title: Higher busulfan dose intensity does not improve outcomes of patients undergoing allogeneic haematopoietic cell transplantation following fludarabine, busulfan-based reduced toxicity conditioning.
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.
authors.affiliation: Osborn Hematopoietic Malignancy and Transplantation Program, MBRCC, West Virginia University, Morgantown, USA. shamadani@hsc.wvu.edu
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hamadani
authors.forename: Michael
authors.initials: M
authors.lastname: Craig
authors.forename: Gary S
authors.initials: GS
authors.lastname: Phillips
authors.forename: Jame
authors.initials: J
authors.lastname: Abraham
authors.forename: William
authors.initials: W
authors.lastname: Tse
authors.forename: Aaron
authors.initials: A
authors.lastname: Cumpston
authors.forename: Laura
authors.initials: L
authors.lastname: Gibson
authors.forename: Scot C
authors.initials: SC
authors.lastname: Remick
authors.forename: Pamela
authors.initials: P
authors.lastname: Bunner
authors.forename: Sonia
authors.initials: S
authors.lastname: Leadmon
authors.forename: Patrick
authors.initials: P
authors.lastname: Elder
authors.forename: Craig
authors.initials: C
authors.lastname: Hofmeister
authors.forename: Sam
authors.initials: S
authors.lastname: Penza
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Efebera
authors.forename: Leslie
authors.initials: L
authors.lastname: Andritsos
authors.forename: Ramiro
authors.initials: R
authors.lastname: Garzon
authors.forename: Don M
authors.initials: DM
authors.lastname: Benson
authors.forename: William
authors.initials: W
authors.lastname: Blum
authors.forename: Steven M
authors.initials: SM
authors.lastname: Devine
mesh_terms: D000328:Adult; D000368:Aged; D002066:Busulfan / Q000008:administration & dosage*; D046528:Chimerism; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D009894:Opportunistic Infections / Q000150:complications; D012008:Recurrence; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D055815:Young Adult
chemical_list: D019653:Myeloablative Agonists; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine