65 results on '"Aljurf, Mahmoud"'
Search Results
2. The Global State of Hematopoietic Cell Transplantation for Multiple Myeloma: An Analysis of the Worldwide Network of Blood and Marrow Transplantation Database and the Global Burden of Disease Study.
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Cowan AJ, Baldomero H, Atsuta Y, Mikhael J, Aljurf M, Seber A, Greinix H, Koh M, Worel N, Libby EN, Pasquini M, Galeano S, Saber W, Iida M, Jaimovich G, Rolon JM, Kodera Y, Benakli M, Nosa BG, Elhaddad A, Szer J, Passweg J, Kroeger N, Weisdorf D, and Niederwieser D
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- Bone Marrow, Europe, Global Burden of Disease, Humans, North America, Retrospective Studies, Transplantation, Autologous, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation, Multiple Myeloma epidemiology, Multiple Myeloma therapy
- Abstract
Multiple myeloma (MM) is a plasma cell neoplasm characterized by destructive bony lesions, anemia, and renal impairment. Access to effective therapy is limited globally. We report the rates and utilization of hematopoietic cell transplantation (HCT) globally from 2006-2015 to better characterize access to HCT for patients with MM. This was an analysis of a retrospective survey of Worldwide Network of Blood and Marrow Transplant sites, conducted annually between 2006-2015. Incidence estimates were from the Global Burden of Disease study. Outcome measures included total number of autologous and allogeneic HCTs by world regions, and percentage of newly diagnosed MM patients who underwent HCT, calculated by the number of transplants per region in calendar year/gross annual incidence of MM per region. From 2006 to 2015, the number of autologous HCT performed worldwide for MM increased by 107%. Utilization of autologous HCT was highest in Northern America and European regions, increasing from 13% to 24% in Northern America, and an increase from 15% to 22% in Europe. In contrast, the utilization of autologous HCT was lower in the Africa/Mediterranean region, with utilization only changing from 1.8% in 2006 to 4% in 2015. The number of first allogeneic HCT performed globally for MM declined after a peak in 2012 by -3% since 2006. Autologous HCT utilization for MM has increased worldwide in high-income regions but remains poorly utilized in Africa and the East Mediterranean. More work is needed to improve access to HCT for MM patients, especially in low to middle income countries. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2020
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3. A Personalized Prediction Model for Outcomes after Allogeneic Hematopoietic Cell Transplant in Patients with Myelodysplastic Syndromes.
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Nazha A, Hu ZH, Wang T, Lindsley RC, Abdel-Azim H, Aljurf M, Bacher U, Bashey A, Cahn JY, Cerny J, Copelan E, DeFilipp Z, Diaz MA, Farhadfar N, Gadalla SM, Gale RP, George B, Gergis U, Grunwald MR, Hamilton B, Hashmi S, Hildebrandt GC, Inamoto Y, Kalaycio M, Kamble RT, Kharfan-Dabaja MA, Lazarus HM, Liesveld JL, Litzow MR, Majhail NS, Murthy HS, Nathan S, Nishihori T, Pawarode A, Rizzieri D, Sabloff M, Savani BN, Schachter L, Schouten HC, Seo S, Shah NN, Solh M, Valcárcel D, Vij R, Warlick E, Wirk B, Wood WA, Yared JA, Alyea E, Popat U, Sobecks RM, Scott BL, Nakamura R, and Saber W
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- Humans, Middle Aged, Mutation, Neoplasm Recurrence, Local, Transplantation Conditioning, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes therapy
- Abstract
Allogeneic hematopoietic stem cell transplantation (HCT) remains the only potentially curative option for myelodysplastic syndromes (MDS). Mortality after HCT is high, with deaths related to relapse or transplant-related complications. Thus, identifying patients who may or may not benefit from HCT is clinically important. We identified 1514 patients with MDS enrolled in the Center for International Blood and Marrow Transplant Research Registry and had their peripheral blood samples sequenced for the presence of 129 commonly mutated genes in myeloid malignancies. A random survival forest algorithm was used to build the model, and the accuracy of the proposed model was assessed by concordance index. The median age of the entire cohort was 59 years. The most commonly mutated genes were ASXL1(20%), TP53 (19%), DNMT3A (15%), and TET2 (12%). The algorithm identified the following variables prior to HCT that impacted overall survival: age, TP53 mutations, absolute neutrophils count, cytogenetics per International Prognostic Scoring System-Revised, Karnofsky performance status, conditioning regimen, donor age, WBC count, hemoglobin, diagnosis of therapy-related MDS, peripheral blast percentage, mutations in RAS pathway, JAK2 mutation, number of mutations/sample, ZRSR2, and CUX1 mutations. Different variables impacted the risk of relapse post-transplant. The new model can provide survival probability at different time points that are specific (personalized) for a given patient based on the clinical and mutational variables that are listed above. The outcomes' probability at different time points may aid physicians and patients in their decision regarding HCT., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. All rights reserved.)
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- 2020
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4. Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide.
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Im A, Rashidi A, Wang T, Hemmer M, MacMillan ML, Pidala J, Jagasia M, Pavletic S, Majhail NS, Weisdorf D, Abdel-Azim H, Agrawal V, Al-Homsi AS, Aljurf M, Askar M, Auletta JJ, Bashey A, Beitinjaneh A, Bhatt VR, Byrne M, Cahn JY, Cairo M, Castillo P, Cerny J, Chhabra S, Choe H, Ciurea S, Daly A, Perez MAD, Farhadfar N, Gadalla SM, Gale R, Ganguly S, Gergis U, Hanna R, Hematti P, Herzig R, Hildebrandt GC, Lad DP, Lee C, Lehmann L, Lekakis L, Kamble RT, Kharfan-Dabaja MA, Khandelwal P, Martino R, Murthy HS, Nishihori T, O'Brien TA, Olsson RF, Patel SS, Perales MA, Prestidge T, Qayed M, Romee R, Schoemans H, Seo S, Sharma A, Solh M, Strair R, Teshima T, Urbano-Ispizua A, Van der Poel M, Vij R, Wagner JL, William B, Wirk B, Yared JA, Spellman SR, Arora M, and Hamilton BK
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- Adult, Cyclophosphamide therapeutic use, Humans, Risk Factors, Transplantation Conditioning, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation adverse effects
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Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. All rights reserved.)
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- 2020
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5. The Role of Donor Lymphocyte Infusion (DLI) in Post-Hematopoietic Cell Transplant (HCT) Relapse for Chronic Myeloid Leukemia (CML) in the Tyrosine Kinase Inhibitor (TKI) Era.
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Schmidt S, Liu Y, Hu ZH, Williams KM, Lazarus HM, Vij R, Kharfan-Dabaja MA, Ortí G, Wiernik PH, Weisdorf D, Kamble RT, Herzig R, Wirk B, Cerny J, Bacher U, Chaudhri NA, Nathan S, Farhadfar N, Aljurf M, Gergis U, Szer J, Seo S, Hsu JW, Olsson RF, Maharaj D, George B, Hildebrandt GC, Agrawal V, Nishihori T, Abdel-Azim H, Alyea E, Popat U, Sobecks R, Scott BL, Holter Chakrabarty J, and Saber W
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- Humans, Lymphocyte Transfusion, Lymphocytes, Protein Kinase Inhibitors therapeutic use, Recurrence, Retrospective Studies, Hematopoietic Stem Cell Transplantation, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy
- Abstract
Treatment for relapse of chronic myeloid leukemia (CML) following hematopoietic cell transplantation (HCT) includes tyrosine kinase inhibitors (TKIs) with or without donor lymphocyte infusions (DLIs), but the most effective treatment strategy is unknown. This study was performed through the Center for International Blood and Marrow Transplant Research (CIBMTR) database. We retrospectively reviewed all patients reported to the CIBMTR registry from 2002 to 2014 who underwent HCT for CML and were alive 30 days postrelapse. A total of 215 HCT recipients relapsed and were analyzed in the following groups: (1) TKI alone (n = 128), (2) TKI with DLI (n = 48), and (3) DLI without TKI (n = 39). In multivariate analysis, disease status prior to HCT had a significant effect on overall survival (OS). Patients who received a DLI alone compared with a TKI with a DLI had inferior survival (hazard ratio, 2.28; 95% confidence interval, 1.23 to 4.24; P= .009). Those who received a TKI alone had similar survival compared with those who received a TKI with a DLI (P = .81). These data support that despite use of TKIs pretransplantation, TKI salvage therapy continues to provide significant survival following relapse in patients with CML following HCT. These data do not suggest that adding a DLI to a TKI adds an improvement in OS., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2020
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6. Predictors of Loss to Follow-Up Among Pediatric and Adult Hematopoietic Cell Transplantation Survivors: A Report from the Center for International Blood and Marrow Transplant Research.
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Buchbinder D, Brazauskas R, Bo-Subait K, Ballen K, Parsons S, John T, Hahn T, Sharma A, Steinberg A, D'Souza A, Kumar AJ, Yoshimi A, Wirk B, Shaw B, Freytes C, LeMaistre C, Bredeson C, Dandoy C, Almaguer D, Marks DI, Szwajcer D, Hale G, Schouten H, Hashem H, Schoemans H, Murthy HS, Lazarus HM, Cerny J, Tay J, Yared JA, Adekola K, Schultz KR, Lehmann L, Burns L, Aljurf M, Diaz MA, Majhail N, Farhadfar N, Kamble R, Olsson R, Schears R, Seo S, Beattie S, Chhabra S, Savani BN, Badawy S, Ganguly S, Ciurea S, Marino S, Gergis U, Kuwatsuka Y, Inamoto Y, Khera N, Hashmi S, Wood W, and Saber W
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- Adult, Aged, Child, Follow-Up Studies, Humans, Survivors, Transplantation Conditioning, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation
- Abstract
Follow-up is integral for hematopoietic cell transplantation (HCT) care to ensure surveillance and intervention for complications. We characterized the incidence of and predictors for being lost to follow-up. Two-year survivors of first allogeneic HCT (10,367 adults and 3865 children) or autologous HCT (7291 adults and 467 children) for malignant/nonmalignant disorders between 2002 and 2013 reported to the Center for International Blood and Marrow Transplant Research were selected. The cumulative incidence of being lost to follow-up (defined as having missed 2 consecutive follow-up reporting periods) was calculated. Marginal Cox models (adjusted for center effect) were fit to evaluate predictors. The 10-year cumulative incidence of being lost to follow-up was 13% (95% confidence interval [CI], 12% to 14%) in adult allogeneic HCT survivors, 15% (95% CI, 14% to 16%) in adult autologous HCT survivors, 25% (95% CI, 24% to 27%) in pediatric allogeneic HCT survivors, and 24% (95% CI, 20% to 29%) in pediatric autologous HCT survivors. Factors associated with being lost to follow-up include younger age, nonmalignant disease, public/no insurance (reference: private), residence farther from the tranplantation center, and being unmarried in adult allogeneic HCT survivors; older age and testicular/germ cell tumor (reference: non-Hodgkin lymphoma) in adult autologous HCT survivors; older age, public/no insurance (reference: private), and nonmalignant disease in pediatric allogeneic HCT survivors; and older age in pediatric autologous HCT survivors. Follow-up focusing on minimizing attrition in high-risk groups is needed to ensure surveillance for late effects., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2020
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7. Maintenance Tyrosine Kinase Inhibitors Following Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelogenous Leukemia: A Center for International Blood and Marrow Transplant Research Study.
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DeFilipp Z, Ancheta R, Liu Y, Hu ZH, Gale RP, Snyder D, Schouten HC, Kalaycio M, Hildebrandt GC, Ustun C, Daly A, Ganguly S, Inamoto Y, Litzow M, Szer J, Savoie ML, Hossain N, Kharfan-Dabaja MA, Hamadani M, Reshef R, Bajel A, Schultz KR, Gadalla S, Gerds A, Liesveld J, Juckett MB, Kamble R, Hashmi S, Abdel-Azim H, Solh M, Bacher U, Lazarus H, Olsson R, Cahn JY, Grunwald MR, Savani BN, Yared J, Rowe JM, Cerny J, Chaudhri NA, Aljurf M, Beitinjaneh A, Seo S, Nishihori T, Hsu JW, Ramanathan M, Alyea E, Popat U, Sobecks R, and Saber W
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- Adult, Humans, Imatinib Mesylate, Protein Kinase Inhibitors therapeutic use, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy
- Abstract
It remains unknown whether the administration of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 after allogeneic hematopoietic cell transplantation (HCT) is associated with improved outcomes for patients with chronic myelogenous leukemia (CML). In this registry study, we analyzed clinical outcomes of 390 adult patients with CML who underwent transplantation between 2007 and 2014 and received maintenance TKI following HCT (n = 89) compared with no TKI maintenance (n = 301), as reported to the Center for International Blood and Marrow Transplant Research. All patients received TKI therapy before HCT. The majority of patients had a disease status of first chronic phase at HCT (n = 240; 62%). The study was conducted as a landmark analysis, excluding patients who died, relapsed, had chronic graft-versus-host disease, or were censored before day +100 following HCT. Of the 89 patients who received TKI maintenance, 77 (87%) received a single TKI and the other 12 (13%) received multiple sequential TKIs. The most common TKIs used for maintenance were dasatinib (n = 50), imatinib (n = 27), and nilotinib (n = 27). As measured from day +100, the adjusted estimates for 5-year relapse (maintenance, 35% versus no maintenance, 26%; P = .11), leukemia-free survival (maintenance, 42% versus no maintenance, 44%; P = .65), or overall survival (maintenance, 61% versus no maintenance, 57%; P = .61) did not differ significantly between patients receiving TKI maintenance or no maintenance. These results remained unchanged in multivariate analysis and were not modified by disease status before transplantation. In conclusion, our data from this day +100 landmark analysis do not demonstrate a significant impact of maintenance TKI therapy on clinical outcomes. The optimal approach to TKI administration in the post-transplantation setting in patients with CML remains undetermined., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2020
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8. Comprehensive Prognostication in Critically Ill Pediatric Hematopoietic Cell Transplant Patients: Results from Merging the Center for International Blood and Marrow Transplant Research (CIBMTR) and Virtual Pediatric Systems (VPS) Registries.
