f22b9bfe6488aea17df9c0cab0e9a10c 329185.pdf e2f60586c9a1c7a055d127ec28136d3d2c02438a 329185.pdf b7315a2ac3682057772656f6fb1c8a0807250c51eb39a0d8f2d25a8aee771c91 329185.pdf Title: Safety of Post-Transplant Cyclophosphamide-Based Prophylaxis in AML Patients with Pre-Existing Cardiac Morbidity Undergoing Allogeneic Hematopoietic Cell Transplantation Subject: Background: Post-transplant cyclophosphamide (PTCy) is a standard graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT). While effective, concerns remain about cyclophosphamide-related cardiotoxicity, especially in patients with pre-existing cardiac morbidity, a population often underrepresented in clinical trials. Objectives: To assess the incidence and outcomes of early (ECE,100 days) and late (LCE, >100 days) cardiac events in acute myeloid leukemia (AML) patients with and without baseline cardiac morbidity undergoing allo-HCT with PTCy. StudyDesign: Retrospective multicenter study by the Grupo Español de Trasplante Hematopoyético y Terapia Celular (GETH-TC) including 461 AML patients (62 with cardiac morbidity) transplanted between 2012 and 2022. Cardiac morbidity was defined by documented cardiac disease or left ventricular ejection fraction < 45%. Cumulative incidence, overall survival (OS), and non-relapse mortality (NRM) were analyzed using competing risks models and adjusted with propensity score matching (PSM) and inverse probability weighting (IPW). Results: Cardiac events occurred in 13.2% of patients: 11% vs. 7% ECE (p = 0.93) and 8% vs. 5.3% LCE (p = 0.85) in those with vs. without cardiac morbidity. Most ECEs were arrhythmias or heart failure. Adjusted analyses confirmed no significant differences in CE incidence, OS, or NRM between groups. Two-year OS was 69% vs. 70% (p = 0.50); NRM was 18% vs. 17% (p = 0.20). ECE was associated with higher mortality in both groups. Conclusions: PTCy is feasible in AML patients with pre-existing cardiac morbidity when combined with comprehensive cardiovascular evaluation and cardio-oncology follow-up, supporting its safe use in broader patient populations with appropriate cardiologic support. Keywords: acute mieloid leukemia; cardio-oncology; cardiotoxicity; post-transplant cyclophosphamide Author: Arnau Torrent-Rodríguez, Enric Cascos, Víctor Navarro Garcés, Estefanía Pérez-López, Mónica Baile-González, Carlos Martín Rodríguez, María Jesús Pascual Cascón, Marta Luque, Albert Esquirol, Carmen Martín Calvo, Felipe Peña-Muñoz, Inmaculada Heras Fernando, Itziar Oiartzabal Ormtegi, Adolfo Jesús Sáez Marín, Sara Fernández-Luis, Juan José Domínguez-García, Sara Villar Fernández, José Luis López Lorenzo, Miguel Fernández de Sanmamed Girón, Leslie González Pinedo, Lucía García-Maño, Ana Pilar González-Rodriguez, Tamara Torrado, Silvia Filaferro, Pascual Basalobre, Guillermo Ortí, Montserrat Rovira, Manuel Jurado Chacón and María Queralt Salas Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Fri Sep 26 10:33:27 2025 CEST ModDate: Fri Sep 26 10:44:02 2025 CEST Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1421827 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- NQWMNC+URWPalladioL-Roma Type 1 Custom yes yes yes 111 0 HQBQWV+VnURWPalladioL Type 1 Custom yes yes yes 112 0 OUGEKC+URWPalladioL-Ital Type 1 Custom yes yes yes 113 0 ZEOOXN+URWPalladioL-Bold Type 1 Custom yes yes yes 114 0 VBAQIR+CMSY10 Type 1 Builtin yes yes yes 151 0 HBUSZR+EURM10 Type 1 Builtin yes yes yes 177 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 192 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 213 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 214 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 247 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 248 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-06-24 04:09:06 CEST RepresentationInformation: 329185.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-06-23 11:38:02 CEST Size: 1421827 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 412 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Methods Children: Item: Title: Study Design and Patient Selection Item: Title: Prior Cardiac Morbidity, Pre-Transplant Cardiac Evaluations and Main Definitions Item: Title: Allo-HCT Information and Main Definitions Item: Title: Endpoint Definition Item: Title: Statistical Analysis Item: Title: Results Children: Item: Title: Patients Characteristics and Allo-HCT Information Item: Title: Cumulative Incidence of Early and Late Cardiac Events Item: Title: Efficacy Outcomes Item: Title: Discussion Item: Title: Conclusions Item: Title: References Info: Title: Safety of Post-Transplant Cyclophosphamide-Based Prophylaxis in AML Patients with Pre-Existing Cardiac Morbidity Undergoing Allogeneic Hematopoietic Cell Transplantation Author: Arnau Torrent-Rodríguez, Enric Cascos, Víctor Navarro Garcés, Estefanía Pérez-López, Mónica Baile-González, Carlos Martín Rodríguez, María Jesús Pascual Cascón, Marta Luque, Albert Esquirol, Carmen Martín Calvo, Felipe Peña-Muñoz, Inmaculada Heras Fernando, Itziar Oiartzabal Ormtegi, Adolfo Jesús Sáez Marín, Sara Fernández-Luis, Juan José Domínguez-García, Sara Villar Fernández, José Luis López Lorenzo, Miguel Fernández de Sanmamed Girón, Leslie González Pinedo, Lucía García-Maño, Ana Pilar González-Rodriguez, Tamara Torrado, Silvia Filaferro, Pascual Basalobre, Guillermo Ortí, Montserrat Rovira, Manuel Jurado Chacón and María Queralt Salas Subject: Background: Post-transplant cyclophosphamide (PTCy) is a standard graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT). While effective, concerns remain about cyclophosphamide-related cardiotoxicity, especially in patients with pre-existing cardiac morbidity, a population often underrepresented in clinical trials. Objectives: To assess the incidence and outcomes of early (ECE,100 days) and late (LCE, >100 days) cardiac events in acute myeloid leukemia (AML) patients with and without baseline cardiac morbidity undergoing allo-HCT with PTCy. StudyDesign: Retrospective multicenter study by the Grupo Español de Trasplante Hematopoyético y Terapia Celular (GETH-TC) including 461 AML patients (62 with cardiac morbidity) transplanted between 2012 and 2022. Cardiac morbidity was defined by documented cardiac disease or left ventricular ejection fraction < 45%. Cumulative incidence, overall survival (OS), and non-relapse mortality (NRM) were analyzed using competing risks models and adjusted with propensity score matching (PSM) and inverse probability weighting (IPW). Results: Cardiac events occurred in 13.2% of patients: 11% vs. 7% ECE (p = 0.93) and 8% vs. 5.3% LCE (p = 0.85) in those with vs. without cardiac morbidity. Most ECEs were arrhythmias or heart failure. Adjusted analyses confirmed no significant differences in CE incidence, OS, or NRM between groups. Two-year OS was 69% vs. 70% (p = 0.50); NRM was 18% vs. 17% (p = 0.20). ECE was associated with higher mortality in both groups. Conclusions: PTCy is feasible in AML patients with pre-existing cardiac morbidity when combined with comprehensive cardiovascular evaluation and cardio-oncology follow-up, supporting its safe use in broader patient populations with appropriate cardiologic support. 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