Busulfan-cyclophosphamide versus total body irradiation–cyclophosphamide as preparative regimen before allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia: What have we learned?

Most of the preparative regimens before allogeneic bone marrow transplantation include cyclophosphamide (Cy) with either busulfan (Bu) or total body irradiation (TBI). The Bu-Cy regimen has shown an advantage in chronic myeloid leukemia and TBI-Cy remains the standard conditioning regimen in acute lymphoblastic leukemia, but results are more conflicting in acute myeloid leukemia (AML). We report here the results of the most important studies comparing these two preparative regimens in AML. Survival is superior in all studies for patients treated with TBI and reached statistical significance in one of four trials. Two of three trials show significantly reduced transplant mortality and leukemia relapse. Higher incidences of veno-occlusive disease and hemorrhagic cystitis are reported with Bu. However, our long-term follow-up is limited, and to date no definitive conclusion can be drawn regarding late side effects. New approaches aiming at minimizing the toxicity without impairing the efficacy, such as targeted Bu plasma levels and nonmyeloablative conditioning regimens, seem promising but need to be evaluated further in future prospective studies.