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Zinter MS, Logan BR, Fretham C, Sapru A, Abraham A, Aljurf MD, Arnold SD, Artz A, Auletta JJ, Chhabra S, Copelan E, Duncan C, Gale RP, Guinan E, Hematti P, Keating AK, Marks DI, Olsson R, Savani BN, Ustun C, Williams KM, Pasquini MC, and Dvorak CC
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- Child, Humans, Infant, Intensive Care Units, Pediatric, Registries, Retrospective Studies, Risk Factors, Critical Illness, Hematopoietic Stem Cell Transplantation
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Critically ill pediatric allogeneic hematopoietic cell transplant (HCT) patients may benefit from early and aggressive interventions aimed at reversing the progression of multiorgan dysfunction. Therefore, we evaluated 25 early risk factors for pediatric intensive care unit (PICU) mortality to improve mortality prognostication. We merged the Virtual Pediatric Systems and Center for International Blood and Marrow Transplant Research databases and analyzed 936 critically ill patients ≤21 years of age who had undergone allogeneic HCT and subsequently required PICU admission between January 1, 2009, and December 31, 2014. Of 1532 PICU admissions, the overall PICU mortality rate was 17.4% (95% confidence interval [CI], 15.6% to 19.4%) but was significantly higher for patients requiring mechanical ventilation (44.0%), renal replacement therapy (56.1%), or extracorporeal life support (77.8%). Mortality estimates increased significantly the longer that patients remained in the PICU. Of 25 HCT- and PICU-specific characteristics available at or near the time of PICU admission, moderate/severe pre-HCT renal injury, pre-HCT recipient cytomegalovirus seropositivity, <100-day interval between HCT and PICU admission, HCT for underlying acute myeloid leukemia, and greater admission organ dysfunction as approximated by the Pediatric Risk of Mortality 3 score were each independently associated with PICU mortality. A multivariable model using these components identified that patients in the top quartile of risk had 3 times greater mortality than other patients (35.1% versus 11.5%, P < .001, classification accuracy 75.2%; 95% CI, 73.0% to 77.4%). These data improve our working knowledge of the factors influencing the progression of critical illness in pediatric allogeneic HCT patients. Future investigation aimed at mitigating the effect of these risk factors is warranted., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2020
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9. Hematopoietic Cell Transplant Consideration for Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia Patients.
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El Fakih R, Savani B, Mohty M, and Aljurf M
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- Allografts, Humans, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Hematopoietic Stem Cell Transplantation, Philadelphia Chromosome, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a relatively new entity characterized by high cytokine receptor and tyrosine kinase signaling resulting in multiple downstream pathway stimulation. The standard diagnostic method, gene expression profiling, is not widely available. Efforts are ongoing to establish easy and clinically applicable diagnostic pathways to facilitate the accurate identification of these patients and thus enable a better understanding of the prognosis and outcomes with different treatment approaches. The rates of complete remission in ALL patients are consistently above 90% with the different induction protocols; however, maintaining remission depends on the risk group of the patient and consolidation therapy. Allogeneic hematopoietic cell transplant (allo-HCT) is particularly beneficial when the risk of relapse is very high and the expected complications with transplant are low. Data on the outcomes of allo-HCT for Ph-like ALL are scarce. In this article we review the published literature on outcomes of Ph-like ALL patients treated using different therapeutic approaches and make recommendations about transplant consideration for these patients., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2020
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10. Worldwide Network for Blood and Marrow Transplantation Recommendations for Establishing a Hematopoietic Stem Cell Transplantation Program in Countries with Limited Resources, Part II: Clinical, Technical, and Socioeconomic Considerations.
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Aljurf M, Weisdorf D, Hashmi S, Nassar A, Gluckman E, Mohty M, Rizzo D, Pasquini M, Hamadani M, Saber W, Hari P, Kharfan-Dabaja M, Majhail N, Gerges U, Hamidieh AA, Hussain F, Elhaddad A, Mahmoud HK, Tbakhi A, Othman TB, Hamladji RM, Bekadja MA, Ahmed P, Bazarbachi A, Adil S, Alkindi S, Ladeb S, Dennison D, Patel M, Lu P, Quessar AE, Okamoto S, Atsuta Y, Alhejazi A, Ayas MF, Ahmed SO, Novitzky N, Srivastava A, Seber A, Solh HE, Ghavamzadeh A, Confer D, Kodera Y, Hildegard G, Szer J, Horowitz MM, and Niederwieser D
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- Humans, Practice Guidelines as Topic, Socioeconomic Factors, Transplantation, Autologous, Transplantation, Homologous, Developing Countries, Hematopoietic Stem Cell Transplantation, Societies, Medical, Transplantation Conditioning
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The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. Although this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state-of-the-art treatments, including transplantation, by providing financial, technological, legal, ethical, and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population and potentially provide long-term cost savings by circumventing the need for their citizens to seek care abroad. The costs of establishing an HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. In addition, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT, and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation for establishing HSCT programs, with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in resource-constrained settings., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2019
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11. Worldwide Network for Blood and Marrow Transplantation Recommendations for Establishing a Hematopoietic Cell Transplantation Program, Part I: Minimum Requirements and Beyond.
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Pasquini MC, Srivastava A, Ahmed SO, Aljurf M, Atsuta Y, Doleysh C, Galeano S, Gluckman E, Greinix H, Hale GA, Hari P, Hashmi SK, Kamani N, Laughlin MJ, Niederwieser D, Seber A, Szer J, Snowden JA, Van Biesen K, Watry P, Weisdorf DJ, and Apperley J
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- Humans, Practice Guidelines as Topic, Transplantation, Autologous, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation, Societies, Medical, Transplantation Conditioning
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Hematopoietic cell transplantation (HCT) is a highly complex procedure that requires a dedicated multidisciplinary team to optimize safety. In addition, institutions may have different needs regarding indications based on regional disease prevalence or may have an interest in developing specialized services. Structured recommendations are not commonly available, however. The Transplant Center and Recipient Issues Standing Committee of the Worldwide Network for Blood and Marrow Transplantation (WBMT) organized a structured review of all pertinent elements for establishing a transplantation program. First, we solicited components from committee members and grouped them into domains (infrastructure, staff, cell processing laboratory, blood banking, laboratory, radiology, pharmacy, HLA testing, ancillary services, and quality). Subsequently, reviewers scored each element on a 7-point scale, ranging from an absolute requirement (score of 1) to not required (score of 7). An independent group of 5 experienced transplantation physicians reviewed the rankings. The minimum requirements for establishing any HCT program were identified among elements with mean score of ≤2.0, and specific elements for allogeneic and autologous HCT were identified. Mean scores of >2.0 to 4.0 were classified as preferred recommendation, and mean scores of >4.0 to ≤ 7.0 were considered ideal recommendations for advanced and complex types of transplantation. This structured set of recommendations guides the prioritization of minimum requirements to establish a transplantation program and set the stage for expansion and further development., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2019
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12. Myeloablative Unrelated Cord Blood Transplantation in Adolescents and Young Adults with Acute Leukemia.
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Hayashi H, Volt F, Sanz J, Petersen E, Dhedin N, Hough R, Milpied N, Angelucci E, Yakoub-Agha I, Michallet M, Michel G, Aljurf M, Kenzey C, Rocha V, Dalle JH, Bader P, Ruggeri A, and Gluckman E
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- Acute Disease, Adolescent, Adult, Age Factors, Child, Child, Preschool, Disease-Free Survival, Female, Humans, Incidence, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Male, Retrospective Studies, Survival Rate, Antilymphocyte Serum administration & dosage, Cord Blood Stem Cell Transplantation, Graft vs Host Disease etiology, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Registries, Unrelated Donors
- Abstract
Outcomes for adolescents and young adults (AYAs) with leukemia differ from other age groups and are still under-represented in clinical research. The aim of this study was to analyze outcomes of umbilical cord blood transplant (UCBT) in AYAs with acute leukemia reported to Eurocord/European Society for Blood and Marrow Transplantation. Patients (N = 504) had acute lymphoblastic (59%) or myeloid leukemia (41%), were aged 15 to 25 years, and received UCBT after myeloablative conditioning regimens between 2004 and 2016. The primary endpoint was 3-year overall survival (OS). Median follow-up was 3.9 years. Transplant was single in 58% and double UCBT in 42%. Three-year OS was 45% and leukemia free survival (LFS) was 41%. Cumulative incidence functions (CIFs) of nonrelapse mortality (NRM) and relapse were 31% and 28%, respectively. CIF of acute graft-versus-host disease (GVHD) grades II to IV at day 100 was 28%. Three-year CIF of chronic GVHD was 25%. In adjusted analysis, better disease status at UCBT (hazard ratio [HR], 2.74; P < .001) and more recent UCBT (HR, 1.43; P = .01) were associated with increased OS, and a similar effect of these factors was observed on LFS. Contrastingly, the use of antithymocyte globulin had a negative effect in LFS. The risk of acute GVHD grades II to IV increased with the use of double UCBT (HR, 1.65; P = .02) and decreased with more recent transplant period (HR, .65; P = .02) and antithymocyte globulin use (HR, .55; P = .01). Outcomes of AYA UCBT improved in more recent years, becoming comparable with pediatric results. Demonstrating the feasibility of UCBT in AYAs facilitates stem cell source selection and provides the basis for future prospective studies., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2019
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13. Inferior Access to Allogeneic Transplant in Disadvantaged Populations: A Center for International Blood and Marrow Transplant Research Analysis.
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Paulson K, Brazauskas R, Khera N, He N, Majhail N, Akpek G, Aljurf M, Buchbinder D, Burns L, Beattie S, Freytes C, Garcia A, Gajewski J, Hahn T, Knight J, LeMaistre C, Lazarus H, Szwajcer D, Seftel M, Wirk B, Wood W, and Saber W
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- Female, Humans, Male, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation methods, Transplantation Conditioning methods
- Abstract
Allogeneic hematopoietic cell transplantation (alloHCT) is offered in a limited number of medical centers and is associated with significant direct and indirect costs. The degree to which social and geographic barriers reduce access to alloHCT is unknown. Data from the Surveillance, Epidemiology and End Results Program (SEER) and the Center for International Blood and Marrow Transplant Research (CIBMTR) were integrated to determine the rate of unrelated donor (URD) alloHCT for acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS) performed between 2000 and 2010 in the 612 counties covered by SEER. The total incidence of AML, ALL, and MDS was determined using SEER, and the number of alloHCTs performed in the same time period and geographic area were determined using the CIBMTR database. We then determined which sociodemographic attributes influenced the rate of alloHCT (rural/urban status, median family size, percentage of residents below the poverty line, and percentage of minority race). In the entire cohort, higher levels of poverty were associated with lower rates of alloHCT (estimated rate ratio [ERR], .86 for a 10% increase in the percentage of the population below the poverty line; P < .01), whereas rural location was not (ERR, .87; P = .11). Thus, patients from areas with higher poverty rates diagnosed with ALL, AML, and MDS are less likely patients from wealthier counties to undergo URD alloHCT. There is need to better understand the reasons for this disparity and to encourage policy and advocacy efforts to improve access to medical care for all., (Copyright © 2019. Published by Elsevier Inc.)
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- 2019
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14. Lower Graft-versus-Host Disease and Relapse Risk in Post-Transplant Cyclophosphamide-Based Haploidentical versus Matched Sibling Donor Reduced-Intensity Conditioning Transplant for Hodgkin Lymphoma.
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Ahmed S, Kanakry JA, Ahn KW, Litovich C, Abdel-Azim H, Aljurf M, Bacher VU, Bejanyan N, Cohen JB, Farooq U, Fuchs EJ, Bolaños-Meade J, Ghosh N, Herrera AF, Hossain NM, Inwards D, Kanate AS, Martino R, Munshi PN, Murthy H, Mussetti A, Nieto Y, Perales MA, Romee R, Savani BN, Seo S, Wirk B, Yared JA, Sureda A, Fenske TS, and Hamadani M
- Subjects
- Adolescent, Adult, Aged, Allografts, Disease-Free Survival, Female, Humans, Male, Middle Aged, Recurrence, Survival Rate, Cyclophosphamide administration & dosage, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Hodgkin Disease mortality, Hodgkin Disease therapy, Siblings, Tissue Donors, Transplantation Conditioning
- Abstract
Classic Hodgkin lymphoma (cHL) patients with relapsed or refractory disease may benefit from allogeneic hematopoietic cell transplantation (allo-HCT), but many lack a matched sibling donor (MSD). Herein, we compare outcomes of 2 reduced-intensity conditioning (RIC) HCT platforms in cHL: T cell-replete related donor haploidentical (haplo) HCT with a post-transplant cyclophosphamide (PTCy)-based approach versus an MSD/calcineurin inhibitor (CNI)-based approach. The study included 596 adult patients who underwent a first RIC allo-HCT for cHL between 2008 and 2016 using either a haplo-PTCy (n = 139) or MSD/CNI-based (n = 457) approach. Overall survival (OS) was the primary endpoint. Secondary endpoints included acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), nonrelapse mortality (NRM), relapse/progression, and progression-free survival (PFS). On multivariate analysis, there was no significant difference between haplo/PTCy and MDS/CNI-based approaches in terms of OS (hazard ratio [HR], 1.07; 95% confidence interval [CI], .79 to 1.45; P = .66) or PFS (HR, .86; 95% CI, .68 to 1.10; P = .22). Haplo/PTCy was associated with a significantly higher risk of grades II to IV aGVHD (odds ratio [OR], 1.73, 95% CI, 1.16 to 2.59; P = .007), but the risk of grades III to IV aGVHD was not significantly different between the 2 cohorts (OR, .61; 95% CI, .29 to 1.27; P = .19). The haplo/PTCy platform provided a significant reduction in cGVHD risk (HR, .45; 95% CI, .32 to .64; P < .001), and a significant reduction in relapse risk (HR, .74; 95% CI, .56 to .97; P = .03). There was a statistically nonsignificant trend toward higher NRM with a haplo/PTCy approach (HR, 1.65; 95% CI, .99 to 2.77; P = .06). Haplo/PTCy-based approaches are associated with lower incidences of cGVHD and relapse, with PFS and OS outcomes comparable with MSD/CNI-based approaches. There was a leaning toward higher NRM with a haplo/PTCy-based platform. These data show that haplo/PTCy allo-HCT in cHL results in survival comparable with MSD/CNI-based allo-HCT., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2019
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15. Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation.
