Total body irradiation versus thiotepa/busulfan-based conditioning regimens for myeloablative allogeneic stem cell transplantation in adults with acute lymphoblastic leukemia

Bone Marrow Transplant. 2024 Aug;59(8):1137-1145. doi: 10.1038/s41409-024-02298-z. Epub 2024 May 16.

Abstract

Total body irradiation (TBI)-based conditioning regimens are generally recommended for allogeneic HSCT (allo-HSCT) in patients with acute lymphoblastic leukemia (ALL). Recent evidence suggests that modern chemotherapy-based regimens may be as effective. This multicenter retrospective study compared the clinical outcomes of myeloablative allo-HSCT with thiotepa, busulfan, and cyclophosphamide/fludarabine (TTB) to TBI-based conditioning. Between 2002 to 2018, 63 and 114 patients received TTB- and TBI-based conditioning regimens, respectively. The 5-year cumulative incidence of relapse was lower in the TBI cohort compared to the TTB cohort (30% [95% CI, 22-38] versus 47% [95% CI, 36-59]; P = 0.03). Multivariate analysis identified T-ALL, Ph-negative B-ALL, and measurable residual disease associated with a higher relapse risk. The 5-year cumulative incidence of non-relapsed mortality (NRM) was significantly lower with TTB (12% [95% CI, 5-20]) compared to TBI (25% [95% CI, 18-33]) (P = 0.001). Multivariate analysis found TBI conditioning, older age, and advanced stages of ALL at transplantation associated with a higher NRM. No statistical difference was seen in overall survival (49% [95% CI, 40-58] and 46% [95% CI, 35-60]) in the TBI and TTB groups, respectively; P = 0.9). The study suggests that TTB-based conditioning may be a promising option for ALL patients undergoing allo-HSCT, as it resulted in similar OS and lower NRM than TBI-based conditioning.

Publication types

  • Multicenter Study
  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Busulfan* / administration & dosage
  • Busulfan* / therapeutic use
  • Female
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Male
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Retrospective Studies
  • Thiotepa* / administration & dosage
  • Thiotepa* / therapeutic use
  • Transplantation Conditioning* / methods
  • Transplantation, Homologous / methods
  • Whole-Body Irradiation* / methods
  • Young Adult

Substances

  • Busulfan
  • Thiotepa