We evaluated the impact of busulfan dose-intensity in patients undergoing reduced toxicity/intensity conditioning allogeneic transplantation in a multicenter retrospective study of 112 consecutive patients. Seventy-five patients were conditioned with busulfan (0.8 mg/kg/dose IV × 8 doses), fludarabine (30mg/m^{2}/day, days −7 to −3), and 6mg/kg of ATG (RIC group), while 37 patients received a more-intense conditioning with busulfan (130mg/m^{2}/day IV, days −6 to −3), fludarabine (40mg/m^{2}/day, days −6 to −3), and 6mg/kg of ATG (RTC group). At baseline both groups were matched for median age, unrelated donor allografts, and HLA-mismatched allografts. More patients in RIC group had high-risk disease, and higher median co-morbidity index. There were no graft rejections. Median time to neutrophil (17 vs. 15 days; p=0.003) and platelet engraftment (16 vs. 11 days; p<0.001) was significantly longer in the RIC group. RTC group had significantly more bacterial (62.2% vs. 32%; p=0.004) and fungal infections (13.5% vs. 1.3% p=0.01). For RIC and RTC groups rates of grade II-IV acute GVHD (34% vs. 40%; p-value=0.54), and chronic GVHD (45% vs. 57%; p-value=0.30) were not significantly different. In similar order at 1-year the cumulative-incidence of non-relapse mortality (NRM) (12% vs. 21%; p-value=0.21) and relapse rates (38% vs. 39%; p=0.96) were not significantly different. Patients in RIC and RTC groups had similar 1-year overall survival (61% vs. 50% p=0.11) and progression free survival (50% vs. 36% p-value=0.39). Our data suggest that merits of higher busulfan dose-intensity in the context of fludarabine/busulfan-based RTC may be offset by higher early morbidity.
【저자키워드】 Allogeneic stem cell transplantation, Graft-versus-host disease, Fludarabine, thymoglobulin, Busulfan, busulfan dose,