Abstract
Post-transplant cyclophosphamide (PTCY) is increasingly used as effective graft-versus-host disease (GvHD) prophylaxis in allogeneic hematopoietic-cell transplantation (allo-HCT). However, PTCY is associated with toxicities. Whether patients with specific comorbidities are more vulnerable to cyclophosphamide-induced toxicity is unclear. We retrospectively evaluated the impact of individual organ dysfunctions for non-relapse mortality (NRM) risk and overall survival (OS) among 5888 adults who underwent PTCY-based allo-HCT for acute myeloid leukemia between 2010 and 2023. In multivariable analyses 5 of the comorbidities (renal, moderate/severe hepatic, cardiac including arrhythmia/valvular disease, severe pulmonary, infection) were independently associated with adverse NRM and OS without influencing relapse rate. A simplified model using the absence (n = 4390), presence of 1 (n = 1229) or presence of 2 or 3 (n = 269) of the comorbidities which were determined individually to contribute to NRM stratified patients into 3 NRM risk (16.2% vs. 21.6% vs. 36%, retrospectively) and OS categories (64% vs. 56% vs. 36.4%, retrospectively). In Cox model, recipients with 2 or 3 comorbidities had an increased hazard ratio for NRM of 2.38 (95% confidence interval [CI], 1.89–3) and for OS of 1.96 (95% CI 1.64–2.33). Whether patients with concomitant diagnoses, as determined here, may benefit from a reduced PTCY dose remains to be evaluated in prospective clinical trials.
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Acknowledgements
We thank the ALWP EBMT staff in the Paris office for data management. The study was accomplished thanks to the contributing centers of the EBMT registry which provided patient data; a complete list appears in the Supplementary Appendix.
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All authors contributed substantially to the manuscript. AS, ML, FC, MM and BPS contributed to the study conception and design as well as to data analysis, or interpretation. ML provided statistical oversight and guidance. AK, DB, AB, SS, AMR, JV, GC, MR, JS, MIR, PB, AE, YK, EB, AN provided patient data and critical feedback. AS drafted the manuscript and all authors critically revised and approved it. Following EBMT publication rules, co-authorship was offered to centers contributing the highest number of patients.
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Spyridonidis, A., Labopin, M., Savani, B.P. et al. The impact of individual comorbidities in transplant recipients receiving post-transplant cyclophosphamide. Bone Marrow Transplant 60, 499–506 (2025). https://doi.org/10.1038/s41409-025-02514-4
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DOI: https://doi.org/10.1038/s41409-025-02514-4
