Comparison between two fludarabine-based reduced-intensity conditioning regimens before allogeneic hematopoietic stem-cell transplantation: Fludarabine/melphalan is associated with higher incidence of acute graft-versus-host disease and non-relapse mortality and lower incidence of relapse than fludarabine/busulfan

Reduced-intensity conditioning (RIC) regimens are increasingly used in allogeneic stem-cell transplantation (SCT). There are no data whether any of these regimens has advantage and in what setting. We retrospectively analyzed SCT outcomes in 151 patients given fludarabine-based RIC for various hematological malignancies; 72 conditioned with fludarabine and intravenous-busulfan (FB) and 79 with fludarabine and melphalan (FM). FM was more myelosuppressive. Grade III-IV organ toxicity occurred in 31 and 53% of FB and FM recipients (P=0.005) and acute graft-versus-host disease grade II-IV in 33 and 53%, respectively (P=0.01). Non- relapse mortality rate (NRM) was 16 and 40%, respectively (P=0.003). Active disease (HR 2.2, P=0.003) and prior autologous SCT (HR 1.7, P=0.04) predicted inferior overall survival (OS). Among patients transplanted in remission, OS was 72 and 36% after FB and FM, respectively (P=0.03) due to increased NRM with FM. Similarly, patients transplanted in active disease experienced higher NRM with FM, however lower relapse rates resulted in equivalent OS. In conclusion, there are marked differences in outcome between RIC regimens that are theoretically dose-equivalent. The FM regimen is more myelosuppressive and toxic but controls disease better. FB was associated with improved survival in patients transplanted in remission. These observations merit further study in prospective studies.