1.
Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improves Transplant Outcomes in Older MDS Patients
Oran, B., Ahn, K. W., Fretham, C., Beitinjaneh, A., Bashey, A., Pawarode, A., Wirk, B., Scott, B. L., Savani, B. N., Bredeson, C., et al
Transplantation and cellular therapy. 2021
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Abstract
Reduced-intensity conditioning (RIC) regimens developed to extend allogeneic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the two most commonly used RIC regimens, intravenous use of fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in myelodysplastic syndrome (MDS). Through CIBMTR, we identified 1045 MDS patients aged = 60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using RIC. CIBMTR's definition of RIC was used: a regimen that incorporated an intravenous busulfan total dose = 7.2 mg/kg, or a low-dose melphalan total dose of = 150 mg/m(2). The two groups, FluBu (n=697) and FluMel (n=448), were comparable for disease and transplant-related characteristics except for the more frequent use of anti-thymocyte globulin or alemtuzumab in the FluBu group (39% vs. 31%). The median age was 67 in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% vs. 44% (p=0.0001). Transplant-related mortality (TRM) was higher with FluMel compared with FluBu (26% vs. 16%, p=0.0001). Since the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was improved at 1-year and beyond with FluMel compared with FluBu (48% vs. 40% at 1 year, p=0.02, and 35% vs. 27% at 3 years, p=0.01). Overall survival (OS) was comparable at 1 year (63% vs. 61%, p=0.4) but significantly improved with FluMel compared with FluBu at 3 years (46% vs. 39%, p=0.03). Our results suggest that FluMel is associated with superior DFS compared with FluBu due to reduced RI in older MDS patients.
PICO Summary
Population
Patients with myelodysplastic syndrome aged >/=60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor, and were reported to the CIBMTR registry (n=1045)
Intervention
Reduced intensity regimen incorporating an intravenous busulfan total dose = 7.2 mg/kg (FluBu, n=697)
Comparison
Reduced intensity regimen incorporating a low-dose melphalan total dose of = 150 mg/m(2) (FluMel, n=448)
Outcome
The two groups were comparable for disease and transplant-related characteristics except for the more frequent use of anti-thymocyte globulin or alemtuzumab in the FluBu group (39% vs. 31%). The median age was 67 in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% vs. 44%. Transplant-related mortality (TRM) was higher with FluMel compared with FluBu (26% vs. 16%). Since the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was improved at 1-year and beyond with FluMel compared with FluBu (48% vs. 40% at 1 year, and 35% vs. 27% at 3 years). Overall survival (OS) was comparable at 1 year (63% vs. 61%) but significantly improved with FluMel compared with FluBu at 3 years (46% vs. 39%). Our results suggest that FluMel is associated with superior DFS compared with FluBu due to reduced RI in older MDS patients.
2.
Indications and Results of HLA-Identical Sibling Hematopoietic Cell Transplantation for Sickle Cell Disease. [Review]
Walters, M. C., De Castro, L. M., Sullivan, K. M., Krishnamurti, L., Kamani, N., Bredeson, C., Neuberg, D., Hassell, K. L., Farnia, S., Campbell, A., et al
Biology of Blood & Marrow Transplantation. 2016;22(2):207-11
Abstract
Although a number of published trials exist of HLA-identical sibling hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) that span 2 decades, when and for whom this therapy should be pursued is a subject of debate. Assessments of the risks of transplant-related complications that include infertility and debilitating graft-versus-host disease and long-term quality of life after successful HCT are difficult to perform without prospective trials in transplant and nontransplant cohorts. However, it is possible to assess the risk of mortality and to compare published rates of survival in individuals with SCD treated and not treated by HCT. In this brief review, projections about mortality risk based on recent published reports are reviewed and summarized. The published data show overall survival and event-free survival rates of 95% and 92%, respectively, in children treated by HLA-identical sibling HCT. The overall survival rates in the Center for International Blood and Marrow Transplant Research (N = 412) and European Blood and Marrow Transplant (N = 487) registries were 91% and 95%, respectively. These results provide broad support for the therapeutic value of HLA-identical sibling HCT for children with SCD and serve as the basis for a strong recommendation in favor of the option of HCT when a suitable donor is available. The experience of HLA-identical sibling HCT in adults with SCD is limited but appears to be similar to results in children. These preliminary observations, however, warrant further investigation. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.