A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission

David I. Marks, Stephen J. Forman, Karl G. Blume, Waleska S. Pérez, Daniel J. Weisdorf, Armand Keating, Robert Peter Gale, Mitchell S. Cairo, Edward A. Copelan, John T. Horan, Hillard M. Lazarus, Mark R. Litzow, Philip L. McCarthy, Kirk R. Schultz, David D. Smith, Michael E. Trigg, Mei Jie Zhang, Mary M. Horowitz

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121 Scopus citations

Abstract

We compared the outcomes of 298 patients with acute lymphoblastic leukemia in first or second complete remission (CR1 or CR2) receiving HLA-matched sibling allografts after cyclophosphamide and total body irradiation (Cy-TBI) conditioning with 204 patients receiving etoposide and TBI. Consequently, 4 groups were compared: Cy-TBI <13 Gy (n = 217), Cy-TBI ≥13 Gy (n = 81), etoposide-TBI <13 Gy (n = 53), and etoposide-TBI ≥13 Gy (n = 151). Analyses of relapse, leukemia-free survival (LFS), and survival were performed separately for CR1 and CR2 transplantations. Transplant-related mortality did not differ by conditioning regimen. In CR1, there were also no significant differences in relapse, LFS, or survival by conditioning regimen. In CR2, these outcomes differed among conditioning groups. In comparison with Cy-TBI <13 Gy, the risks of relapse, treatment failure (inverse of LFS), and mortality tended to be lower with etoposide (regardless of TBI dose) or with TBI doses ≥13 Gy. For both CR1 and CR2 transplantations, causes of death were similar among the groups; disease recurrence accounted for 47% of deaths. We conclude that for HLA-identical sibling allografts for acute lymphoblastic leukemia in CR2, there is an advantage in substituting etoposide for Cy or, when Cy is used, in increasing the TBI dose to ≥13 Gy.

Original languageEnglish (US)
Pages (from-to)438-453
Number of pages16
JournalBiology of Blood and Marrow Transplantation
Volume12
Issue number4
DOIs
StatePublished - Apr 2006

Bibliographical note

Funding Information:
Supported by Public Health Service grant no. U24-CA76518 from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Heart, Lung and Blood Institute; Office of Naval Research; Health Resources Services Administration (Department of Health and Human Services); and grants from AABB, Aetna; AIG Medical Excess; American Red Cross; Amgen, Inc.; an anonymous donation to the Medical College of Wisconsin; AnorMED, Inc.; Berlex Laboratories, Inc.; Biogen IDEC, Inc.; Blue Cross and Blue Shield Association; BRT Laboratories, Inc.; Celgene Corp.; Cell Therapeutics, Inc.; CelMed Biosciences; Cubist Pharmaceuticals; Dynal Biotech, LLC; Edwards Lifesciences RMI; Endo Pharmaceuticals, Inc.; Enzon Pharmaceuticals, Inc.; ESP Pharma; Fujisawa Healthcare, Inc.; Gambro BCT, Inc.; Genzyme Corporation; GlaxoSmithKline, Inc.; Histogenetics, Inc.; Human Genome Sciences; ILEX Oncology, Inc.; Kirin Brewery Company; Ligand Pharmaceuticals, Inc.; Merck & Company; Millennium Pharmaceuticals; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec; National Center for Biotechnology Information; National Leukemia Research Association; National Marrow Donor Program; NeoRx Corporation; Novartis Pharmaceuticals, Inc.; Novo Nordisk Pharmaceuticals; Ortho Biotech, Inc.; Osiris Therapeutics, Inc.; Pall Medical; Pfizer, Inc.; Pharmion Corp.; QOL Medical; Roche Laboratories; StemCyte, Inc.; Stemco Biomedical; StemSoft Software, Inc.; SuperGen, Inc.; Sysmex; The Marrow Foundation; THERAKOS, a Johnson & Johnson Co.; University of Colorado Cord Blood Bank; Valeant Pharmaceuticals; ViaCell, Inc.; ViraCor Laboratories; WB Saunders Mosby Churchill; and Wellpoint Health Network. The contents of this article are the responsibility of the authors and do not represent the official views of the National Cancer Institute.

Keywords

  • Acute lymphoblastic leukemia
  • Conditioning regimen
  • Cyclophosphamide
  • Etoposide
  • Sibling allografts
  • Total body irradiation

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