSC coculture as a result of HLA-DR downregulation and indolamin-2,3-dioxygenase activation. Additionally, allospecific CD8(+) T cell-mediated lysis of ECFCs was reduced in cocultures. ECFC/MSC coapplication in immunodeficient mice not only promoted the generation of improved blood vessel architecture after 6 weeks, but also reduced intragraft immune cell infiltration and endothelial HLA-DR expression following PBMC reconstitution. Crosstalk between UC-derived ECFCs and MSCs after combined transplantation can lower the risk of ECFC rejection, thus enabling their coapplication for therapeutic vasculogenesis. Stem Cells 2017;35:1233-1245. © 2017 AlphaMed Press.

  18. Pancreas Transplantation

    PubMed Central

    Sutherland, David ER

    2010-01-01

    Diabetes mellitus is generally treated with oral diabetic drugs and/or insulin. However, the morbidity and mortality associated with this condition increases over time, even in patients receiving intensive insulin treatment, and this is largely attributable to diabetic complications or the insulin therapy itself. Pancreas transplantation in humans was first conducted in 1966, since when there has been much debate regarding the legitimacy of this procedure. Technical refinements and the development of better immunosuppressants and better postoperative care have brought about marked improvements in patient and graft survival and a reduction in postoperative morbidity. Consequently, pancreas transplantation has become the curative treatment modality for diabetes, particularly for type I diabetes. An overview of pancreas transplantation is provided herein, covering the history of pancreas transplantation, indications for transplantation, cadaveric and living donors, surgical techniques, immunosuppressants, and outcome following pancreas transplantation. The impact of successful pancreas transplantation on the complications of diabetes will also be reviewed briefly. PMID:21253293

  19. Cytomegalovirus infection and disease reduce 10-year cardiac allograft vasculopathy-free survival in heart transplant recipients.

    PubMed

    Johansson, Inger; Andersson, Rune; Friman, Vanda; Selimovic, Nedim; Hanzen, Lars; Nasic, Salmir; Nyström, Ulla; Sigurdardottir, Vilborg

    2015-12-24

    Cytomegalovirus (CMV) is associated with an increased risk of cardiac allograft vasculopathy (CAV), the major limiting factor for long-term survival after heart transplantation (HTx). The purpose of this study was to evaluate the impact of CMV infection during long-term follow-up after HTx. A retrospective, single-centre study analyzed 226 HTx recipients (mean age 45 ± 13 years, 78 % men) who underwent transplantation between January 1988 and December 2000. The incidence and risk factors for CMV infection during the first year after transplantation were studied. Risk factors for CAV were included in an analyses of CAV-free survival within 10 years post-transplant. The effect of CMV infection on the grade of CAV was analyzed. Survival to 10 years post-transplant was higher in patients with no CMV infection (69 %) compared with patients with CMV disease (55 %; p = 0.018) or asymptomatic CMV infection (54 %; p = 0.053). CAV-free survival time was higher in patients with no CMV infection (6.7 years; 95 % CI, 6.0-7.4) compared with CMV disease (4.2 years; CI, 3.2-5.2; p < 0.001) or asymptomatic CMV infection (5.4 years; CI, 4.3-6.4; p = 0.013). In univariate analysis, recipient age, donor age, coronary artery disease (CAD), asymptomatic CMV infection and CMV disease were significantly associated with CAV-free survival. In multivariate regression analysis, CMV disease, asymptomatic CMV infection, CAD and donor age remained independent predictors of CAV-free survival at 10 years post-transplant. CAV-free survival was significantly reduced in patients with CMV disease and asymptomatic CMV infection compared to patients without CMV infection. These findings highlight the importance of close monitoring of CMV viral load and appropriate therapeutic strategies for preventing asymptomatic CMV infection.

  20. A high sodium intake reduces antiproteinuric response to renin-angiotensin-aldosterone system blockade in kidney transplant recipients.

    PubMed

    Monfá, Elena; Rodrigo, Emilio; Belmar, Lara; Sango, Cristina; Moussa, Fozi; Ruiz San Millán, Juan Carlos; Piñera, Celestino; Fernández-Fresnedo, Gema; Arias, Manuel

    Post-transplant proteinuria is associated with lower graft and patient survival. Renin-angiotensin-aldosterone system blockers are used to reduce proteinuria and improve renal outcome. Although it is known that a high salt intake blunts the antiproteinuric effect of ACEI and ARB drugs in non-transplant patients, this effect has not been studied in kidney transplant recipients. To analyse the relationship between sodium intake and the antiproteinuric effect of ACEI/ARB drugs in kidney transplant recipients. We selected 103 kidney transplant recipients receiving ACEI/ARB drugs for more than 6 months due to proteinuria>1 g/day. Proteinuria was analysed at baseline and at 6 months after starting ACEI/ARB treatment. Salt intake was estimated by urinary sodium to creatinine ratio (uNa/Cr). Proteinuria fell to less than 1g/day in 46 patients (44.7%). High uNa/Cr was associated with a smaller proteinuria decrease (r=-0.251, P=.011). The percentage proteinuria reduction was significantly lower in patients in the highest uNa/Cr tertile [63.9% (IQR 47.1%), 60.1% (IQR 55.4%), 38.9% (IQR 85.5%), P=.047]. High uNa/Cr independently relates (OR 2.406 per 100 mEq/g, 95% CI: 1.008-5.745, P=.048) to an antiproteinuric response <50% after renin-angiotensin-aldosterone system blockade. A high salt intake results in a smaller proteinuria decrease in kidney transplant recipients with proteinuria treated with ACEI/ARB drugs. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  1. Comparison of Intensive Chemotherapy and Hypomethylating Agents before Allogeneic Stem Cell Transplantation for Advanced Myelodysplastic Syndromes: A Study of the Myelodysplastic Syndrome Subcommittee of the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplant Research.

    PubMed

    Potter, Victoria T; Iacobelli, Simona; van Biezen, Anja; Maertens, Johann; Bourhis, Jean-Henri; Passweg, Jakob R; Yakhoub-Agha, Ibrahim; Tabrizi, Reza; Bay, Jacques-Olivier; Chevallier, Patrice; Chalandon, Yves; Huynh, Anne; Cahn, Jean Yves; Ljungman, Per; Craddock, Charles; Lenhoff, Stig; Russell, N H; Fegueux, Nathalie; Socié, Gerard; Benedetto, Bruno; Meijer, Ellen; Mufti, G J; de Witte, Theo; Robin, Marie; Kröger, Nicolaus

    2016-09-01

    The European Society for Blood and Marrow Transplant Research data set was used to retrospectively analyze the outcomes of hypomethylating therapy (HMA) compared with those of conventional chemotherapy (CC) before hematopoietic stem cell transplantation (HSCT) in 209 patients with advanced myelodysplastic syndromes. Median follow-up was 22.1 months and the median age of the group was 57.6 years with 37% of the population older than > 60 years. The majority of patients (59%) received reduced-intensity conditioning and 34% and 27% had intermediate-2 and high international prognostic scoring system (IPSS) scores. At time of HSCT, 32% of patients did not achieve complete remission (CR) and 13% had primary refractory disease. On univariate analysis, outcomes at 3 years were not significantly different between HMA and CC for overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM): OS (42% versus 35%), RFS (29% versus 31%), CIR (45% versus 40%), and NRM (26% versus 28%). Comparing characteristics of the groups, there were more patients < 55 years old, more patients in CR (68% versus 32%), and fewer patients with primary refractory disease in the CC group than in the HMA group (10% versus 19%, P < .001). Patients with primary refractory disease had worse outcomes than those in CR with regard to OS (hazard ratio [HR], 2.42; 95% confidence interval [CI], 1.41 to 4.13; P = .001), RFS (HR, 2.27; 95% CI, 1.37 to 3.76; P = .001), and NRM (HR, 2.49; 95% CI, 1.18 to 5.26; P = .016). In addition, an adverse effect of IPSS-R cytogenetic risk group was evident for RFS. In summary, outcomes after HSCT are similar for patients receiving HMA compared with those receiving CC, despite the higher proportion of patients with primary refractory disease in the HMA group. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  2. A retrospective study of long-term treatment outcomes for reduced vocal intensity in hypokinetic dysarthria.

    PubMed

    Watts, Christopher R

    2016-01-01

    Reduced vocal intensity is a core impairment of hypokinetic dysarthria in Parkinson's disease (PD). Speech treatments have been developed to rehabilitate the vocal subsystems underlying this impairment. Intensive treatment programs requiring high-intensity voice and speech exercises with clinician-guided prompting and feedback have been established as effective for improving vocal function. Less is known, however, regarding long-term outcomes of clinical benefit in speakers with PD who receive these treatments. A retrospective cohort design was utilized. Data from 78 patient files across a three year period were analyzed. All patients received a structured, intensive program of voice therapy focusing on speaking intent and loudness. The dependent variable for all analyses was vocal intensity in decibels (dBSPL). Vocal intensity during sustained vowel production, reading, and novel conversational speech was compared at pre-treatment, post-treatment, six month follow-up, and twelve month follow-up periods. Statistically significant increases in vocal intensity were found at post-treatment, 6 months, and 12 month follow-up periods with intensity gains ranging from 5 to 17 dB depending on speaking condition and measurement period. Significant treatment effects were found in all three speaking conditions. Effect sizes for all outcome measures were large, suggesting a strong degree of practical significance. Significant increases in vocal intensity measured at 6 and 12 moth follow-up periods suggested that the sample of patients maintained treatment benefit for up to a year. These findings are supported by outcome studies reporting treatment outcomes within a few months post-treatment, in addition to prior studies that have reported long-term outcome results. The positive treatment outcomes experienced by the PD cohort in this study are consistent with treatment responses subsequent to other treatment approaches which focus on high-intensity, clinician guided motor

  3. Fast maximum intensity projection algorithm using shear warp factorization and reduced resampling.

    PubMed

    Fang, Laifa; Wang, Yi; Qiu, Bensheng; Qian, Yuancheng

    2002-04-01

    Maximal intensity projection (MIP) is routinely used to view MRA and other volumetric angiographic data. The straightforward implementation of MIP is ray casting that traces a volumetric data set in a computationally expensive manner. This article reports a fast MIP algorithm using shear warp factorization and reduced resampling that drastically reduced the redundancy in the computations for projection, thereby speeding up MIP by more than 10 times.

  4. The “House Calls” Trial: A Randomized Controlled Trial to Reduce Racial Disparities in Live Donor Kidney Transplantation: Rationale and Design

    PubMed Central

    Rodrigue, James R.; Pavlakis, Martha; Egbuna, Ogo; Paek, Mathew; Waterman, Amy D.; Mandelbrot, Didier A.

    2012-01-01

    Despite a substantially lower rate of live donor kidney transplantation among Black Americans compared to White Americans, there are few systematic efforts to reduce this racial disparity. This paper describes the rationale and design of a randomized controlled trial aims evaluating the comparative effectiveness of three different educational interventions for increasing live donor kidney transplantation in Black Americans. This trial is a single-site, urn-randomized controlled trial with a planned enrollment of 180 Black Americans awaiting kidney transplantation. Patients are randomized to receive transplant education in one of three education conditions: through group education at their homes (e.g., House Calls), or through group (Group-Based) or individual education (Individual Counseling) in the transplant.. The primary outcome of the trial is the occurrence of a live donor kidney transplant, with secondary outcomes including living donor inquiries and evaluations as well as changes in patient live donor kidney transplantation readiness, willingness, knowledge, and concerns. Sex, gender, dialysis status, and quality of life are evaluated as moderating factors. Findings from this clinical trial have the potential to inform strategies for reducing racial disparities in live donor kidney transplantation. Similar trials have been developed recently to broaden the evaluation of House Calls as an innovative disparity-reducing intervention in kidney transplantation. Trial Registration: Clinicaltrials.gov NCT00785265 PMID:22510472

  5. Bilateral native nephrectomy reduces systemic oxalate level after combined liver-kidney transplant: A case report.

    PubMed

    Villani, Vincenzo; Gupta, Neena; Elias, Nahel; Vagefi, Parsia A; Markmann, James F; Paul, Elahna; Traum, Avram Z; Yeh, Heidi

    2017-03-05

    Primary hyperoxaluria type 1 (PH1) is a rare liver enzymatic defect that causes overproduction of plasma oxalate. Accumulation of oxalate in the kidney and subsequent renal failure are fatal to PH1 patients often in pediatric age. Combined liver and kidney transplantation is the therapy of choice for end-stage renal disease due to PH1. Levels of plasma oxalate remain elevated for several months after liver transplantation, as the residual body oxalate is slowly excreted. Patients with persistent hyperoxaluria after transplant often require hemodialysis, and accumulation of residual oxalate in the kidney can induce graft dysfunction. As the native kidneys are the main target of calcium oxalate accumulation, we postulated that removal of native kidneys could drastically decrease total body oxalate levels after transplantation. Here, we report a case of bilateral nephrectomy at the time of combined liver-kidney transplantation in a pediatric PH1 patient. Bilateral nephrectomy induced a rapid decrease in plasma oxalate to normal levels in less than 20 days, compared to the several months reported in the literature. Our results suggest that removal of native kidneys could be an effective strategy to decrease the need for hemodialysis and the risk of renal dysfunction after combined liver-kidney transplantation in patients with PH1.

  6. The influence of reduced light intensity on the response of benthic diatoms to herbicide exposure.

    PubMed

    Wood, Rebecca J; Mitrovic, Simon M; Lim, Richard P; Kefford, Ben J

    2016-09-01

    Herbicide pollution events in aquatic ecosystems often coincide with increased turbidity and reduced light intensity. It is therefore important to determine whether reduced light intensity can influence herbicide toxicity, especially to primary producers such as benthic diatoms. Benthic diatoms collected from 4 rivers were exposed to herbicides in 48 h rapid toxicity tests under high light (100 µmol m(-2)  s(-1) ) and low light (20 µmol m(-2)  s(-1) ) intensities. The effects of 2 herbicides (atrazine and glyphosate) were assessed on 26 freshwater benthic diatom taxa. There was no significant interaction of light and herbicide effects at the community level or on the majority (22 of 26) of benthic diatom taxa. This indicates that low light levels will likely have only a minor influence on the response of benthic diatoms to herbicides. Environ Toxicol Chem 2016;35:2252-2260. © 2016 SETAC. © 2016 SETAC.

  7. Fuel treatment effectiveness in reducing fire intensity and spread rate - An experimental overview

    Treesearch

    Eric Mueller; Nicholas Skowronski; Albert Simeoni; Kenneth Clark; Robert Kremens; William Mell; Michael Gallagher; Jan Thomas; Alexander Filkov; Mohamad El Houssami; John Hom; Bret Butler

    2014-01-01

    Fuel treatments represent a significant component of the wildfire mitigation strategy in the United States. However, the lack of research aimed at quantifying the explicit effectiveness of fuel treatments in reducing wildfire intensity and spread rate limits our ability to make educated decisions about the type and placement of these treatments. As part of a larger...

  8. Postmortem and ex vivo carbon monoxide ventilation reduces injury in rat lungs transplanted from non-heart-beating donors.

    PubMed

    Dong, Boming; Stewart, Paul W; Egan, Thomas M

    2013-08-01

    We sought to determine whether ventilation of lungs after death in non-heart-beating donors with carbon monoxide during warm ischemia and ex vivo lung perfusion and after transplant would reduce ischemia-reperfusion injury and improve lung function. One hour after death, Sprague-Dawley rats were ventilated for another hour with 60% oxygen (control group) or 500 ppm carbon monoxide in 60% oxygen (CO-vent group; n=6/group). Then, lungs were flushed with 20 mL cold Perfadex, stored cold for 1 hour, then warmed to 37 °C in an ex vivo lung perfusion circuit perfused with Steen solution. At 37 °C, lungs were ventilated for 15 minutes with alveolar gas with or without 500 ppm carbon monoxide, then perfusion-cooled to 20 °C, flushed with cold Perfadex and stored cold for 2 hours. The left lung was transplanted using a modified cuff technique. Recipients were ventilated with 60% oxygen with or without carbon monoxide. One hour after transplant, we measured blood gases from the left pulmonary vein and aorta, and wet-to-dry ratio of both lungs. The RNA and protein extracted from graft lungs underwent real-time polymerase chain reaction and Western blotting, and measurement of cyclic guanosine monophosphate by enzyme-linked immunosorbent assay. Carbon monoxide ventilation begun 1 hour after death reduced wet/dry ratio after ex vivo lung perfusion. After transplantation, the carbon monoxide-ventilation group had better oxygenation; higher levels of tissue cyclic guanosine monophosphate, heme oxidase-1 expression, and p38 phosphorylation; reduced c-Jun N-terminal kinase phosphorylation; and reduced expression of interleukin-6 and interleukin-1β messenger RNA. Administration of carbon monoxide to the deceased donor and non-heart-beating donor lungs reduces ischemia-reperfusion injury in rat lungs transplanted from non-heart-beating donors. Therapy to the deceased donor via the airway may improve post-transplant lung function. Copyright © 2013 The American Association for

  9. CD16⁺ monocytes with smooth muscle cell characteristics are reduced in human renal chronic transplant dysfunction.

    PubMed

    Boersema, M; van den Born, J C; van Ark, J; Harms, G; Seelen, M A; van Dijk, M C R F; van Goor, H; Navis, G J; Popa, E R; Hillebrands, J L

    2015-05-01

    In chronic transplant dysfunction (CTD), persistent (allo)immune-mediated inflammation eventually leads to tissue remodeling including neointima formation in intragraft arteries. We previously showed that recipient-derived neointimal α-SMA(+) smooth muscle-like cells are present in human renal allografts with CTD. Human PBMC contain myeloid cells capable of differentiating into α-SMA(+) cells in vitro; the phenotype of the ancestral subset is as yet unknown. This study aimed to investigate whether monocyte subsets contain cells with smooth muscle-like cell differentiation capacity and whether CTD in renal transplant recipients is associated with a shift in these monocyte subsets. To accomplish this goal, monocyte subsets from healthy controls were sorted based on CD14 and CD16 expression to investigate gene expression levels of mesenchymal markers α-SMA and SM22α. CD14(+)/CD16(++) monocytes displayed increased α-SMA and SM22α mRNA expression compared with CD14(++)/CD16(-) monocytes, suggesting increased differentiation potential toward smooth muscle-like cells. Flow cytometry revealed that in non-CTD transplant recipients the percentage of CD14(+)/CD16(++) monocytes was reduced, with an even further reduction in patients with CTD. To determine a potential correlation between CD14(+)/CD16(++) monocytes and α-SMA(+) cell outgrowth potential in vitro, PBMC of healthy controls and transplant recipients with and without CTD were cultured under fibrotic culture conditions, and indeed a significant correlation (p=0.0002, r=0.62) was observed. Finally, double staining for α-SMA and CD16 revealed presence of α-SMA(+)CD16(+) cells in kidney explants from CTD patients, albeit at very low numbers. Our data represent evidence that, compared to CD14(++)CD16(-) monocytes, CD14(+)CD16(++) monocytes have an increased expression of smooth muscle cell-associated genes. This monocyte subpopulation is reduced in renal transplant patients with CTD, possibly due to selective

  10. Role of in-hospital care quality in reducing anxiety and readmissions of kidney transplant recipients.

    PubMed

    Chandrasekaran, Aravind; Anand, Gopesh; Sharma, Luv; Pesavanto, Todd; Hauenstein, Mary Lou; Nguyen, Michelle; Gadkari, Mrinalini; Moffatt-Bruce, Susan

    2016-09-01

    A total of 17,000 patients receive kidney transplants each year in the United States. The 30-day readmission rate for kidney transplant recipients is over 30%. Our research focuses on the relationship between the quality of care delivered during the patient's hospital stay for a kidney transplant, and the patient health outcomes and readmissions related to the transplant. We interviewed 20 kidney transplant recipients at a major transplant center in the United States. Findings from these interviews were used to inform the data collection using structured surveys, which were administered to an additional 77 kidney transplant recipients. We used ordinary least squares regression to predict the effects of two dimensions of in-hospital care quality-information consistency and empathetic care delivery-on level of patient anxiety 1 week following discharge. Further, we estimated a logistic regression to predict the effect of anxiety, combined with the two dimensions of in-hospital care quality, on occurrence of 30-day readmissions. Patient anxiety levels 1 wk after discharge are significantly associated with information consistency and empathetic delivery of care. Patient anxiety 1 wk after discharge is associated with occurrence of 30-d readmissions. The logistic regression model indicates that the risk of getting readmitted is 110% higher for a one unit increase in patient anxiety level 1 wk after discharge. Finally, patient anxiety fully mediates the effects of consistency of information and empathetic care delivery on occurrence of 30-d readmissions (50.96% of the effect is mediated). Our study suggests two ways of preventing readmissions through reduction of postdischarge anxiety: (1) standardizing in-hospital care, so that information received by patients is consistent, and (2) by training caregivers to be more empathetic toward patients during the delivery of this information. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Piloting a Coping Skills Group Intervention to Reduce Depression and Anxiety Symptoms in Patients Awaiting Kidney or Liver Transplant.

