Conditioning regimen Addition of low-dose busulfan to cyclophosphamide in aplastic anemia patients prior to allogeneic bone marrow transplantation to reduce rejection

Summary: Busulfan was added at the dose of 4 mg/kg to 200 mg/kg cyclophosphamide in 81 patients (3–53 years, median 24) with aplastic anemia to reduce graft rejection. Graftversus-host disease (GVHD) prophylaxis comprised cyclosporine–methotrexate. The number of prior transfusions was 0–276 (median 26), and 48% had received prior immunosuppressive therapy. Two patients experienced primary graft failure, and 10secondary rejection at 28– 1001 days (median 317 days). The cumulative incidence of rejection was 22%; for heavily transfused patients (X50U) it was 43% compared to 16% for the rest (P ¼ 0.06). Overall survival rate at 8 years was 56%; patients who received p15 and 415 transfusions was 78 and 50%, respectively (P ¼ 0.01), whereas it was 67 and 28% for p50and 450transfusions, respectively (P ¼ 0.002). In multivariate analysis, higher number of prior transfusions, shorter period of immunosuppression with cyclosporine and GVHD were associated with inferior survival; moreover, a higher risk of graft rejection were associated with a higher number of prior transfusions and a trend was observed for a shorter cyclosporine administration. Low-dose busulfan is feasible and may be helpful in patients exposed to o50transfusions. However, rejection remains a significant problem, mainly in heavily transfused patients. Bone Marrow Transplantation (2004) 33 ,9 –13.