Iv Busulfan (Bu) With Fludarabine (Flu) Or Cyclophosphamide (Cy) - Comparing Ablative Conditioning Regimens For Allogeneic Transplantation In Amlimds.

Abstract As part of our evaluation of Flu as immunosuppressive (and DNA damage repair inhibiting) agent, and as an alternative to Cy in combination with IV Bu, preparing AML/MDS patients for allogeneic transplant (AlloSCT), we postulated that the IV Bu-Flu regimen would yield improved safety, yet increased antileukemic efficacy. We now compared two consecutive series of patients receiving pretransplant conditioning therapy with either IV Bu-Flu or IV BuCy2. Methods: Flu 40 mg/m2 IV was given once daily, each dose followed immediately by Bu 130 mg/m2 IV over 3 hr (days −6 till −3) (n=128 patients), and in the IV BuCy2 the Bu was given at 0.8 mg/kg over 2 hr every 6 hr for 16 doses (days −7 till −4), followed by Cy 60 mg/kg on days −3 and −2 (n=73 patients). Patients with an unrelated (MUD) or mismatched donor received ATG on days −3 to −1. Graft-versus-host disease (GVHD) prophylaxis was based on tacrolimus and mini-methotrexate. Patients: Median age was 46 (19–66) (IV Bu-Flu group) and 39 (13–64) (IV BuCy2 group) years, respectively. At transplant 45% and 46% patients were in CR1–3, the remainder had active disease. Cytogenetic risk categories were equivalent for the two groups, with poor or intermediate risk in 88 % in the IV Bu-Flu, and in 82 % of the BuCy2group. Donors were HLA-identical siblings (SIBS) in 53 %, and 73%, MUDs in 39% and 15 %, others in 8 % and 12% respectively. Median follow-up for patients still alive (August 2004) was 15 mos (3–37; n=78) for the IV Bu-Flu group, and 45 mos (24–76; n=27)) for the IV BuCy2 patients. Results: Both regimens were well tolerated; 100-day treatment-related mortality (TRM) was for SIB/MUD 2.7 / 2% after IV Bu-Flu, and 7 / 9% in the IV BuCy2 group, respectively. Overall, one-year TRM was for 7% after IV Bu-Flu and 18% after IV BuCy2. The overall aGvHD rates were 42% and 45%. 2-year overall survival (OS) were 50% for the IV Bu-Flu group, 42% after IV BuCy2. For patients transplanted in CR the 2-yr OS and event-free survival were 69% and 68 % after IV Bu-Flu, and 48% and 41% in the IV BuCy2. We conclude, that IV Bu-Flu is a safe and highly effective, reduced toxicity myeloablative conditioning regimen for AML/MDS. Its antileukemic efficacy appears to be at least equal to what is experienced with the IV BuCy2 regimen. Thus, our data demonstrate the IV Bu-Flu regimen to be a new standard for myeloablative conditioning therapy for alloSCT in AML/MDS. Figure Figure