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Saad A, Lamb L, Wang T, Hemmer MT, Spellman S, Couriel D, Alousi A, Pidala J, Abdel-Azim H, Agrawal V, Aljurf M, Beitinjaneh AM, Bhatt VR, Buchbinder D, Byrne M, Cahn JY, Cairo M, Castillo P, Chhabra S, Diaz MA, Farhan S, Floisand Y, Frangoul HA, Gadalla SM, Gajewski J, Gale RP, Gandhi M, Gergis U, Hamilton BK, Hematti P, Hildebrandt GC, Kamble RT, Kanate AS, Khandelwal P, Lazaryan A, MacMillan M, Marks DI, Martino R, Mehta PA, Nishihori T, Olsson RF, Patel SS, Qayed M, Rangarajan HG, Reshef R, Ringden O, Savani BN, Schouten HC, Schultz KR, Seo S, Shaffer BC, Solh M, Teshima T, Urbano-Ispizua A, Verdonck LF, Vij R, Waller EK, William B, Wirk B, Yared JA, Yu LC, Arora M, and Hashmi S
- Subjects
- Acute Disease, Adolescent, Adult, Allografts, CD4-CD8 Ratio, Disease-Free Survival, Female, HLA Antigens, Humans, Male, Middle Aged, Recurrence, Survival Rate, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Graft vs Host Disease blood, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Leukemia blood, Leukemia mortality, Leukemia therapy, Myelodysplastic Syndromes blood, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy, Peripheral Blood Stem Cell Transplantation
- Abstract
Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. Correlative analysis was performed between CD3
+ T cell dose and the risk of graft-versus-host-disease (GVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Using maximum likelihood estimation, we identified CD3+ T cell dose cutoff that separated the risk of acute GVHD (aGVHD) grade II-IV in both the MSD and MUD groups. A CD3+ T cell dose cutoff of 14 × 107 cells/kg identified MSD/low CD3+ (n = 223) and MSD/high CD3+ (n = 1214), and a dose of 15 × 107 cells/kg identified MUD/low CD3+ (n = 197) and MUD/high CD3+ (n = 1102). On univariate analysis, the MSD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MSD/low CD3+ group (33% versus 25%; P = .009). There were no differences between the 2 groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. The MUD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MUD/low CD3+ group (49% versus 41%; P = .04). There were no differences between the 2 groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of the MSD and MUD groups failed to show an association between CD3+ T cell dose and the risk of either aGVHD grade II-IV (P = .10 and .07, respectively) or cGVHD (P = .80 and .30, respectively). Subanalysis of CD4+ T cells, CD8+ T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3+ T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4+ and CD8+ T cell doses were not possible given our small sample size., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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16. Inferior Outcomes with Cyclosporine and Mycophenolate Mofetil after Myeloablative Allogeneic Hematopoietic Cell Transplantation.
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Hamilton BK, Liu Y, Hemmer MT, Majhail N, Ringden O, Kim D, Costa L, Stuart R, Alousi A, Pidala JA, Couriel DR, Aljurf M, Antin JH, Bredeson C, Cahn JY, Cairo M, Choi SW, Dandoy C, Gale RP, Gergis U, Hematti P, Inamoto Y, Kamble RT, MacMillan M, Marks DI, Nemecek E, Nishihori T, Saad A, Savani BN, Schriber J, Seo S, Socié G, Teshima T, Verdonck LF, Waller EK, Wirk M, Spellman SR, Arora M, and Chhabra S
- Subjects
- Adolescent, Adult, Aged, Allografts, Disease-Free Survival, Female, Humans, Male, Middle Aged, Survival Rate, Cyclosporine administration & dosage, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Mycophenolic Acid administration & dosage
- Abstract
Combination therapy with a calcineurin inhibitor (CNI), such as cyclosporine (CSA) or tacrolimus (Tac), and methotrexate (MTX) or mycophenolate mofetil (MMF) is a widely used approach to graft-versus-host disease (GVHD) prevention. Data on the comparative effectiveness of MMF compared with MTX are limited and conflicting, however. We analyzed data from the Center for International Blood and Marrow Transplant Research for adult patients undergoing first myeloablative hematopoietic cell transplantation (HCT) from an HLA-identical matched related donor (MRD; n = 3979) or matched unrelated donor (URD; n = 4163) using CSA+MMF, CSA+MTX, Tac+MMF, or Tac+MTX for GVHD prevention between 2000 and 2013. Within the MRD cohort, 2252 patients received CSA+MTX, 1391 received Tac+MTX, 114 received CSA+MMF, and 222 received Tac+MMF. Recipients of CSA+MMF had a higher incidence of acute GVHD grade II-IV (hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.24 to 2.20; P < .001) and grade III-IV (HR, 1.92; 95% CI, 1.31 to 2.83; P < .001) compared with Tac+MTX. The use of CSA+MMF was also associated with inferior overall survival (OS) (HR, 2.31; 95% CI, 1.73 to 3.09; P < .001) due to higher transplantation-related mortality (TRM) (HR, 4.03; 95% CI, 2.61 to 6.23; P < .001) compared with Tac+MTX. Within the URD cohort, 974 patients received CSA+MTX, 2697 received Tac+MTX, 68 received CSA+MMF, and 424 received Tac+MMF. CSA+MMF was again significantly associated with a higher incidence of grade III-IV acute GVHD (HR, 2.31; 95% CI, 1.57 to 3.42; P <0001), worse OS (HR, 2.36; 95% CI, 1.67 to 3.35; P < .001), and higher TRM (HR, 3.09; 95% CI, 2.00 to 4.77; P < .001), compared with Tac+MTX and other regimens. Thus, this large retrospective comparison of MMF versus MTX in combination with CSA or Tac demonstrates significantly worse GVHD and survival outcomes with CSA+MMF compared with Tac+MTX., (Copyright © 2019. Published by Elsevier Inc.)
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- 2019
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17. Association of Antiepileptic Medications with Outcomes after Allogeneic Hematopoietic Cell Transplantation with Busulfan/Cyclophosphamide Conditioning.
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McCune JS, Wang T, Bo-Subait K, Aljurf M, Beitinjaneh A, Bubalo J, Cahn JY, Cerny J, Chhabra S, Cumpston A, Dupuis LL, Lazarus HM, Marks DI, Maziarz RT, Norkin M, Prestidge T, Mineishi S, Krem MM, Pasquini M, and Martin PJ
- Subjects
- Adolescent, Adult, Aged, Allografts, Anticonvulsants adverse effects, Busulfan adverse effects, Child, Child, Preschool, Cyclophosphamide adverse effects, Disease-Free Survival, Female, Humans, Infant, Male, Middle Aged, Phenytoin adverse effects, Survival Rate, Anticonvulsants administration & dosage, Busulfan administration & dosage, Cyclophosphamide administration & dosage, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation, Phenytoin administration & dosage, Seizures drug therapy, Seizures etiology, Seizures mortality, Transplantation Conditioning
- Abstract
High-dose busulfan (BU) followed by high-dose cyclophosphamide (CY) before allogeneic hematopoietic cell transplantation (HCT) has long been used as treatment for hematologic malignancies. Administration of phenytoin or newer alternative antiepileptic medications (AEMs) prevents seizures caused by BU. Phenytoin induces enzymes that increase exposure to active CY metabolites in vivo, whereas alternative AEMs do not have this effect. Lower exposure to active CY metabolites with the use of alternative AEMs could decrease the risk of toxicity but might increase the risk of recurrent malignancy after HCT. Previous studies have not determined whether outcomes with alternative AEMs differ from those with phenytoin in patients treated with BU/CY before allogeneic HCT. We studied a cohort of 2155 patients, including 1460 treated with phenytoin and 695 treated with alternative AEMs, who received BU/CY before allogeneic HCT between 2004 and 2014. We found no differences suggesting decreased overall survival or relapse-free survival or increased risks of relapse, nonrelapse mortality, acute or chronic graft-versus-host disease, or regimen-related toxicity associated with the use of alternative AEMs compared with phenytoin. The risk of dialysis was lower in the alternative AEM group than in the phenytoin group. Alternative AEMs are safe for prevention of seizures after BU administration and can avoid the undesirable toxicities and drug interactions caused by phenytoin., (Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2019
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18. Role of Physical Therapy before and after Hematopoietic Stem Cell Transplantation: White Paper Report.
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Mohammed J, Smith SR, Burns L, Basak G, Aljurf M, Savani BN, Schoemans H, Peric Z, Chaudhri NA, Chigbo N, Alfred A, Bakhsh H, Salooja N, Chris Chim A, and Hashmi SK
- Subjects
- Humans, Hematopoietic Stem Cell Transplantation methods, Physical Therapy Modalities standards, Research Report standards, Transplantation Conditioning methods
- Abstract
Hematopoietic stem cell transplantation (HSCT) patients can suffer from various musculoskeletal problems resulting in long-term functional incapacity. Physical therapy (PT), as a part of the healthcare team, has been historically advocated for regaining functional capacity and improving quality of life post-HSCT. Because of the nature of this condition and the burden of post-transplant complications, this patient group requires a unique approach toward their rehabilitation that takes into account their complex musculoskeletal presentation ranging from fascia, muscle, tendons, bones, and ligaments. However, to our knowledge there is no universal standardized PT protocol or pathway to help guide rehab specialists to achieve optimal gains for this patient group, and anecdotal evidence suggests that these patients do not always receive the PT care they require. Hence, in collaboration with the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation, the Survivorship Special Interest Group of the American Society of Blood and Marrow Transplantation, and the Quality of Life Committee of the Eastern Mediterranean Blood and Marrow Transplantation, herein the Physical Therapy Association for Graft Versus Host Disease provides a brief review on role of PT in mitigating musculoskeletal complications in HSCT patients and makes evidence-based recommendations for incorporation of PT into routine HSCT care., (Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2019
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19. Non-Graft-versus-Host Disease Ocular Complications after Hematopoietic Cell Transplantation: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation.
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Inamoto Y, Petriček I, Burns L, Chhabra S, DeFilipp Z, Hematti P, Rovó A, Schears R, Shah A, Agrawal V, Ahmed A, Ahmed I, Ali A, Aljurf M, Alkhateeb H, Beitinjaneh A, Bhatt N, Buchbinder D, Byrne M, Callander N, Fahnehjelm K, Farhadfar N, Gale RP, Ganguly S, Hashmi S, Hildebrandt GC, Horn E, Jakubowski A, Kamble RT, Law J, Lee C, Nathan S, Penack O, Pingali R, Prasad P, Pulanic D, Rotz S, Shreenivas A, Steinberg A, Tabbara K, Tichelli A, Wirk B, Yared J, Basak GW, Battiwalla M, Duarte R, Savani BN, Flowers MED, Shaw BE, and Valdés-Sanz N
- Subjects
- Eye Diseases diagnosis, Eye Diseases prevention & control, Eye Diseases therapy, Humans, Incidence, Mass Screening, Patient Care Team, Risk Factors, Eye Diseases etiology, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Non-graft-versus-host disease (GVHD) ocular complications are generally uncommon after hematopoietic cell transplantation (HCT) but can cause prolonged morbidity affecting activities of daily living and quality of life. Here we provide an expert review of non-GVHD ocular complications in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Complications discussed in this review include cataracts, glaucoma, ocular infections, ocular involvement with malignancy, ischemic microvascular retinopathy, central retinal vein occlusion, retinal hemorrhage, retinal detachment and ocular toxicities associated with medications. We summarize the incidence, risk factors, screening, prevention, and treatment of individual complications and generate evidence-based recommendations. Baseline ocular evaluation before HCT should be considered in all patients who undergo HCT. Follow-up evaluations should be considered according to clinical signs and symptoms and risk factors. Better preventive strategies and treatments remain to be investigated for individual ocular complications after HCT. Both transplantation physicians and ophthalmologists should be knowledgeable about non-GVHD ocular complications and provide comprehensive collaborative team care., (Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2019
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20. Clinical Utilization of Chimeric Antigen Receptor T Cells in B Cell Acute Lymphoblastic Leukemia: An Expert Opinion from the European Society for Blood and Marrow Transplantation and the American Society for Blood and Marrow Transplantation.
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Kansagra AJ, Frey NV, Bar M, Laetsch TW, Carpenter PA, Savani BN, Heslop HE, Bollard CM, Komanduri KV, Gastineau DA, Chabannon C, Perales MA, Hudecek M, Aljurf M, Andritsos L, Barrett JA, Bachanova V, Bonini C, Ghobadi A, Gill SI, Hill J, Kenderian S, Kebriaei P, Nagler A, Maloney D, Liu HD, Shah NN, Kharfan-Dabaja MA, Shpall EJ, Mufti GJ, Johnston L, Jacoby E, Bazarbachi A, DiPersio JF, Pavletic SZ, Porter DL, Grupp SA, Sadelain M, Litzow MR, Mohty M, and Hashmi SK
- Subjects
- Antigens, CD19 immunology, Child, Critical Pathways, Drug Approval, Humans, Practice Patterns, Physicians', Societies, Medical, United States, Young Adult, Expert Testimony, Immunotherapy, Adoptive methods, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma therapy, Receptors, Antigen, T-Cell therapeutic use
- Abstract
On August 30, 2017 the US Food and Drug Administration approved tisagenlecleucel (Kymriah; Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present, ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring, and disease assessments. To address these issues experts representing the American Society for Blood and Marrow Transplant, the European Society for Blood and Marrow Transplantation, the International Society of Cell and Gene Therapy, and the Foundation for the Accreditation of Cellular Therapy formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved., (Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2019
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21. Effect of Conditioning Regimen Dose Reduction in Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation.
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Brunstein CG, Pasquini MC, Kim S, Fei M, Adekola K, Ahmed I, Aljurf M, Agrawal V, Auletta JJ, Battiwalla M, Bejanyan N, Bubalo J, Cerny J, Chee L, Ciurea SO, Freytes C, Gadalla SM, Gale RP, Ganguly S, Hashmi SK, Hematti P, Hildebrandt G, Holmberg LA, Lahoud OB, Landau H, Lazarus HM, de Lima M, Mathews V, Maziarz R, Nishihori T, Norkin M, Olsson R, Reshef R, Rotz S, Savani B, Schouten HC, Seo S, Wirk BM, Yared J, Mineishi S, Rogosheske J, and Perales MA
- Subjects
- Adult, Aged, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Lymphoma drug therapy, Lymphoma mortality, Lymphoma therapy, Male, Middle Aged, Mortality, Multiple Myeloma drug therapy, Multiple Myeloma mortality, Multiple Myeloma therapy, Recurrence, Transplantation, Autologous, Antineoplastic Agents administration & dosage, Drug Dosage Calculations, Hematopoietic Stem Cell Transplantation methods, Obesity, Transplantation Conditioning methods
- Abstract
Data are limited on whether to adjust high-dose chemotherapy before autologous hematopoietic cell transplant (autoHCT) in obese patients. This study explores the effects of dose adjustment on the outcomes of obese patients, defined as body mass index (BMI) ≥ 30 kg/m
2 . Dose adjustment was defined as a reduction in standard dosing ≥20%, based on ideal, reported dosing and actual weights. We included 2 groups of US patients who had received autoHCT between 2008 and 2014. Specifically, we included patients with multiple myeloma (MM, n = 1696) treated with high-dose melphalan and patients with Hodgkin or non-Hodgkin lymphomas (n = 781) who received carmustine, etoposide, cytarabine, and melphalan conditioning. Chemotherapy dose was adjusted in 1324 patients (78%) with MM and 608 patients (78%) with lymphoma. Age, sex, BMI, race, performance score, comorbidity index, and disease features (stage at diagnosis, disease status, and time to transplant) were similar between dose groups. In multivariate analyses for MM, adjusting for melphalan dose and for center effect had no impact on overall survival (P = .894) and treatment-related mortality (TRM) (P = .62), progression (P = .12), and progression-free survival (PFS; P = .178). In multivariate analyses for lymphoma, adjusting chemotherapy doses did not affect survival (P = .176), TRM (P = .802), relapse (P = .633), or PFS (P = .812). No center effect was observed in lymphoma. This study demonstrates that adjusting chemotherapy dose before autoHCT in obese patients with MM and lymphoma does not influence mortality. These results do not support adjusting chemotherapy dose in this population., (Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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22. Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplantation.
