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

Partow Kebriaei, Claudio Anasetti, Mei Jie Zhang, Hai Lin Wang, Ibrahim Aldoss, Marcos de Lima, H. Jean Khoury, Brenda M. Sandmaier, Mary M. Horowitz, Andrew Artz, Nelli Bejanyan, Stefan Ciurea, Hillard M. Lazarus, Robert Peter Gale, Mark Litzow, Christopher Bredeson, Matthew D. Seftel, Michael A. Pulsipher, Jaap Jan Boelens, Joseph AlvarnasRichard Champlin, Stephen Forman, Vinod Pullarkat, Daniel Weisdorf, David I. Marks

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)726-733
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume24
Issue number4
DOIs
StatePublished - Apr 2018

Bibliographical note

Funding Information:
The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement 5U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-15-1-0848 and N00014-16-1-2020 from the Office of Naval Research; and grants from Alexion; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; AstraZeneca; Be The Match Foundation; *Bluebird Bio, Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; Cellular Dynamics International, Inc.; *Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Genentech, Inc.; Genzyme Corporation; *Gilead Sciences, Inc.; Health Research, Inc.; Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Jeff Gordon Children's Foundation; Leukemia and Lymphoma Society; Medac, GmbH; MedImmune; Medical College of Wisconsin; *Merck & Co., Inc.; Mesoblast; MesoScale Diagnostics, Inc.; *Miltenyi Biotec; National Marrow Donor Program; Neovii Biotech NA, Inc.; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Otsuka Pharmaceutical Co., Ltd.; PCORI; Perkin Elmer, Inc.; Pfizer, Inc.; *Sanofi US; *Seattle Genetics; *Spectrum Pharmaceuticals; St. Baldrick's Foundation; *Sunesis Pharmaceuticals, Inc.; Swedish Orphan Biovitrum, Inc.; Takeda Oncology; Telomere Diagnostics, Inc.; University of Minnesota; and *WellPoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government.

Funding Information:
The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement 5U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-15-1-0848 and N00014-16-1-2020 from the Office of Naval Research ; and grants from Alexion ; * Amgen, Inc. ; Anonymous donation to the Medical College of Wisconsin ; Astellas Pharma US ; AstraZeneca ; Be The Match Foundation ; * Bluebird Bio, Inc. ; * Bristol Myers Squibb Oncology ; * Celgene Corporation ; Cellular Dynamics International, Inc. ; * Chimerix, Inc. ; Fred Hutchinson Cancer Research Center ; Gamida Cell Ltd. ; Genentech, Inc. ; Genzyme Corporation ; * Gilead Sciences, Inc. ; Health Research, Inc. ; Roswell Park Cancer Institute ; HistoGenetics, Inc. ; Incyte Corporation ; Janssen Scientific Affairs, LLC ; * Jazz Pharmaceuticals, Inc. ; Jeff Gordon Children's Foundation ; Leukemia and Lymphoma Society ; Medac, GmbH ; MedImmune ; Medical College of Wisconsin ; * Merck & Co., Inc. ; Mesoblast ; MesoScale Diagnostics, Inc. ; * Miltenyi Biotec ; National Marrow Donor Program ; Neovii Biotech NA, Inc. ; Novartis Pharmaceuticals Corporation ; Onyx Pharmaceuticals ; Optum Healthcare Solutions, Inc. ; Otsuka America Pharmaceutical, Inc. ; Otsuka Pharmaceutical Co., Ltd. ; PCORI ; Perkin Elmer, Inc. ; Pfizer, Inc. ; * Sanofi US ; * Seattle Genetics ; * Spectrum Pharmaceuticals ; St. Baldrick's Foundation ; * Sunesis Pharmaceuticals, Inc. ; Swedish Orphan Biovitrum, Inc. ; Takeda Oncology ; Telomere Diagnostics, Inc. ; University of Minnesota ; and * WellPoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government.

Publisher Copyright:
© 2018

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

Keywords

  • Acute lymphoblastic leukemia
  • Allogeneic transplant
  • Busulfan
  • Total body irradiation

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