Risk of Posttransplant Cyclophosphamide-related Cardiotoxicity in Allogeneic Stem Cell Transplantation

BACKGROUND: Although posttransplant cyclophosphamide (PT-Cy) is currently widely used to prevent graft-vs-host disease after allogeneic hematopoietic stem cell transplantation (alloHSCT), concerns remain regarding its cardiotoxicity. The aim in this study was to assess the association between early cardiotoxicity occurring within the first 100 days posttransplant and PT-Cy. METHODS: We conducted a monocentric retrospective observational study including all consecutive patients who underwent alloHSCT at Saint Louis University Hospital between July 2011 and July 2023. The primary endpoint was a composite of early cardiotoxicity, including cardiovascular death, heart failure (HF), myocarditis, pericardial disease, cardiac arrhythmias, and acute arterial events. Propensity-score matching was performed to balance characteristics between patients who received posttransplant PT-Cy and those who did not. Predictors of early cardiotoxicity were analyzed using Fine and Gray subdistribution hazard models. RESULTS: Among 1381 patients, 143 (10%) experienced early cardiotoxicity within 100 days posttransplant. The most frequent events were HF (53%), cardiac arrhythmias (20%), and pericardial disease (19%). Age (subdistribution hazard ratio [sHR] 1.01, 95% confidence interval [CI] 1.00-1.03, P = 0.028), prior HF (sHR 2.02, 95% CI 1.04-3.93, P = 0.037), prior cancer therapy-related cardiac dysfunction (sHR 4.24, 95% CI 2.05-8.78, P < 0.001), hypertension (sHR 1.54, 95% CI 1.00-2.36, P = 0.047), and PT-Cy (sHR 1.62, 95% CI 1.07-2.44, P = 0.022) were independently associated with early cardiotoxicity. After 1:1 propensity-score matching, the administration of PT-Cy remained associated with cardiotoxicity (HR 2.00, 95% CI 1.05-3.80, P = 0.035). CONCLUSIONS: The administration of PT-Cy was independently associated with an increased risk of early cardiotoxicity, particularly HF. These results underscore the need for early cardiovascular risk assessment and tailored surveillance, particularly in patients receiving PT-Cy.