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.
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Data from this study can be made available upon reasonable request from the corresponding author.
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Acknowledgements
We thank Nicole Raus and Viviane Fossat, data manager from the SFGM-TC. Medical writing for this manuscript was assisted by MPIYP (MC Béné), Paris, France.
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MJ and PC designed the study, interpreted the data and wrote the manuscript. MJ performed all the statistical analysis. All coauthors contributed data to the EBMT registry, reviewed the article, and approved the final version. PC and MJ conceived and designed the study, interpreted the results and drafted the manuscript. MJ performed the statistical analyses and generated the figures. EB, ED, ML, AB, HLW, AH, AST, AC, PT, FB, RD, JOB, MS, PCe, MA, LS, TM, MTR, EF, JC, SC, CEB, AV, AG, PP, ALB, TG, contributed to patient care and data collection. All authors critically revised the manuscript and approved the final version.
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Jullien, M., Brissot, E., Daguindau, E. et al. 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). https://doi.org/10.1038/s41409-025-02709-9
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DOI: https://doi.org/10.1038/s41409-025-02709-9
