Risk of Posttransplant Cyclophosphamide-related Cardiotoxicity in Allogeneic Stem Cell Transplantation
Rayane Hadjali1, Florian Chevillon2, Benjamin Sibilia3
1Department of Cardiology, University Hospital of Lariboisière (AP-HP), Paris, France.
Insights
Post-transplant cyclophosphamide (PT-Cy) use in allogeneic stem cell transplants is linked to increased early cardiotoxicity, especially heart failure. Patients receiving PT-Cy require vigilant cardiovascular monitoring post-transplant.
Area of Science:
- Hematopoietic Stem Cell Transplantation
- Cardiovascular Medicine
- Immunosuppression Therapy
Background:
- Post-transplant cyclophosphamide (PT-Cy) is a standard immunosuppressive regimen for preventing graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (alloHSCT).
- Concerns exist regarding the potential cardiotoxicity associated with PT-Cy, necessitating further investigation into its early effects.
Purpose of the Study:
- To evaluate the association between PT-Cy administration and the occurrence of early cardiotoxicity within 100 days post-alloHSCT.
- To identify risk factors for early cardiotoxicity in patients undergoing alloHSCT.
Main Methods:
- A retrospective observational study was conducted on 1,381 patients who underwent alloHSCT.
- Early cardiotoxicity was defined as a composite endpoint including cardiovascular death, heart failure, myocarditis, pericardial disease, arrhythmias, and acute arterial events.
- Propensity-score matching and Fine-and-Gray subdistribution hazard models were used to analyze the association between PT-Cy and cardiotoxicity.
Main Results:
- 10% of patients experienced early cardiotoxicity within 100 days post-transplant, with heart failure being the most common event (53%).
- Independent predictors of early cardiotoxicity included older age, prior heart failure, prior cancer therapy-related cardiac dysfunction, hypertension, and PT-Cy administration.
- After propensity-score matching, PT-Cy remained significantly associated with an increased risk of cardiotoxicity (HR=2.00).
Conclusions:
- PT-Cy administration is independently associated with a higher risk of early cardiotoxicity, particularly heart failure, following alloHSCT.
- These findings highlight the critical need for early cardiovascular risk assessment and tailored surveillance strategies for patients receiving PT-Cy.
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.
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