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: Simrit Parmar, Gabriela Rondon, Marcos de Lima, Peter Thall, Ronald Bassett, Paolo Anderlini, Partow Kebriaei, Issa Khouri, Prasanth Ganesan, Richard Champlin, Sergio Giralt
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 19 Issue 3 Pg. 474-80 (Mar 2013) ISSN: 1523-6536 [Electronic] United States
• PMID: 23220013 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Immunosuppressive Agents
• Myeloablative Agonists
• Vidarabine
• Busulfan
• fludarabine

Topics

• Administration, Oral
• Aged
• Busulfan (pharmacology, therapeutic use)
• Drug Administration Schedule
• Female
• Graft vs Host Disease (prevention & control)
• Hematologic Neoplasms (immunology, mortality, pathology, therapy)
• Hematopoietic Stem Cell Transplantation
• Histocompatibility Testing
• Humans
• Immunosuppressive Agents (therapeutic use)
• Injections, Intravenous
• Male
• Middle Aged
• Myeloablative Agonists (pharmacology, therapeutic use)
• Survival Analysis
• Transplantation Conditioning
• Transplantation, Homologous
• Vidarabine (analogs & derivatives, pharmacology, therapeutic use)