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Norkin M, Shaw BE, Brazauskas R, Tecca HR, Leather HL, Gea-Banacloche J, T Kamble R, DeFilipp Z, Jacobsohn DA, Ringden O, Inamoto Y, A Kasow K, Buchbinder D, Shaw P, Hematti P, Schears R, Badawy SM, Lazarus HM, Bhatt N, Horn B, Chhabra S, M Page K, Hamilton B, Hildebrandt GC, Yared JA, Agrawal V, M Beitinjaneh A, Majhail N, Kindwall-Keller T, Olsson RF, Schoemans H, Gale RP, Ganguly S, A Ahmed I, Schouten HC, L Liesveld J, Khera N, Steinberg A, Shah AJ, Solh M, Marks DI, Rybka W, Aljurf M, Dietz AC, Gergis U, George B, Seo S, Flowers MED, Battiwalla M, Savani BN, Riches ML, and Wingard JR
- Subjects
- Adolescent, Adult, Age Factors, Aged, Allografts, Child, Child, Preschool, Chronic Disease, Female, Humans, Incidence, Infant, Infant, Newborn, Male, Middle Aged, Time Factors, Hematopoietic Stem Cell Transplantation, Immunosuppression Therapy adverse effects, Infections mortality, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy
- Abstract
We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for ≥2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-HCT, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% (95% CI, 1.4% to 2.3%) in pediatric subjects; P < .001). In adults, the 2 most significant risks for developing LFI were increasing age (20 to 39, 40 to 54, and ≥55 years versus 18 to 19 years) with hazard ratios (HRs) of 3.12 (95% CI, 1.33 to 7.32), 3.86 (95% CI, 1.66 to 8.95), and 5.49 (95% CI, 2.32 to 12.99) and a history of chronic graft-versus-host disease GVHD (cGVHD) with ongoing immunosuppression at 2 years post-HCT compared with no history of GVHD with (HR, 3.87; 95% CI, 2.59 to 5.78). In pediatric subjects, the 3 most significant risks for developing LFI were a history of cGVHD with ongoing immunosuppression (HR, 9.49; 95% CI, 4.39 to 20.51) or without ongoing immunosuppression (HR, 2.7; 95% CI, 1.05 to 7.43) at 2 years post-HCT compared with no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function compared with diagnosis of acute myelogenous leukemia (HR, 2.30; 95% CI, 1.19 to 4.42), and age >10 years (HR, 1.92; 95% CI, 1.15 to 3.2). This study emphasizes the importance of continued vigilance for late infections after HCT and institution of support strategies aimed at decreasing the risk of cGVHD., (Copyright © 2018. Published by Elsevier Inc.)
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- 2019
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23. Comparative Analysis of Calcineurin Inhibitor-Based Methotrexate and Mycophenolate Mofetil-Containing Regimens for Prevention of Graft-versus-Host Disease after Reduced-Intensity Conditioning Allogeneic Transplantation.
- Author
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Chhabra S, Liu Y, Hemmer MT, Costa L, Pidala JA, Couriel DR, Alousi AM, Majhail NS, Stuart RK, Kim D, Ringden O, Urbano-Ispizua A, Saad A, Savani BN, Cooper B, Marks DI, Socie G, Schouten HC, Schoemans H, Abdel-Azim H, Yared J, Cahn JY, Wagner J, Antin JH, Verdonck LF, Lehmann L, Aljurf MD, MacMillan ML, Litzow MR, Solh MM, Qayed M, Hematti P, Kamble RT, Vij R, Hayashi RJ, Gale RP, Martino R, Seo S, Hashmi SK, Nishihori T, Teshima T, Gergis U, Inamoto Y, Spellman SR, Arora M, and Hamilton BK
- Subjects
- Adult, Aged, Allografts, Disease-Free Survival, Female, Humans, Male, Middle Aged, Retrospective Studies, Siblings, Survival Rate, Calcineurin Inhibitors administration & dosage, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Leukemia mortality, Leukemia therapy, Methotrexate administration & dosage, Mycophenolic Acid administration & dosage, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy, Tacrolimus administration & dosage, Transplantation Conditioning
- Abstract
The combination of a calcineurin inhibitor (CNI) such as tacrolimus (TAC) or cyclosporine (CYSP) with methotrexate (MTX) or with mycophenolate mofetil (MMF) has been commonly used for graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), but there are limited data comparing efficacy of the 2 regimens. We evaluated 1564 adult patients who underwent RIC alloHCT for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) from 2000 to 2013 using HLA-identical sibling (matched related donor [MRD]) or unrelated donor (URD) peripheral blood graft and received CYSP or TAC with MTX or MMF for GVHD prophylaxis. Primary outcomes of the study were acute and chronic GVHD and overall survival (OS). The study divided the patient population into 4 cohorts based on regimen: MMF-TAC, MMF-CYSP, MTX-TAC, and MTX-CYSP. In the URD group, MMF-CYSP was associated with increased risk of grade II to IV acute GVHD (relative risk [RR], 1.78; P < .001) and grade III to IV acute GVHD (RR, 1.93; P = .006) compared with MTX-TAC. In the URD group, use of MMF-TAC (versus MTX-TAC) lead to higher nonrelapse mortality. (hazard ratio, 1.48; P = .008). In either group, no there was no difference in chronic GVHD, disease-free survival, and OS among the GVHD prophylaxis regimens. For RIC alloHCT using MRD, there are no differences in outcomes based on GVHD prophylaxis. However, with URD RIC alloHCT, MMF-CYSP was inferior to MTX-based regimens for acute GVHD prevention, but all the regimens were equivalent in terms of chronic GVHD and OS. Prospective studies, targeting URD recipients are needed to confirm these results., (Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2019
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24. Country-Level Macroeconomic Indicators Predict Early Post-Allogeneic Hematopoietic Cell Transplantation Survival in Acute Lymphoblastic Leukemia: A CIBMTR Analysis.
- Author
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Wood WA, Brazauskas R, Hu ZH, Abdel-Azim H, Ahmed IA, Aljurf M, Badawy S, Beitinjaneh A, George B, Buchbinder D, Cerny J, Dedeken L, Diaz MA, Freytes CO, Ganguly S, Gergis U, Almaguer DG, Gupta A, Hale G, Hashmi SK, Inamoto Y, Kamble RT, Adekola K, Kindwall-Keller T, Knight J, Kumar L, Kuwatsuka Y, Law J, Lazarus HM, LeMaistre C, Olsson RF, Pulsipher MA, Savani BN, Schultz KR, Saad AA, Seftel M, Seo S, Shea TC, Steinberg A, Sullivan K, Szwajcer D, Wirk B, Yared J, Yong A, Dalal J, Hahn T, Khera N, Bonfim C, Atsuta Y, and Saber W
- Subjects
- Adolescent, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Male, Survival Analysis, Transplantation Conditioning mortality, Hematopoietic Stem Cell Transplantation economics, Precursor Cell Lymphoblastic Leukemia-Lymphoma economics, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Transplantation Conditioning economics
- Abstract
For patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic cell transplantation (alloHCT) offers a potential cure. Life-threatening complications can arise from alloHCT that require the application of sophisticated health care delivery. The impact of country-level economic conditions on post-transplantation outcomes is not known. Our objective was to assess whether these variables were associated with outcomes for patients transplanted for ALL. Using data from the Center for Blood and Marrow Transplant Research, we included 11,261 patients who received a first alloHCT for ALL from 303 centers across 38 countries between the years of 2005 and 2013. Cox regression models were constructed using the following macroeconomic indicators as main effects: Gross national income per capita, health expenditure per capita, and Human Development Index (HDI). The outcome was overall survival at 100 days following transplantation. In each model, transplants performed within lower resourced environments were associated with inferior overall survival. In the model with the HDI as the main effect, transplants performed in the lowest HDI quartile (n = 697) were associated with increased hazard for mortality (hazard ratio, 2.42; 95% confidence interval, 1.64 to 3.57; P < .001) in comparison with transplants performed in the countries with the highest HDI quartile. This translated into an 11% survival difference at 100 days (77% for lowest HDI quartile versus 88% for all other quartiles). Country-level macroeconomic indices were associated with lower survival at 100 days after alloHCT for ALL. The reasons for this disparity require further investigation., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2018
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25. Autologous Transplantation in Follicular Lymphoma with Early Therapy Failure: A National LymphoCare Study and Center for International Blood and Marrow Transplant Research Analysis.
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Casulo C, Friedberg JW, Ahn KW, Flowers C, DiGilio A, Smith SM, Ahmed S, Inwards D, Aljurf M, Chen AI, Choe H, Cohen J, Copelan E, Farooq U, Fenske TS, Freytes C, Gaballa S, Ganguly S, Jethava Y, Kamble RT, Kenkre VP, Lazarus H, Lazaryan A, Olsson RF, Rezvani AR, Rizzieri D, Seo S, Shah GL, Shah N, Solh M, Sureda A, William B, Cumpston A, Zelenetz AD, Link BK, and Hamadani M
- Subjects
- Adult, Female, Humans, Lymphoma, Follicular mortality, Male, Middle Aged, Rituximab therapeutic use, Secondary Prevention, Survival Analysis, Young Adult, Graft Rejection mortality, Hematopoietic Stem Cell Transplantation mortality, Lymphoma, Follicular therapy, Transplantation, Autologous mortality
- Abstract
Patients with follicular lymphoma (FL) experiencing early therapy failure (ETF) within 2 years of frontline chemoimmunotherapy have poor overall survival (OS). We analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) and the National LymphoCare Study (NLCS) to determine whether autologous hematopoietic cell transplant (autoHCT) can improve outcomes in this high-risk FL subgroup. ETF was defined as failure to achieve at least partial response after frontline chemoimmunotherapy or lymphoma progression within 2 years of frontline chemoimmunotherapy. We identified 2 groups: the non-autoHCT cohort (patients from the NLCS with ETF not undergoing autoHCT) and the autoHCT cohort (CIBMTR patients with ETF undergoing autoHCT). All patients received rituximab-based chemotherapy as frontline treatment; 174 non-autoHCT patients and 175 autoHCT patients were identified and analyzed. There was no difference in 5-year OS between the 2 groups (60% versus 67%, respectively; P = .16). A planned subgroup analysis showed that patients with ETF receiving autoHCT soon after treatment failure (≤1 year of ETF; n = 123) had higher 5-year OS than those without autoHCT (73% versus 60%, P = .05). On multivariate analysis, early use of autoHCT was associated with significantly reduced mortality (hazard ratio, .63; 95% confidence interval, .42 to .94; P = .02). Patients with FL experiencing ETF after frontline chemoimmunotherapy lack optimal therapy. We demonstrate improved OS when receiving autoHCT within 1 year of treatment failure. Results from this unique collaboration between the NLCS and CIBMTR support consideration of early consolidation with autoHCT in select FL patients experiencing ETF., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2018
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26. Assessment of Impact of HLA Type on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia.
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Hill BT, Ahn KW, Hu ZH, Aljurf M, Beitinjaneh A, Cahn JY, Cerny J, Kharfan-Dabaja MA, Ganguly S, Ghosh N, Grunwald MR, Inamoto Y, Kindwall-Keller T, Nishihori T, Olsson RF, Saad A, Seftel M, Seo S, Szer J, Tallman M, Ustun C, Wiernik PH, Maziarz RT, Kalaycio M, Alyea E, Popat U, Sobecks R, and Saber W
- Subjects
- Adolescent, Adult, Aged, Allografts, Disease-Free Survival, Female, Humans, Male, Middle Aged, Survival Rate, HLA Antigens, Hematopoietic Stem Cell Transplantation, Histocompatibility Testing, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Leukemia, Lymphocytic, Chronic, B-Cell therapy
- Abstract
Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplantation (allo-HCT) for medically fit patients. Although the use of allo-HCT has declined since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT, the only known curative treatment for CLL. The potential benefit of transplantation is most likely due to the presence of alloreactive donor T cells that mediate the graft-versus-leukemia (GVL) effect. The recognition of potentially tumor-specific antigens in the context of class I and II major histocompatibility complex on malignant B lymphocytes by donor T cells may be influenced by subtle differences in the highly polymorphic HLA locus. Given previous reports of specific HLA alleles impacting the incidence of CLL and the clinical outcomes of allo-HCT for CLL, we sought to study the overall survival and progression-free survival of a large cohort of patients with CLL who underwent allo-HCT from fully HLA-matched related and unrelated donors at Center for International Blood and Marrow Transplant Research transplantation centers. We found no statistically significant association of allo-HCT outcomes in CLL based on previously reported HLA combinations. Additional study is needed to further define the immunologic features that portend a more favorable GVL effect after allo-HCT for CLL., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2018
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27. Influence of Age on Acute and Chronic GVHD in Children Undergoing HLA-Identical Sibling Bone Marrow Transplantation for Acute Leukemia: Implications for Prophylaxis.