    PubMed

    Craig, Julie Anne; Miner, Dee; Remtulla, Tasneem; Miller, Janet; Zanussi, Lauren W

    2017-02-01

    The authors evaluated the use of a coping skills group (CSG) therapy intervention to decrease depression and anxiety and increase healthy coping skills in a population of kidney and liver transplant candidates. The study, using a pre-posttest design, piloted a CSG with a convenience sample of 41 consenting participants on a waiting list or in workup for kidney or liver transplant. Two transplant social workers led five eight-week closed psychoeducational groups. Coping skills, depression symptoms, and anxiety symptoms were assessed preintervention, postintervention, and at follow-up one month later. Results suggest that the CSG group created significant changes in some coping areas, such as decreasing the use of denial and self-blame and increasing the use of acceptance, religion, and instrumental supports. In this study, instrumental supports are strategies such as seeking assistance, finding information, or asking for advice about what to do. The effects on instrumental supports did not sustain at the one-month follow-up. Anxiety and depression scores were significantly reduced, and these changes were sustained at one-month follow-up. This study supports the use of a group-based psychosocial intervention for the pretransplant population and will be most relevant to social workers practicing in the transplant field. © 2016 National Association of Social Workers.

  12. Clinical and immunological correction of DOCK8 deficiency by allogeneic hematopoietic stem cell transplantation following a reduced toxicity conditioning regimen.

    PubMed

    Boztug, Heidrun; Karitnig-Weiß, Cäcilia; Ausserer, Bernd; Renner, Ellen D; Albert, Michael H; Sawalle-Belohradsky, Julie; Belohradsky, Bernd H; Mann, Georg; Horcher, Ernst; Rümmele-Waibel, Alexandra; Geyeregger, Rene; Lakatos, Karoly; Peters, Christina; Lawitschka, Anita; Matthes-Martin, Susanne

    2012-10-01

    Dedicator of cytokinesis 8 protein (DOCK8) deficiency is a combined immunodeficiency disorder characterized by an expanding clinical picture with typical features of recurrent respiratory or gastrointestinal tract infections, atopic eczema, food allergies, chronic viral infections of the skin, and blood eosinophilia often accompanied by elevated serum IgE levels. The only definitive treatment option is allogeneic hematopoietic stem cell transplantation (HSCT). We report a patient with early severe manifestation of DOCK8 deficiency, who underwent unrelated allogeneic HSCT at the age of 3 years following a reduced toxicity conditioning regimen. The transplant course was complicated by pulmonary aspergilloma pretransplantation, adenovirus (ADV) reactivation, and cytomegalovirus (CMV) pneumonitis 4 weeks after transplantation. With antifungal and antiviral treatment the patient recovered. Seven months after transplantation the patient is in excellent clinical condition. Eczematous rash, chronic viral skin infections, and food allergies have subsided, associated with normalization of IgE levels and absolute numbers of eosinophils. Chimerism analysis shows stable full donor chimerism. DOCK8 deficiency can be successfully cured by allogeneic HSCT. This treatment option should be considered early after diagnosis, as opportunistic infections and malignancies that occur more frequently during the natural course of the disease are associated with higher morbidity and mortality.

  13. MRPack: Multi-Algorithm Execution Using Compute-Intensive Approach in MapReduce

    PubMed Central

    2015-01-01

    Large quantities of data have been generated from multiple sources at exponential rates in the last few years. These data are generated at high velocity as real time and streaming data in variety of formats. These characteristics give rise to challenges in its modeling, computation, and processing. Hadoop MapReduce (MR) is a well known data-intensive distributed processing framework using the distributed file system (DFS) for Big Data. Current implementations of MR only support execution of a single algorithm in the entire Hadoop cluster. In this paper, we propose MapReducePack (MRPack), a variation of MR that supports execution of a set of related algorithms in a single MR job. We exploit the computational capability of a cluster by increasing the compute-intensiveness of MapReduce while maintaining its data-intensive approach. It uses the available computing resources by dynamically managing the task assignment and intermediate data. Intermediate data from multiple algorithms are managed using multi-key and skew mitigation strategies. The performance study of the proposed system shows that it is time, I/O, and memory efficient compared to the default MapReduce. The proposed approach reduces the execution time by 200% with an approximate 50% decrease in I/O cost. Complexity and qualitative results analysis shows significant performance improvement. PMID:26305223

  14. MRPack: Multi-Algorithm Execution Using Compute-Intensive Approach in MapReduce.

    PubMed

    Idris, Muhammad; Hussain, Shujaat; Siddiqi, Muhammad Hameed; Hassan, Waseem; Syed Muhammad Bilal, Hafiz; Lee, Sungyoung

    2015-01-01

    Large quantities of data have been generated from multiple sources at exponential rates in the last few years. These data are generated at high velocity as real time and streaming data in variety of formats. These characteristics give rise to challenges in its modeling, computation, and processing. Hadoop MapReduce (MR) is a well known data-intensive distributed processing framework using the distributed file system (DFS) for Big Data. Current implementations of MR only support execution of a single algorithm in the entire Hadoop cluster. In this paper, we propose MapReducePack (MRPack), a variation of MR that supports execution of a set of related algorithms in a single MR job. We exploit the computational capability of a cluster by increasing the compute-intensiveness of MapReduce while maintaining its data-intensive approach. It uses the available computing resources by dynamically managing the task assignment and intermediate data. Intermediate data from multiple algorithms are managed using multi-key and skew mitigation strategies. The performance study of the proposed system shows that it is time, I/O, and memory efficient compared to the default MapReduce. The proposed approach reduces the execution time by 200% with an approximate 50% decrease in I/O cost. Complexity and qualitative results analysis shows significant performance improvement.

  15. Lung Transplant

    MedlinePlus

    ... will recover in the hospital’s intensive care unit (ICU) before moving to a hospital room for one to three weeks. Your doctor may recommend pulmonary rehabilitation after your lung transplant surgery to help you ...

  16. Nestin-expressing stem cells from the hair follicle can differentiate into motor neurons and reduce muscle atrophy after transplantation to injured nerves.

    PubMed

    Liu, Fang; Zhang, Chuansen; Hoffman, Robert M

    2014-02-01

    We have previously shown that nestin-expressing hair follicle stem cells from the mouse and human are multipotent and can differentiate into many cell types, including neurons and glial cells. The nestin-expressing hair follicle stem cells can effect nerve and spinal cord repair upon transplantation in mouse models. In the present study, nestin-expressing hair follicle stem cells expressing red fluorescent protein (RFP) were induced by retinoic acid and fetal bovine serum to differentiate and then transplanted together with Matrigel into the transected distal sciatic or tibial nerve stump of transgenic nude mice ubiquitously expressing green fluorescent protein (GFP). Control mice were transplanted with Matrigel only. The transplanted cells appeared neuron like, with large round nuclei and long extensions. Immunofluorescence staining showed that some of the transplanted cells in the distal nerve stump expressed the neuron marker Tuj1 as well as motor neuron markers Isl 1/2 and EN1. These transplanted cells contacted each other as well as host nerve fibers. Two weeks post-transplantation, nerve fibers in the distal sciatic nerve stump of the transplanted mice had greater expression of motor neuron markers and neurotrophic factor-3 than those in the Matrigel-only transplanted mice. Muscle fiber areas in the nestin-expressing stem cell plus Matrigel-transplanted animals were much bigger than that in the Matrigel-only transplanted animals after 4 weeks. The present results suggest that transplanted nestin-expressing hair follicle stem cells can differentiate into motor neurons and reduce muscle atrophy after sciatic nerve transection. This study demonstrates a new and accessible neuron source to reduce muscle atrophy after nerve injury.

  17. Neural precursor cell transplantation enhances functional recovery and reduces astrogliosis in bilateral compressive/contusive cervical spinal cord injury.

    PubMed

    Wilcox, Jared T; Satkunendrarajah, Kajana; Zuccato, Jeffrey A; Nassiri, Farshad; Fehlings, Michael G

    2014-10-01

    Spinal cord injury has a significant societal and personal impact. Although the majority of injuries involve the cervical spinal cord, few studies of cell transplantation have used clinically relevant models of cervical spinal cord injury, limiting translation into clinical trials. Given this knowledge gap, we sought to examine the effects of neural stem/precursor cell (NPC) transplants in a rodent model of bilateral cervical contusion-compression spinal cord injury. Bilateral C6-level clip contusion-compression injuries were performed in rats, which were then blindly randomized at 2 weeks after injury into groups receiving adult brain-derived NPCs, vehicle, or sham operation. Long-term survival of NPCs was evident at 10 weeks after transplant. Cell grafts were localized rostrocaudally surrounding the lesion, throughout white and gray matter. Graft-derived cells were found within regions of gliotic scar and motor tracts and deposited myelin around endogenous axons. The majority of NPCs developed an oligodendroglial phenotype with greater neuronal profiles in rostral grafts. Following NPC transplantation, white matter was significantly increased compared with control. Astrogliosis and glial scar deposition, measured by GFAP-positive and chondroitin sulfate proteoglycan-positive volume, was significantly reduced. Forelimb grip strength, fine motor control during locomotion, and axonal conduction (by in vivo electrophysiology) was greater in cell-treated animals compared with vehicle controls. Transplantation of NPCs in the bilaterally injured cervical spinal cord results in significantly improved spinal cord tissue and forelimb function, warranting further study in preclinical cervical models to improve this treatment paradigm for clinical translation. ©AlphaMed Press.

  18. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia

    PubMed Central

    Zhang, Mei-Jie; Bacigalupo, Andrea A.; Bashey, Asad; Appelbaum, Frederick R.; Aljitawi, Omar S.; Armand, Philippe; Antin, Joseph H.; Chen, Junfang; Devine, Steven M.; Fowler, Daniel H.; Luznik, Leo; Nakamura, Ryotaro; O’Donnell, Paul V.; Perales, Miguel-Angel; Pingali, Sai Ravi; Porter, David L.; Riches, Marcie R.; Ringdén, Olle T. H.; Rocha, Vanderson; Vij, Ravi; Weisdorf, Daniel J.; Champlin, Richard E.; Horowitz, Mary M.; Fuchs, Ephraim J.; Eapen, Mary

    2015-01-01

    We studied adults with acute myeloid leukemia (AML) after haploidentical (n = 192) and 8/8 HLA-matched unrelated donor (n = 1982) transplantation. Haploidentical recipients received calcineurin inhibitor (CNI), mycophenolate, and posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis; 104 patients received myeloablative and 88 received reduced intensity conditioning regimens. Matched unrelated donor transplant recipients received CNI with mycophenolate or methotrexate for GVHD prophylaxis; 1245 patients received myeloablative and 737 received reduced intensity conditioning regimens. In the myeloablative setting, day 30 neutrophil recovery was lower after haploidentical compared with matched unrelated donor transplants (90% vs 97%, P = .02). Corresponding rates after reduced intensity conditioning transplants were 93% and 96% (P = .25). In the myeloablative setting, 3-month acute grade 2-4 (16% vs 33%, P < .0001) and 3-year chronic GVHD (30% vs 53%, P < .0001) were lower after haploidentical compared with matched unrelated donor transplants. Similar differences were observed after reduced intensity conditioning transplants, 19% vs 28% (P = .05) and 34% vs 52% (P = .002). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 45% (95% CI, 36-54) and 50% (95% CI, 47-53) after haploidentical and matched unrelated donor transplants (P = .38). Corresponding rates after reduced intensity conditioning transplants were 46% (95% CI, 35-56) and 44% (95% CI, 0.40-47) (P = .71). Although statistical power is limited, these data suggests that survival for patients with AML after haploidentical transplantation with posttransplant cyclophosphamide is comparable with matched unrelated donor transplantation. PMID:26130705

  19. Is It Useful to Measure Efficiency Indices of a Deceased-Donor Kidney Transplant Program in One Intensive Care Unit?

    PubMed

    Lausevic, M; Vujadinovic, D; Aleksic, V; Lassiter, D; Naumovic, R

    2015-01-01

    Before 2010, donor detection rate and donor conversion rate at our tertiary level care institution were low. To assess the effectiveness of the implemented organizational changes, an analysis of organizational indicators with the use of the DOPKI (Improving the Knowledge and Practices in Organ Donation) project was conducted. Three groups of DOPKI indicators were used: indicators of the potential for deceased organ donation, indicators on areas for improvement in the deceased donation process, and indicators of program effectiveness. We compared the 3-year period before instituting organizational measures with the 3-year period after the changes. Significant differences in almost all DOPKI indicators were found. Most importantly, the number of actual donors has increased significantly, pointing to the effectiveness of the organizational measures that we put in place in 2010. In addition, the study highlights the value of the use of DOPKI indicators in one intensive care unit to improve the transplant program on a hospital level. We conclude by arguing that despite the lack of a uniform national database, DOPKI indicators could still be useful for improving the quality of donor programs. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Can harms associated with high-intensity drinking be reduced by increasing the price of alcohol?

    PubMed

    Byrnes, Joshua; Shakeshaft, Anthony; Petrie, Dennis; Doran, Christopher

    2013-01-01

    Increasing the price of alcohol is consistently shown to reduce the average level of consumption. However, the evidence for the effect of increasing the price on high-intensity drinking is both limited and equivocal. The aim of this analysis is to estimate the effect of changes in price on patterns of consumption. Self-reported patterns of alcohol consumption and demographic data were obtained from the Australian National Drug Strategy Household Surveys, conducted in 2001, 2004 and 2007. A pooled three-stage least-squares estimator was used to simultaneously model the impact of the price on the frequency (measured in days) of consuming no, low, moderate and high quantities of alcohol. A 1% increase in the price of alcohol was associated with a statistically significant increase of 6.41 days per year on which no alcohol is consumed (P ≤ 0.049), and a statistically significant decrease of 7.30 days on which 1-4 standard drinks are consumed (P ≤ 0.021). There was no statistically significant change for high or moderate-intensity drinking. For Australia, and countries with a similar pattern of predominant high-intensity drinking, taxation policies that increase the price of alcohol and are very efficient at decreasing harms associated with reduced average consumption may be relatively inefficient at decreasing alcohol harms associated with high-intensity drinking. © 2012 Australasian Professional Society on Alcohol and other Drugs.

  1. Predictive Modeling of Massive Transfusion Requirements During Liver Transplantation and Its Potential to Reduce Utilization of Blood Bank Resources.

    PubMed

    Pustavoitau, Aliaksei; Lesley, Maggie; Ariyo, Promise; Latif, Asad; Villamayor, April J; Frank, Steven M; Rizkalla, Nicole; Merritt, William; Cameron, Andrew; Dagher, Nabil; Philosophe, Benjamin; Gurakar, Ahmet; Gottschalk, Allan

    2017-05-01

    Patients undergoing liver transplantation frequently but inconsistently require massive blood transfusion. The ability to predict massive transfusion (MT) could reduce the impact on blood bank resources through customization of the blood order schedule. Current predictive models of MT for blood product utilization during liver transplantation are not generally applicable to individual institutions owing to variability in patient population, intraoperative management, and definitions of MT. Moreover, existing models may be limited by not incorporating cirrhosis stage or thromboelastography (TEG) parameters. This retrospective cohort study included all patients who underwent deceased-donor liver transplantation at the Johns Hopkins Hospital between 2010 and 2014. We defined MT as intraoperative transfusion of > 10 units of packed red blood cells (pRBCs) and developed a multivariable predictive model of MT that incorporated cirrhosis stage and TEG parameters. The accuracy of the model was assessed with the goodness-of-fit test, receiver operating characteristic analysis, and bootstrap resampling. The distribution of correct patient classification was then determined as we varied the model threshold for classifying MT. Finally, the potential impact of these predictions on blood bank resources was examined. Two hundred three patients were included in the study. Sixty (29.6%) patients met the definition for MT and received a median (interquartile range) of 19.0 (14.0-27.0) pRBC units intraoperatively compared with 4.0 units (1.0-6.0) for those who did not satisfy the criterion for MT. The multivariable model for predicting MT included Model for End-stage Liver Disease score, whether simultaneous liver and kidney transplant was performed, cirrhosis stage, hemoglobin concentration, platelet concentration, and TEG R interval and angle. This model demonstrated good calibration (Hosmer-Lemeshow goodness-of-fit test P = .45) and good discrimination (c statistic: 0.835; 95

  2. Muscle injury after low-intensity downhill running reduces running economy.

    PubMed

    Baumann, Cory W; Green, Michael S; Doyle, J Andrew; Rupp, Jeffrey C; Ingalls, Christopher P; Corona, Benjamin T

    2014-05-01

    Contraction-induced muscle injury may reduce running economy (RE) by altering motor unit recruitment, lowering contraction economy, and disturbing running mechanics, any of which may have a deleterious effect on endurance performance. The purpose of this study was to determine if RE is reduced 2 days after performing injurious, low-intensity exercise in 11 healthy active men (27.5 ± 5.7 years; 50.05 ± 1.67 VO2peak). Running economy was determined at treadmill speeds eliciting 65 and 75% of the individual's peak rate of oxygen uptake (VO2peak) 1 day before and 2 days after injury induction. Lower extremity muscle injury was induced with a 30-minute downhill treadmill run (6 × 5 minutes runs, 2 minutes rest, -12% grade, and 12.9 km·h(-1)) that elicited 55% VO2peak. Maximal quadriceps isometric torque was reduced immediately and 2 days after the downhill run by 18 and 10%, and a moderate degree of muscle soreness was present. Two days after the injury, steady-state VO2 and metabolic work (VO2 L·km(-1)) were significantly greater (4-6%) during the 65% VO2peak run. Additionally, postinjury VCO2, VE and rating of perceived exertion were greater at 65% but not at 75% VO2peak, whereas whole blood-lactate concentrations did not change pre-injury to postinjury at either intensity. In conclusion, low-intensity downhill running reduces RE at 65% but not 75% VO2peak. The results of this study and other studies indicate the magnitude to which RE is altered after downhill running is dependent on the severity of the injury and intensity of the RE test.

