4.2 Article

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

Journal

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume 24, Issue 4, Pages 726-733

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2017.11.025

Keywords

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

Funding

  1. Public Health Service Grant from National Cancer Institute (NCI) [5U24-CA076518]
  2. National Heart, Lung, and Blood Institute (NHLBI)
  3. National Institute of Allergy and Infectious Diseases (NIAID)
  4. NHLBI [5U10HL069294]
  5. NCI
  6. Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]
  7. Office of Naval Research [N00014-15-1-0848, N00014-16-1-2020]
  8. Alexion
  9. Amgen, Inc.
  10. NATIONAL CANCER INSTITUTE [U24CA076518, P30CA016672] Funding Source: NIH RePORTER
  11. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [U10HL069294] Funding Source: NIH RePORTER

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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. (C) 2018 Published by Elsevier Inc. on behalf of the American Society for Blood and Marrow Transplantation.

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