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Qayed M, Wang T, Hemmer MT, Spellman S, Arora M, Couriel D, Alousi A, Pidala J, Abdel-Azim H, Aljurf M, Ayas M, Bitan M, Cairo M, Choi SW, Dandoy C, Delgado D, Gale RP, Hale G, Frangoul H, Kamble RT, Kharfan-Dabaja M, Lehman L, Levine J, MacMillan M, Marks DI, Nishihori T, Olsson RF, Hematti P, Ringden O, Saad A, Satwani P, Savani BN, Schultz KR, Seo S, Shenoy S, Waller EK, Yu L, Horowitz MM, and Horan J
- Subjects
- Acute Disease, Adolescent, Age Factors, Allografts, Child, Child, Preschool, Chronic Disease, Female, HLA Antigens, Humans, Infant, Male, Retrospective Studies, Bone Marrow Transplantation, Graft vs Host Disease etiology, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Leukemia mortality, Leukemia therapy, Siblings, Tissue Donors
- Abstract
Relapse remains the major cause of mortality after hematopoietic cell transplantation (HCT) for pediatric acute leukemia. Previous research has suggested that reducing the intensity of calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis may be an effective strategy for abrogating the risk of relapse in pediatric patients undergoing matched sibling donor (MSD) HCT. We reasoned that the benefits of this strategy could be maximized by selectively applying it to those patients least likely to develop GVHD. We conducted a study of risk factors for GVHD, to risk-stratify patients based on age. Patients age <18 years with leukemia who received myeloablative, T cell-replete MSD bone marrow transplantation and calcineurin inhibitor-based GVHD prophylaxis between 2000 and 2013 and were entered into the Center for International Blood and Marrow Transplant Research registry were included. The cumulative incidence of grade II-IV acute GVHD (aGVHD) was 19%, that of grade II-IV aGVHD 7%, and that of chronic GVHD (cGVHD) was 16%. Compared with age 13 to 18 years, age 2 to 12 years was associated with a lower risk of grade II-IV aGVHD (hazard ratio [HR], .42; 95% confidence interval [CI], .26 to .70; P = .0008), grade II-IV aGVHD (HR, .24; 95% CI, .10 to .56; P = .001), and cGVHD (HR, .32; 95% CI, .19 to .54; P < .001). Compared with 2000-2004, the risk of grade II-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR, .36; 95% CI, .20 to .65; P = .0007) and in 2009-2013 (HR, .24; 95% CI. .11 to .53; P = .0004). Similarly, the risk of grade III-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR, .23; 95% CI, .08 to .65; P = .0056) and 2009-2013 (HR, .16; 95% CI, .04 to .67; P = .0126) compared with those doing so in 2000-2004. We conclude that aGVHD rates have decreased significantly over time, and that children age 2 to 12 years are at very low risk for aGVHD and cGVHD. These results should be validated in an independent analysis, because these patients with high-risk malignancies may be good candidates for trials of reduced GVHD prophylaxis., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2018
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28. Clinical Practice Recommendations on Indication and Timing of Hematopoietic Cell Transplantation in Mature T Cell and NK/T Cell Lymphomas: An International Collaborative Effort on Behalf of the Guidelines Committee of the American Society for Blood and Marrow Transplantation.
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Kharfan-Dabaja MA, Kumar A, Ayala E, Hamadani M, Reimer P, Gisselbrecht C, d'Amore F, Jantunen E, Ishida T, Bazarbachi A, Foss F, Advani R, Fenske TS, Lazarus HM, Friedberg JW, Aljurf M, Sokol L, Tobinai K, Tse E, Burns LJ, Chavez JC, Reddy NM, Suzuki R, Ahmed S, Nademanee A, Mohty M, Gopal AK, Fanale MA, Pro B, Moskowitz AJ, Sureda A, Perales MA, Carpenter PA, and Savani BN
- Subjects
- Adult, Aged, Guidelines as Topic, Humans, Middle Aged, United States, Hematopoietic Stem Cell Transplantation methods, Lymphoma, T-Cell, Peripheral therapy, T-Lymphocytes metabolism
- Abstract
Recognizing the significant biological and clinical heterogeneity of mature T cell and natural killer (NK)/T cell lymphomas, the American Society for Blood and Marrow Transplantation invited experts to develop clinical practice recommendations related to the role of autologous hematopoietic cell transplantation (auto-HCT) and allogeneic HCT (allo-HCT) for specific histological subtypes. We used the GRADE methodology to aid in moving from evidence to decision making and ultimately to generating final recommendations. Auto-HCT in front-line consolidation is recommended in peripheral T cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T cell lymphoma (AITL), anaplastic large cell lymphoma-anaplastic lymphoma kinase (ALCL-ALK)-negative, NK/T cell (disseminated), enteropathy-associated T cell lymphoma (EATL), and hepatosplenic lymphomas. Auto-HCT in relapsed-sensitive disease is recommended for NK/T cell (localized and disseminated), EATL, subcutaneous panniculitis-like T cell, and ALCL-ALK-positive lymphomas. Auto-HCT is also recommended for PTCL-NOS, AITL, and ALCL-ALK-negative lymphomas if not performed as front-line therapy. Auto-HCT in refractory (primary or relapsed) disease is not recommended for any of the histological subtypes discussed. Allo-HCT in front-line consolidation is recommended for NK/T cell (disseminated), adult T cell leukemia/lymphoma (ATLL; acute and lymphoma type), and hepatosplenic lymphomas. Allo-HCT for relapsed-sensitive disease is recommended for PTCL-NOS, AITL, ALCL-ALK-negative, ALCL-ALK-positive, NK/T cell (localized and disseminated), ATLL (acute, lymphoma type, smoldering/chronic), mycosis fungoides/Sezary syndrome (advanced stage IIB-IVB or tumor stage/extracutaneous), EATL, subcutaneous panniculitis-like T cell, and hepatosplenic lymphoma. Allo-HCT in refractory (primary or relapsed refractory) disease is recommended for any aforementioned histological subtypes. Emerging novel therapies will likely be incorporated into the pretransplantation, peritransplantation, and post-transplantation algorithms (auto-HCT or allo-HCT) with the goals of optimizing efficacy and improving outcomes. We acknowledge that there are unique clinical scenarios not covered by these recommendations that may require individualized decisions., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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29. Survival and Late Effects after Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancy at Less than Three Years of Age.
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Vrooman LM, Millard HR, Brazauskas R, Majhail NS, Battiwalla M, Flowers ME, Savani BN, Akpek G, Aljurf M, Bajwa R, Baker KS, Beitinjaneh A, Bitan M, Buchbinder D, Chow E, Dandoy C, Dietz AC, Diller L, Gale RP, Hashmi SK, Hayashi RJ, Hematti P, Kamble RT, Kasow KA, Kletzel M, Lazarus HM, Malone AK, Marks DI, O'Brien TA, Olsson RF, Ringden O, Seo S, Steinberg A, Yu LC, Warwick A, Shaw B, and Duncan C
- Subjects
- Age Factors, Allografts, Child, Preschool, Chronic Disease, Disease-Free Survival, Female, Follow-Up Studies, Humans, Infant, Male, Survival Rate, Graft vs Host Disease mortality, Graft vs Host Disease therapy, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Very young children undergoing hematopoietic cell transplantation (HCT) are a unique and vulnerable population. We analyzed outcomes of 717 patients from 117 centers who survived relapse free for ≥1 year after allogeneic myeloablative HCT for hematologic malignancy at <3 years of age, between 1987 and 2012. The median follow-up was 8.3 years (range, 1.0 to 26.4 years); median age at follow-up was 9 years (range, 2 to 29 years). Ten-year overall and relapse-free survival were 87% (95% confidence interval [CI], 85% to 90%) and 84% (95% CI, 81% to 87%). Ten-year cumulative incidence of relapse was 11% (95% CI, 9% to 13%). Of 84 deaths, relapse was the leading cause (43%). Chronic graft-versus-host-disease 1 year after HCT was associated with increased risk of mortality (hazard ratio [HR], 2.1; 95% CI, 1.3 to 3.3; P = .0018). Thirty percent of patients experienced ≥1 organ toxicity/late effect >1 year after HCT. The most frequent late effects included growth hormone deficiency/growth disturbance (10-year cumulative incidence, 23%; 95% CI, 19% to 28%), cataracts (18%; 95% CI, 15% to 22%), hypothyroidism (13%; 95% CI, 10% to 16%), gonadal dysfunction/infertility requiring hormone replacement (3%; 95% CI, 2% to 5%), and stroke/seizure (3%; 95% CI, 2% to 5%). Subsequent malignancy was reported in 3.6%. In multivariable analysis, total body irradiation (TBI) was predictive of increased risk of cataracts (HR, 17.2; 95% CI, 7.4 to 39.8; P < .001), growth deficiency (HR, 3.5; 95% CI, 2.2 to 5.5; P < .001), and hypothyroidism (HR, 5.3; 95% CI, 3.0 to 9.4; P < .001). In summary, those who survived relapse free ≥1 year after HCT for hematologic malignancy at <3 years of age had favorable overall survival. Chronic graft-versus-host-disease and TBI were associated with adverse outcomes. Future efforts should focus on reducing the risk of relapse and late effects after HCT at early age., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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30. Outcomes after Umbilical Cord Blood Transplantation for Myelodysplastic Syndromes.
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Gerds AT, Woo Ahn K, Hu ZH, Abdel-Azim H, Akpek G, Aljurf M, Ballen KK, Beitinjaneh A, Bacher U, Cahn JY, Chhabra S, Cutler C, Daly A, DeFilipp Z, Gale RP, Gergis U, Grunwald MR, Hale GA, Hamilton BK, Jagasia M, Kamble RT, Kindwall-Keller T, Nishihori T, Olsson RF, Ramanathan M, Saad AA, Solh M, Ustun C, Valcárcel D, Warlick E, Wirk BM, Kalaycio M, Alyea E, Popat U, Sobecks R, and Saber W
- Subjects
- Adolescent, Adult, Aged, Cord Blood Stem Cell Transplantation adverse effects, Graft vs Host Disease etiology, Graft vs Host Disease mortality, Humans, Middle Aged, Myelodysplastic Syndromes complications, Myelodysplastic Syndromes mortality, Probability, Recurrence, Risk Assessment, Survival Analysis, Transplantation Conditioning, Treatment Outcome, Young Adult, Cord Blood Stem Cell Transplantation mortality, Myelodysplastic Syndromes therapy
- Abstract
For patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation, umbilical cord blood transplantation (UCBT) has become an acceptable alternative donor source in the absence of a matched sibling or unrelated donor. To date, however, there have been few published series dedicated solely to describing the outcomes of adult patients with myelodysplastic syndrome (MDS) who have undergone UCBT. Between 2004 and 2013, 176 adults with MDS underwent UCBT as reported to the Center for International Blood and Marrow Transplant Research. Median age at the time of transplantation was 56 years (range, 18-73 years). The study group included 10% with very low, 23% with low, 19% with intermediate, 19% with high, and 13% with very high-risk Revised International Prognostic Scoring System (IPSS-R) scores. The 100-day probability of grade II-IV acute graft-versus-host disease (GVHD) was 38%, and the 3-year probability of chronic GVHD was 28%. The probabilities of relapse and transplantation-related mortality (TRM) at 3 years were 32% and 40%, respectively, leading to a 3-year disease-free survival (DFS) of 28% and an overall survival (OS) of 31%. In multivariate analysis, increasing IPSS-R score at the time of HCT was associated with inferior TRM (P = .0056), DFS (P = .018), and OS (P = .0082), but not with GVHD or relapse. The presence of pretransplantation comorbidities was associated with TRM (P = .001), DFS (P = .02), and OS (P = .001). Reduced-intensity conditioning was associated with increased risk of relapse (relative risk, 3.95; 95% confidence interval, 1.78-8.75; P < .001), and although a higher proportion of myeloablative UCBTs were performed in patients with high-risk disease, the effect of conditioning regimen intensity was the same regardless of IPSS-R score. For some individuals who lack a matched sibling or unrelated donor, UCBT can result in long-term DFS; however, the success of UCBT in this population is hampered by a high rate of TRM., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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31. Allogeneic Hematopoietic Cell Transplantation for Adult Chronic Myelomonocytic Leukemia.
- Author
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Liu HD, Ahn KW, Hu ZH, Hamadani M, Nishihori T, Wirk B, Beitinjaneh A, Rizzieri D, Grunwald MR, Sabloff M, Olsson RF, Bajel A, Bredeson C, Daly A, Inamoto Y, Majhail N, Saad A, Gupta V, Gerds A, Malone A, Tallman M, Reshef R, Marks DI, Copelan E, Gergis U, Savoie ML, Ustun C, Litzow MR, Cahn JY, Kindwall-Keller T, Akpek G, Savani BN, Aljurf M, Rowe JM, Wiernik PH, Hsu JW, Cortes J, Kalaycio M, Maziarz R, Sobecks R, Popat U, Alyea E, and Saber W
- Subjects
- Adult, Aged, Bone Marrow Transplantation mortality, Hematopoietic Stem Cell Transplantation mortality, Humans, Leukemia, Myelomonocytic, Chronic diagnosis, Leukemia, Myelomonocytic, Chronic mortality, Middle Aged, Prognosis, Retrospective Studies, Risk Factors, Survival Rate, Transplantation, Homologous, Young Adult, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myelomonocytic, Chronic therapy
- Abstract
Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for patients with chronic myelomonocytic leukemia (CMML); however, few data exist regarding prognostic factors and transplantation outcomes. We performed this retrospective study to identify prognostic factors for post-transplantation outcomes. The CMML-specific prognostic scoring system (CPSS) has been validated in subjects receiving nontransplantation therapy and was included in our study. From 2001 to 2012, 209 adult subjects who received HCT for CMML were reported to the Center for International Blood and Marrow Transplant Research. The median age at transplantation was 57 years (range, 23 to 74). Median follow-up was 51 months (range, 3 to 122). On multivariate analyses, CPSS scores, Karnofsky performance status (KPS), and graft source were significant predictors of survival (P = .004, P = .01, P = .01, respectively). Higher CPSS scores were not associated with disease-free survival, relapse, or transplantation-related mortality. In a restricted analysis of subjects with relapse after HCT, those with intermediate-2/high risk had a nearly 2-fold increased risk of death after relapse compared to those with low/intermediate-1 CPSS scores. Respective 1-year, 3-year, and 5-year survival rates for low/intermediate-1 risk subjects were 61% (95% confidence interval [CI], 52% to 72%), 48% (95% CI, 37% to 59%), and 44% (95% CI, 33% to 55%), and for intermediate-2/high risk subjects were 38% (95% CI, 28% to 49%), 32% (95% CI, 21% to 42%), and 19% (95% CI, 8% to 29%). We conclude that higher CPSS score at time of transplantation, lower KPS, and a bone marrow graft are associated with inferior survival after HCT. Further investigation of CMML disease-related biology may provide insights into other risk factors predictive of post-transplantation outcomes., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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32. Erratum to "Filgrastim-Stimulated Bone Marrow Compared with Filgrastim-Mobilized Peripheral Blood in Myeloablative Sibling Allografting for Patients with Hematologic Malignancies: A Randomized Canadian Blood and Marrow Transplant Group Study" [Biol Blood Marrow Transplant 2016;22:1410-1415].