  3. Alpha 1-antitrypsin reduces inflammation and enhances mouse pancreatic islet transplant survival.

    PubMed

    Koulmanda, Maria; Bhasin, Manoj; Fan, Zhigang; Hanidziar, Dusan; Goel, Nipun; Putheti, Prabhakar; Movahedi, Babak; Libermann, Towia A; Strom, Terry B

    2012-09-18

    The promise of islet cell transplantation cannot be fully realized in the absence of improvements in engraftment of resilient islets. The marginal mass of islets surviving the serial peritransplant insults may lead to exhaustion and thereby contribute to an unacceptably high rate of intermediate and long-term graft loss. Hence, we have studied the effects of treatment with alpha 1-antitrypsin (AAT) in a syngeneic nonautoimmune islet graft model. A marginal number of syngeneic mouse islets were transplanted into nonautoimmune diabetic hosts and islet function was analyzed in control and AAT treated hosts. In untreated controls, marginal mass islet transplants did not restore euglycemia. Outcomes were dramatically improved by short-term AAT treatment. Transcriptional profiling identified 1,184 differentially expressed transcripts in AAT-treated hosts at 3 d posttransplantation. Systems-biology-based analysis revealed AAT down-regulated regulatory hubs formed by inflammation-related molecules (e.g., TNF-α, NF-κB). The conclusions yielded by the systems-biology analysis were rigorously confirmed by QRT-PCR and immunohistology. These data suggest that short-term AAT treatment of human islet transplant recipients may be worthy of a clinical trial.

  4. Cytomegalovirus-induced gammadelta T cells associate with reduced cancer risk after kidney transplantation.

    PubMed

    Couzi, Lionel; Levaillant, Yann; Jamai, Abdellah; Pitard, Vincent; Lassalle, Regis; Martin, Karin; Garrigue, Isabelle; Hawchar, Omar; Siberchicot, François; Moore, Nicholas; Moreau, Jean-François; Dechanet-Merville, Julie; Merville, Pierre

    2010-01-01

    An increase in the number of blood gammadelta T cells follows cytomegalovirus (CMV) infection in kidney transplant recipients. These cells react against CMV-infected cells and tumor epithelial cells in vitro. We hypothesized that these CMV-induced gammadelta T cells play a protective role against cancer in kidney transplant recipients. We performed a longitudinal case-control study involving 18 recipients who developed cancer between 2 and 6 yr after transplantation and 45 recipients who did not. The median percentage of gammadelta T cells among total lymphocytes in patients with malignancies was significantly lower compared with that in control patients at 6, 12, and 18 mo before the diagnosis of cancer. Patients with a gammadelta T cell percentage of more than 4% were protected from cancer. An increase of the Vdelta2(neg) gammadelta T cell subset significantly associated with lower incidence of cancer only in recipients who experienced pre- or postgraft CMV infection. Finally, a retrospective follow-up of 131 recipients for 8 yr revealed that CMV-naive recipients had an approximately 5-fold higher risk of cancer compared with CMV-exposed patients. In summary, these results suggest a protective role of CMV exposure against cancer in kidney transplant recipients.

  5. Selecting suitable solid organ transplant donors: Reducing the risk of donor-transmitted infections.

    PubMed

    Jr, Christopher S Kovacs; Koval, Christine E; van Duin, David; de Morais, Amanda Guedes; Gonzalez, Blanca E; Avery, Robin K; Mawhorter, Steven D; Brizendine, Kyle D; Cober, Eric D; Miranda, Cyndee; Shrestha, Rabin K; Teixeira, Lucileia; Mossad, Sherif B

    2014-06-24

    Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via transplantation. Donor-transmitted infections cause increased morbidity and mortality to the recipient. In recent years, a series of high-profile transmissions of infections have occurred in organ recipients prompting increased attention on the process of improving the selection of an appropriate donor that balances the shortage of needed allografts with an approach that mitigates the risk of donor-transmitted infection to the recipient. Important advances focused on improving donor screening diagnostics, using previously excluded high-risk donors, and individualizing the selection of allografts to recipients based on their prior infection history are serving to increase the donor pool and improve outcomes after transplant. This article serves to review the relevant literature surrounding this topic and to provide a suggested approach to the selection of an appropriate solid organ transplant donor.

  6. Selecting suitable solid organ transplant donors: Reducing the risk of donor-transmitted infections

    PubMed Central

    Jr, Christopher S Kovacs; Koval, Christine E; van Duin, David; de Morais, Amanda Guedes; Gonzalez, Blanca E; Avery, Robin K; Mawhorter, Steven D; Brizendine, Kyle D; Cober, Eric D; Miranda, Cyndee; Shrestha, Rabin K; Teixeira, Lucileia; Mossad, Sherif B

    2014-01-01

    Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via transplantation. Donor-transmitted infections cause increased morbidity and mortality to the recipient. In recent years, a series of high-profile transmissions of infections have occurred in organ recipients prompting increased attention on the process of improving the selection of an appropriate donor that balances the shortage of needed allografts with an approach that mitigates the risk of donor-transmitted infection to the recipient. Important advances focused on improving donor screening diagnostics, using previously excluded high-risk donors, and individualizing the selection of allografts to recipients based on their prior infection history are serving to increase the donor pool and improve outcomes after transplant. This article serves to review the relevant literature surrounding this topic and to provide a suggested approach to the selection of an appropriate solid organ transplant donor. PMID:25032095

  7. Thoracic transplantation.

    PubMed

    Shumway, N E

    2000-07-01

    Experimental orthotopic transplantation of the heart was accomplished in 1959. Long-term survival was achieved in 1965 with a chemical immunosuppression protocol substantially different from that used for renal and hepatic transplants. Performance characteristics of the transplanted denervated heart were found to differ only slightly from normal. It appeared by the time of the Clinical Congress of the American College of Surgeons in October 1967 that clinical heart transplantation might be justified if the concept of brain death could be legally recognized. The Stanford program in clinical heart transplantation was inaugurated on January 6, 1968 and has been in continuous operation. To date, more than 1000 patients have undergone transplantation of the heart with the 5-year survival at 75%. The first long-term success in lung transplantation occurred at Stanford in 1981, with transplantation of the heart and both lungs. In 1990 the concept of living pulmonary lobar donors was introduced and is slowly finding its clinical role. The steroid-sparing capability of cyclosporine made possible both successful lung and pediatric heart transplantation. Only the donor shortage remains as a substantial barrier to widespread thoracic transplantation. Xenotransplantation is under intense scrutiny, with some encouraging experimental results. Development of the artificial heart continues to offer some relief for patients with end-stage heart disease.

  8. Protective effect of reduced glutathione and venous systemic oxygen persufflation on rat steatotic graft following liver transplantation.

    PubMed

    Ye, Sheng; Dong, Jiahong; Han, Benli

    2010-01-01

    The aim of this study is to explore the protective effect of high-dose reduced glutathione (GSH) preconditioning and venous systemic oxygen persufflation (VSOP) on rat steatotic liver grafts following transplantation. Steatotic liver model was established by feeding rats a high-fat, high-cholesterol diet, and infusing stomach with 50% alcohol (1 mL/100g body weight/d) for 6 wk. In the pretreated group, short-term and high-dose of GSH administration and VSOP were performed. In rat orthotopic liver transplantation model, the recipient survival, liver function, hepatic microcirculation blood flow, hepatic redox, hepatocytes apoptosis and necrosis, and hepatic ultrastructure alteration were observed. In the pretreated rat steatotic grafts, hepatic GSH (from 29.43 +/- 4.83 to 41.56 +/- 8.51mg/mgprot), superoxide dismutase (SOD) (from 48.32 +/- 6.27 to 67.74 +/- 7.68 NU/mgprot), and adenosine triphosphate (ATP) (from 1.61 +/- 0.20 to 2.28 +/- 0.09 micromoles/g) were significantly increased (P < 0.05), whereas malondialdehyde (MDA) was significantly decreased (from 7.20 +/- 2.18 to 4.63 +/- 0.58 nmol/mgprot, P < 0.05). The hepatocyte necrosis of fatty liver graft was significantly reduced in the pretreated group when compared with non-treated fatty ones (37.71% +/- 9.69% versus 16.63% +/- 5.53%; t = 3.777, P = 0.014), and significantly improved liver function and hepatic ultrastructure were observed in the pretreated fatty liver group after operation. The animal survival after transplanted with fatty liver was significantly improved (chi(2) = 4.07, P = 0.0436). A short course pretreatment with high-dose GSH and oxygen persufflation during cold preservation effectively protect steatotic liver grafts from ischemic damage and significantly improve early survival rate in a rat fatty liver transplantation model.

  9. XIAP inhibition of β-cell apoptosis reduces the number of islets required to restore euglycemia in a syngeneic islet transplantation model.

    PubMed

    Plesner, Annette; Soukhatcheva, Galina; Korneluk, Robert G; Verchere, C Bruce

    2010-01-01

    Clinical pancreatic islet transplantation has great promise as a treatment for type 1 diabetes but despite recent advances, it is still limited by the need for lifelong immunosuppression, restricted availability of donor islets, and uncertainty regarding long-term graft survival. Using a syngeneic, suboptimal islet transplantation model, we asked whether adenoviral overexpression of an anti-apoptotic protein, the X-linked inhibitor of apoptosis protein (XIAP) would protect transplanted islet cells from death and reduce the number of islets required for successful transplantation. Transplantation of 100 XIAP-expressing islets into the kidney capsule of syngeneic Balb/c mice restored euglycemia in 86% of recipients, where transplantation of 100 islets transduced with a control adenovirus expressing LacZ restored euglycemia in only 27% of recipients. Analysis of islet grafts by insulin/TUNEL double immunostaining revealed fewer apoptotic beta-cells in recipients of XIAP- compared with LacZ-expressing grafts (0.8±0.5 vs. 2.4±0.8 double-positive cells/graft), suggesting that XIAP enhances graft success by inhibiting β-cell apoptosis in the immediate post-transplant period. In summary, XIAP overexpression inhibits beta cell apoptosis in syngeneic islet transplants, thereby reducing the number of islets and decreasing the number of days required to restore euglycemia. These data raise the possibility that ex vivo XIAP gene transfer in islets prior to transplantation has the potential to increase the number of donor islets available for transplantation and may enhance graft function and long-term transplant success.

  10. Automated drug dispensing system reduces medication errors in an intensive care setting.

    PubMed

    Chapuis, Claire; Roustit, Matthieu; Bal, Gaëlle; Schwebel, Carole; Pansu, Pascal; David-Tchouda, Sandra; Foroni, Luc; Calop, Jean; Timsit, Jean-François; Allenet, Benoît; Bosson, Jean-Luc; Bedouch, Pierrick

    2010-12-01

    We aimed to assess the impact of an automated dispensing system on the incidence of medication errors related to picking, preparation, and administration of drugs in a medical intensive care unit. We also evaluated the clinical significance of such errors and user satisfaction. Preintervention and postintervention study involving a control and an intervention medical intensive care unit. Two medical intensive care units in the same department of a 2,000-bed university hospital. Adult medical intensive care patients. After a 2-month observation period, we implemented an automated dispensing system in one of the units (study unit) chosen randomly, with the other unit being the control. The overall error rate was expressed as a percentage of total opportunities for error. The severity of errors was classified according to National Coordinating Council for Medication Error Reporting and Prevention categories by an expert committee. User satisfaction was assessed through self-administered questionnaires completed by nurses. A total of 1,476 medications for 115 patients were observed. After automated dispensing system implementation, we observed a reduced percentage of total opportunities for error in the study compared to the control unit (13.5% and 18.6%, respectively; p<.05); however, no significant difference was observed before automated dispensing system implementation (20.4% and 19.3%, respectively; not significant). Before-and-after comparisons in the study unit also showed a significantly reduced percentage of total opportunities for error (20.4% and 13.5%; p<.01). An analysis of detailed opportunities for error showed a significant impact of the automated dispensing system in reducing preparation errors (p<.05). Most errors caused no harm (National Coordinating Council for Medication Error Reporting and Prevention category C). The automated dispensing system did not reduce errors causing harm. Finally, the mean for working conditions improved from 1.0±0.8 to 2

  11. Effect of He-Ne laser irradiation and low-intensity millimeter waves on transplanted tumor growth

    NASA Astrophysics Data System (ADS)

    Brill, Gregory E.; Panina, Nadezda P.

    1995-01-01

    In experiments on white rats the influence of He-Ne laser radiation ((lambda) -- 632.8 nm, power density -- 1.5 mW/cm2) and electromagnetic field of extremely high frequency (42.0 - 43.3 GHz, 1 mW/cm2) on transplantability and growth of fibroadenomas of mammary glands, and influence of low power laser irradiation on transplantability and growth of Walker carcinosarcoma were investigated. Skin at the site of future transplantation underwent irradiation. He-Ne laser and EHF-radiation were stated to change properties of tissue accepting tumor cells. A single laser irradiation of the inoculation site of Walker carcinosarcoma cells produced no effect on tumor transplantability, but increased the average life span of animals. Laser and EHF irradiation increase the transplantability of fibroadeonomas but depress growth and rate of multiplication of tumor cells.

  12. Subcutaneous Transplantation of Neural Precursor Cells in Experimental Autoimmune Encephalomyelitis Reduces Chemotactic Signals in the Central Nervous System

    PubMed Central

    Ravanidis, Stylianos; Poulatsidou, Kyriaki Nepheli; Lagoudaki, Roza; Touloumi, Olga; Polyzoidou, Elena; Lourbopoulos, Athanasios; Nousiopoulou, Evangelia; Theotokis, Paschalis; Kesidou, Evangelia; Tsalikakis, Dimitrios; Karacostas, Dimitrios; Grigoriou, Maria; Chlichlia, Katerina

    2015-01-01

    Neural precursor cell (NPC) transplantation has been proposed as a therapy for multiple sclerosis (MS) and other degenerative disorders of the central nervous system (CNS). NPCs are suggested to exert immune modulation when they are transplanted in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Herein, we explore whether the effect of NPC transplantation on the clinical course and the pathological features of EAE is combined with the modulation of chemokines levels expressed in the inflamed CNS. NPCs were isolated from brains of neonatal C57/Bl6 mice and were subcutaneously administered in female mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Clinical signs of the disease and transcript analysis of the CNS in the acute phase were performed. In addition, the presence of inflammatory components in the spinal cord was evaluated and ex vivo proliferation of lymphocytes was measured. NPC recipients exhibited ameliorated clinical outcome and less pronounced pathological features in their spinal cord. Downregulation of chemokine mRNA levels throughout the CNS was correlated with diminished Mac-3-, CD3-, and CD4-positive cells and reduced expression levels of antigen-presenting molecules in the spinal cord. Moreover, NPC transplantation resulted in lymphocyte-related, although not splenocyte-related, peripheral immunosuppression. We conclude that NPCs ameliorated EAE potentially by modulating the levels of chemokines expressed in the inflamed CNS, thus resulting in the impaired recruitment of immune cells. These findings further contribute to the better understanding of NPCs’ immunomodulatory properties in neuroinflammatory disorders, and may lead to faster translation into potential clinical use. Significance Endogenous neural precursor cells of the central nervous system are able to migrate and differentiate toward mature cells to repair an injury. There is increasing evidence that autologous transplantation of these cells in

  13. Intensity of MRI Gadolinium Enhancement in Cerebral Adrenoleukodystrophy: A Biomarker for Inflammation and Predictor of Outcome following Transplantation in Higher Risk Patients.

    PubMed

    Miller, W P; Mantovani, L F; Muzic, J; Rykken, J B; Gawande, R S; Lund, T C; Shanley, R M; Raymond, G V; Orchard, P J; Nascene, D R

    2016-02-01

    Outcomes following hematopoietic stem cell transplantation for higher risk childhood-onset cerebral adrenoleukodystrophy are variable. We explored whether a brain MR imaging gadolinium intensity scoring system improves prediction of neurologic outcome. We developed a 4-point scale of gadolinium intensity relative to the choroid plexus: 0 = no enhancement; 1 = hypointense; 2 = isointense; 3 = hyperintense. The interobserver concordance of the scale was assessed on 30 randomly chosen studies. Scores were generated for 64 evaluable patients and compared with CSF chitotriosidase levels, a known inflammatory marker correlating with outcomes following transplantation. For 25 evaluable higher risk patients (Loes ≥10), the gadolinium intensity score was compared with longer term posttransplantation clinical change. The gadolinium intensity scoring system showed good interobserver reproducibility (κ = 0.72). Of 64 evaluable boys, the score positively correlated with average concomitant CSF chitotriosidase activity in nanograms/milliliter/hour: 0: 2717, n = 5; 1: 3218, n = 13; 2: 6497, n = 23; and 3: 12,030, n = 23 (P < .01). For 25 evaluable higher risk patients, more intense pretransplantation brain MR imaging gadolinium enhancement predicted greater average loss on the adrenoleukodystrophy neurologic function scale following transplantation: 0/1: adrenoleukodystrophy neurologic function scale score difference = 4.3, n = 7; 2/3: adrenoleukodystrophy neurologic function scale score difference = 10.4, n = 18 (P = .05). Gadolinium enhancement intensity on brain MR imaging can be scored simply and reproducibly for cerebral adrenoleukodystrophy. The enhancement score significantly correlates with chitotriosidase. In boys with higher risk cerebral disease (Loes ≥10), the enhancement score itself predicts neurologic outcome following treatment. Such data may help guide treatment decisions for clinicians and families. © 2016 by American Journal of Neuroradiology.

