Thiotepa-busulfan-fludarabine compared to clofarabine-based conditioning for haploidentical transplant with posttransplant cyclophosphamide in patients with myeloid malignancies: a retrospective study from the SFGM-TC

Bone Marrow Transplant. 2025 Dec;60(12):1592-1600. doi: 10.1038/s41409-025-02709-9. Epub 2025 Sep 15.

Abstract

The optimal reduced-intensity conditioning (RIC) regimen for haploidentical hematopoietic stem cells transplantation (haplo-HSCT) using post-transplant cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis has yet to be determined. Potential RIC regimen for haplo-HSCT in myeloid malignancies include Clofarabine-Baltimore (CloB) and TBF (thiotepa-busulfan-fludarabine). This multicenter retrospective study compared 297 adult patients receiving CloB (n = 59) or TBF (n = 238). The main diagnoses were acute myeloid leukemia (63%), 36% having adverse risk features. Median follow-up was 22.7 months. No significant differences were observed in overall (OS), progression-free (PFS), or GVHD-free relapse-free survival. However, 2-year non-relapse mortality (NRM) was higher after TBF (34% vs 21%, HR: 0.38; 95%CI: 0.20-0.75, p = 0.005), although the relapse incidence was lower (13% vs 23%, HR: 1.94; 95%CI: 0.98-3.87, p = 0.059). A 1:1 propensity score matching allowed the comparison of 53 CloB with 53 TBF. CloB was associated with improved 2-year OS (63% vs 44%, p = 0.02) due to a higher 2-year NRM in the TBF group (48% vs 19%, p = 0.002). By multivariate analysis, CloB remained associated with better OS (HR 0.52, 95% I 0.28-0.99, p = 0.045) and TBF with higher NRM (HR 3.43, 95%CI 1.59-7.41, p = 0.002). These results suggest that CloB is superior to TBF as a RIC regimen prior to haplo-HSCT.

Publication types

  • Multicenter Study
  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Busulfan* / administration & dosage
  • Busulfan* / pharmacology
  • Busulfan* / therapeutic use
  • Clofarabine* / administration & dosage
  • Clofarabine* / pharmacology
  • Clofarabine* / therapeutic use
  • Cyclophosphamide* / administration & dosage
  • Cyclophosphamide* / pharmacology
  • Cyclophosphamide* / therapeutic use
  • Female
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Leukemia, Myeloid, Acute* / therapy
  • Male
  • Middle Aged
  • Retrospective Studies
  • Thiotepa* / administration & dosage
  • Thiotepa* / pharmacology
  • Thiotepa* / therapeutic use
  • Transplantation Conditioning / methods
  • Transplantation, Haploidentical / methods
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Vidarabine / pharmacology
  • Vidarabine / therapeutic use
  • Young Adult

Substances

  • Busulfan
  • Clofarabine
  • Cyclophosphamide
  • fludarabine
  • Thiotepa
  • Vidarabine