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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
Author(s) -
Hamadani Mehdi,
Craig Michael,
Phillips Gary S.,
Abraham Jame,
Tse William,
Cumpston Aaron,
Gibson Laura,
Remick Scot C.,
Bunner Pamela,
Leadmon Sonia,
Elder Patrick,
Hofmeister Craig,
Penza Sam,
Efebera Yvonne,
Andritsos Leslie,
Garzon Ramiro,
Benson Don M.,
Blum William,
Devine Steven M.
Publication year - 2011
Publication title -
hematological oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 44
eISSN - 1099-1069
pISSN - 0278-0232
DOI - 10.1002/hon.985
Subject(s) - busulfan , fludarabine , medicine , gastroenterology , toxicity , cumulative incidence , transplantation , surgery , hematopoietic stem cell transplantation , chemotherapy , cyclophosphamide
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/m 2 /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/m 2 /day IV, days −6 to −3), fludarabine (40 mg/m 2 /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.