Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia

• Type of Material: Article
• Authors: Partow Kebriaei, University of Texas MD Anderson Cancer Center; Claudio Anasetti, Moffitt Cancer Center; Mei-Jie Zhang, Medical College of Wisconsin; Hai-Lin Wang, Medical College of Wisconsin; Ibrahim Aldoss, City of Hope National Medical Center; Marcos de Lima, University Hospitals Case Medical Center; Hanna Khoury, Emory University; Brenda M. Sandmaier, University of Washington; Mary M. Horowitz, Medical College of Wisconsin; Andrew Artz, The University of Chicago; Nelli Bejanyan, University of Minnesota Medical Center, Fairview; Stefan Ciurea, University of Texas MD Anderson Cancer Center; Hillard M. Lazarus, University Hospitals Case Medical Center; Robert Peter Gale, Imperial College London; Mark Litzow, Mayo Clinic; Christopher Bredeson, Ottawa Hospital Research Institute; Matthew D. Seftel, CancerCare Manitoba; Michael A. Pulsipher, USC Keck School of Medicine; Jaap-Jan Boelens, University Medical Center Utrecht; Muna Qayed, Emory University
• Language: English
• Date: 2018-04-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbmt.2017.11.025
• Title of Journal or Parent Work: Biology of Blood and Marrow Transplantation
• ISSN: 1083-8791
• Volume: 24
• Issue: 4
• Start Page: 726
• End Page: 733
• Grant/Funding Information: See publication for full funding statement.
• Keywords: Precursor Cell Lymphoblastic Leukemia-Lymphoma; Busulfan; Whole-Body Irradiation; Middle Aged; Follow-Up Studies; Humans; Acute lymphoblastic leukemia; Transplantation Conditioning; Survival Rate; Allografts; Disease-Free Survival; Total body irradiation; Hematopoietic Stem Cell Transplantation; Adolescent; Female; Adult; Male; Allogeneic transplant; Administration, Intravenous
• Research Categories: Health Sciences, Oncology; Health Sciences, Pharmacology

Abstract

Total body irradiation (TBI) has been included in standard conditioning for acute lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non-TBI regimens have incorporated busulfan (Bu) to decrease toxicity. This retrospective study analyzed TBI and Bu on outcomes of ALL patients 18–60 years old, in first or second complete remission (CR), undergoing HLA-compatible sibling, related, or unrelated donor HCT, who reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014. TBI plus etoposide (25%) or cyclophosphamide (75%) was used in 819 patients, and intravenous Bu plus fludarabine (41%), clofarabine (30%), cyclophosphamide (15%), or melphalan (13%) was used in 299 patients. Bu-containing regimens were analyzed together, since no significant differences for patient outcomes were noted between them. Bu patients were older, with better performance status; took longer to achieve first CR and receive HCT; were treated more recently; and were more likely to receive peripheral blood grafts, antithymocyte globulin, or tyrosine kinase inhibitors. With median follow-up of 3.6 years for Bu and 5.3 years for TBI, adjusted 3-year outcomes showed treatment-related mortality Bu 19% versus TBI 25% (P =.04); relapse Bu 37% versus TBI 28% (P =.007); disease-free survival (DFS) Bu 45% versus TBI 48% (P =.35); and overall survival (OS) Bu 57% versus TBI 53% (P =.35). In multivariate analysis, Bu patients had higher risk of relapse (relative risk, 1.46; 95% confidence interval, 1.15 to 1.85; P =.002) compared with TBI patients. Despite the higher relapse, Bu-containing conditioning led to similar OS and DFS following HCT for ALL.