  14. Strain-induced Damage Reduces Echo Intensity Changes in Tendon during Loading

    PubMed Central

    Duenwald-Kuehl, Sarah; Lakes, Roderic; Vanderby, Ray

    2012-01-01

    Tendon functionality is related to its mechanical properties. Tendon damage leads to a reduction in mechanical strength and altered biomechanical behavior, and therefore leads to compromised ability to carry out normal functions such as joint movement and stabilization. Damage can also accumulate in the tissue and lead to failure. A noninvasive method with which to measure such damage potentially could quantify structural compromise from tendon injury and track improvement over time. In this study, tendon mechanics are measured before and after damage is induced by “overstretch” (strain exceeding the elastic limit of the tissue) using a traditional mechanical test system while ultrasonic echo intensity (average gray scale brightness in a B-mode image) is recorded using clinical ultrasound. The diffuse damage caused by overstretch lowered the stress at a given strain in the tissue and decreased viscoelastic response. Overstretch also lowered echo intensity changes during stress relaxation and cyclic testing. As the input strain during overstretch increased, stress levels and echo intensity changes decreased. Also, viscoelastic parameters and time-dependent echo intensity changes were reduced. PMID:22542220

  15. Clinical effect of reducing curing times with high-intensity LED lights

    PubMed Central

    Ward, Justin D.; Wolf, Bethany J.; Leite, Luis P.; Zhou, Jing

    2016-01-01

    Objective To evaluate the clinical performance of brackets cured with a high-intensity, light-emitting diode (LED) with a shorter curing time. Materials and Methods Thirty-four patients and a total of 680 brackets were examined using a randomized split-mouth design. The maxillary right and mandibular left quadrants were cured for 6 seconds with a high-intensity LED light (3200 mW/cm2) and the maxillary left and mandibular right quadrants were cured for 20 seconds with a standard-intensity LED light (1200 mW/cm2). Alternating patients had the quadrants inverted for the curing protocol. The number and date of each first-time bracket failure was recorded from 199 to 585 days posttreatment. Results The bracket failure rate was 1.18% for both curing methods. The proportion of bracket failure was not significantly different between curing methods (P = 1.000), genders (P = 1.000), jaws (P = .725), sides (P = .725), or quadrants (P = .547). Posterior teeth exhibited a greater proportion of failures (2.21%) relative to anterior teeth (0.49%), although the difference was not statistically significant (P = .065). Conclusions No difference was found in bond failure rates between the two curing methods. Both methods showed bond failure rates low enough to be considered clinically sufficient. The high-intensity LED light used with a shorter curing time may be considered an advantage due to the reduced chair time. PMID:25760887

  16. Rubber transcystic drainage reduces the post-removal biliary complications in liver transplantation: a matched case-control study.

    PubMed

    Panaro, F; Glaise, A; Miggino, M; Bouyabrine, H; Carabalona, Jp; Gallix, B; Navarro, F

    2013-01-01

    Bile duct (BD) complications continue to be the "Achilles' heel" of liver transplantation, and the utilization of bile duct drainage is still on debate. We describe the results of a less invasive rubber trancystic biliary drainage (TBD) compared to a standard silicone T-tube (TT). The transplanted patients (n = 248), over a period of 5 years with a TBD (n = 20), were matched 1:2 with control patients with a TT (n = 40). Primary end points were the overall incidence of BD complications and graft and patient survival. Secondary end points included the complications after the drainage removal. Although the bile duct leakage rates were not significantly different between both groups, the TT group had a significantly higher rate of overall 1-year BD stenosis (40 versus 10 %) (p = 0.036). Three-year patient/graft survival rates were 83.2/80.1 and 84.4/84.4 % for the TT and TBD groups, respectively. The postoperative BD complications, after drainage removal (peritonitis and stenosis), were significantly reduced (p = 0.011) with the use of a TBD. The use of rubber TBD in liver transplant recipients does not increase the number of BD complications compared to the T-tube. Furthermore, less BD anastomotic stenosis and post-removal complications were observed in the TBD group compared to the TT group.

  17. Galactose therapy reduces proteinuria in patients with recurrent focal segmental glomerulosclerosis after kidney transplantation.

    PubMed

    Robson, Kate; Hill, Prudence; Langsford, David; Dwyer, Karen; Goodman, David; Langham, Robyn

    2015-03-01

    Primary focal segmental glomerulosclerosis is an important cause of end-stage kidney disease with a high rate of recurrent disease after kidney transplantation. Current therapy achieves remission in only half of patients. Recent interest has focused on the potential role of galactose in binding and inactivating the putative circulating permeability factor, supported by in vitro and clinical case report studies. Orally active and without major adverse effects, galactose has a favourable treatment profile compared with current immunosuppressive treatment options. We describe our experience using galactose therapy in two patients with recurrent focal segmental glomerulosclerosis after renal transplantation. Galactose was associated with symptomatic improvement and stabilization of graft function in one case; the other case was complicated by concurrent malignancy. In both cases, we observed a marked reduction in proteinuria with galactose treatment.

  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. Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection.

    PubMed

    Porubsky, Stefan; Wang, Shijun; Kiss, Eva; Dehmel, Stefan; Bonrouhi, Mahnaz; Dorn, Tatjana; Luckow, Bruno; Brakebusch, Cord; Gröne, Hermann-Josef

    2011-01-01

    Rhoh is a hematopoietic system-specific GTPase. Rhoh-deficient T cells have been shown to have a defect in TCR signaling manifested during their thymic development. Our aims were to investigate the phenotype of peripheral Rhoh-deficient T cells and to explore in vivo the potential benefit of Rhoh deficiency in a clinically relevant situation, in which T-cell inhibition is desirable. In murine allogenic kidney transplantation, Rhoh deficiency caused a significant 75% reduction of acute and chronic transplant rejection accompanied by 75% lower alloantigen-specific antibody levels and significantly better graft function. This effect was independent of the lower T-cell numbers in Rhoh-deficient recipients, because injection of equal numbers of Rhoh-deficient or control T cells into kidney transplanted mice with SCID led again to a significant 60% reduction of rejection. Mixed lymphocyte reaction revealed that the weaker alloreactivity was associated with a 85% lower cytotoxicity and a 50-80% lower cytokine release in Rhoh-deficient T cells without an influence on the secretion itself. Antigen uptake and presentation in DC were unaffected by Rhoh deficiency. These findings stress the importance of Rhoh for the function of peripheral T cells. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Reducing stress and anxiety in caregivers of lung transplant patients: benefits of mindfulness meditation.

    PubMed

    Haines, J; Spadaro, K C; Choi, J; Hoffman, L A; Blazeck, A M

    2014-01-01

    Caregivers are a vital resource in the care of transplant candidates or recipients. However, few strategies have been tested that attempt to decrease the stress and anxiety they commonly encounter. To test the feasibility of using mindfulness-based stress reduction (MBSR) techniques to decrease stress and anxiety in caregivers of lung transplant candidates/recipients who required admission to an acute care facility. 30 caregivers of lung transplant candidates/recipients were recruited during hospitalization of their significant other. Each completed the perceived stress scale (PSS) and state trait anxiety inventory (STAI) before and 4 weeks after receiving a DVD that demonstrated MBSR techniques. Participants were asked to practice MBSR techniques for 5-15 min a day for 4 weeks. The participants had a mean±SD age of 55.6±13.6 years; 77% of participants were female and 93% Caucasian. The mean PSS and STAI (trait and anxiety) scores of caregivers were higher than population norms pre- and post-intervention. Scores for caregivers who stated they watched the entire DVD and practiced MBSR techniques as requested (n=15) decreased significantly from pre- to post-testing for perceived stress (p=0.001), state anxiety (p=0.003) and trait anxiety (p=0.006). Scores for those who watched some or none of the DVD (n=15) did not change significantly. Caregivers can benefit from stress reduction techniques using MBSR.

  1. Isochoric heating of reduced mass targets by ultra-intense laser produced relativistic electrons

    SciTech Connect

    Neumayer, P; Lee, H J; Offerman, D; Shipton, E; Kemp, A; Kritcher, A L; Doppner, T; Back, C A; Glenzer, S H

    2009-02-04

    We present measurements of the chlorine K-alpha emission from reduced mass targets, irradiated with ultra-high intensity laser pulses. Chlorinated plastic targets with diameters down to 50 micrometers and mass of a few 10{sup -8} g were irradiated with up to 7 J of laser energy focused to intensities of several 10{sup 19} W/cm{sup 2}. The conversion of laser energy to K-alpha radiation is measured, as well as high resolution spectra that allow observation of line shifts, indicating isochoric heating of the target up to 18 eV. A zero-dimensional 2-temperature equilibration model, combined with electron impact K-shell ionization and post processed spectra from collisional radiative calculations reproduces the observed K-alpha yields and line shifts, and shows the importance of target expansion due to the hot electron pressure.

  2. Reducing infection transmission in solid organ transplantation through donor nucleic acid testing: a cost-effectiveness analysis.

    PubMed

    Lai, J C; Kahn, J G; Tavakol, M; Peters, M G; Roberts, J P

    2013-10-01

    For solid organ transplant (SOT) donors, nucleic acid-amplification testing (NAT) may reduce human immunodeficiency virus (HIV) and hepatitis C virus (HCV) transmission over antibody (Ab) testing given its shorter detection window period. We compared SOT donor NAT + Ab versus Ab alone using decision models to estimate incremental cost-effectiveness ratios (ICERs; cost per quality-adjusted life year [QALY] gained) from the societal perspective across a range of HIV/HCV prevalence values and NAT costs. The cost per QALY gained was calculated for two scenarios: (1) favorable: low cost ($150/donor)/high prevalence (HIV: 1.5%; HCV: 18.2%) and (2) unfavorable: high cost ($500/donor)/low prevalence (HIV: 0.1%; HCV: 1.5%). In the favorable scenario, adding NAT screening cost $161 013 per QALY gained for HIV was less costly) for HCV, and cost $86 653 per QALY gained for HIV/HCV combined. For the unfavorable scenario, the costs were $15 568 484, $221 006 and $10 077 599 per QALY gained, respectively. Universal HCV NAT + Ab for donors appears cost-effective to reduce infection transmission from SOT donors, while HIV NAT + Ab is not, except where HIV NAT is ≤$150/donor and prevalence is ≥1.5%. Our analyses provide important data to facilitate the decision to implement HIV and HCV NAT for deceased SOT donors and shape national policy regarding how to reduce infection transmission in SOT. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  3. Walk or run? Is high-intensity exercise more effective than moderate-intensity exercise at reducing cardiovascular risk?

    PubMed

    Rankin, A J; Rankin, A C; MacIntyre, P; Hillis, W S

    2012-05-01

    The benefits of exercise in the prevention of cardiovascular disease are irrefutable. However, the optimum 'dose' of exercise in order to derive the maximum cardiovascular benefit is not certain. Current national and international guidelines advocate the benefits of moderate-intensity exercise. The relative benefits of vigorous versus moderate-intensity exercise have been studied in large epidemiological studies, addressing coronary heart disease and mortality, as well as smaller randomized clinical trials which assessed effects on cardiovascular risk factors. There is evidence that exercise intensity, rather than duration or frequency, is the most important variable in determining cardioprotection. Applying this evidence into practice must take into account the impact of baseline fitness, compliance and the independent risk associated with a sedentary lifestyle. This review aims to evaluate the role of exercise intensity in the reduction of cardiovascular risk, and answer the question: should you be advising your patients to walk or run?

  4. Intrastriatal transplantation of cross-species fetal striatal cells reduces abnormal movements in a primate model of Huntington disease.

    PubMed Central

    Hantraye, P; Riche, D; Maziere, M; Isacson, O

    1992-01-01

    Huntington disease is a neurological movement disorder involving massive neuronal death in the caudate-putamen region of the brain. Neither preventive nor curative therapy exists for this disease. The implantation of cross-species striatal neural precursor cells into the lesioned striatum of nonhuman primates (baboons) reduced the abnormal movements seen in the disease model. These abnormal movements reappeared after immunological rejection of the implanted striatal cells and were not modified by transplantation with nonstriatal cells. These findings encourage further experimentation toward the use of cell sources other than human fetal cells in a potential clinical application to Huntington disease. Images PMID:1533285

  5. Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial

    PubMed Central

    De Simone, P; Nevens, F; De Carlis, L; Metselaar, H J; Beckebaum, S; Saliba, F; Jonas, S; Sudan, D; Fung, J; Fischer, L; Duvoux, C; Chavin, K D; Koneru, B; Huang, M A; Chapman, W C; Foltys, D; Witte, S; Jiang, H; Hexham, J M; Junge, G

    2012-01-01

    In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30±5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced-exposure tacrolimus (EVR+Reduced TAC) or (iii) standard-exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7% versus 9.7% (−3.0%; 95% CI −8.7, 2.6%; p<0.001 for noninferiority [12% margin]). tBPAR occurred in 2.9% of EVR+Reduced TAC patients versus 7.0% of TAC Controls (p = 0.035). The change in adjusted estimated GFR from randomization to month 12 was superior with EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m2, 97.5% CI 3.74, 13.27 mL/min/1.73 m2, p<0.001 for superiority). Drug discontinuation for adverse events occurred in 25.7% of EVR+Reduced TAC and 14.1% of TAC Controls (relative risk 1.82, 95% CI 1.25, 2.66). Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95% CI 1.03, 3.00). Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function, compared to a standard tacrolimus exposure regimen 12 months after liver transplantation. PMID:22882750

  6. Autologous subcutaneous adipose tissue transplants improve adipose tissue metabolism and reduce insulin resistance and fatty liver in diet-induced obesity rats.

    PubMed

    Torres-Villalobos, Gonzalo; Hamdan-Pérez, Nashla; Díaz-Villaseñor, Andrea; Tovar, Armando R; Torre-Villalvazo, Ivan; Ordaz-Nava, Guillermo; Morán-Ramos, Sofía; Noriega, Lilia G; Martínez-Benítez, Braulio; López-Garibay, Alejandro; Torres-Landa, Samuel; Ceballos-Cantú, Juan C; Tovar-Palacio, Claudia; Figueroa-Juárez, Elizabeth; Hiriart, Marcia; Medina-Santillán, Roberto; Castillo-Hernández, Carmen; Torres, Nimbe

    2016-09-01

    Long-term dietary and pharmacological treatments for obesity have been questioned, particularly in individuals with severe obesity, so a new approach may involve adipose tissue transplants, particularly autologous transplants. Thus, the aim of this study was to evaluate the metabolic effects of autologous subcutaneous adipose tissue (SAT) transplants into two specific intraabdominal cavity sites (omental and retroperitoneal) after 90 days. The study was performed using two different diet-induced obesity (DIO) rat models: one using a high-fat diet (HFD) and the other using a high-carbohydrate diet (HCHD). Autologous SAT transplant reduced hypertrophic adipocytes, improved insulin sensitivity, reduced hepatic lipid content, and fasting serum-free fatty acids (FFAs) concentrations in the two DIO models. In addition, the reductions in FFAs and glycerol were accompanied by a greater reduction in lipolysis, assessed via the phosphorylation status of HSL, in the transplanted adipose tissue localized in the omentum compared with that localized in the retroperitoneal compartment. Therefore, the improvement in hepatic lipid content after autologous SAT transplant may be partially attributed to a reduction in lipolysis in the transplanted adipose tissue in the omentum due to the direct drainage of FFAs into the liver. The HCHD resulted in elevated fasting and postprandial serum insulin levels, which were dramatically reduced by the autologous SAT transplant. In conclusion, the specific intraabdominal localization of the autologous SAT transplant improved the carbohydrate and lipid metabolism of adipose tissue in obese rats and selectively corrected the metabolic parameters that are dependent on the type of diet used to generate the DIO model. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  7. Face in profile view reduces perceived facial expression intensity: an eye-tracking study.

    PubMed

    Guo, Kun; Shaw, Heather

    2015-02-01

    Recent studies measuring the facial expressions of emotion have focused primarily on the perception of frontal face images. As we frequently encounter expressive faces from different viewing angles, having a mechanism which allows invariant expression perception would be advantageous to our social interactions. Although a couple of studies have indicated comparable expression categorization accuracy across viewpoints, it is unknown how perceived expression intensity and associated gaze behaviour change across viewing angles. Differences could arise because diagnostic cues from local facial features for decoding expressions could vary with viewpoints. Here we manipulated orientation of faces (frontal, mid-profile, and profile view) displaying six common facial expressions of emotion, and measured participants' expression categorization accuracy, perceived expression intensity and associated gaze patterns. In comparison with frontal faces, profile faces slightly reduced identification rates for disgust and sad expressions, but significantly decreased perceived intensity for all tested expressions. Although quantitatively viewpoint had expression-specific influence on the proportion of fixations directed at local facial features, the qualitative gaze distribution within facial features (e.g., the eyes tended to attract the highest proportion of fixations, followed by the nose and then the mouth region) was independent of viewpoint and expression type. Our results suggest that the viewpoint-invariant facial expression processing is categorical perception, which could be linked to a viewpoint-invariant holistic gaze strategy for extracting expressive facial cues.

  8. In-hospital fellow coverage reduces communication errors in the surgical intensive care unit.

    PubMed

    Williams, Mallory; Alban, Rodrigo F; Hardy, James P; Oxman, David A; Garcia, Edward R; Hevelone, Nathanael; Frendl, Gyorgy; Rogers, Selwyn O

    2014-06-01

    Staff coverage strategies of intensive care units (ICUs) impact clinical outcomes. High-intensity staff coverage strategies are associated with lower morbidity and mortality. Accessible clinical expertise, team work, and effective communication have all been attributed to the success of this coverage strategy. We evaluate the impact of in-hospital fellow coverage (IHFC) on improving communication of cardiorespiratory events. A prospective observational study performed in an academic tertiary care center with high-intensity staff coverage. The main outcome measure was resident to fellow communication of cardiorespiratory events during IHFC vs home coverage (HC) periods. Three hundred twelve cardiorespiratory events were collected in 114 surgical ICU patients in 134 study days. Complete data were available for 306 events. One hundred three communication errors occurred. IHFC was associated with significantly better communication of events compared to HC (P<.0001). Residents communicated 89% of events during IHFC vs 51% of events during HC (P<.001). Communication patterns of junior and midlevel residents were similar. Midlevel residents communicated 68% of all on-call events (87% IHFC vs 50% HC, P<.001). Junior residents communicated 66% of events (94% IHFC vs 52% HC, P<.001). Communication errors were lower in all ICUs during IHFC (P<.001). IHFC reduced communication errors. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Subnormothermic ex vivo liver perfusion reduces endothelial cell and bile duct injury after donation after cardiac death pig liver transplantation.

