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.

Chaim Sheba Medical Center Department of Hematology Tel Hashomer Israel

Erasmus MC Cancer Institute Rotterdam Netherlands

Hematology BMT and Institute of Cellular Therapy University of Patras Patras Greece

Hospital Clinic Barcelona Spain

Hospital Santa Creu i Sant Pau Barcelona Spain

Institute of Hematology and Blood Transfusion Prague Czech Republic

IRCCS Ospedale Policlinico San Martino Genova Italy

IRCCS Ospedale San Raffaele s r l Milano Italy

Leiden University Medical Hospital Leiden Netherlands

Medicana International Hospital Istanbul Istanbul Turkey

Programme de Transplantation and Therapie Cellulaire Marseille France

RM Gorbacheva Research Institute Pavlov University St Petersburg Russian Federation

Saint EBMT Unit Sorbonne University Antoine Hospital AP HP INSERM UMRs 938 Paris France

Servicio de Hematología Hospital Gral Univ Gregorio Marañon Madrid Spain

Sorbonne University Saint Antoine Hospital Paris France

Turku University Hospital Turku Finland

Universita Cattolica S Cuore Rome Italy

University Hospital La Fe Departament de Medicine Universitat de Valencia Valencia Spain

University Medical Center Groningen Groningen Netherlands

Vanderbilt University Medical Center Department of Hematology Nashville TN USA

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