Early Cardiac Events after Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide. Subanalysis exploring cardiac toxicity conducted on behalf of GETH-TC

Filipe R Pinto¹Enric Cascos²Estefanía Pérez-López³Mónica Baile-González³Carlos Martín Rodríguez³María Jesús Pascual Cascón⁴Marta Luque⁴Albert Esquirol⁵Carmen Martín⁶Felipe Peña-Muñóz⁷Inmaculada Heras⁸Itziar Oiartzabal Ormtegi⁹Adolfo Jesús Sáez Marín¹⁰Sara Fernández-Luis¹¹Juan José Domínguez-García¹¹Sara Villar Fernandez¹²Jose Luis Lopez Lorenzo¹³Miguel Fernández de Sanmamed Girón¹⁴Leslie González Pinedo¹⁴Lucía García¹⁵Ana Pilar Gonzalez-Rodriguez¹⁶Tamara Torrado¹⁷Silvia Filaferro¹⁸Pascual Basalobre¹⁸Alberto López-García¹³Guillermo Orti¹⁹Manuel Jurado Chacón^18,20Maria Queralt Salas^2*

• ¹Serviço de Hematologia Clínica, Unidade Local de Saúde de Santo António, Porto, Portugal
• ²Hospital Clinic of Barcelona, Barcelona, Catalonia, Spain
• ³Complejo Asistencial Universitario de Salamanca/IBSAL, Salamanca, Spain
• ⁴Hospital Regional Universitario de Málaga, Málaga, Spain
• ⁵Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain
• ⁶Hospital Reina Sofía de Córdoba, Cordova, Spain
• ⁷Catalan Institute of Oncology, Barcelona, Catalonia, Spain
• ⁸Hospital General Universitario Morales Meseguer, Murcia, Murcia, Spain
• ⁹Donostia University Hospital, San Sebastian, Spain
• ¹⁰Servicio de Hematología y Hemoterapia, Hospital Universitario 12 de Octubre, Madrid, Asturias, Spain
• ¹¹Marqués de Valdecilla University Hospital, Santander, Cantabria, Spain
• ¹²University Clinic of Navarra, Pamplona, Navarre, Spain
• ¹³University Hospital Fundación Jiménez Díaz, Madrid, Madrid, Spain
• ¹⁴University Hospital of Gran Canaria Dr. Negrin, Las Palmas de Gran Canaria, Spain
• ¹⁵Hospital Universitario Son Espases, Palma de Mallorca, Spain
• ¹⁶Central University Hospital of Asturias, Oviedo, Spain
• ¹⁷A Coruña University Hospital Complex (CHUAC), A Coruña, Spain
• ¹⁸Grupo Español de Trasplante de Progenitores Hematopoyéticos y Terapia Celular, Spain, Spain
• ¹⁹Vall d'Hebron University Hospital, Barcelona, Catalonia, Spain
• ²⁰Virgen de las Nieves University Hospital, Granada, Spain

This retrospective multicenter study investigates the incidence and predictors of early cardiac events (ECE) in haplo-HCT recipients treated with 50 mg/kg/day of PTCY. A cohort of 268 patients with acute myeloid leukemia (AML) treated with anthracycline-based induction therapies and undergoing their first haplo-HCT between 2011 and 2022 was analyzed. ECE included any new cardiac event within 100 days post-transplant, with cumulative incidence estimated considering death and relapse as competing events. The median patient age was 57 years (range:18–79). Pre-transplant comorbidities included hypertension (n=60, 22.4%), dyslipidemia (n=35, 13.1%), diabetes mellitus (n=18, 6.7%), and prior cardiac history (n=38, 14.2%) patients. ECE occurred in 23 (8.6%) patients, at a median of 19 days (IQR: 5-66), and with a day +100 cumulative incidence of 8.6% (95% CI: 6.1–12.3). Pericardial effusion/pericarditis (n=10, 43.5%), arrhythmias (n=7, 30.4%), and heart failure (n=4, 17.4%) were the most prevalent complications. Severe (CTCAE grade 3–4) events were observed in 30.4%, with four deaths (17.4%) directly attributed to ECE. Univariate analysis (UVA) identified dyslipidemia (HR: 3.87, p=0.001), hypertension (HR: 2.76, p=0.015), and moderate-severe veno-occlusive disease (HR: 4.94, p=0.002) as significant ECE predictors. ECE negatively impacted post-transplant outcomes, with lower overall survival (HR: 1.78, p=0.04) and higher non-relapse mortality (HR: 2.87, p=0.005). While ECE incidence following haplo-HCT with PTCY was low, its association with worse survival highlights the need for cardiovascular risk management and post-transplant cardiac monitoring to mitigate complications.