Total body irradiation versus busulfan based intermediate intensity conditioning for stem cell transplantation in ALL patients >45 years-a registry-based study by the Acute Leukemia Working Party of the EBMT

Bone Marrow Transplant. 2023 Aug;58(8):874-880. doi: 10.1038/s41409-023-01966-w. Epub 2023 May 5.

Abstract

Allogeneic hematopoietic cell transplantation is a potentially curative treatment in high-risk acute lymphoblastic leukemia (ALL). Conditioning regimens based on ≥12 Gray total body irradiation (TBI) represent the current standard in patients ≤45 years, whereas elderly patients frequently receive intermediate intensity conditioning (IIC) to reduce toxicity. To evaluate the role of TBI as a backbone of IIC in ALL, a retrospective, registry-based study included patients >45 years transplanted from matched donors in first complete remission, who had received either fludarabine/TBI 8 Gy (FluTBI8, n = 262), or the most popular, irradiation-free alternative fludarabine/busulfan, comprising busulfan 6.4 mg/kg (FluBu6.4, n = 188) or 9.6 mg/kg (FluBu9.6, n = 51). At two years, overall survival (OS) was 68.5%, 57%, and 62.2%, leukemia-free survival (LFS) was 58%, 42.7%, and 45%, relapse incidence (RI) was 27.2%, 40%, and 30.9%, and non-relapse-mortality (NRM) was 23.1%, 20.7%, and 26.8% for patients receiving FluTBI8Gy, FluBu6.4, and FluBu9.6, respectively. In multivariate analysis, the risk of NRM, acute and chronic graft-versus-host disease was not influenced by conditioning. However, RI was higher after FluBu6.4 (hazard ratio [HR] [95% CI]: 1.85 [1.16-2.95]), and LFS was lower after both FluBu6.4 (HR: 1.56 [1.09-2.23]) and FluBu9.6 (HR: 1.63 [1.02-2.58]) as compared to FluTBI8. Although only resulting in a non-significant advantage in OS, this observation indicates a stronger anti-leukemic efficacy of TBI-based intermediate intensity conditioning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Busulfan / therapeutic use
  • Graft vs Host Disease*
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Leukemia, Myeloid, Acute* / therapy
  • Recurrence
  • Registries
  • Retrospective Studies
  • Stem Cell Transplantation
  • Transplantation Conditioning / methods
  • Whole-Body Irradiation

Substances

  • Busulfan