AUTOLOGOUS BONE-MARROW TRANSPLANTATION EV ACUTE MYELOID-LEUKEMIA - THE UNIVERSITY-OF-MINNESOTA EXPERIENCE

Purpose: To report the outcome of autologous bone marrow transplantati on for patients with acute myeloid leukemia (AML) in first or greater complete remission (CR) treated by autologous bone marrow transplantat ion using two different preparatory regimens. Methods and Materials: B etween September 1986 and August 1993, 75 patients with AML ranging in age from 6 months to 58 years underwent autologous bone marrow transp lantation using previously harvested and frozen unpurged (n = 6) or 4- hydroperoxycyclophosphamide purged marrows (n = 69). Patients were in first CR (n = 44) or beyond first CR (n = 31). The preparative regimen consisted of 120 mg/kg of cyclophosphamide (CY) and 1320 cGy total bo dy irradiation (TBI) in eight fractions over 4 days (CY/TBI) in 29 pat ients; and 16 mg/kg of Busulfan (BU) and 200 mg/kg of CY (BU/CY) in 46 patients. Thirty-five of these 75 patients (18 CY/TBI and 17 BU/CY) m ere part of a randomized trial comparing the two preparative regimens. Results: At 2 years, overall survival and disease-free survival (DFS) were 49% [95% confidence interval (C.I.) 37-61%] and 33% (95% C.I. 32 -55%), respectively. Patients in first CR had a significantly better o utcome than patients beyond first CR with an estimated 2-year DFS of 5 9% (95% C.I. 44-74%) vs. 21% (95% C.I. 5-36%, log-rank p = 0.0001), re spectively. For patients conditioned with CY/TBI, the estimated 2-year DFS was 52% compared to 39% for BU/CY (log-rank p = 0.35). Estimated 2-year relapse rates were 44% vs. 56% (log-rank p = 0.40), respectivel y. For patients in first CR, no differences in DFS were observed betwe en the two regimens (2-year estimates 69% vs. 55% log-rank p = 0.52). Patients beyond first CR had a significantly improved DFS with the CY/ TBI regimen (2-year estimates of 38% vs. 7%, log-rank p = 0.04). No di fferences were found between the two regimens in terms of time to WBC engraftment, absolute neutrophil count of > 500, incidence of bacterem ias, or median time to hospital discharge. Interstitial pneumonitis de veloped in two patients (one BU/CY, one CY/TBI) and venoocclusive dise ase developed in seven BU/CY patients (Fishers exact test p = 0.04). C onclusions: For patients beyond first CR, the CY/TBI regimen provided a better outcome, with a significantly better disease-free survival an d less venoocclusive disease. For patients in first CR, no significant difference between the two regimens was found. The high relapse rate, especially for patients with advanced disease, emphasizes the need fo r early transplantation and for new strategies to improve outcome. Cop yright (C) 1996 Elsevier Science Inc.