Faculty Collaboration Database

Higher busulfan dose intensity does not improve outcomes of patients undergoing allogeneic haematopoietic cell transplantation following fludarabine, busulfan-based reduced toxicity conditioning. Hematol Oncol 2011 Dec;29(4):202-10

Date

03/02/2011

Pubmed ID

21360728

Pubmed Central ID

PMC3557914

DOI

10.1002/hon.985

Scopus ID

2-s2.0-80052987567 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

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.

Author List

Hamadani M, Craig M, Phillips GS, Abraham J, Tse W, Cumpston A, Gibson L, Remick SC, Bunner P, Leadmon S, Elder P, Hofmeister C, Penza S, Efebera Y, Andritsos L, Garzon R, Benson DM Jr, Blum W, Devine SM

Author

Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Busulfan
Chimerism
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Myeloablative Agonists
Opportunistic Infections
Recurrence
Transplantation Conditioning
Transplantation, Homologous
Vidarabine
Young Adult