    PubMed

    Knaak, Jan M; Spetzler, Vinzent N; Goldaracena, Nicolas; Boehnert, Markus U; Bazerbachi, Fateh; Louis, Kristine S; Adeyi, Oyedele A; Minkovich, Leonid; Yip, Paul M; Keshavjee, Shaf; Levy, Gary A; Grant, David R; Selzner, Nazia; Selzner, Markus

    2014-11-01

    An ischemic-type biliary stricture (ITBS) is a common feature after liver transplantation using donation after cardiac death (DCD) grafts. We compared sequential subnormothermic ex vivo liver perfusion (SNEVLP; 33°C) with cold storage (CS) for the prevention of ITBS in DCD liver grafts in pig liver transplantation (n = 5 for each group). Liver grafts were stored for 10 hours at 4°C (CS) or preserved with combined 7-hour CS and 3-hour SNEVLP. Parameters of hepatocyte [aspartate aminotransferase (AST), international normalized ratio (INR), factor V, and caspase 3 immunohistochemistry], endothelial cell (EC; CD31 immunohistochemistry and hyaluronic acid), and biliary injury and function [alkaline phosphatase (ALP), total bilirubin, and bile lactate dehydrogenase (LDH)] were determined. Long-term survival (7 days) after transplantation was similar between the SNEVLP and CS groups (60% versus 40%, P = 0.13). No difference was observed between SNEVLP- and CS-treated animals with respect to the peak of serum INR, factor V, or AST levels within 24 hours. CD31 staining 8 hours after transplantation demonstrated intact EC lining in SNEVLP-treated livers (7.3 × 10(-4) ± 2.6 × 10(-4) cells/μm(2)) but not in CS-treated livers (3.7 × 10(-4) ± 1.3 × 10(-4) cells/μm(2) , P = 0.03). Posttransplant SNEVLP animals had decreased serum ALP and serum bilirubin levels in comparison with CS animals. In addition, LDH in bile fluid was lower in SNEVLP pigs versus CS pigs (14 ± 10 versus 60 ± 18 μmol/L, P = 0.02). Bile duct histology revealed severe bile duct necrosis in 3 of 5 animals in the CS group but none in the SNEVLP group (P = 0.03). Sequential SNEVLP preservation of DCD grafts reduces bile duct and EC injury after liver transplantation. © 2014 American Association for the Study of Liver Diseases.

  10. Mindfulness meditation training to reduce symptom distress in transplant patients: rationale, design, and experience with a recycled waitlist.

    PubMed

    Gross, Cynthia R; Kreitzer, Mary Jo; Reilly-Spong, Maryanne; Winbush, Nicole Y; Schomaker, E Katherine; Thomas, William

    2009-02-01

    Solid organ transplant recipients must take immune suppressive medications that have side effects, cause complications, and lead to distressing symptoms that reduce health-related quality of life (QOL). Mindfulness meditation has been shown to reduce these symptoms in other patient populations, and it is unlikely to interfere with the immune suppressive medication regimen. This article describes the design and rationale of a clinical trial to determine whether training in mindfulness meditation can reduce depression, anxiety and insomnia after transplantation, and summarizes baseline characteristics of the participants. Transplant recipients were randomized in equal numbers to one of three arms: a Mindfulness-based Stress Reduction (MBSR) program consisting of 8 weeks of group instruction, home practice and telephone monitoring; a time and attention control Health Education program; or a waitlist arm. After serving 6 months as waitlist controls, these participants were re-randomized to MBSR or Health Education. Evaluations were obtained at baseline (prior to the active interventions), 8 weeks, 6 months, and 1 year (after randomization to MBSR or Health Education only). The primary analysis will compare composite symptom scores between MBSR and Health Education, initially or after serving in the waitlist. Subsequent analyses will compare these two groups on depression, anxiety, and insomnia symptom scales and secondary outcomes of health-related QOL, actigraphy, and health care utilization. A separate analysis, using only data collected before re-randomization, will compare short-term outcomes between the waitlist and active treatment arms. One hundred fifty recipients were randomized and 72% of waitlist participants (31/43) were recycled to an active intervention after 6 months. Patient characteristics were balanced across trial arms after initial and secondary randomizations. Transplant recipients are a very select population. Their adherence to the intervention

  11. [Reducing patient pressure sore incidence in the surgical intensive care unit].

    PubMed

    Chung, Hui-Ting; Shu, Ling-Hui; Pan, Chao-Chun; Yang, Shu-Yen; Chen, Wan-I

    2011-06-01

    Pressure ulcers were an increasingly significant problem among patients in the authors' ward. The eight patients diagnosed with pressure ulcers (0.42% of all inpatients) during the first half of 2009 represented a 140% increase over the first half of 2008 (0.28% of all inpatients). This project was designed to reduce pressure ulcer incidence in the surgical intensive care unit (ICU) to 0.05%. Intervention measures included: 1) holding professional training on preventing pressure ulcers; 2) specifying appropriate patient turnover tools; 3) creating and distributing to nurses a proper turnover technique and positioning manual; 4) creating and distributing to nurses a comprehensive patient skin inspection checklist; and 5) organizing a permanent pressure ulcer care quality and audit committee. Pressure ulcer incidence fell from 0.42% to 0.04% following implementation of the methods. Results demonstrate the effectiveness of using the proposed methods to reduce pressure ulcer incidence and enhance nursing care quality.

  12. Benson Relaxation Technique in Reducing Pain Intensity in Women After Cesarean Section.

    PubMed

    Solehati, Tetti; Rustina, Yeni

    2015-06-01

    Post-cesarean section women experience pain due to operative trauma. Pain sensation can be reduced by pain management. Pharmacological and non-pharmacological treatments can be used. The Benson Relaxation Technique is a non-pharmacological way suitable to reduce pain, but there are limited studies on its post-cesarean section use. This study aimed to determine the effect of Benson Relaxation Technique in reducing pain intensity in women after cesarean section. This was a quasi-experiment study with pre and post-test design. A prospective, not blind, randomized assign, two groups parallel study was conducted in Cibabat hospital Cimahi as intervention group (IG) and Sartika Asih hospital as control group (CG). Post cesarean section women with quota sampling who met the inclusion criteria were consecutively assigned to either experimental (n = 30) or control group (n = 30). Women in the experimental group received the Benson relaxation technique and those in the control group received regular care from the health workers. The outcome pain severity was measured by visual analogue scale. Those instruments were applied before and after intervention. The mean of pain score before intervention at CG was 4.43 cm. It was decreased to 4.40 cm (1 min), 4.27 cm (12 h), 4.10 cm (24 h), 4.00 cm (36 h), 3.93 cm (48 h), 3.83 cm (60 h), 3.67 cm (72 h) and 3.51 cm (84 h). Meanwhile, the IG was 4.97 cm. It was decreased to 4.90 cm (1 min), 4.23 cm (12 h), 3.57 cm (24 h), 3.03 cm (36 h), 2.77 cm (48 h), 2.73 cm (60 h), 2.67 cm (72 h) and 2.63 cm (84 h). The study found a significant difference comparing pain intensity before and after the intervention in CG and IG (P = 0.001), but pain reduced in IG more than CG. The Benson relaxation could reduce pain intensity in women after cesarean section.

  13. Vertical intensity modulation for improved radiographic penetration and reduced exclusion zone

    NASA Astrophysics Data System (ADS)

    Bendahan, J.; Langeveld, W. G. J.; Bharadwaj, V.; Amann, J.; Limborg, C.; Nosochkov, Y.

    2016-09-01

    In the present work, a method to direct the X-ray beam in real time to the desired locations in the cargo to increase penetration and reduce exclusion zone is presented. Cargo scanners employ high energy X-rays to produce radiographic images of the cargo. Most new scanners employ dual-energy to produce, in addition to attenuation maps, atomic number information in order to facilitate the detection of contraband. The electron beam producing the bremsstrahlung X-ray beam is usually directed approximately to the center of the container, concentrating the highest X-ray intensity to that area. Other parts of the container are exposed to lower radiation levels due to the large drop-off of the bremsstrahlung radiation intensity as a function of angle, especially for high energies (>6 MV). This results in lower penetration in these areas, requiring higher power sources that increase the dose and exclusion zone. The capability to modulate the X-ray source intensity on a pulse-by-pulse basis to deliver only as much radiation as required to the cargo has been reported previously. This method is, however, controlled by the most attenuating part of the inspected slice, resulting in excessive radiation to other areas of the cargo. A method to direct a dual-energy beam has been developed to provide a more precisely controlled level of required radiation to highly attenuating areas. The present method is based on steering the dual-energy electron beam using magnetic components on a pulse-to-pulse basis to a fixed location on the X-ray production target, but incident at different angles so as to direct the maximum intensity of the produced bremsstrahlung to the desired locations. The details of the technique and subsystem and simulation results are presented.

  14. Antioxidant capacity reduced in scallions grown under elevated CO 2 independent of assayed light intensity

    NASA Astrophysics Data System (ADS)

    Levine, Lanfang H.; Paré, Paul W.

    2009-10-01

    Long-duration manned space missions mandate the development of a sustainable life support system and effective countermeasures against damaging space radiation. To mitigate the risk of inevitable exposure to space radiation, cultivation of fresh fruits and vegetables rich in antioxidants is an attractive alternative to pharmacological agents. However it has yet to be established whether antioxidant properties of crops can be preserved or enhanced in a space environment where environmental conditions differ from that which plants have acclimated to on earth. Scallion ( Allium fistulosum) rich in antioxidant vitamins C and A, and flavonoids was used as a model plant to study the impact of a range of CO 2 concentrations and light intensities that are likely encountered in a space habitat on food quality traits. Scallions were hydroponically grown in controlled environmental chambers under a combination of 3 CO 2 concentrations of 400, 1200 and 4000 μmol mol -1 and 3 light intensity levels of 150, 300, 450 μmol m -2 s -1. Total antioxidant activity (TAA) of scallion extracts was determined using a radical cation scavenging assay. Both elevated CO 2 and increasing light intensity enhanced biomass accumulation, but effects on TAA (based on dry weight) differed. TAA was reduced for plants grown under elevated CO 2, but remained unchanged with increases in light intensity. Elevated CO 2 stimulated greater biomass production than antioxidants, while an increase in photosynthetic photo flux promoted the synthesis of antioxidant compounds at a rate similar to that of biomass. Consequently light is a more effective stimulus than CO 2 for antioxidant production.

  15. An intensive effort to reduce fertility in Taoyuan County, Taiwan: 1973 intermediate report.

    PubMed

    Sun, T H

    1974-08-01

    From 1951 to 1973, the crude birthrate in Taiwan declined more than 50%; there is still work to be done to reduce the annual growth rate to less than 1%. This reduction was due to a change in the age composition of the population, an increase in the age at marriage, and reduced marital fertility (contraception and induced abortion). Further reductions will rely mainly on further reductions in marital fertility. An intensive family planning program, reaching 60% of eligible couples and concentrating on the pill, loop, and condom methods, has been active since 1964. Fertility will decline when the ideal family size lowers and when son preference is eliminated. 2 high fertility counties, Taipei and Taoyuan, were selected for intensified activity in 1972. Imp roved activities included: 1) systematic home visits and use of a control card system, 2) strengthened supervision of workers, 3) improved training and publicity programs, 4) use of incentives for loop referrals, and 5) encouragement of word-of-mouth publicity by satisfied contraceptors. Schedules and targets were met or exceeded. The long-range results cannot be measured yet. Reasons for the greater success of the project in Taoyuan than in Taipei are examined. Lessons learned from the project are enumerated. It can be seen that intensive local government operations can be successful, particularly when more and better paid workers are used.

  16. High intensity and reduced volume training attenuates stress and recovery levels in elite swimmers.

    PubMed

    Elbe, Anne-Marie; Rasmussen, Camilla P; Nielsen, Glen; Nordsborg, Nikolai B

    2016-01-01

    This study investigated the effect of increased high-intensity interval training (HIT) at the expense of total training volume on the stress and recovery levels of elite swimmers. Forty-one elite swimmers participated in the study and were randomly assigned to either a HIT or a control group (CON). Eleven swimmers did not complete the questionnaires. For 12 weeks both groups trained ~12 h per week. The amount of HIT was ~5 h vs. 1 h, and total distance was ~17 km vs. ~35 km per week for HIT and CON, respectively. HIT was performed as 6-10 × 10-30 s maximal effort interspersed by 2-4 min of rest. The Recovery Stress Questionnaire - Sport was used to measure the swimmers' stress and recovery levels. After the 12 week intervention, the general stress level was 16.6% (2.6-30.7%; mean and 95% CI) lower and the general recovery level was 6.5% (0.7-12.4%) higher in HIT compared to the CON, after adjusting for baseline values. No significant effects could be observed in sports-specific stress or sports-specific recovery. The results indicate that increasing training intensity and reducing training volume for 12 weeks can reduce general stress and increase general recovery levels in competitive swimmers.

  17. Dark chocolate supplementation reduces the oxygen cost of moderate intensity cycling.

    PubMed

    Patel, Rishikesh Kankesh; Brouner, James; Spendiff, Owen

    2015-01-01

    Dark chocolate (DC) is abundant in flavanols which have been reported to increase the bioavailability and bioactivity of nitric oxide (NO). Increasing NO bioavailability has often demonstrated reduced oxygen cost and performance enhancement during submaximal exercise. Nine moderately-trained male participants volunteered to undertake baseline (BL) measurements that comprised a cycle V̇O(2max) test followed by cycling at 80% of their established gas exchange threshold (GET) for 20-min and then immediately followed by a two-minute time-trial (TT). Using a randomised crossover design participants performed two further trials, two weeks apart, with either 40 g of DC or white chocolate (WC) being consumed daily. Oxygen consumption, RER, heart rate and blood lactate (BLa) were measured during each trial. DC consumption increased GET and TT performance compared to both BL and WC (P < 0.05). DC consumption increased V̇O(2max) by 6% compared to BL (P < 0.05), but did not reach statistical significance compared to WC. There were no differences in the moderate-intensity cycling for V̇O₂, RER, BLa and heart rate between conditions, although, V̇O₂ and RER exhibited consistently lower trends following DC consumption compared to BL and WC, these did not reach statistical significance. Chronic supplementation with DC resulted in a higher GET and enhanced TT performance. Consequently, ingestion of DC reduced the oxygen cost of moderate intensity exercise and may be an effective ergogenic aid for short-duration moderate intensity exercise.

  18. Endocrine, metabolic, nutritional and body composition abnormalities are common in advanced intensively-treated (transplanted) multiple myeloma.

    PubMed

    Greenfield, D M; Boland, E; Ezaydi, Y; Ross, R J M; Ahmedzai, S H; Snowden, J A

    2014-07-01

    Modern treatment strategies have increased life expectancy in multiple myeloma, but little is known about the endocrine, metabolic and nutritional status of long-term survivors. We performed endocrine, metabolic, bone, body composition and nutritional evaluations in 32 patients with intensively-treated, advanced but stable, myeloma a median duration of 6 years from diagnosis and three lines of intensive treatment, including at least one haematopoietic SCT procedure. All patients were off active treatment. There was a high prevalence of endocrine dysfunction: hypothyroidism (9%), hypogonadism (65% males) and elevated prolactin (19%). Adrenocortical function was preserved despite large cumulative corticosteroid pretreatment. Biochemical markers were consistent with postmenopausal status in all females and infertility in males. Nutritionally, 59% were vitamin D insufficient/deficient, reduced serum folate in 25% and vitamin B12 in 6%. Total body DEXA scanning confirmed 'sarcopenic-obesity' in 65%, but reduced bone density was seen in a minority. We conclude that potentially correctable endocrine, metabolic and nutritional abnormalities are prevalent in heavily-treated patients with stable multiple myeloma. Preservation of bone supports the efficacy of bisphosphonate treatment from diagnosis, but sarcopenic-obesity may contribute to frailty. Ultimately, multi-system screening and appropriate interventions may optimise quality of long-term survival and further studies are warranted.

  19. Reduced dietary intake of simple sugars alters perceived sweet taste intensity but not perceived pleasantness.

    PubMed

    Wise, Paul M; Nattress, Laura; Flammer, Linda J; Beauchamp, Gary K

    2016-01-01

    Individuals who adhere to reduced-sodium diets come to prefer less salt over time, but it is unclear whether sweet taste perception is modulated by reduced sugar intake. The objective was to determine how a substantial reduction in dietary intake of simple sugars affects sweetness intensity and pleasantness of sweet foods and beverages. Healthy men and women aged 21-54 y participated for 5 mo. After the baseline month, 2 subject groups were matched for demographic characteristics, body mass index, and intake of simple sugars. One group (n = 16; 13 of whom completed key experimental manipulations) was randomly assigned to receive a low-sugar diet during the subsequent 3 mo, with instructions to replace 40% of calories from simple sugars with fats, proteins, and complex carbohydrates. The other (control) group (n = 17; 16 of whom completed the study) did not change their sugar intake. During the final month, both groups chose any diet they wished. Each month subjects rated the sweetness intensity and pleasantness of vanilla puddings and raspberry beverages that varied in sucrose concentration. ANOVA showed no systematic differences between groups in rated sweetness during the baseline or first diet month. During the second diet month, the low-sugar group rated low-sucrose pudding samples as more intense than did the control group (significant group-by-concentration interaction, P = 0.002). During the third diet month, the low-sugar subjects rated both low and high concentrations in puddings as ∼40% sweeter than did the control group (significant effect of group, P = 0.01). A weaker effect on rated sweetness was obtained for the beverages. Rated pleasantness was not affected for either of the stimuli. This experiment provides empirical evidence that changes in consumption of simple sugars influence perceived sweet taste intensity. More work is needed to determine whether sugar intake ultimately shifts preferences for sweet foods and beverages. This trial was

  20. Combined heart-kidney transplant improves post-transplant survival compared with isolated heart transplant in recipients with reduced glomerular filtration rate: Analysis of 593 combined heart-kidney transplants from the United Network Organ Sharing Database.

