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.

BACKGROUND: Fludarabine 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).

METHODS: The 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.

RESULTS: At 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).

CONCLUSIONS: These 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.