ALLOGENEIC MARROW TRANSPLANTATION FOR MYELODYSPLASTIC SYNDROME WITH ADVANCED DISEASE MORPHOLOGY - A PHASE-II STUDY OF BUSULFAN, CYCLOPHOSPHAMIDE, AND TOTAL-BODY IRRADIATION AND ANALYSIS OF PROGNOSTIC FACTORS

Purpose: To determine if an intensive preparative regimen of busulfan (BU), cyclophosphamide (CY), and total-body irradiation (TBI) could im prove outcome after marrow transplantation for advanced morphology mye lodysplasia (refractory anemia with excess blasts [RAEB], RAEB in tran sformation [RAEB-T], and chronic myelomonocytic leukemia [CMML]) compa red with that obtained with conventional CY/TBI and to analyze prognos tic factors for transplantation for myelodysplasia. Patients and Metho ds: A phase II study was conducted; of 31; patients (median age, 41 ye ars) treated with BU (7 mg/kg), CY (50 mg/kg), TBI (12 Gy), and human leukocyte antigen (HLA)-matched (n = 23) or -mismatched (n = 2) relate d or unrelated donor (n = 6) marrow transplantation. Results were comp ared with 44 historical control patients treated with CY (120 mg/kg) a nd TBI. Results: The 3-year actuarial disease-free survival (DFS) rate was similar for the BU/CY/TBI group and the CY/TBI group (23% v 30%, P = .6), but there were trends toward lower relapse rates (28% v 54%, P = .27) and higher nonrelapse mortality rates (68% v 36%, P = .12) am ong the current patients compared with historical controls. Multivaria te analysis showed that a normal karyotype pretransplant and the use o f methotrexate as parr of posttransplant immunosuppression were associ ated with improved survival and reduced nonrelapse mortality. Univaria te analysis showed significant differences in relapse rates based on m arrow source (57% for HLA genotypically matched marrow v 18% for all o thers, P = .04) and on disease morphology (66% for RAEB-T v 38% for RA EB and CMML, P = .05). Conclusion: Patients with advanced morphology m yelodysplasia tolerated the intensified BU/CY/TBI preparative regimen and reduced posttransplant immunosuppression poorly. Novel transplant procedures are needed to reduce relapse rates without increasing nonre lapse mortality rates. In addition, transplantation before progression to RAEB-T, if possible, may reduce the risk of relapse. (C) 1996 by A merican Society of Clinical Oncology.