    PubMed

    Karamlou, Tara; Welke, Karl F; McMullan, D Michael; Cohen, Gordon A; Gelow, Jill; Tibayan, Frederick A; Mudd, James M; Slater, Matthew S; Song, Howard K

    2014-01-01

    Criteria for simultaneous heart-kidney transplant (HKTx) recipients are unclear. We characterized the evolution of combined HKTx in the United States over time compared with isolated heart transplantation (HTx) and determined factors maximizing post-transplant survival. We focused on whether a threshold estimated glomerular filtration rate (eGFR) could be identified that justified combined transplantation. A supplemented United Network Organ Sharing Dataset identified HTx and HKTx recipients from 2000 to 2010. eGFR was calculated for HTx and recipients were grouped into eGFR quintiles. Time-related mortality was compared among recipients, with multivariable factors sought using Cox proportional hazard regression models. We identified 26,183 HTx recipients, of whom 593 were HKTx recipients. HTx increased modestly over time (3.6%), whereas prevalence of HKTx increased dramatically (147%). Risk-unadjusted survival was similar among HTx recipients (8.4 ± 0.04 years) and HKTx recipients (7.7 ± 0.2 years) (P = .76). Isolated HTx recipients in the lowest eGFR quintile had decreased survival (P < .001), but those in the third eGFR quintile had superior survival, suggesting a benefit in this subgroup. HTx recipients in the lowest eGFR quintile (eGFR less than mean 37 mL/minute) had worse survival than combined HKTx recipients (7.1 ± 0.07 vs 7.7 ± 0.2; P < .001). Multivariable factors for increased mortality among HTx recipients included lower eGFR, higher recent panel reactive antibody score, older age, African American race, diabetes, longer ischemic time, and certain diagnoses. Performance of combined HKTx is increasing out of proportion to isolated HTx. eGFR is an important determinant of improved HTx survival. Combined HKTx recovers post-transplant survival in patients with eGFR <37 mL/minute and can be recommended in this subgroup. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  1. Living-Donor Kidney Transplantation: Reducing Financial Barriers to Live Kidney Donation--Recommendations from a Consensus Conference.

    PubMed

    Tushla, Lara; Rudow, Dianne LaPointe; Milton, Jennifer; Rodrigue, James R; Schold, Jesse D; Hays, Rebecca

    2015-09-04

    Live-donor kidney transplantation (LDKT) is the best treatment for eligible people with late-stage kidney disease. Despite this, living kidney donation rates have declined in the United States in recent years. A potential source of this decline is the financial impact on potential and actual living kidney donors (LKDs). Recent evidence indicates that the economic climate may be associated with the decline in LDKT and that there are nontrivial financial ramifications for some LKDs. In June 2014, the American Society of Transplantation's Live Donor Community of Practice convened a Consensus Conference on Best Practices in Live Kidney Donation. The conference included transplant professionals, patients, and other key stakeholders (with the financial support of 10 other organizations) and sought to identify best practices, knowledge gaps, and opportunities pertaining to living kidney donation. This workgroup was tasked with exploring systemic and financial barriers to living kidney donation. The workgroup reviewed literature that assessed the financial effect of living kidney donation, analyzed employment and insurance factors, discussed international models for addressing direct and indirect costs faced by LKDs, and summarized current available resources. The workgroup developed the following series of recommendations to reduce financial and systemic barriers and achieve financial neutrality for LKDs: (1) allocate resources for standardized reimbursement of LKDs' lost wages and incidental costs; (2) pass legislation to offer employment and insurability protections to LKDs; (3) create an LKD financial toolkit to provide standardized, vetted education to donors and providers about options to maximize donor coverage and minimize financial effect within the current climate; and (4) promote further research to identify systemic barriers to living donation and LDKT to ensure the creation of mitigation strategies.

  2. Human Neural Progenitor Transplantation Rescues Behavior and Reduces α-Synuclein in a Transgenic Model of Dementia with Lewy Bodies.

    PubMed

    Goldberg, Natalie R S; Marsh, Samuel E; Ochaba, Joseph; Shelley, Brandon C; Davtyan, Hayk; Thompson, Leslie M; Steffan, Joan S; Svendsen, Clive N; Blurton-Jones, Mathew

    2017-02-22

    Synucleinopathies are a group of neurodegenerative disorders sharing the common feature of misfolding and accumulation of the presynaptic protein α-synuclein (α-syn) into insoluble aggregates. Within this diverse group, Dementia with Lewy Bodies (DLB) is characterized by the aberrant accumulation of α-syn in cortical, hippocampal, and brainstem neurons, resulting in multiple cellular stressors that particularly impair dopamine and glutamate neurotransmission and related motor and cognitive function. Recent studies show that murine neural stem cell (NSC) transplantation can improve cognitive or motor function in transgenic models of Alzheimer's and Huntington's disease, and DLB. However, examination of clinically relevant human NSCs in these models is hindered by the challenges of xenotransplantation and the confounding effects of immunosuppressant drugs on pathology and behavior. To address this challenge, we developed an immune-deficient transgenic model of DLB that lacks T-, B-, and NK-cells, yet exhibits progressive accumulation of human α-syn (h-α-syn)-laden inclusions and cognitive and motor impairments. We demonstrate that clinically relevant human neural progenitor cells (line CNS10-hNPCs) survive, migrate extensively and begin to differentiate preferentially into astrocytes following striatal transplantation into this DLB model. Critically, grafted CNS10-hNPCs rescue both cognitive and motor deficits after 1 and 3 months and, furthermore, restore striatal dopamine and glutamate systems. These behavioral and neurochemical benefits are likely achieved by reducing α-syn oligomers. Collectively, these results using a new model of DLB demonstrate that hNPC transplantation can impact a broad array of disease mechanisms and phenotypes and suggest a cellular therapeutic strategy that should be pursued. © Stem Cells Translational Medicine 2017.

  3. High cycling cadence reduces carbohydrate oxidation at given low intensity metabolic rate.

    PubMed

    Beneke, R; Alkhatib, A

    2015-03-01

    Cycling cadence (RPM)-related differences in blood lactate concentration (BLC) increase with increasing exercise intensity, whilst corresponding divergences in oxygen uptake ([Formula: see text]O2) and carbon dioxide production ([Formula: see text]CO2) decrease. Aim of the present study was to test whether a higher RPM reduces the fraction (%) of the [Formula: see text]O2 used for carbohydrate oxidation (relCHO) at a given BLC. Eight males (23.9 ± 1.6 yrs; 177 ± 3 cm; 70.3 ± 3.4 kg) performed incremental load tests at 50 and 100 RPM. BLC, [Formula: see text]O2 and [Formula: see text]CO2 were measured. At respiratory exchange ratios (RER) < 1, relCHO were calculated and the constant determining 50 % relCHO (kCHO) was approximated as a function of the BLC. At submaximal workload [Formula: see text]O2, [Formula: see text]CO2, and relCHO were lower (all p < 0.002; η(2) > 0.209) at 50 than at 100 RPM. No differences were observed in [Formula: see text]O2peak (3.96 ± 0.22 vs. 4.00 ± 0.25 l · min (-1)) and RERpeak (1.18 ± 0.02 vs. 1.15 ± 0.02). BLC was lower (p < 0.001; η(2) = 0.680) at 50 than at 100 RPM irrespective of cycling intensity. At 50 RPM, kCHO (4.2 ± 1.4 (mmol · l (-1))(3)) was lower (p = 0.043; η(2) = 0.466) than at 100 RPM (5.9 ± 1.9 (mmol · l (-1))(3)). This difference in kCHO reflects a reduced CHO oxidation at a given BLC at 100 than at 50 RPM. At a low exercise intensity, a higher cycling cadence can substantially reduce the reliance on CHO at a given metabolic rate and/or BLC.

  4. 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

  5. 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.

  6. Decreasing maintenance fluids in normotensive trauma patients may reduce intensive care unit stay and ventilator days.

    PubMed

    Barmparas, Galinos; Ko, Ara; Harada, Megan Y; Zaw, Andrea A; Murry, Jason S; Smith, Eric J T; Ashrafian, Sogol; Sun, Beatrice J; Ley, Eric J

    2016-02-01

    The purpose of the study is to determine if excessive fluid administration is associated with a prolonged hospital course and worse outcomes. In July 2013, all normotensive trauma patients admitted to the surgical intensive care unit (ICU) were administered crystalloids at 30 mL/h ("to keep open [TKO]") and were compared to patients admitted during the preceding 6 months who were placed on a rate between 125 mL/h to 150 mL/h (non-TKO). The primary outcomes were ICU, hospital, and ventilator days. A total of 101 trauma patients met inclusion criteria: 56 (55.4%) in the TKO and 45 (44.6%) in the non-TKO group. Overall, the 2 groups were similar in regard to age, Injury Severity Score, Acute Physiology and Chronic Health Evaluation IV scores, and the need for mechanical ventilation. TKO had no effect on renal function compared to non-TKO with similarities in maximum hospital creatinine. TKO patients had lower ICU stay (2.7 ± 1.5 vs 4.1 ± 4.6 days; P = .03) and ventilator days (1.4 ± 0.5 vs 5.5 ± 4.8 days; P < .01). A protocol that encourages admission basal fluid rate of TKO or 30 mL/h in normotensive trauma patients is safe, reduces fluid intake, and may be associated with a shorter intensive care unit course and fewer ventilator days. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Reduced clot debris size using standing waves formed via high intensity focused ultrasound

    NASA Astrophysics Data System (ADS)

    Guo, Shifang; Du, Xuan; Wang, Xin; Lu, Shukuan; Shi, Aiwei; Xu, Shanshan; Bouakaz, Ayache; Wan, Mingxi

    2017-09-01

    The feasibility of utilizing high intensity focused ultrasound (HIFU) to induce thrombolysis has been demonstrated previously. However, clinical concerns still remain related to the clot debris produced via fragmentation of the original clot potentially being too large and hence occluding downstream vessels, causing hazardous emboli. This study investigates the use of standing wave fields formed via HIFU to disintegrate the thrombus while achieving a reduced clot debris size in vitro. The results showed that the average diameter of the clot debris calculated by volume percentage was smaller in the standing wave mode than in the travelling wave mode at identical ultrasound thrombolysis settings. Furthermore, the inertial cavitation dose was shown to be lower in the standing wave mode, while the estimated cavitation bubble size distribution was similar in both modes. These results show that a reduction of the clot debris size with standing waves may be attributed to the particle trapping of the acoustic potential well which contributed to particle fragmentation.

  8. Amiloride reduces the taste intensity of Na+ and Li+ salts and sweeteners.

    PubMed Central

    Schiffman, S S; Lockhead, E; Maes, F W

    1983-01-01

    The diuretic amiloride, a potent inhibitor of sodium transport in a variety of epithelial systems, was applied to the human tongue. Application of amiloride reduced the taste intensity of sodium and lithium salts and of sweeteners ranging widely in chemical structure. The sweeteners included saccharides, glycosides, dipeptides, proteins, and amino acids. Amiloride did not affect perception of potassium or calcium salts, bitter and sour tastes, or amino acids without a sweet or salty component. These findings were supported by neurophysiological studies in rat, which showed that amiloride diminished the NaCl response relative to KCl. The results are consistent with the position that an amiloride-sensitive transport mechanism is involved in taste perception of sodium and lithium salts and of sweeteners. PMID:6577473

  9. Simulations of High-Intensity Short-Pulse Lasers Incident on Reduced Mass Targets

    NASA Astrophysics Data System (ADS)

    King, Frank W.

    This thesis presents the results of a series of fully kinetic particle-in-cell (PIC) simulations of reduced mass targets with pre-plasma subjected to high-intensity short-pulse lasers. The simulations are performed in one, two, and three dimensions. The results of these simulations show that the creation of an electrostatic collisionless ion shock in the preplasma controls the creation of an above solid density ion perturbation in the target bulk, and this determines the reduced mass target heating and deformation. The ion perturbation is initiated by a population of high-energy electrons that rapidly spread throughout the target and reflux. The perturbation spreads longitudinally and transversely through the target and results in compression followed by the destruction of the target. This deformation requires a kinetic treatment due to the generation of non-equilibrium particle distributions and the role of ballistic electrons and ions. Kinetic and fluid simulations are compared and both exhibit the basic features of the above solid density ion perturbation, but the magnitude of the effect and the speed of propagation vary significantly between the two methods. Kinetic simulations do not naturally include equation-of-state physics and other aspects of the problem. Both approaches are complementary. The requirements on spatial resolution, particle count, and other numerical parameters are addressed in this work. From these simulations, the behavior of the reduced mass targets is found to vary significantly depending on the laser focal spot size or the intensity of the laser pulse. This occurs even if the energy and power of the laser pulses are held constant. The number of dimensions used in the particle-in-cell simulations has been observed to have a significant effect on late-time heating of the target, but not during or shortly after laser excitation. This is due to the representation of the equilibration process as the initial population of laser heated

  10. Caffeine intake improves intense intermittent exercise performance and reduces muscle interstitial potassium accumulation.

    PubMed

    Mohr, Magni; Nielsen, Jens Jung; Bangsbo, Jens

    2011-11-01

    The effect of oral caffeine ingestion on intense intermittent exercise performance and muscle interstitial ion concentrations was examined. The study consists of two studies (S1 and S2). In S1, 12 subjects completed the Yo-Yo intermittent recovery level 2 (Yo-Yo IR2) test with prior caffeine (6 mg/kg body wt; CAF) or placebo (PLA) intake. In S2, 6 subjects performed one low-intensity (20 W) and three intense (50 W) 3-min (separated by 5 min) one-legged knee-extension exercise bouts with (CAF) and without (CON) prior caffeine supplementation for determination of muscle interstitial K(+) and Na(+) with microdialysis. In S1 Yo-Yo IR2 performance was 16% better (P < 0.05) in CAF compared with PLA. In CAF, plasma K(+) at the end of the Yo-Yo IR2 test was 5.2 ± 0.1 mmol/l with no difference between the trials. Plasma free fatty acids (FFA) were higher (P < 0.05) in CAF than PLA at rest and remained higher (P < 0.05) during exercise. Peak blood glucose (8.0 ± 0.6 vs. 6.2 ± 0.4 mmol/l) and plasma NH(3) (137.2 ± 10.8 vs. 113.4 ± 13.3 μmol/l) were also higher (P < 0.05) in CAF compared with PLA. In S2 interstitial K(+) was 5.5 ± 0.3, 5.7 ± 0.3, 5.8 ± 0.5, and 5.5 ± 0.3 mmol/l at the end of the 20-W and three 50-W periods, respectively, in CAF, which were lower (P < 0.001) than in CON (7.0 ± 0.6, 7.5 ± 0.7, 7.5 ± 0.4, and 7.0 ± 0.6 mmol/l, respectively). No differences in interstitial Na(+) were observed between CAF and CON. In conclusion, caffeine intake enhances fatigue resistance and reduces muscle interstitial K(+) during intense intermittent exercise.

  11. Lymphocyte Redox Imbalance and Reduced Proliferation after a Single Session of High Intensity Interval Exercise

    PubMed Central

    Tossige-Gomes, Rosalina; Costa, Karine Beatriz; Ottone, Vinícius de Oliveira; Magalhães, Flávio de Castro; Amorim, Fabiano Trigueiro; Rocha-Vieira, Etel

    2016-01-01

    This study investigated whether an acute session of high-intensity interval training (HIIT) is sufficient to alter lymphocyte function and redox status. Sixteen young healthy men underwent a HIIT session on a cycloergometer, consisting of eight bouts of 1 min at 90–100% of peak power, with 75 seconds of active recovery at 30 W between bouts. Venous blood was collected before, immediately after, and 30 minutes after the HIIT session. In response to Staphylococcus aureus superantigen B (SEB) stimulation, lymphocyte proliferation decreased and the IL-2 concentration increased after the HIIT session. However, the HIIT session had no effect on lymphocyte proliferation or IL-2 response to phytohemagglutinin stimulation. The HIIT session also induced lymphocyte redox imbalance, characterized by an increase in the concentration of thiobarbituric acid reactive substances and a decrease in the activity of the antioxidant enzyme catalase. Lymphocyte viability was not affected by the HIIT session. The frequencies of CD25+ and CD69+ T helper and B lymphocytes in response to superantigen stimulation were lower after exercise, suggesting that superantigen-induced lymphocyte activation was reduced by HIIT. However, HIIT also led to a reduction in the frequency of CD4+ and CD19+ cells, so the frequencies of CD25+ and CD69+ cells within the CD4 and CD19 cell populations were not affected by HIIT. These data indicate that the reduced lymphocyte proliferation observed after HIIT is not due to reduced early lymphocyte activation by superantigen. Our findings show that an acute HIIT session promotes lymphocyte redox imbalance and reduces lymphocyte proliferation in response to superantigenic, but not to mitogenic stimulation. This observation cannot be explained by alteration of the early lymphocyte activation response to superantigen. The manner in which lymphocyte function modulation by an acute HIIT session can affect individual immunity and susceptibility to infection is important

  12. Lymphocyte Redox Imbalance and Reduced Proliferation after a Single Session of High Intensity Interval Exercise.

    PubMed

    Tossige-Gomes, Rosalina; Costa, Karine Beatriz; Ottone, Vinícius de Oliveira; Magalhães, Flávio de Castro; Amorim, Fabiano Trigueiro; Rocha-Vieira, Etel

    2016-01-01

    This study investigated whether an acute session of high-intensity interval training (HIIT) is sufficient to alter lymphocyte function and redox status. Sixteen young healthy men underwent a HIIT session on a cycloergometer, consisting of eight bouts of 1 min at 90-100% of peak power, with 75 seconds of active recovery at 30 W between bouts. Venous blood was collected before, immediately after, and 30 minutes after the HIIT session. In response to Staphylococcus aureus superantigen B (SEB) stimulation, lymphocyte proliferation decreased and the IL-2 concentration increased after the HIIT session. However, the HIIT session had no effect on lymphocyte proliferation or IL-2 response to phytohemagglutinin stimulation. The HIIT session also induced lymphocyte redox imbalance, characterized by an increase in the concentration of thiobarbituric acid reactive substances and a decrease in the activity of the antioxidant enzyme catalase. Lymphocyte viability was not affected by the HIIT session. The frequencies of CD25+ and CD69+ T helper and B lymphocytes in response to superantigen stimulation were lower after exercise, suggesting that superantigen-induced lymphocyte activation was reduced by HIIT. However, HIIT also led to a reduction in the frequency of CD4+ and CD19+ cells, so the frequencies of CD25+ and CD69+ cells within the CD4 and CD19 cell populations were not affected by HIIT. These data indicate that the reduced lymphocyte proliferation observed after HIIT is not due to reduced early lymphocyte activation by superantigen. Our findings show that an acute HIIT session promotes lymphocyte redox imbalance and reduces lymphocyte proliferation in response to superantigenic, but not to mitogenic stimulation. This observation cannot be explained by alteration of the early lymphocyte activation response to superantigen. The manner in which lymphocyte function modulation by an acute HIIT session can affect individual immunity and susceptibility to infection is important

  13. Providing parents with individualised support in a neonatal intensive care unit reduced stress, anxiety and depression.

