Reduced-Intensity Conditioning With Fludarabine and Busulfan Versus Fludarabine and Melphalan for Patients With Acute Myeloid Leukemia: A Report From the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

BACKGROUNDFludarabine plus busulfan (FB) and fludarabine plus melphalan (FM) are 2 widely used reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation (allo-SCT). METHODSThe current survey compared transplantation outcomes for a cohort of 394 acute myeloid leukemia (AML) patients given bone marrow or peripheral blood stem cells from human leukocyte antigen-identical siblings after FB (n=218) or FM (n=176). Patients given manipulated grafts and those given T-cell-depleting agents (anti-thymocyte globulins or alemtuzumab) were not included. RESULTSAt the time of transplantation, 266 patients (68%) were experiencing their first complete remission (CR), 69 (18%) were experiencing a later CR, and 59 (15%) had advanced disease. The incidences of acute and chronic graft-versus-host disease were similar in the 2 groups of patients. The 2-year relapse incidence (RI), nonrelapse mortality (NRM) rate, leukemia-free survival (LFS) rate, and overall survival (OS) rate were 31%3%, 18%3%, 51%+/- 4%, and 54%+/- 4%, respectively, for FB patients and 20%+/- 3% (P=.007), 20%+/- 3% (P=.4), 60%+/- 4% (P=.08), and 62%+/- 4% (P=.2), respectively, for FM patients. Among FB patients given intravenous busulfan (n=81), the 2-year RI, NRM, LFS, and OS rates were 26%+/- 5% (P=.43 vs FM patients), 25%+/- 6% (P=.18), 49%+/- 7% (P=.07), and 54%+/- 7% (P=.13), respectively. In multivariate analyses, FM was associated with a lower RI (hazard ratio [HR], 0.5; P=.01) and a trend toward higher NRM (HR, 1.6; P=.1) with similar LFS (HR, 0.8; P=.2) and OS (HR, 0.9; P=.6). CONCLUSIONSThese results suggest that although FM provides better AML control than FB as an RIC regimen for allo-SCT, the 2 regimens provide similar survival. Multicenter randomized studies are needed to confirm these findings. Cancer 2015;121:1048-1055. (c) 2014 American Cancer Society. Fludarabine and melphalan provide better acute myeloid leukemia control than fludarabine and busulfan as a reduced-intensity conditioning regimen for allogeneic hematopoietic stem cell transplantation. Fludarabine plus busulfan and fludarabine plus melphalan provide similar overall survival.