- Author
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Couban S, Aljurf M, Lachance S, Walker I, Toze C, Rubinger M, Lipton JH, Lee SJ, Szer J, Doocey R, Lewis ID, Huebsch L, Howson-Jan K, Lalancette M, Almohareb F, Chaudhri N, Ivison S, Broady R, Levings M, Fairclough D, Devins G, Szwajcer D, Foley R, Smith C, Panzarella T, Kerr H, Kariminia A, and Schultz KR
- Published
- 2017
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33. Refining the Role of Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia as Novel Therapies Emerge.
- Author
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El Fakih R, Kharfan-Dabaja MA, and Aljurf M
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- Adult, Consolidation Chemotherapy, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation mortality, Humans, Precision Medicine, Remission Induction, Risk Assessment, Hematopoietic Stem Cell Transplantation statistics & numerical data, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Acute lymphoblastic leukemia (ALL) is a rare adult neoplasm. The disorder consists of precursor B or T phenotypes. In the pediatric population, ALL was a success story in that 80% of children with ALL enjoy long-term survival. In adults, similar complete remission rates are achieved with current induction regimens; however, less than 50% of patients are alive at 5 years, with most deaths due to relapsed disease. Accordingly, optimizing post remission consolidation therapy might improve in outcomes. Such strategies may include chemotherapy and autologous or allogeneic transplant. Moreover, the ability to modify such therapy based on better disease risk stratification while taking into account patient characteristics such as performance status and presence of comorbidities is necessary to tailor treatment accordingly. Here, we review available medical literature on the use of hematopoietic cell transplantation as a consolidation modality in the treatment of adult ALL., (Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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34. Infection Rates among Acute Leukemia Patients Receiving Alternative Donor Hematopoietic Cell Transplantation.
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Ballen K, Woo Ahn K, Chen M, Abdel-Azim H, Ahmed I, Aljurf M, Antin J, Bhatt AS, Boeckh M, Chen G, Dandoy C, George B, Laughlin MJ, Lazarus HM, MacMillan ML, Margolis DA, Marks DI, Norkin M, Rosenthal J, Saad A, Savani B, Schouten HC, Storek J, Szabolcs P, Ustun C, Verneris MR, Waller EK, Weisdorf DJ, Williams KM, Wingard JR, Wirk B, Wolfs T, Young JH, Auletta J, Komanduri KV, Lindemans C, and Riches ML
- Subjects
- Acute Disease, Adolescent, Adult, Aged, Cord Blood Stem Cell Transplantation adverse effects, Cord Blood Stem Cell Transplantation mortality, Female, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation mortality, Histocompatibility, Humans, Incidence, Infections mortality, Leukemia mortality, Male, Middle Aged, Retrospective Studies, Survival Analysis, Unrelated Donors, Young Adult, Hematopoietic Stem Cell Transplantation adverse effects, Infections etiology, Leukemia complications, Leukemia therapy
- Abstract
Alternative graft sources (umbilical cord blood [UCB], matched unrelated donors [MUD], or mismatched unrelated donors [MMUD]) enable patients without a matched sibling donor to receive potentially curative hematopoietic cell transplantation (HCT). Retrospective studies demonstrate comparable outcomes among different graft sources. However, the risk and types of infections have not been compared among graft sources. Such information may influence the choice of a particular graft source. We compared the incidence of bacterial, viral, and fungal infections in 1781 adults with acute leukemia who received alternative donor HCT (UCB, n= 568; MUD, n = 930; MMUD, n = 283) between 2008 and 2011. The incidences of bacterial infection at 1 year were 72%, 59%, and 65% (P < .0001) for UCB, MUD, and MMUD, respectively. Incidences of viral infection at 1 year were 68%, 45%, and 53% (P < .0001) for UCB, MUD, and MMUD, respectively. In multivariable analysis, bacterial, fungal, and viral infections were more common after either UCB or MMUD than after MUD (P < .0001). Bacterial and viral but not fungal infections were more common after UCB than MMUD (P = .0009 and <.0001, respectively). The presence of viral infection was not associated with an increased mortality. Overall survival (OS) was comparable among UCB and MMUD patients with Karnofsky performance status (KPS) ≥ 90% but was inferior for UCB for patients with KPS < 90%. Bacterial and fungal infections were associated with poorer OS. Future strategies focusing on infection prevention and treatment are indicated to improve HCT outcomes., Competing Interests: DISCLOSURES Conflict of Interest: The authors report no conflict of interest, (Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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35. Filgrastim-Stimulated Bone Marrow Compared with Filgrastim-Mobilized Peripheral Blood in Myeloablative Sibling Allografting for Patients with Hematologic Malignancies: A Randomized Canadian Blood and Marrow Transplant Group Study.
- Author
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Couban S, Aljurf M, Lachance S, Walker I, Toze C, Rubinger M, Lipton JH, Lee SJ, Szer J, Doocey R, Lewis ID, Huebsch L, Howson-Jan K, Lalancette M, Almohareb F, Chaudhri N, Ivison S, Broady R, Levings M, Fairclough D, Devins G, Szwajcer D, Foley R, Smith C, Panzarella T, Kerr H, Kariminia A, and Schultz KR
- Subjects
- Adolescent, Adult, Aged, Female, Graft Survival, Graft vs Host Disease etiology, Humans, Male, Middle Aged, Myeloablative Agonists therapeutic use, Siblings, Survival Rate, Transplantation, Homologous, Treatment Outcome, Young Adult, Bone Marrow drug effects, Bone Marrow Transplantation methods, Filgrastim pharmacology, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Mobilization methods, Peripheral Blood Stem Cell Transplantation methods
- Abstract
In adult hematopoietic cell transplantation (HCT), filgrastim-mobilized peripheral blood (G-PB) has largely replaced unstimulated marrow for allografting. Although the use of G-PB results in faster hematopoietic recovery, it is also associated with more chronic graft-versus-host disease (cGVHD). A potential alternative allograft is filgrastim-stimulated marrow (G-BM), which we hypothesized may be associated with prompt hematopoietic recovery but with less cGVHD. We conducted a phase 3, open-label, multicenter randomized trial of 230 adults with hematologic malignancies receiving allografts from siblings after myeloablative conditioning to compare G-PB with G-BM. The primary endpoint was time to treatment failure, defined as a composite of extensive cGVHD, relapse/disease progression, and death. With a median follow-up of 36 months (range, 9.6 to 48), comparing G-BM with G-PB, there was no difference between the 2 arms with respect to the primary outcome of this study (hazard ratio [HR], .91; 95% confidence interval [CI], .68 to 1.22; P = .52). However, the cumulative incidence of overall cGVHD was lower with G-BM (HR, .66; 95% CI, .46 to .95; P = .007) and there was no difference in the risk of relapse or progression (P = .35). The median times to neutrophil recovery (P = .0004) and platelet recovery (P = .012) were 3 days shorter for recipients allocated to G-PB compared with those allocated to G-BM, but there were no differences in secondary engraftment-related outcomes, such as time to first hospital discharge (P = .17). In addition, there were no graft failures in either arm. This trial demonstrates that, compared with G-PB, the use of G-BM allografts leads to a significantly lower rate of overall cGVHD without a loss of the graft-versus-tumor effect and comparable overall survival. Our findings suggest that further study of this type of allograft is warranted., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2016
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36. Comparing Outcomes with Bone Marrow or Peripheral Blood Stem Cells as Graft Source for Matched Sibling Transplants in Severe Aplastic Anemia across Different Economic Regions.
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Kumar R, Kimura F, Ahn KW, Hu ZH, Kuwatsuka Y, Klein JP, Pasquini M, Miyamura K, Kato K, Yoshimi A, Inamoto Y, Ichinohe T, Wood WA Jr, Wirk B, Seftel M, Rowlings P, Marks DI, Schultz KR, Gupta V, Dedeken L, George B, Cahn JY, Szer J, Lee JW, Ho AY, Fasth A, Hahn T, Khera N, Dalal J, Bonfim C, Aljurf M, Atsuta Y, and Saber W
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Japan, Male, Middle Aged, Retrospective Studies, Socioeconomic Factors, Anemia, Aplastic mortality, Anemia, Aplastic therapy, Bone Marrow Transplantation, Graft Rejection mortality, Peripheral Blood Stem Cell Transplantation, Siblings
- Abstract
Bone marrow (BM) is the preferred graft source for hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) compared with mobilized peripheral blood stem cells (PBSCs). We hypothesized that this recommendation may not apply to those regions where patients present later in their disease course, with heavier transfusion load and with higher graft failure rates. Patients with SAA who received HSCT from an HLA-matched sibling donor from 1995 to 2009 and reported to the Center for International Blood and Marrow Transplant Research or the Japan Society for Hematopoietic Cell Transplantation were analyzed. The study population was categorized by gross national income per capita and region/countries into 4 groups. Groups analyzed were high-income countries (HIC), which were further divided into United States-Canada (n = 486) and other HIC (n = 1264); upper middle income (UMIC) (n = 482); and combined lower-middle, low-income countries (LM-LIC) (n = 142). In multivariate analysis, overall survival (OS) was highest with BM as graft source in HIC compared with PBSCs in all countries or BM in UMIC or LM-LIC (P < .001). There was no significant difference in OS between BM and PBSCs in UMIC (P = .32) or LM-LIC (P = .23). In LM-LIC the 28-day neutrophil engraftment was higher with PBSCs compared with BM (97% versus 77%, P = .002). Chronic graft-versus-host disease was significantly higher with PBSCs in all groups. Whereas BM should definitely be the preferred graft source for HLA-matched sibling HSCT in SAA, PBSCs may be an acceptable alternative in countries with limited resources when treating patients at high risk of graft failure and infective complications., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2016
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37. Graft-versus-Host Disease after HLA-Matched Sibling Bone Marrow or Peripheral Blood Stem Cell Transplantation: Comparison of North American Caucasian and Japanese Populations.
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Kanda J, Brazauskas R, Hu ZH, Kuwatsuka Y, Nagafuji K, Kanamori H, Kanda Y, Miyamura K, Murata M, Fukuda T, Sakamaki H, Kimura F, Seo S, Aljurf M, Yoshimi A, Milone G, Wood WA, Ustun C, Hashimi S, Pasquini M, Bonfim C, Dalal J, Hahn T, Atsuta Y, and Saber W
- Subjects
- Acute Disease, Adolescent, Adult, Asian People, Chronic Disease, Female, Graft vs Host Disease ethnology, Graft vs Host Disease mortality, Graft vs Host Disease pathology, Histocompatibility Testing, Humans, Leukemia ethnology, Leukemia mortality, Leukemia pathology, Male, Middle Aged, Recurrence, Risk, Severity of Illness Index, Siblings, Survival Analysis, Tissue Donors, Transplantation, Homologous, White People, Bone Marrow Transplantation, Graft vs Host Disease therapy, Leukemia therapy, Peripheral Blood Stem Cell Transplantation
- Abstract
The risk of acute graft-versus-host disease (GVHD) after HLA-matched sibling bone marrow transplantation (BMT) is lower in Japanese than in Caucasian patients. However, race may have differential effect on GVHD dependent on the graft source. North American Caucasian and Japanese patients receiving their first allogeneic BMT or peripheral blood stem cell transplantation from an HLA-matched sibling for leukemia were eligible. BMT was performed in 13% of the Caucasian patients and in 53% of the Japanese patients. On multivariate analysis, the interaction term between race and graft source was not significant in any of the models, indicating that graft source does not affect the impact of race on outcomes. The risk of grade III or IV acute GVHD was significantly lower in the Japanese patients compared with the Caucasian patients (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57 to 0.96), which resulted in lower risk of nonrelapse mortality in the Japanese patients (HR, 0.69; 95% CI, 0.54 to 0.89). The risk of relapse was also lower in this group. The lower risks of nonrelapse mortality and relapse resulted in lower overall mortality rates among the Japanese patients. In conclusion, our data indicate that irrespective of graft source, the risk of severe acute GVHD is lower in Japanese patients, resulting in a lower risk of nonrelapse mortality., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2016
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38. Hematopoietic Cell Transplantation Outcomes in Monosomal Karyotype Myeloid Malignancies.
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Pasquini MC, Zhang MJ, Medeiros BC, Armand P, Hu ZH, Nishihori T, Aljurf MD, Akpek G, Cahn JY, Cairo MS, Cerny J, Copelan EA, Deol A, Freytes CO, Gale RP, Ganguly S, George B, Gupta V, Hale GA, Kamble RT, Klumpp TR, Lazarus HM, Luger SM, Liesveld JL, Litzow MR, Marks DI, Martino R, Norkin M, Olsson RF, Oran B, Pawarode A, Pulsipher MA, Ramanathan M, Reshef R, Saad AA, Saber W, Savani BN, Schouten HC, Ringdén O, Tallman MS, Uy GL, Wood WA Jr, Wirk B, Pérez WS, Batiwalla M, and Weisdorf DJ
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Female, Humans, Infant, Karyotype, Male, Middle Aged, Myelodysplastic Syndromes mortality, Treatment Outcome, Young Adult, Hematopoietic Stem Cell Transplantation methods, Myelodysplastic Syndromes therapy, Transplantation Conditioning methods
- Abstract
The presence of monosomal karyotype (MK+) in acute myeloid leukemia (AML) is associated with dismal outcomes. We evaluated the impact of MK+ in AML (MK+AML, n = 240) and in myelodysplastic syndrome (MDS) (MK+MDS, n = 221) on hematopoietic cell transplantation outcomes compared with other cytogenetically defined groups (AML, n = 3360; MDS, n = 1373) as reported to the Center for International Blood and Marrow Transplant Research from 1998 to 2011. MK+ AML was associated with higher disease relapse (hazard ratio, 1.98; P < .01), similar transplantation-related mortality (TRM) (hazard ratio, 1.01; P = .90), and worse survival (hazard ratio, 1.67; P < .01) compared with those outcomes for other cytogenetically defined AML. Among patients with MDS, MK+ MDS was associated with higher disease relapse (hazard ratio, 2.39; P < .01), higher TRM (hazard ratio, 1.80; P < .01), and worse survival (HR, 2.02; P < .01). Subset analyses comparing chromosome 7 abnormalities (del7/7q) with or without MK+ demonstrated higher mortality for MK+ disease in for both AML (hazard ratio, 1.72; P < .01) and MDS (hazard ratio, 1.79; P < .01). The strong negative impact of MK+ in myeloid malignancies was observed in all age groups and using either myeloablative or reduced-intensity conditioning regimens. Alternative approaches to mitigate disease relapse in this population are needed., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2016
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39. Comparison of Characteristics and Outcomes of Trial Participants and Nonparticipants: Example of Blood and Marrow Transplant Clinical Trials Network 0201 Trial.
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Khera N, Majhail NS, Brazauskas R, Wang Z, He N, Aljurf MD, Akpek G, Atsuta Y, Beattie S, Bredeson CN, Burns LJ, Dalal JD, Freytes CO, Gupta V, Inamoto Y, Lazarus HM, LeMaistre CF, Steinberg A, Szwajcer D, Wingard JR, Wirk B, Wood WA, Joffe S, Hahn TE, Loberiza FR, Anasetti C, Horowitz MM, and Lee SJ
- Subjects
- Adolescent, Adult, Aged, Antilymphocyte Serum therapeutic use, Bone Marrow Transplantation mortality, Child, Child, Preschool, Disease-Free Survival, Female, Graft vs Host Disease epidemiology, Graft vs Host Disease etiology, Humans, Immunosuppressive Agents therapeutic use, Infant, Infant, Newborn, Inpatients statistics & numerical data, Male, Middle Aged, Myeloablative Agonists therapeutic use, Patient Selection, Peripheral Blood Stem Cell Transplantation mortality, Proportional Hazards Models, Recurrence, Registries, Remission Induction, Research Subjects statistics & numerical data, Survival Analysis, T-Lymphocytes immunology, Transplantation Conditioning methods, Treatment Outcome, Unrelated Donors, Young Adult, Bone Marrow Transplantation statistics & numerical data, Peripheral Blood Stem Cell Transplantation statistics & numerical data, Randomized Controlled Trials as Topic statistics & numerical data
- Abstract
Controversy surrounds the question of whether clinical trial participants have better outcomes than comparable patients who are not treated on a trial. We explored this question using a recent large, randomized, multicenter study comparing peripheral blood (PB) with bone marrow transplantation from unrelated donors, conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). We compared characteristics and outcomes of study participants (n = 494) and nonparticipants (n = 1384) who appeared eligible and received similar treatment without enrolling on the BMT CTN trial at participating centers during the study time period. Data were obtained from the Center for International Blood and Marrow Transplant Research. Outcomes were compared between the 2 groups using Cox proportional hazards regression models. No significant differences in age, sex, disease distribution, race/ethnicity, HLA matching, comorbidities, and interval from diagnosis to hematopoietic cell transplantation were seen between the participants and nonparticipants. Nonparticipants were more likely to have lower performance status, lower risk disease, and older donors, and to receive myeloablative conditioning and antithymocyte globulin. Nonparticipants were also more likely to receive PB grafts, the intervention tested in the trial (66% versus 50%, P < .001). Overall survival, transplantation-related mortality, and incidences of acute or chronic graft-versus-host disease were comparable between the 2 groups though relapse was higher (hazard ratio, 1.22; 95% confidence interval, 1.02 to 1.46; P = .028) in nonparticipants. Despite differences in certain baseline characteristics, survival was comparable between study participants and nonparticipants. The results of the BMT CTN trial appear generalizable to the population of trial-eligible patients., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2015
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40. HLA Mismatch Is Associated with Worse Outcomes after Unrelated Donor Reduced-Intensity Conditioning Hematopoietic Cell Transplantation: An Analysis from the Center for International Blood and Marrow Transplant Research.
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Verneris MR, Lee SJ, Ahn KW, Wang HL, Battiwalla M, Inamoto Y, Fernandez-Vina MA, Gajewski J, Pidala J, Munker R, Aljurf M, Saber W, Spellman S, and Koreth J
- Subjects
- Adolescent, Adult, Aged, Disease-Free Survival, Female, Graft vs Host Disease etiology, Graft vs Host Disease mortality, Hematopoietic Stem Cell Transplantation mortality, Histocompatibility Testing, Humans, Kaplan-Meier Estimate, Leukemia mortality, Leukemia therapy, Living Donors, Male, Middle Aged, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy, Proportional Hazards Models, Registries, Retrospective Studies, Treatment Outcome, Young Adult, HLA Antigens immunology, Hematopoietic Stem Cell Transplantation statistics & numerical data, Histocompatibility, Transplantation Conditioning methods
- Abstract
Over the past 2 decades, reduced-intensity conditioning allogeneic hematopoietic cell transplantation (RIC HCT) has increased substantially. Many patients do not have fully HLA-matched donors, and the impact of HLA mismatch on RIC HCT has not been examined in large cohorts. We analyzed 2588 recipients of 8/8 HLA-high resolution matched (n = 2025) or single-locus mismatched (n = 563) unrelated donor (URD) RIC HCT from 1999 to 2011. Overall survival (OS) was the primary outcome. Secondary endpoints included treatment-related mortality (TRM), relapse, disease-free survival (DFS), and acute/chronic graft-versus-host disease (GVHD). Adjusted 1- and 3-year OS was better in 8/8- versus 7/8-matched recipients (54.7% versus 48.8%, P = .01, and 37.4% versus 30.9%, P = .005, respectively). In multivariate models 7/8 URD RIC HCT recipients had more grades II to IV acute GVHD (RR = 1.29, P = .0034), higher TRM (RR = 1.52, P < .0001), and lower DFS (RR = 1.12, P = .0015) and OS (RR = 1.25, P = .0001), with no difference in relapse or chronic GVHD. In subgroup analysis, inferior transplant outcomes were noted regardless of the HLA allele mismatched. Previously reported permissive mismatches at HLA-C (C*03:03/C*03:04) and HLA-DP1 (based on T cell-epitope matching) were not associated with better outcomes. Although feasible, single-locus mismatch in RIC URD HCT is associated with inferior outcomes., (Copyright © 2015 American Society for Blood and Marrow Transplantation. All rights reserved.)
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- 2015
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41. The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen.
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Urbano-Ispizua A, Pavletic SZ, Flowers ME, Klein JP, Zhang MJ, Carreras J, Montoto S, Perales MA, Aljurf MD, Akpek G, Bredeson CN, Costa LJ, Dandoy C, Freytes CO, Fung HC, Gale RP, Gibson J, Hamadani M, Hayashi RJ, Inamoto Y, Inwards DJ, Lazarus HM, Maloney DG, Martino R, Munker R, Nishihori T, Olsson RF, Rizzieri DA, Reshef R, Saad A, Savani BN, Schouten HC, Smith SM, Socié G, Wirk B, Yu LC, and Saber W
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Combined Modality Therapy, Disease-Free Survival, Female, Follow-Up Studies, Histocompatibility, Humans, Immunosuppressive Agents therapeutic use, Kaplan-Meier Estimate, Lymphoma drug therapy, Lymphoma mortality, Lymphoma pathology, Lymphoma physiopathology, Male, Middle Aged, Proportional Hazards Models, Recurrence, Rituximab administration & dosage, Treatment Outcome, Young Adult, Graft vs Host Disease complications, Hematopoietic Stem Cell Transplantation, Lymphoma therapy, Transplantation Conditioning methods
- Abstract
The purpose of this study was to analyze the impact of graft-versus-host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients with a diagnosis of Hodgkin lymphoma, diffuse large B cell lymphoma, follicular lymphoma (FL), peripheral T cell lymphoma, or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor hematopoietic cell transplantation between 1997 and 2009 were included. Two thousand six hundred eleven cases were included. A reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplantations. In a multivariate analysis of myeloablative cases (n = 970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n = 1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (risk ratio [RR], .51; P = .049) and in MCL (RR, .41; P = .019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR, .14; P = .007; and RR, .15; P = .0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment-related mortality and overall survival (OS) in FL cases but did not affect treatment-related mortality, OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in FL and MCL patients., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2015
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42. The Sequence of Cyclophosphamide and Myeloablative Total Body Irradiation in Hematopoietic Cell Transplantation for Patients with Acute Leukemia.
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Holter-Chakrabarty JL, Pierson N, Zhang MJ, Zhu X, Akpek G, Aljurf MD, Artz AS, Baron F, Bredeson CN, Dvorak CC, Epstein RB, Lazarus HM, Olsson RF, Selby GB, Williams KM, Cooke KR, Pasquini MC, and McCarthy PL
- Subjects
- Acute Disease, Adolescent, Adult, Child, Child, Preschool, Female, Graft vs Host Disease etiology, Graft vs Host Disease immunology, Graft vs Host Disease mortality, Humans, Immunosuppressive Agents therapeutic use, Infant, Infant, Newborn, Leukemia immunology, Leukemia mortality, Leukemia pathology, Male, Middle Aged, Prospective Studies, Recurrence, Risk, Siblings, Survival Analysis, Transplantation, Homologous, Unrelated Donors, Whole-Body Irradiation, Cyclophosphamide therapeutic use, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia therapy, Myeloablative Agonists therapeutic use, Transplantation Conditioning
- Abstract
Limited clinical data are available to assess whether the sequencing of cyclophosphamide (Cy) and total body irradiation (TBI) changes outcomes. We evaluated the sequence in 1769 (CyTBI, n = 948; TBICy, n = 821) recipients of related or unrelated hematopoietic cell transplantation who received TBI (1200 to 1500 cGY) for acute leukemia from 2003 to 2010. The 2 cohorts were comparable for median age, performance score, type of leukemia, first complete remission, Philadelphia chromosome-positive acute lymphoblastic leukemia, HLA-matched siblings, stem cell source, antithymocyte globulin use, TBI dose, and type of graft-versus-host disease (GVHD) prophylaxis. The sequence of TBI did not significantly affect transplantation-related mortality (24% versus 23% at 3 years, P = .67; relative risk, 1.01; P = .91), leukemia relapse (27% versus 29% at 3 years, P = .34; relative risk, .89, P = .18), leukemia-free survival (49% versus 48% at 3 years, P = .27; relative risk, .93; P = .29), chronic GVHD (45% versus 47% at 1 year, P = .39; relative risk, .9; P = .11), or overall survival (53% versus 52% at 3 years, P = .62; relative risk, .96; P = .57) for CyTBI and TBICy, respectively. Corresponding cumulative incidences of sinusoidal obstruction syndrome were 4% and 6% at 100 days (P = .08), respectively. This study demonstrates that the sequence of Cy and TBI does not impact transplantation outcomes and complications in patients with acute leukemia undergoing hematopoietic cell transplantation with myeloablative conditioning., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2015
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43. Impact of conditioning regimen on outcomes for patients with lymphoma undergoing high-dose therapy with autologous hematopoietic cell transplantation.
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Chen YB, Lane AA, Logan B, Zhu X, Akpek G, Aljurf M, Artz A, Bredeson CN, Cooke KR, Ho VT, Lazarus HM, Olsson R, Saber W, McCarthy P, and Pasquini MC
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Busulfan therapeutic use, Carmustine therapeutic use, Cyclophosphamide therapeutic use, Cytarabine therapeutic use, Drug Administration Schedule, Etoposide therapeutic use, Female, Hodgkin Disease immunology, Hodgkin Disease mortality, Hodgkin Disease pathology, Humans, Lymphoma, Non-Hodgkin immunology, Lymphoma, Non-Hodgkin mortality, Lymphoma, Non-Hodgkin pathology, Male, Melphalan therapeutic use, Middle Aged, Retrospective Studies, Survival Analysis, Transplantation, Autologous, Whole-Body Irradiation, Hematopoietic Stem Cell Transplantation, Hodgkin Disease therapy, Lymphoma, Non-Hodgkin therapy, Myeloablative Agonists therapeutic use, Registries, Transplantation Conditioning methods
- Abstract
There are limited data to guide the choice of high-dose therapy (HDT) regimen before autologous hematopoietic cell transplantation (AHCT) for patients with Hodgkin (HL) and non-Hodgkin lymphoma (NHL). We studied 4917 patients (NHL, n = 3905; HL, n = 1012) who underwent AHCT from 1995 to 2008 using the most common HDT platforms: carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) (n = 1730); cyclophosphamide, BCNU, and etoposide (CBV) (n = 1853); busulfan and cyclophosphamide (BuCy) (n = 789); and total body irradiation (TBI)-containing treatment (n = 545). CBV was divided into CBV(high) and CBV(low) based on BCNU dose. We analyzed the impact of regimen on development of idiopathic pulmonary syndrome (IPS), transplantation-related mortality (TRM), and progression-free and overall survival. The 1-year incidence of IPS was 3% to 6% and was highest in recipients of CBV(high) (hazard ratio [HR], 1.9) and TBI (HR, 2.0) compared with BEAM. One-year TRM was 4% to 8%, respectively, and was similar between regimens. Among patients with NHL, there was a significant interaction between histology, HDT regimen, and outcome. Compared with BEAM, CBV(low) (HR, .63) was associated with lower mortality in follicular lymphoma (P < .001), and CBV(high) (HR, 1.44) was associated with higher mortality in diffuse large B cell lymphoma (P = .001). For patients with HL, CBV(high) (HR, 1.54), CBV(low) (HR, 1.53), BuCy (HR, 1.77), and TBI (HR, 3.39) were associated with higher mortality compared with BEAM (P < .001). The impact of specific AHCT regimen on post-transplantation survival is different depending on histology; therefore, further studies are required to define the best regimen for specific diseases., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2015
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44. Comparison of outcomes of allogeneic transplantation for chronic myeloid leukemia with cyclophosphamide in combination with intravenous busulfan, oral busulfan, or total body irradiation.
- Author
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Copelan EA, Avalos BR, Ahn KW, Zhu X, Gale RP, Grunwald MR, Hamadani M, Hamilton BK, Hale GA, Marks DI, Waller EK, Savani BN, Costa LJ, Ramanathan M, Cahn JY, Khoury HJ, Weisdorf DJ, Inamoto Y, Kamble RT, Schouten HC, Wirk B, Litzow MR, Aljurf MD, van Besien KW, Ustun C, Bolwell BJ, Bredeson CN, Fasan O, Ghosh N, Horowitz MM, Arora M, Szer J, Loren AW, Alyea EP, Cortes J, Maziarz RT, Kalaycio ME, and Saber W
- Subjects
- Administration, Intravenous, Administration, Oral, Adolescent, Adult, Allografts, Disease-Free Survival, Female, Humans, Male, Middle Aged, Siblings, Survival Rate, Whole-Body Irradiation, Busulfan administration & dosage, Cyclophosphamide administration & dosage, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Myeloablative Agonists administration & dosage, Transplantation Conditioning
- Abstract
Cyclophosphamide (Cy) in combination with busulfan (Bu) or total body irradiation (TBI) is the most commonly used myeloablative conditioning regimen in patients with chronic myeloid leukemia (CML). We used data from the Center for International Bone Marrow Transplantation Research to compare outcomes in adults who underwent hematopoietic cell transplantation for CML in first chronic phase after myeloablative conditioning with Cy in combination with TBI, oral Bu, or intravenous (i.v.) Bu. Four hundred thirty-eight adults received human leukocyte antigen (HLA)-matched sibling grafts and 235 received well-matched grafts from unrelated donors (URD) from 2000 through 2006. Important differences existed between the groups in distribution of donor relation, exposure to tyrosine kinase inhibitors, and year of transplantation. In multivariate analysis, relapse occurred less frequently among patients receiving i.v. Bu compared with TBI (relative risk [RR], .36; P = .022) or oral Bu (RR, .39; P = .028), but nonrelapse mortality and survival were similar. A significant interaction was detected between donor relation and the main effect in leukemia-free survival (LFS). Among recipients of HLA-identical sibling grafts, but not URD grafts, LFS was better in patients receiving i.v. Bu (RR, .53; P = .025) or oral Bu (RR, .64; P = .017) compared with TBI. In CML in first chronic phase, Cy in combination with i.v. Bu was associated with less relapse than TBI or oral Bu. LFS was better after i.v. or oral Bu compared with TBI., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2015
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45. Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research.
