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<p>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 (<i>n</i> = 4390), presence of 1 (<i>n</i> = 1229) or presence of 2 or 3 (<i>n</i> = 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.</p>

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The impact of individual comorbidities in transplant recipients receiving post-transplant cyclophosphamide

  • 期刊论文

  • 发表日期：

    2025年2月5日

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  • Alexandros Spyridonidis,
  • Myriam Labopin,
  • Bipin P. Savani,
  • Alexander Kulagin,
  • Didier Blaise,
  • Annoek E. C. Broers,
  • Simona Sica,
  • Anna Maria Raiola,
  • Jan Vydra,
  • Goda Choi,
  • Montserrat Rovira,
  • Mi Kwon,
  • Jaime Sanz,
  • Maija Itäla-Remes,
  • Peter von dem Borne,
  • Albert Esquirol,
  • Yener Koc,
  • Eolia Brissot,
  • Arnon Nagler,
  • Mohamad Mohty,
  • Fabio Ciceri

摘要

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.