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Myeloablative haploidentical BMT with posttransplant cyclophosphamide for hematologic malignancies in children and adults
Symons, H. J., Zahurak, M., Cao, Y., Chen, A., Cooke, K., Gamper, C., Klein, O., Llosa, N., Zambidis, E. T., Ambinder, R., et al
Blood advances. 2020;4(16):3913-3925
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Abstract
Promising results have been reported for patients with high-risk hematologic malignancies undergoing HLA-haploidentical bone marrow transplantation (haploBMT) with posttransplantation cyclophosphamide (PTCy), but there are few data on outcomes with myeloablative conditioning in this context. We report the results of a single-institution, prospective phase 2 trial of myeloablative haploBMT using busulfan-based or total body irradiation-based conditioning in 96 children or adults (median age, 42 years; range, 1-65 years) with high-risk hematologic malignancies. Recovery of neutrophils and platelets occurred at a median of 24 and 29 days. Engraftment of donor cells with chimerism >95% was achieved in 91%. The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and grades III to IV at day 100 was 11% and 4%, and of chronic GVHD at 6 and 12 months was 4% and 15%, with 6% moderate to severe. The cumulative incidence of nonrelapse mortality was 6% at 100 days and 11% at 1 year (19% in those aged >55 years). The cumulative incidence of relapse at 1 year was 35%; at 3 years, it was 43%. In multivariable analysis, relapse was associated with increased age (P = .02 for age 20-55 years and P = .02 for age >55 years) and with minimal residual disease before transplantation (P = .05). The overall survival at 1 and 3 years is 73% and 54%, and event-free survival at 1 and 3 years is 57% and 49%. We show that haploBMT with PTCy after myeloablative conditioning is safe and efficacious for adult and pediatric patients with hematologic malignancies. Careful consideration must be given to using myeloablative conditioning in patients age >55 years. This trial was registered at www.clinicaltrials.gov as #NCT00796562.
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Nonmyeloablative Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide for Pediatric and Young Adult Patients with High-Risk Hematologic Malignancies
Klein, O. R., Buddenbaum, J., Tucker, N., Chen, A. R., Gamper, C. J., Loeb, D., Zambidis, E., Llosa, N. J., Huo, J. S., Robey, N., et al
Biology of Blood & Marrow Transplantation. 2017;23(2):325-332
Abstract
Lower-intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious for adult patients with hematologic malignancies. We report data for pediatric/young adult patients with high-risk hematologic malignancies (n=40) treated with nonmyeloablative haploidentical BMT with post-transplantation cyclophosphamide from 2003 to 2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplantation immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus. Donor engraftment occurred in 29 of 32 (91%), with median time to engraftment of neutrophils >500/micro L of 16 days (range, 13 to 22) and for platelets >20,000/micro L without transfusion of 18 days (range, 12 to 62). Cumulative incidences of acute graft-versus-host disease (GVHD) grades II to IV and grades III and IV at day 100 were 33% and 5%, respectively. The cumulative incidence of chronic GVHD was 23%, with 7% moderate-to-severe chronic GVHD, according to National Institutes of Health consensus criteria. Transplantation-related mortality (TRM) at 1 year was 13%. The cumulative incidence of relapse at 2 years was 52%. With a median follow-up of 20 months (range, 3 to 148), 1-year actuarial overall and event-free survival were 56% and 43%, respectively. Thus, we demonstrate excellent rates of engraftment, GVHD, and TRM in pediatric/young adult patients treated with this regimen. This approach is a widely available, safe, and feasible option for pediatric and young adult patients with high-risk hematologic malignancies, including those with a prior history of myeloablative BMT and/or those with comorbidities or organ dysfunction that preclude eligibility for myeloablative BMT.Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
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Single-Agent Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis after Human Leukocyte Antigen-Matched Related Bone Marrow Transplantation for Pediatric and Young Adult Patients with Hematologic Malignancies
Jacoby, E., Chen, A., Loeb, D. M., Gamper, C. J., Zambidis, E., Llosa, N. J., Huo, J., Cooke, K. R., Jones, R., Fuchs, E., et al
Biology of Blood & Marrow Transplantation. 2016;22(1):112-8
Abstract
High-dose cyclophosphamide given after HLA-matched related and unrelated allogeneic bone marrow transplantation (BMT) for patients with hematologic malignancies is effective single-agent graft-versus-host disease (GVHD) prophylaxis in adults. Data describing outcomes for pediatric and young adult patients have not been reported. Between the years 2007 and 2013, 29 pediatric and young adult patients ages <21 years of age treated at our institution for high-risk hematologic malignancies underwent myeloablative HLA-matched related T cell-replete BMT. Eleven patients received post-transplantation cyclophosphamide (PTCy) as single-agent GVHD prophylaxis and were followed prospectively. Eighteen patients received calcineurin inhibitor (CNI)-based standard GVHD prophylaxis and were studied retrospectively as a control group. No acute GVHD (aGVHD) developed in patients receiving PTCy, whereas patients receiving CNI-based GVHD prophylaxis had cumulative incidences of grades II to IV and grades III and IV aGVHD of 27% and 5%, respectively. No patients receiving PTCy developed chronic GHVD, compared to 1 in the control group. Two-year overall survival was similar between the 2 groups (54% PTCy versus 58% CNI-based prophylaxis), as was event-free survival (42% PTCy versus 47% CNI-based). The 5-year cumulative incidence of relapse was 58% for PTCy and 42% for CNI-based GVHD prophylaxis (P = .45). These results suggest that PTCy is a safe and efficacious method of GVHD prophylaxis after an HLA-matched related BMT in the pediatric and young adult population that affords patients to be off all post-transplantation immunosuppression on day +5. Copyright © 2016 American Society for Blood and Marrow Transplantation. All rights reserved.