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Arai S, Arora M, Wang T, Spellman SR, He W, Couriel DR, Urbano-Ispizua A, Cutler CS, Bacigalupo AA, Battiwalla M, Flowers ME, Juckett MB, Lee SJ, Loren AW, Klumpp TR, Prockup SE, Ringdén OT, Savani BN, Socié G, Schultz KR, Spitzer T, Teshima T, Bredeson CN, Jacobsohn DA, Hayashi RJ, Drobyski WR, Frangoul HA, Akpek G, Ho VT, Lewis VA, Gale RP, Koreth J, Chao NJ, Aljurf MD, Cooper BW, Laughlin MJ, Hsu JW, Hematti P, Verdonck LF, Solh MM, Norkin M, Reddy V, Martino R, Gadalla S, Goldberg JD, McCarthy PL, Pérez-Simón JA, Khera N, Lewis ID, Atsuta Y, Olsson RF, Saber W, Waller EK, Blaise D, Pidala JA, Martin PJ, Satwani P, Bornhäuser M, Inamoto Y, Weisdorf DJ, Horowitz MM, and Pavletic SZ
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Chronic Disease, Female, Graft vs Host Disease mortality, Graft vs Host Disease pathology, Humans, Infant, Infant, Newborn, International Cooperation, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Leukemia, Myeloid, Acute pathology, Leukemia, Myeloid, Acute therapy, Male, Middle Aged, Myeloablative Agonists therapeutic use, Myelodysplastic Syndromes pathology, Myelodysplastic Syndromes therapy, Odds Ratio, Survival Analysis, Transplantation, Homologous, Bone Marrow Transplantation adverse effects, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myeloid, Acute mortality, Myelodysplastic Syndromes mortality
- Abstract
Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. Multivariate analysis showed an increased incidence of cGVHD in more recent years (odds ratio = 1.19, P < .0001), and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research., (Copyright © 2015 American Society for Blood and Marrow Transplantation. All rights reserved.)
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- 2015
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46. Hospital length of stay in the first 100 days after allogeneic hematopoietic cell transplantation for acute leukemia in remission: comparison among alternative graft sources.
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Ballen KK, Joffe S, Brazauskas R, Wang Z, Aljurf MD, Akpek G, Dandoy C, Frangoul HA, Freytes CO, Khera N, Lazarus HM, LeMaistre CF, Mehta P, Parsons SK, Szwajcer D, Ustun C, Wood WA, and Majhail NS
- Subjects
- Adolescent, Adult, Cohort Studies, Female, Humans, Length of Stay, Male, Middle Aged, Survival Analysis, Tissue Donors, Transplantation Conditioning methods, Treatment Outcome, Unrelated Donors, Young Adult, Cord Blood Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Several studies have shown comparable survival outcomes with different graft sources, but the relative resource needs of hematopoietic cell transplantation (HCT) by graft source have not been well studied. We compared total hospital length of stay in the first 100 days after HCT in 1577 patients with acute leukemia in remission who underwent HCT with an umbilical cord blood (UCB), matched unrelated donor (MUD), or mismatched unrelated donor (MMUD) graft between 2008 and 2011. To ensure a relatively homogenous study population, the analysis was limited to patients with acute myelogenous leukemia and acute lymphoblastic leukemia in first or second complete remission who underwent HCT in the United States. To account for early deaths, we compared the number of days alive and out of the hospital in the first 100 days post-transplantation. For children who received myeloablative conditioning, the median time alive and out of the hospital in the first 100 days was 50 days for single UCB recipients, 54 days for double UCB recipients, and 60 days for MUD bone marrow (BM) recipients. In multivariate analysis, use of UCB was significantly associated with fewer days alive and out of the hospital compared with MUD BM. For adults who received myeloablative conditioning, the median time alive and out of the hospital in first 100 days was 52 days for single UCB recipients, 55 days for double UCB recipients, 69 days for MUD BM recipients, 75 days for MUD peripheral blood stem cell (PBSC) recipients, 63 days for MMUD BM recipients, and 67 days for MMUD PBSC recipients. In multivariate analysis, UCB and MMUD BM recipients had fewer days alive and out of the hospital compared with recipients of other graft sources. For adults who received a reduced-intensity preparative regimen, the median time alive and out of the hospital during the first 100 days was 65 days for single UCB recipients, 63 days for double UCB recipients, 79 days for MUD PBSC recipients, and 79 days for MMUD PBSC recipients. Similar to the other 2 groups, receipt of UCB was associated with a fewer days alive and out of the hospital. In conclusion, length of stay in the first 100 days post-transplantation varies by graft source and is longer for UCB HCT recipients. These data provide insight into the resource needs of patients who undergo HCT with these various graft sources., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2014
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47. Early failure of frontline rituximab-containing chemo-immunotherapy in diffuse large B cell lymphoma does not predict futility of autologous hematopoietic cell transplantation.
- Author
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Hamadani M, Hari PN, Zhang Y, Carreras J, Akpek G, Aljurf MD, Ayala E, Bachanova V, Chen AI, Chen YB, Costa LJ, Fenske TS, Freytes CO, Ganguly S, Hertzberg MS, Holmberg LA, Inwards DJ, Kamble RT, Kanfer EJ, Lazarus HM, Marks DI, Nishihori T, Olsson R, Reddy NM, Rizzieri DA, Savani BN, Solh M, Vose JM, Wirk B, Maloney DG, Smith SM, Montoto S, Saber W, Alpdogan O, Cashen A, Dandoy C, Finke R, Gale R, Gibson J, Hsu JW, Janakiraman N, Laughlin MJ, Lill M, Cairo MS, Munker R, Rowlings PA, Schouten HC, Shea TC, Stiff PJ, and Waller EK
- Subjects
- Adult, Aged, Antibodies, Monoclonal, Murine-Derived administration & dosage, Cohort Studies, Disease Progression, Disease-Free Survival, Female, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Lymphoma, Large B-Cell, Diffuse drug therapy, Male, Middle Aged, Prognosis, Rituximab, Transplantation Conditioning adverse effects, Transplantation, Autologous, Treatment Failure, Treatment Outcome, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Large B-Cell, Diffuse therapy, Transplantation Conditioning methods
- Abstract
The poor prognosis for patients with diffuse large B cell lymphoma (DLBCL) who relapse within 1 year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes for chemosensitive DLBCL patients between 2000 and 2011 in 2 cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1 year of initial diagnosis. The ERF cohort was compared with those relapsing >1 year after initial diagnosis (late rituximab failure [LRF] cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS) of ERF versus LRF cohorts at 3 years were 9% (95% confidence interval [CI], 6% to 13%) versus 9% (95% CI, 5% to 13%), 47% (95% CI, 41% to 52%) versus 39% (95% CI, 33% to 46%), 44% (95% CI, 38% to 50%) versus 52% (95% CI, 45% to 59%), and 50% (95% CI, 44% to 56%) versus 67% (95% CI, 60% to 74%), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk [RR], 1.31; P = .34). The ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR, 2.08; P < .001) and overall mortality (RR, 3.75; P <.001) within the first 9 months after autologous HCT. Beyond this period, PFS and OS were not significantly different between the ERF and LRF cohorts. Autologous HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS, 44%) and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2014
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48. Outcome of allogeneic stem cell transplantation for patients transformed to myelodysplastic syndrome or leukemia from severe aplastic anemia: a report from the MDS Subcommittee of the Chronic Malignancies Working Party and the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation.
- Author
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Hussein AA, Halkes CM, Socié G, Tichelli A, von dem Borne PA, Schaap MN, Foa R, Ganser A, Dufour C, Bacigalupo A, Locasciulli A, Aljurf M, Peters C, Robin M, van Biezen AA, Volin L, De Witte T, Marsh J, Passweg JR, and Kröger N
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Europe, Female, Humans, Infant, Leukemia, Male, Middle Aged, Myelodysplastic Syndromes, Neoplasm Recurrence, Local, Treatment Outcome, Young Adult, Anemia, Aplastic therapy, Hematopoietic Stem Cell Transplantation adverse effects, Transplantation Conditioning adverse effects, Transplantation, Homologous adverse effects
- Abstract
One hundred and forty patients who had undergone hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) transformation after treatment of severe aplastic anemia (SAA) were identified in the European Group for Blood and Marrow Transplantation (EBMT) database. The median age at HSCT was 29 years (range, 1 to 66 years). The transplant donor was related in 49% cases and unrelated in 51% cases. The 5-year probability of relapse was 17%, and that of nonrelapse mortality was 41%. The 5-year overall survival was 45% ± 9%, better for patients untreated and patients in remission compared with patients with refractory disease. Our data indicate that allogeneic HSCT leads to prolonged survival in close to one-half of the patients transforming to MDS or AML from SAA., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2014
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49. Outcomes of human leukocyte antigen-matched sibling donor hematopoietic cell transplantation in chronic lymphocytic leukemia: myeloablative versus reduced-intensity conditioning regimens.
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Sobecks RM, Leis JF, Gale RP, Ahn KW, Zhu X, Sabloff M, de Lima M, Brown JR, Inamoto Y, Hale GA, Aljurf MD, Kamble RT, Hsu JW, Pavletic SZ, Wirk B, Seftel MD, Lewis ID, Alyea EP, Cortes J, Kalaycio ME, Maziarz RT, and Saber W
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Siblings, Tissue Donors, Treatment Outcome, HLA Antigens immunology, Hematopoietic Stem Cell Transplantation methods, Leukemia, Lymphocytic, Chronic, B-Cell therapy, Transplantation Conditioning methods
- Abstract
Allogeneic hematopoietic cell transplantation (HCT) can cure some chronic lymphocytic leukemia (CLL) subjects. This study compared outcomes of myeloablative (MA) and reduced-intensity conditioning (RIC) transplants from HLA-matched sibling donors (MSD) for CLL. From 1995 to 2007, information regarding 297 CLL subjects was reported to the Center of International Blood and Marrow Transplant Research; of these, 163 underwent MA and 134 underwent RIC MSD HCT. The MA subjects underwent transplantation less often after 2000 and less commonly received antithymocyte globulin (4% versus 13%, P = .004) or prior antibody therapy (14% versus 53%; P < .001). RIC was associated with a greater likelihood of platelet recovery and less grade 2 to 4 acute graft-versus-host disease compared with MA conditioning. One- and 5-year treatment-related mortality (TRM) were 24% (95% confidence intervals [CI], 16% to 33%) versus 37% (95% CI, 30% to 45%; P = .023), and 40% (95% CI, 29% to 51%) versus 54% (95% CI, 46% to 62%; P = .036), respectively, and the relapse/progression rates at 1 and 5 years were 21% (95% CI, 14% to 29%) versus 10% (95% CI, 6% to 15%; P = .020), and 35% (95% CI, 26% to 46%) versus 17% (95% CI, 12% to 24%; P = .003), respectively. MA conditioning was associated with better progression-free (PFS) (relative risk, .60; 95% CI, .37 to .97; P = .038) and 3-year survival in transplantations before 2001, but for subsequent years, RIC was associated with better PFS and survival (relative risk, 1.49 [95% CI, .92 to 2.42]; P = .10; and relative risk, 1.86 [95% CI, 1.11 to 3.13]; P = .019). Pretransplantation disease status was the most important predictor of relapse (P = .003) and PFS (P = .0007) for both forms of transplantation conditioning. MA and RIC MSD transplantations are effective for CLL. Future strategies to decrease TRM and reduce relapses are warranted., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2014
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50. Outcomes of hematopoietic cell transplantation for diffuse large B cell lymphoma transformed from follicular lymphoma.
- Author
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Wirk B, Fenske TS, Hamadani M, Zhang MJ, Hu ZH, Akpek G, Aljurf MD, Armand P, Ayala E, Bachanova V, Bolwell B, Cairo MS, Cashen A, Chen YB, Costa LJ, Farhan S, Freytes CO, Gajewski JL, Gibson J, Hale GA, Holmberg LA, Hsu JW, Inwards DJ, Kamble RT, Maharaj D, Maziarz RT, Munker R, Nath R, Reddy NM, Reeder CB, Rizzieri DA, Sauter CS, Savani BN, Schouten HC, Sureda A, Vose JM, Waller EK, Wiernik PH, Gale RP, Burns LJ, and Saber W
- Subjects
- Adult, Aged, Disease-Free Survival, Female, Humans, Lymphoma, Follicular pathology, Lymphoma, Large B-Cell, Diffuse pathology, Male, Middle Aged, Proportional Hazards Models, Survival Analysis, Transplantation, Homologous, Treatment Outcome, Young Adult, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Follicular therapy, Lymphoma, Large B-Cell, Diffuse therapy, Transplantation Conditioning methods
- Abstract
There are limited data on the outcomes of autologous or allogeneic hematopoietic cell transplantation (HCT) in diffuse large B cell lymphoma transformed from follicular lymphoma. We analyzed transplantation outcomes in 141 subjects with biopsy-proven diffuse large B-cell lymphoma transformed from follicular lymphoma reported to the Center for International Blood and Marrow Transplant Research between 1990 and 2009. Two groups were identified: autologous HCT (auto-HCT; n = 108) and allogeneic HCT (allo-HCT; n = 33). Fewer auto-HCTs were done for transformed follicular lymphoma in 2003 to 2009, with a shift favoring allo-HCT. Auto-HCT was associated with a 1-year nonrelapse mortality (NRM) of 8% (95% confidence interval [CI], 4% to 14%), 5-year progression-free survival of 35% (95% CI, 26% to 45%), and 5-year overall survival of 50% (95% CI, 40% to 59%). In contrast, allo-HCT was associated with a 1-year NRM of 41% (95% CI, 23% to 58%), 5-year progression-free survival of 18% (95% CI, 6% to 35%), and 5-year overall survival of 22% (95% CI, 8% to 41%). Auto-HCT for transformed follicular lymphoma achieves sustained remission in a high proportion of subjects. The high NRM of allo-HCT offset any benefit that might be associated with this transplantation modality., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
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