title: Dose intensification of busulfan in the preparative regimen is associated with improved survival: a phase I/II controlled, randomized study.
abstract: Dose intensity is important for disease control in patients undergoing allogeneic stem cell transplantation. We conducted a phase I/II controlled, adoptive, randomized study to determine the optimal dosing schedule of i.v. busulfan. Patients aged ≤75 years with advanced hematologic malignancies with human leukocyte antigen-compatible donor were eligible. All patients received fludarabine at 30 mg/m(2)/d for 4 days, and busulfan was administered in different doses in oral or i.v. formulations. As determined by the phase I trial, i.v. busulfan at a dose of 11.2 mg/kg/d was used for the phase II expansion cohort. Altogether, 80 patients with a median age of 56 years were enrolled. Forty percent had active disease at the time of transplantation. Engraftment occurred in 91%, and a complete response was achieved in 79% of patients posttransplantation. At a median follow-up of 91 months in the surviving patients, the outcomes for i.v. busulfan dose of 11.2 mg/kg/d versus other doses were as follows: nonrelapse mortality, 34% versus 23% (P = .4); cumulative incidence of relapse, 43% versus 68% (P = .02); relapse-free survival, 25% versus 9% (P = .017); and overall survival, 27% versus 9% (P = .02). We conclude that optimizing i.v. busulfan dose intensity in the preparative regimen may overcome disease-associated poor prognostic factors.
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas at MD Anderson Cancer Center, Houston, TX 77030, USA. sparmar@mdanderson.org
authors.forename: Simrit
authors.initials: S
authors.lastname: Parmar
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rondon
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
authors.forename: Peter
authors.initials: P
authors.lastname: Thall
authors.forename: Ronald
authors.initials: R
authors.lastname: Bassett
authors.forename: Paolo
authors.initials: P
authors.lastname: Anderlini
authors.forename: Partow
authors.initials: P
authors.lastname: Kebriaei
authors.forename: Issa
authors.initials: I
authors.lastname: Khouri
authors.forename: Prasanth
authors.initials: P
authors.lastname: Ganesan
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
mesh_terms: D000284:Administration, Oral; D000368:Aged; D002066:Busulfan / Q000494:pharmacology / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine