Optimal conditioning chemotherapy for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains uncertain. Myeloablative regimens such as fludarabine/busulfan are favored over reduced-intensity fludarabine/melphalan (Flu/Mel); however, it is not known if Flu/Mel is inferior. We analyzed hematopoietic cell transplantation recipients with AML and MDS who received fludarabine with once-daily intravenous busulfan targeted to either area under the curve (AUC) 5300 µM*L/min (Flu/Bu 5300) (n = 246) or AUC 3500 µM*L/min (Flu/Bu 3500) (n = 81), or Flu/Mel (n = 69). Flu/Bu regimens were compared separately to Flu/Mel. After 2-year follow-up, no differences in overall or relapse-free survival were found between Flu/Bu 5300 or 3500 versus Flu/Mel though relapse rates were significantly higher; 33.1% (p = 0.024), 44.6% (p = 0.002), versus 19.4%, respectively. Flu/Bu 5300 (p = 0.008) and Flu/Bu 3500 (p < 0.001) groups were prognostic for relapse compared to Flu/Mel. Flu/Mel yields lower relapse rates and similar survival benefit when compared to Flu/Bu 3500 or 5300 µM*L/min.
Keywords: Fludarabine; acute myeloid leukemia; busulfan; melphalan; myelodysplastic syndrome.