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Early Cardiac Toxicity Associated With Post-Transplant Cyclophosphamide in Allogeneic Stem Cell Transplantation
Rémy Duléry1,2,3, Razan Mohty1, Myriam Labopin1,4
1Department of Clinical Hematology and Cellular Therapy, Saint Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Insights
Post-transplant cyclophosphamide (PT-Cy) increases early cardiac events (ECE) after haploidentical stem cell transplants. Patients experiencing cardiac events post-transplant have reduced survival, highlighting risks for older adults.
Area of Science:
- Hematopoietic Stem Cell Transplantation
- Cardiology
- Immunosuppression
Background:
- Post-transplant cyclophosphamide (PT-Cy) is standard for haploidentical HSCT to prevent graft-versus-host disease.
- Data on PT-Cy's cardiac risks are limited.
Purpose of the Study:
- To determine the incidence and clinical characteristics of cardiac events following PT-Cy.
Main Methods:
- Compared outcomes in 136 PT-Cy patients versus 195 non-PT-Cy patients.
- Focused on early cardiac events (ECE) within 100 days post-HSCT.
- All patients underwent systematic cardiac monitoring.
Main Results:
- ECE incidence was 19% with PT-Cy vs. 6% without (p<0.001).
- Common ECE included left ventricular dysfunction, pulmonary edema, pericarditis, and arrhythmias.
- PT-Cy use, older age, and prior cyclophosphamide exposure increased ECE risk.
Conclusions:
- PT-Cy is linked to increased early cardiac events post-HSCT.
- Cardiac events after HSCT negatively impact overall survival.
- Patient selection for PT-Cy should consider cardiac risk, especially for older adults or those with prior cyclophosphamide exposure.
Background:
Post-transplant cyclophosphamide (PT-Cy) has become a standard of care in haploidentical hematopoietic stem cell transplantation (HSCT) to reduce the risk of graft-versus-host disease. However, data on cardiac events associated with PT-Cy are scarce.
Objectives:
This study sought to assess the incidence and clinical features of cardiac events associated with PT-Cy.
Methods:
The study compared clinical outcomes between patients who received PT-Cy (n = 136) and patients who did not (n = 195), with a focus on early cardiac events (ECE) occurring within the first 100 days after HSCT. All patients had the same systematic cardiac monitoring.
Results:
The cumulative incidence of ECE was 19% in the PT-Cy group and 6% in the no-PT-Cy group (p < 0.001). The main ECE occurring after PT-Cy were left ventricular systolic dysfunction (13%), acute pulmonary edema (7%), pericarditis (4%), arrhythmia (3%), and acute coronary syndrome (2%). Cardiovascular risk factors were not associated with ECE. In multivariable analysis, the use of PT-Cy was associated with ECE (hazard ratio: 2.7; 95% confidence interval: 1.4 to 4.9; p = 0.002]. Older age, sequential conditioning regimen, and Cy exposure before HSCT were also associated with a higher incidence of ECE. Finally, a history of cardiac events before HSCT and ECE had a detrimental impact on overall survival.
Conclusions:
PT-Cy is associated with a higher incidence of ECE occurring within the first 100 days after HSCT. Patients who have a cardiac event after HSCT have lower overall survival. These results may help to improve the selection of patients who are eligible to undergo HSCT with PT-Cy, especially older adult patients and patients with previous exposure to Cy.
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