Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission: comparison of intravenous busulfan plus cyclophosphamide (Cy) versus total-body irradiation plus Cy as conditioning regimen--a report from the acute leukemia working party of the European group for blood and marrow transplantation

J Clin Oncol. 2013 Oct 1;31(28):3549-56. doi: 10.1200/JCO.2013.48.8114. Epub 2013 Aug 26.

Abstract

Purpose: Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable bioavailability and a safer toxicity profile than the oral formulation. Comparative studies of outcomes have been performed between oral Bu/Cy and Cy/TBI, but there have been no comparative trials in the era of IV Bu.

Patients and methods: We performed a retrospective registry-based study comparing outcomes of patients with AML in first or second remission after alloSCT from sibling donors who underwent IV Bu/Cy (n = 795) or Cy/TBI (n = 864) conditioning.

Results: Engraftment rate was 98% and 99% after IV Bu/Cy and Cy/TBI, respectively. Grade 2 to 4 acute graft-versus-host disease (GVHD) was significantly lower in the IV Bu/Cy compared with Cy/TBI group (P < .001). Similarly, chronic GVHD was significantly lower in the IV Bu/Cy compared with Cy/TBI group (P = .003). Cumulative incidence of 2-year nonrelapse mortality (NRM; ± standard deviation [SD]) was 12% ± 1% in the IV Bu/Cy group and 15% ± 2% in the Cy/TBI group (P = .14), and 2-year relapse incidence (RI; ± SD) was 26% ± 3% and 21% ± 1%, respectively (P = .012). Leukemia-free survival (LFS) rate (± SD) was 61% ± 2% after IV Bu/Cy and 64% ± 2% after Cy/TBI (P = .27). In multivariable analysis, adjusting for differences between both groups, patients who received IV Bu/Cy had lower acute and chronic GVHD, higher RI, and a trend toward lower NRM. LFS was not statistically different between the two conditioning regimens.

Conclusion: This retrospective study shows that final outcomes after myeloablative conditioning using IV Bu/Cy were not statistically different from those after Cy/TBI.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Busulfan / administration & dosage
  • Chemoradiotherapy
  • Cyclophosphamide / administration & dosage
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Injections, Intravenous
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy*
  • Neoplasm Staging
  • Prognosis
  • Remission Induction
  • Retrospective Studies
  • Survival Rate
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Whole-Body Irradiation*
  • Young Adult

Substances

  • Cyclophosphamide
  • Busulfan