    PubMed

    Cano Giménez, Evelyn; Sánchez-Luna, Manuel

    2015-07-01

    This study assessed the effectiveness of an individualised intervention to reduce parental stress, anxiety and depression in a neonatal intensive care unit (NICU). Parents of infants admitted to the NICU for a minimum of 4 weeks underwent a five-step individualised intervention programme delivered by a psychologist. The study population comprised 40 mothers and 25 fathers in the intervention group and 40 mothers and 29 fathers in the control group who received the standard support. Similar stress levels were observed in both groups before the intervention. However, after 15 days, the group that received the individualised intervention showed a statistically significant lower level of anxiety, with none of the mothers and fathers in the intervention group reporting anxiety, compared with 2.5% of mothers and 10.3% of fathers in the control group. At discharge, 50% of mothers and 80% of fathers in the intervention group reported no level of depression, compared to all the mothers and fathers in the control group. An intervention programme individualised to the needs of mothers and fathers with infants admitted to a NICU for at least 4 weeks was effective in reducing anxiety and depression compared to the standard care. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  14. Optimization of collimator parameters to reduce rectal dose in intensity-modulated prostate treatment planning

    SciTech Connect

    Chapek, Julie . E-mail: Julie.chapek@hci.utah.edu; Tobler, Matt; Toy, Beau J.; Lee, Christopher M.; Leavitt, Dennis D.

    2005-01-01

    The inability to avoid rectal wall irradiation has been a limiting factor in prostate cancer treatment planning. Treatment planners must not only consider the maximum dose that the rectum receives throughout a course of treatment, but also the dose that any volume of the rectum receives. As treatment planning techniques have evolved and prescription doses have escalated, limitations of rectal dose have remained an area of focus. External pelvic immobilization devices have been incorporated to aid in daily reproducibility and lessen concern for daily patient motion. Internal immobilization devices (such as the intrarectal balloon) and visualization techniques (including daily ultrasound or placement of fiducial markers) have been utilized to reduce the uncertainty of intrafractional prostate positional variation, thus allowing for minimization of treatment volumes. Despite these efforts, prostate volumes continue to abut portions of the rectum, and the necessary volume expansions continue to include portions of the anterior rectal wall within high-dose regions. The addition of collimator parameter optimization (both collimator angle and primary jaw settings) to intensity-modulated radiotherapy (IMRT) allows greater rectal sparing compared to the use of IMRT alone. We use multiple patient examples to illustrate the positive effects seen when utilizing collimator parameter optimization in conjunction with IMRT to further reduce rectal doses.

  15. Reducing Sedentary Behavior Versus Increasing Moderate-to-Vigorous Intensity Physical Activity in Older Adults.

    PubMed

    Barone Gibbs, Bethany; Brach, Jennifer S; Byard, Tom; Creasy, Seth; Davis, Kelliann K; McCoy, Stephanie; Peluso, Anna; Rogers, Renee J; Rupp, Kristie; Jakicic, John M

    2017-03-01

    To compare the effects of behavioral interventions targeting decreased sedentary behavior versus increased moderate-to-vigorous intensity physical activity (MVPA) in older adults. Inactive older adults ( N = 38, 68 ± 7 years old, 71% female) were randomized to 12-week interventions targeting decreased sedentary behavior ( Sit Less) or increased MVPA ( Get Active). The SenseWear armband was used to objectively assess activity in real time. Assessments included a blinded armband, the Community Health Activites Model Program for Senior (CHAMPS) questionnaire, 400-meter walk, and the Short Physical Performance Battery (SPPB). Objectively measured MVPA increased in Get Active (75 ± 22 min/week, p < .001); self-reported MVPA increased in both groups ( p < .05). Sedentary behavior did not change in either group (all p > .05). Only the Sit Less group improved the SPPB score (0.5 ± 0.3, p = .046). Targeting reduced sedentary behavior had a greater effect on physical function among inactive but high functioning older adults over 12 weeks. Future studies of longer duration and combining increased MVPA with reduced sedentary behavior are needed.

  16. [Investigation of Intravenous Azithromycin Treatment Safety When Reducing Solvent for Intensive Care Unit Patients].

    PubMed

    Haruki, Yuto; Hagiya, Hideharu; Sakuma, Akiko; Haruki, Mai; Oka, Yasue; Sugiyama, Tetsuhiro; Kawakami, Yasuhiro; Kondo, Sachiyo

    2015-01-01

    Intravenous azithromycin (AZM) was approved for use in December 2011 in Japan. In general, intravenous AZM injections are diluted to 1 mg/mL, with a total infusion volume of 500 mL to avoid phlebitis. Patients in intensive care units (ICUs) require small infusion volumes. We retrospectively evaluated the total AZM infusion volume in 65 ICU patients receiving AZM treatment from December 2011 to August 2014. Thirteen patients (20.0%) received a reduced volume [100 mL (5 mg/mL) or 250 mL (2 mg/mL)] using an infusion pump over 2 h. No peripheral phlebitis was observed in any patient. Based on this result, it is assumed that AZM can be safely administered to ICU patients even though the volume of solvent is reduced. AZM is widely recommended for the treatment of community-acquired respiratory infections and is used in patients with severe infections. Further investigation is required in additional patients to understand the effects of AZM volume reduction in greater detail.

  17. Myeloablative versus Reduced-Intensity Conditioning in Patients with Myeloid Malignancies: A Propensity Score-Matched Analysis.

    PubMed

    Sibai, Hassan; Falcone, Umberto; Deotare, Uday; Michelis, Fotios V; Uhm, Jieun; Gupta, Vikas; Kuruvilla, John; Lipton, Jeffrey H; Seftel, Matthew D; Messner, Hans A; Kim, Dennis Dong Hwan

    2016-12-01

    Reduced-intensity conditioning (RIC) has been shown to have similar overall survival (OS) but higher relapse rates compared with myeloablative (MAC) regimens in patients with myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Using propensity score matching (PSM) analysis, well-balanced pairs of different variables can be compared effectively. We retrospectively compared allo-HSCT recipients with acute myeloid leukemia or myelodysplasia receiving a RIC regimen (FBT200; fludarabine 30 mg/m(2)/day for 4 days, busulfan 3.2 mg/kg/day for 2 days, and total body irradiation [TBI] 200 cGy) or MAC regimen (FBT400; fludarabine 50 mg/m(2)/day for 4 days, busulfan 3.2 mg/kg/day for 4 days, and TBI 400 cGy). A total of 248 patients (121 in the RIC group and 127 in the MAC group) were included in the analysis. No statistically significant difference was observed in 2-year OS (RIC group, 45.2 ± 5.0%; MAC group, 51.7 ± 5.2%; P = .541), nonrelapse mortality (NRM; RIC group, 28.7 ± 2.8% MAC group, 34.7 ± 4.6%; P = .368), and acute graft-versus-host disease (GVHD) (P = .171) or chronic GVHD (P = .605) at 1 year. The cumulative incidence of relapse (CIR) at 2 years was statistically significantly different between the 2 groups, however (RIC, 26.1 ± 2.6%; MAC, 14.2 ± 3.5%; P = .033). When PSM was applied to the study population, 42 case-control pairs were evenly matched. PSM analysis confirmed no statistically significant difference in 2-year OS (RIC, 49.0 ± 9.1%; MAC, 54.9 ± 7.7%; P = .718), NRM (RIC, 22.2 ± 2.3%; MAC, 33.3 ± 2.8%; P = .238), or CIR (RIC, 25.7 ± 2.6%; MAC, 9.5 ± 1.1%; P = .315) in the PSM pairs. Our findings demonstrate that after applying PSM, FBT 200 RIC conditioning has comparable OS, NRM, and CIR to FBT 400 MAC conditioning before allo-HSCT.

  18. Mechanisms for reduced pulmonary diffusing capacity in haematopoietic stem-cell transplantation recipients.

    PubMed

    Barisione, Giovanni; Bacigalupo, Andrea; Brusasco, Claudia; Scanarotti, Chiara; Penco, Susanna; Bassi, Anna Maria; Lamparelli, Teresa; Garlaschi, Alessandro; Pellegrino, Riccardo; Brusasco, Vito

    2014-04-01

    Lung diffusing capacity for CO (DLCO) is compromised in haematopoietic stem-cell transplantation (HSCT) recipients. We derived alveolar-capillary membrane conductance (DM,CO) and pulmonary capillary volume (VC) from DLCO and diffusing capacity for NO (DLNO). Forty patients were studied before and 6 weeks after HSCT. Before HSCT, DLNO and DLCO were significantly lower than in 30 healthy controls. DM,CO was ∼40% lower in patients than in controls (p<0.001), whereas VC did not differ significantly. After HSCT, DLNO and DM,CO further decreased, the latter by ∼22% from before HSCT (p<0.01) while VC did not change significantly. Lung density, serum CRP and reactive oxygen metabolites were significantly increased, with the latter being correlated (R2=0.71, p<0.001) with the decrement in DLNO. We conclude that DLNO and, to a lesser extent, DLCO are compromised before HSCT mainly due to a DM,CO reduction. A further reduction of DM,CO without VC loss occurs after HSCT, possibly related to development of oedema, or interstitial fibrosis, or both. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Intensive lifestyle modification reduces Lp-PLA2 in dyslipidemic HIV/HAART patients.

    PubMed

    Wooten, Joshua S; Nambi, Preethi; Gillard, Baiba K; Pownall, Henry J; Coraza, Ivonne; Scott, Lynne W; Nambi, Vijay; Ballantyne, Christie M; Balasubramanyam, Ashok

    2013-06-01

    Patients with dyslipidemia associated with HIV-1 infection and highly active antiretroviral therapy (HAART) have elevated levels of Lp-PLA2 and CCL5/regulated on activation, normal T-cell expressed and secreted (RANTES), which may increase the risk of cardiovascular disease. This study aimed to determine whether an intensive diet and exercise (D/E) program, independently or combined with fenofibrate or niacin, could reduce Lp-PLA2 or RANTES. Patients with hypertriglyceridemic HIV on stable HAART (n = 107) were randomized to one of five interventions: 1) usual care, 2) D/E with placebos, 3) D/E with fenofibrate and placebo, 4) D/E with niacin and placebo, or 5) D/E with fenofibrate and niacin for 24 wk. Lp-PLA2 and RANTES concentrations were measured in fasting plasma samples at baseline and postintervention. General linear models were used to compare Lp-PLA2 and RANTES levels between the five groups postintervention, controlling for baseline levels, age, body mass index, CD4 T-cell count, viral load, duration of infection, and HAART. At baseline, fasting plasma Lp-PLA2 (388.5 ± 127.5 ng·mL) and RANTES (43.8 ± 25.5 ng·mL) levels were elevated when compared with healthy controls. Posttreatment Lp-PLA2 mass was lower in patients who received D/E only (323.0 ± 27.2 ng·mL), D/E plus fenofibrate (327.2 ± 25.9 ng·mL), and D/E plus niacin (311.1 ± 27.8 ng·mL) when compared with patients receiving usual care (402.2 ± 25.3 ng·mL). RANTES concentrations were not significantly affected by any intervention. Elevated plasma Lp-PLA2 mass can be reduced by an intensive D/E program in patients with HIV/HAART-associated dyslipidemia. RANTES is elevated but is not reduced by lifestyle modification, fenofibrate, or niacin.

  20. Intensive Lifestyle Modification Reduces Lp-PLA2 in Dyslipidemic HIV/HAART Patients

    PubMed Central

    Wooten, Joshua S.; Nambi, Preethi; Gillard, Baiba K.; Pownall, Henry J.; Coraza, Ivonne; Scott, Lynne W.; Nambi, Vijay; Ballantyne, Christie M.; Balasubramanyam, Ashok

    2013-01-01

    Patients with dyslipidemia associated with HIV-1 infection and highly active antiretroviral therapy (HAART) have elevated levels of Lp-PLA2 and CCL5/RANTES, which may increase risk of cardiovascular disease. Purpose This study aimed to determine whether an intensive diet and exercise (D/E) program, independently or combined with fenofibrate or niacin, could reduce Lp-PLA2 or RANTES. Methods Hypertriglyceridemic HIV patients on stable HAART (n=107) were randomized to one of five interventions: 1) Usual Care (UC); 2) D/E with placebos; 3) D/E with fenofibrate and placebo; 4) D/E with niacin and placebo; or 5) D/E with fenofibrate and niacin for 24 weeks. Lp-PLA2 and RANTES concentrations were measured in fasting plasma samples at baseline and post-intervention. General linear models were used to compare Lp-PLA2 and RANTES levels between the five groups post-intervention, controlling for baseline levels, age, BMI, CD4+ T-cell count, viral load, duration of infection, and HAART. Results At baseline, fasting plasma Lp-PLA2 (388.5 ± 127.5 ng/mL) and RANTES (43.8 ± 25.5 ng/mL) levels were elevated when compared to healthy controls. Post-treatment Lp-PLA2 mass was lower in patients who received D/E only (323.0 ± 27.2 ng/mL), D/E plus fenofibrate (327.2 ± 25.9 ng/mL) and D/E plus niacin (311.1 ± 27.8 ng/mL) when compared to patients receiving UC (402.2 ± 25.3 ng/mL). RANTES concentrations were not significantly affected by any intervention. Conclusions Elevated plasma Lp-PLA2 mass can be reduced by an intensive diet and exercise program in patients with HIV/HAART-associated dyslipidemia. RANTES is elevated but is not reduced by lifestyle modification, fenofibrate or niacin. PMID:23299761

  1. Using real time process measurements to reduce catheter related bloodstream infections in the intensive care unit

    PubMed Central

    Wall, R; Ely, E; Elasy, T; Dittus, R; Foss, J; Wilkerson, K; Speroff, T

    2005-01-01

    

Problem: Measuring a process of care in real time is essential for continuous quality improvement (CQI). Our inability to measure the process of central venous catheter (CVC) care in real time prevented CQI efforts aimed at reducing catheter related bloodstream infections (CR-BSIs) from these devices. Design: A system was developed for measuring the process of CVC care in real time. We used these new process measurements to continuously monitor the system, guide CQI activities, and deliver performance feedback to providers. Setting: Adult medical intensive care unit (MICU). Key measures for improvement: Measured process of CVC care in real time; CR-BSI rate and time between CR-BSI events; and performance feedback to staff. Strategies for change: An interdisciplinary team developed a standardized, user friendly nursing checklist for CVC insertion. Infection control practitioners scanned the completed checklists into a computerized database, thereby generating real time measurements for the process of CVC insertion. Armed with these new process measurements, the team optimized the impact of a multifaceted intervention aimed at reducing CR-BSIs. Effects of change: The new checklist immediately provided real time measurements for the process of CVC insertion. These process measures allowed the team to directly monitor adherence to evidence-based guidelines. Through continuous process measurement, the team successfully overcame barriers to change, reduced the CR-BSI rate, and improved patient safety. Two years after the introduction of the checklist the CR-BSI rate remained at a historic low. Lessons learnt: Measuring the process of CVC care in real time is feasible in the ICU. When trying to improve care, real time process measurements are an excellent tool for overcoming barriers to change and enhancing the sustainability of efforts. To continually improve patient safety, healthcare organizations should continually measure their key clinical processes in real

  2. Maintaining reduced noise levels in a resource-constrained neonatal intensive care unit by operant conditioning.

    PubMed

    Ramesh, A; Denzil, S B; Linda, R; Josephine, P K; Nagapoornima, M; Suman Rao, P N; Swarna Rekha, A

    2013-03-01

    To evaluate the efficacy of operant conditioning in sustaining reduced noise levels in the neonatal intensive care unit (NICU). Quasi-experimental study on quality of care. Level III NICU of a teaching hospital in south India. 26 staff employed in the NICU. (7 Doctors, 13 Nursing staff and 6 Nursing assistants). Operant conditioning of staff activity for 6 months. This method involves positive and negative reinforcement to condition the staff to modify noise generating activities. Comparing noise levels in decibel: A weighted [dB (A)] before conditioning with levels at 18 and 24 months after conditioning. Decibel: A weighted accounts for noise that is audible to human ears. Operant conditioning for 6 months sustains the reduced noise levels to within 62 dB in ventilator room 95% CI: 60.4 - 62.2 and isolation room (95% CI: 55.8 - 61.5). In the preterm room, noise can be maintained within 52 dB (95% CI: 50.8 - 52.6). This effect is statistically significant in all the rooms at 18 months (P = 0.001). At 24 months post conditioning there is a significant rebound of noise levels by 8.6, 6.7 and 9.9 dB in the ventilator, isolation and preterm room, respectively (P =0.001). Operant conditioning for 6 months was effective in sustaining reduced noise levels. At 18 months post conditioning, the noise levels were maintained within 62 dB (A), 60 dB (A) and 52 dB (A) in the ventilator, isolation and pre-term room, respectively. Conditioning needs to be repeated at 12 months in the ventilator room and at 18 months in the other rooms.

  3. Orthotopic bone transplantation in mice. III. Methods of reducing the immune response and their effect on healing

    SciTech Connect

    Kliman, M.; Halloran, P.F.; Lee, E.; Esses, S.; Fortner, P.; Langer, F.

    1981-01-01

    Various methods of reducing the immune response to allogeneic bone grafts, either by pretreating the graft or by immunosuppressing the recipient, were compared. Tibial grafts from B10.D2 mice, either untreated or pretreated in various ways, were transplanted into B10 recipients. The antibody response was followed and the extent of bone healing at 4 months was assessed. Pretreatment of the graft by X-irradiation, freezing, or by incubation in alloantisera (either anti-H-2 or anti-Ia) reduced or abolished the immunogenicity of the graft. Immunosuppression of the recipient with methotrexate or antilymphocyte serum (ALS) also greatly depressed the antibody response. But when healing was assessed, none of these treatments except ALS improved the delayed healing of the bone allografts. The reason for this failure was probably that X-irradiation, freezing, alloantiserum pretreatment, and methotrexate all interfered with bone healing directly, whereas ALS did not. We conclude that many methods will reduce the immune response to allogeneic bone, but that only ALS will improve the healing of the allogeneic bone. Furthermore, as a corollary to the observation that pretreatment with anti-Ia serum markedly reduced the immunogenicity of bone allografts, we conclude that much of the immunogenicity of bone allografts is attributable to a population of Ia-positive cells.

  4. Reduced platelet transfusions and earlier platelet engraftment using alemtuzumab-based conditioning regimen in allogeneic stem cell transplantation.

