Increased risk of chronic graft-versus-host disease, obstructive bronchiolitis, and alopecia with busulfan versus total body irradiation: Long-term results of a randomized trial in allogeneic marrow recipients with leukemia

Leukemic patients receiving marrow from HLA-identical sibling donors were r andomized to treatment with either busulfan 16 mg/kg (n = 88) or total body irradiation ([TBI] n = 79) in addition to cyclophosphamide 120 mg/kg, The patients were observed for a period of 5 to 9 years. Busulfan-treated patie nts had an increased risk of veno-occlusive disease (VOD) of the liver (12% v 1%, P = .01) and hemorrhagic cystitis (32% v 10%, P = .003). Acute graft -versus-host disease (GVHD) was similar in the two groups, but the 7-year c umulative incidence of chronic GVHD was 59% in the busulfan-treated group v ersus 47% in the TBI group (P = .05). Death from GVHD was more common in th e busulfan group (22% v 3%, P < .001). Obstructive bronchiolitis occurred i n 26% of the busulfan patients but in only 5% of the TBI patients (P < .01) . Complete alopecia developed in 8 busulfan patients and partial alopecia i n 17, versus five with partial alopecia in the TBI group (P < .001). Catara cts occurred in 5 busulfan-treated patients and 16 TBI patients (P = .02). The incidence of relapse after 7 years was 29% in both groups. Seven-year t ransplant-related mortality (TRM) in patients with early disease was 21% in the busulfan group and 12% in the TBI group. In patients with more advance d disease, the corresponding figures were 64% and 22%, respectively (P = .0 04). Leukemia-free survival (LFS) in patients with early disease was 68% in busulfan-treated patients and 66% in TBI patients. However, 7-year LFS in patients with more advanced disease was 17% in the busulfan group versus 49 % in the TBI group (P < .01). In patients with chronic myeloid leukemia (CM L) in first chronic phase, 7-year LFS was 72% and 83% in the two groups, re spectively. (C) 1999 by The American Society of Hematology.