PHASE-II STUDY OF BUSULFAN, CYCLOPHOSPHAMIDE AND FRACTIONATED TOTAL-BODY IRRADIATION AS A PREPARATORY REGIMEN FOR ALLOGENEIC BONE-MARROW TRANSPLANTATION IN PATIENTS WITH ADVANCED MYELOID MALIGNANCIES

A previous phase I dose escalation study determined that the maximum t olerated doses of busulfan and cyclophosphamide that could be combined with 12.0 Gy of total body irradiation were 7 mg/kg and 50 mg/kg, res pectively. A phase II study of these three agents was carried out in 5 6 patients with advanced myeloid malignancies receiving allogeneic bon e marrow transplants from HLA-identical donors. Cyclosporine with meth otrexate or with prednisone was administered for prophylaxis against g raft-versus-host disease. Grade 3 (n = 8) and 4 (n = 3) regimen-relate d toxicity occurred in 20% of patients, which was the maximum predicte d from the phase I study. The 2-year actuarial probabilities of non-re lapse mortality and relapse were 0.52 and 0.55, respectively. Fourteen patients survive, 12 in remission, 581-1761 days post-transplant. The actuarial probabilities of disease-free survival for patients with re current acute myeloid leukemia and advanced chronic myeloid leukemia a t 2 years were 20% and 23%, respectively. When compared with our histo rical experience in patients receiving other treatment regimens, there was no apparent improvement in disease-free survival.