    PubMed

    Neumann, Thomas; Schneidewind, Laila; Thiele, Thomas; Schulze, Meike; Klenner, Anne F; Busemann, Christoph; Pink, Daniel; Greinacher, Andreas; Dölken, Gottfried; Krüger, William H

    2016-05-01

    In patients undergoing allogeneic stem cell transplantation, conditioning regimens containing alemtuzumab instead of anti-thymocyte globulin (ATG) may result in an earlier platelet engraftment and a reduced number of platelet transfusions. We performed a retrospective, single-center, case-control study analyzing time to engraftment and transfusion needs using alemtuzumab in comparison with ATG as part of conditioning protocol. Median values for time to platelet engraftment, number of transfused platelet concentrates and number of transfused red cell concentrates were 12 versus 19.5 days (p < 0.001), 2 versus 14 (p < 0.001) and 6 versus 14.5 (p = 0.003) in the alemtuzumab and ATG group. Time to leukocyte engraftment did not differ with median 15 days in both groups. Patients in the ATG group showed a significant higher decrease in platelet count during conditioning (68 vs. 29 %, p = 0.001), leading to significant lower median platelet counts at the day of stem cell infusion (38 vs. 95.5 Gpt/l, p = 0.008), and higher values for median C-reactive protein after first antibody infusion (69.0 vs. 43.6 mg/l, p = 0.001) compared with alemtuzumab group. Test for significance was done by using Wilcoxon rank-sum test. Subgroup analysis considering the type of ATG used (Thymoglobulin vs. ATG Fresenius) revealed that differences between alemtuzumab and ATG group were more due to effects of ATG Fresenius than Thymoglobulin. The use of alemtuzumab in comparison with ATG as part of the conditioning regimen may be an approach to reduce the number of transfused platelet and red cell concentrates after allogeneic stem cell transplantation.

  5. Reducing environmental risk by improving N management in intensive Chinese agricultural systems.

    PubMed

    Ju, Xiao-Tang; Xing, Guang-Xi; Chen, Xin-Ping; Zhang, Shao-Lin; Zhang, Li-Juan; Liu, Xue-Jun; Cui, Zhen-Ling; Yin, Bin; Christie, Peter; Zhu, Zhao-Liang; Zhang, Fu-Suo

    2009-03-03

    Excessive N fertilization in intensive agricultural areas of China has resulted in serious environmental problems because of atmospheric, soil, and water enrichment with reactive N of agricultural origin. This study examines grain yields and N loss pathways using a synthetic approach in 2 of the most intensive double-cropping systems in China: waterlogged rice/upland wheat in the Taihu region of east China versus irrigated wheat/rainfed maize on the North China Plain. When compared with knowledge-based optimum N fertilization with 30-60% N savings, we found that current agricultural N practices with 550-600 kg of N per hectare fertilizer annually do not significantly increase crop yields but do lead to about 2 times larger N losses to the environment. The higher N loss rates and lower N retention rates indicate little utilization of residual N by the succeeding crop in rice/wheat systems in comparison with wheat/maize systems. Periodic waterlogging of upland systems caused large N losses by denitrification in the Taihu region. Calcareous soils and concentrated summer rainfall resulted in ammonia volatilization (19% for wheat and 24% for maize) and nitrate leaching being the main N loss pathways in wheat/maize systems. More than 2-fold increases in atmospheric deposition and irrigation water N reflect heavy air and water pollution and these have become important N sources to agricultural ecosystems. A better N balance can be achieved without sacrificing crop yields but significantly reducing environmental risk by adopting optimum N fertilization techniques, controlling the primary N loss pathways, and improving the performance of the agricultural Extension Service.

  6. Noble Gas (Argon and Xenon)-Saturated Cold Storage Solutions Reduce Ischemia-Reperfusion Injury in a Rat Model of Renal Transplantation

    PubMed Central

    Irani, Y.; Pype, J.L.; Martin, A.R.; Chong, C.F.; Daniel, L.; Gaudart, J.; Ibrahim, Z.; Magalon, G.; Lemaire, M.; Hardwigsen, J.

    2011-01-01

    Background Following kidney transplantation, ischemia-reperfusion injury contributes to adverse outcomes. The purpose of this study was to determine whether a cold-storage solution saturated with noble gas (xenon or argon) could limit ischemia-reperfusion injury following cold ischemia. Methods Sixty Wistar rats were randomly allocated to 4 experimental groups. Kidneys were harvested and then stored for 6 h before transplantation in cold-storage solution (Celsior®) saturated with either air, nitrogen, xenon or argon. A syngenic orthotopic transplantation was performed. Renal function was determined on days 7 and 14 after transplantation. Transplanted kidneys were removed on day 14 for histological and immunohistochemical analyses. Results Creatinine clearance was significantly higher and urinary albumin significantly lower in the argon and xenon groups than in the other groups at days 7 and 14. These effects were considerably more pronounced for argon than for xenon. In addition, kidneys stored with argon, and to a lesser extent those stored with xenon, displayed preserved renal architecture as well as higher CD-10 and little active caspase-3 expression compared to other groups. Conclusion Argon- or xenon-satured cold-storage solution preserved renal architecture and function following transplantation by reducing ischemia-reperfusion injury. PMID:22470401

  7. Earth Battery: An Approach for Reducing the Carbon and Water Intensity of Energy

    NASA Astrophysics Data System (ADS)

    Buscheck, T. A.; Bielicki, J. M.; Randolph, J.

    2016-12-01

    Mitigating climate change requires a range of measures, including increased use of renewable and low-carbon energy and reducing the CO2 intensity of fossil energy use. Our approach, called the Earth Battery, uses the storage of supercritical CO2, N2, or pressurized air to enable utility-scale energy storage needed for increased use of variable renewable energy and low-carbon baseload power. When deployed with CO2, the Earth Battery is designed to address the major deployment barriers to CO2 capture, utilization, and storage (CCUS) by managing overpressure and creating a business case for CO2 storage. We use the huge fluid and thermal storage capacity of the earth, together with overpressure driven by CO2, N2, or pressurized air storage, to harvest, store, and dispatch energy from subsurface (geothermal) and surface (solar, fossil) thermal resources, as well as excess energy from electric grids. The storage of CO2, N2, or air enables the earth to function as a low-carbon energy-system hub. Stored CO2, N2, or air plays three key roles: (1) as a supplemental fluid that creates pressure to efficiently recirculate working fluids that store and recover energy, (2) as a working fluid for efficient, low-water-intensity electricity conversion, and (3) as a shock absorber to allow diurnal and seasonal recharge/discharge cycles with minimal pressure oscillations, providing large pressure-storage capacity, with reduced risk of induced seismicity or leakage of stored CO2. To keep reservoir pressures in a safe range, a portion of the produced brine is diverted to generate water. Concentric rings of injection and production wells create a hydraulic divide to store pressure, CO2, N2/air, and thermal energy. Such storage can take excess power from the grid and excess thermal energy, and dispatch that energy when it is demanded. The system is pressurized and heated when power supply exceeds demand and depressurized when demand exceeds supply. The Earth Battery is designed for

  8. Outcome of conditioning intensity in acute myeloid leukemia with monosomal karyotype in patients over 45 year-old: A study from the acute leukemia working party (ALWP) of the European group of blood and marrow transplantation (EBMT).

    PubMed

    Poiré, Xavier; Labopin, Myriam; Cornelissen, Jan J; Volin, Liisa; Richard Espiga, Carlos; Veelken, J Hendrik; Milpied, Noël; Cahn, Jean-Yves; Yacoub-Agha, Ibrahim; van Imhoff, Gustaaf W; Michallet, Mauricette; Michaux, Lucienne; Nagler, Arnon; Mohty, Mohamad

    2015-08-01

    Acute myeloid leukemia with monosomal karyotype (MK AML) carries a very poor prognosis, even after allogeneic stem cell transplantation (SCT). However, SCT remains the only curative option in this high-risk population. Because myeloablative conditioning regimen (MAC) is associated with less relapse, we hypothesized that more intensive conditioning regimen might be beneficial for MK AML patients. We reviewed 303 patients over age 45 diagnosed with either de novo or secondary MK AML. One hundred and five patients received a MAC and 198 a reduced-intensity conditioning (RIC). The median age at SCT was 57-year-old, significantly lower in the MAC (53-year-old) than in the RIC group (59-year-old). The median follow-up was 42 months (range, 3 - 156 months). The 3-year overall survival (OS), leukemia-free survival (LFS), and relapse rate (RR) were not significantly different between both groups with overall values of 34%, 29%, and 51%, respectively. On the contrary, the 3-year nonrelapse mortality (NRM) was significantly higher in MAC recipients (28%) compared with RIC patients (16%, P = 0.004). The incidence of Grades II to IV acute graft-versus-host disease (GvHD) was significantly higher after a MAC (30.5%) than after a RIC (19.3%, P = 0.02). That of chronic GvHD was comparable between both groups (35%) and did not impact on LFS. Interestingly, within our MK AML cohort, hypodiploidy was significantly associated with worse outcomes. Due to reduced toxicity and comparable OS, LFS, and RR, RIC appears as a good transplant option in the very high-risk population, including older patients, diagnosed with MK AML.

  9. Emotional intensity reduces later generalized anxiety disorder symptoms when fear of anxiety and negative problem-solving appraisal are low.

    PubMed

    Sugiura, Yoshinori; Sugiura, Tomoko

    2015-08-01

    While research based on the emotion dysregulation model indicates a positive relationship between intense emotions and generalized anxiety disorder (GAD) symptoms, emotion-focused intervention involves the use of techniques to enhance emotional experiences, based on the notion that GAD patients are engaging in avoidance strategies. To reveal the conditions under which intense emotions lead to reduced GAD symptoms, we designed a longitudinal study to monitor changes in GAD symptoms among students (N = 129) over 3 months. Our focus was on possible moderators of the effect of emotional intensity. Results indicated that when fear of emotions and negative appraisals about problem solving were low, negative emotional intensity reduced later GAD symptoms. Moreover, under the condition of high responsibility to continue thinking, emotional intensity tended to reduce later GAD symptoms. Results suggest that reduced fear of emotions and reduced negative appraisals about problem solving may enhance the use of emotional processing techniques (e.g., emotional exposure). The interaction between responsibility to continue thinking and emotional intensity requires further examination.

  10. Bacteria killing nanotechnology Bio-Kil effectively reduces bacterial burden in intensive care units.

    PubMed

    Hsueh, P-R; Huang, H-C; Young, T-G; Su, C-Y; Liu, C-S; Yen, M-Y

    2014-04-01

    A contaminated hospital environment has been identified as an important reservoir of pathogens causing healthcare-associated infections. This study is to evaluate the efficacy of bacteria killing nanotechnology Bio-Kil on reducing bacterial counts in an intensive care unit (ICU). Two single-bed rooms (S-19 and S-20) in the ICU were selected from 7 April to 27 May 2011. Ten sets of new textiles (pillow cases, bed sheets, duvet cover, and patient clothing) used by patients in the two single-bed rooms were provided by the sponsors. In the room S-20, the 10 sets of new textiles were washed with Bio-Kil; the room walls, ceiling, and air-conditioning filters were treated with Bio-Kil; and the surfaces of instruments (respirator, telephone, and computer) were covered with Bio-Kil-embedded silicon pads. Room S-19 served as the control. We compared the bacterial count on textiles and environment surfaces as well as air samples between the two rooms. A total of 1,364 samples from 22 different sites in each room were collected. The mean bacterial count on textiles and environmental surfaces in room S-20 was significantly lower than that in room S-19 (10.4 vs 49.6 colony-forming units [CFU]/100 cm(2); P < 0.001). Room S-20 had lower bacterial counts in air samples than room S-19 (33.4-37.6 vs 21.6-25.7 CFU/hour/plate; P < 0.001). The density of microbial isolations was significantly greater among patients admitted to room S-19 than those to room S-20 (9.15 vs 5.88 isolates per 100 patient-days, P < 0.05). Bio-Kil can significantly reduce bacterial burden in the environment of the ICU.

  11. Moderate, but not vigorous, intensity exercise training reduces C-reactive protein.

    PubMed

    Fedewa, Michael V; Hathaway, Elizabeth D; Higgins, Simon; Forehand, Ronald L; Schmidt, Michael D; Evans, Ellen M

    2017-08-28

    Sprint interval cycle training is a contemporary popular mode of training but its relative efficacy, under conditions of matched energy expenditure, to reduce risk factors for cardiometabolic disease is incompletely characterised, especially in young women. The purpose of this investigation was to determine the relative efficacy of six weeks of moderate-intensity cycling (MOD-C) and vigorous sprint-interval cycling (VIG-SIC) on lipid profile, insulin (INS) and insulin resistance using the homeostatic model assessment (HOMA-IR) and C-reactive protein (CRP) in inactive, overweight/obese (OW/OB) young women. Participants (BMI ≥25 kg/m(2), waist circumference ≥88 cm) were randomly assigned to MOD-C (20-30 min at 60-70% of heart rate reserve(HRR)) or VIG-SIC (5-7 repeated bouts 30-second maximal effort sprints, followed by four minutes of active recovery) supervised training three days/week for six weeks, with each group matched on energy expenditure. Adiposity (%Fat) was measured using dual x-ray absorptiometry. Forty-four participants (20.4 ± 1.6 years, 65.9% Caucasian, 29.8 ± 4.1 kg/m(2)) were included in the analysis. The improvement in CRP observed in the MOD-C group was larger than the VIG-C group (p = .034). Overall, high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels improved following training (p < .05); however, total cholesterol, triglyceride, INS and HOMA-IR did not improve (p > .05). These results indicate MOD-C training may be more effective in reducing CRP than VIG-SIC.

  12. Reduced-toxicity conditioning with fludarabine, once-daily intravenous busulfan, and antithymocyte globulins prior to allogeneic stem cell transplantation: results of a multicenter prospective phase 2 trial.

    PubMed

    Mohty, Mohamad; Malard, Florent; Blaise, Didier; Milpied, Noel; Furst, Sabine; Tabrizi, Resa; Guillaume, Thierry; Vigouroux, Stéphane; El-Cheikh, Jean; Delaunay, Jacques; Le Gouill, Steven; Moreau, Philippe; Labopin, Myriam; Chevallier, Patrice

    2015-02-15

    The optimal intensity of myeloablation delivered as part of a reduced-intensity/toxicity conditioning (RIC/RTC) regimen to decrease the recurrence rate, without increasing nonrecurrence mortality (NRM), remains to be established. The current phase 2, prospective, multicenter trial aimed to assess the efficacy and safety of an RIC/RTC regimen based on busulfan at a dose of 130 mg/m(2) /day intravenously for 3 days, fludarabine at a dose of 30 mg/m(2) /day for 5 days, and antithymocyte globulins at a dose of 2.5 mg/kg/day for 2 days. A total of 80 patients (median age, 53 years; range, 25-64 years) with hematological malignancies were included. With a median follow-up of 21 months (range, 12-36.5 months), the Kaplan-Meier estimates of overall and disease-free survival at 2 years were 62% (95% confidence interval [95% CI], 51%-73%) and 50% (95% CI, 33%-57%), respectively. The cumulative incidences of grade 2 to 4 acute graft-versus-host disease (GVHD) and chronic GVHD (all grades) were 29% (95% CI, 19%-39%) and 35% (95% CI, 24%-46%), respectively. At 2 years, the cumulative incidence of recurrence/disease progression and NRM were 44% (95% CI, 31%-56%) and 11% (95% CI, 6%-19%), respectively. Patient age, diagnosis, donor type, sex, presence of comorbidities, and the Hematopoietic cell transplantation-specific comorbidities index did not appear to have any statistically significant impact on NRM, recurrence/disease progression, disease-free survival, or overall survival. The RIC/RTC regimen used in the current study appeared to be safe, with a low NRM rate at 2 years noted among high-risk patients, and efficient disease control, warranting prospective phase 3 trials. © 2014 American Cancer Society.

  13. Intermediate care to intensive care triage: A quality improvement project to reduce mortality.

    PubMed

    Hager, David N; Chandrashekar, Pranav; Bradsher, Robert W; Abdel-Halim, Ali M; Chatterjee, Souvik; Sawyer, Melinda; Brower, Roy G; Needham, Dale M

    2017-08-03

    Medical patients whose care needs exceed what is feasible on a general ward, but who do not clearly require critical care, may be admitted to an intermediate care unit (IMCU). Some IMCU patients deteriorate and require medical intensive care unit (MICU) admission. In 2012, staff in the Johns Hopkins IMCU expressed concern that patient acuity and the threshold for MICU admission were too high. Further, shared triage decision-making between residents and supervising physicians did not consistently occur. To improve our triage process, we used a 4Es quality improvement framework (engage, educate, execute, evaluate) to (1) educate residents and fellows regarding principles of triage and (2) facilitate real-time communication between MICU residents conducting triage and supervising physicians. Among patients transferred from the IMCU to the MICU during baseline (n=83;July-December 2012) and intervention phases (n=94;July-December 2013), unadjusted mortality decreased from 34% to 21% (p=0.06). After adjusting for severity of illness, admitting diagnosis, and bed availability, the odds of death were lower during the intervention vs. baseline phase (OR 0.33; 95%CI 0.11-0.98). Using a structured quality improvement process targeting triage education and increased resident/supervisor communication, we demonstrated reduced mortality among patients transferred from the IMCU to the MICU. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. A novel method of rejection of brood parasitic eggs reduces parasitism intensity in a cowbird host

    PubMed Central

    De Mársico, María C.; Gloag, Ros; Ursino, Cynthia A.; Reboreda, Juan C.

    2013-01-01

    The hosts of brood parasitic birds are under strong selection pressure to recognize and remove foreign eggs from their nests, but parasite eggs may be too large to be grasped whole and too strong to be readily pierced by the host's bill. Such operating constraints on egg removal are proposed to force some hosts to accept parasite eggs, as the costs of deserting parasitized clutches can outweigh the cost of rearing parasites. By fitting microcameras inside nests, we reveal that the Neotropical baywing (Agelaioides badius), a host of the screaming cowbird (Molothrus rufoaxillaris) and shiny cowbird (Molothrus bonariensis), instead circumvents such constraints by kicking parasite eggs out of the nest. To our knowledge, this is the first report of a passerine bird using its feet to remove objects from the nest. Kick-ejection was an all-or-nothing response. Baywings kick-ejected parasite eggs laid before their own first egg and, if heavily parasitized, they ejected entire clutches and began again in the same nest. Few baywings were able to rid their nests of every parasite egg, but their novel ejection method allowed them to reduce the median parasitism intensity by 75 per cent (from four to one cowbird eggs per nest), providing an effective anti-parasite defence. PMID:23485877

  15. [Reducing patient pressure sore incidence density in the pediatric