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Higher busulfan dose intensity does not improve outcomes of patients undergoing allogeneic haematopoietic cell transplantation following fludarabine, busulfan-based reduced toxicity conditioning†
Article first published online: 28 FEB 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Volume 29, Issue 4, pages 202–210, December 2011
How to Cite
Hamadani, M., Craig, M., Phillips, G. S., Abraham, J., Tse, W., Cumpston, A., Gibson, L., Remick, S. C., Bunner, P., Leadmon, S., Elder, P., Hofmeister, C., Penza, S., Efebera, Y., Andritsos, L., Garzon, R., Benson, D. M., Blum, W. and Devine, S. M. (2011), Higher busulfan dose intensity does not improve outcomes of patients undergoing allogeneic haematopoietic cell transplantation following fludarabine, busulfan-based reduced toxicity conditioning. Hematol. Oncol., 29: 202–210. doi: 10.1002/hon.985
- Issue published online: 12 DEC 2011
- Article first published online: 28 FEB 2011
- Manuscript Accepted: 30 JAN 2011
- Manuscript Received: 24 JAN 2011
- busulfan dose;
- allogeneic stem-cell transplantation;
- graft-versus-host disease
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 (30 mg/m2/day, days −7 to −3), and 6 mg/kg of ATG [reduced intensity conditioning (RIC) group], while 37 patients received a more-intense conditioning with busulfan (130 mg/m2/day IV, days −6 to −3), fludarabine (40 mg/m2/day, days −6 to −3) and 6 mg/kg of ATG [reduced toxicity conditioning (RTC) group]. At baseline both groups were matched for median age, unrelated donor allografts, and human leukocyte antigen-mismatched allografts. More patients in RIC group had high-risk disease, and higher median comorbidity index. There were no graft rejections. Median time to neutrophil (17 days vs. 15 days; p = 0.003) and platelet engraftment (16 days 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 grades 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 the merits of higher busulfan dose intensity in the context of fludarabine/busulfan-based RTC may be offset by higher early morbidity. Copyright © 2011 John Wiley & Sons, Ltd.