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. 2021 Jun 15;3(2):250-259.
doi: 10.1016/j.jaccao.2021.02.011. eCollection 2021 Jun.

Early Cardiac Toxicity Associated With Post-Transplant Cyclophosphamide in Allogeneic Stem Cell Transplantation

Rémy Duléry  1   2   3 , Razan Mohty  1 , Myriam Labopin  1   4 , Simona Sestili  1 , Florent Malard  1   2   3 , Eolia Brissot  1   2   3 , Giorgia Battipaglia  1 , Clémence Médiavilla  1 , Anne Banet  1   2 , Zoé Van de Wyngaert  1   2 , Annalisa Paviglianiti  1 , Ramdane Belhocine  1 , Françoise Isnard  1 , Simona Lapusan  1 , Rosa Adaeva  1 , Anne Vekhoff  1 , Tounes Ledraa  1 , Ollivier Legrand  1   2 , Ariel Cohen  2   5 , Agnès Bonnin  1 , Stéphane Ederhy  5 , Mohamad Mohty  1   2   3
Affiliations

Early Cardiac Toxicity Associated With Post-Transplant Cyclophosphamide in Allogeneic Stem Cell Transplantation

Rémy Duléry et al. JACC CardioOncol. .

Abstract

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.

Keywords: CI, confidence interval; CVD, cardiovascular disease; CVRF, cardiovascular risk factor; Cy, cyclophosphamide; ECE, early cardiac events; GRFS, graft-versus-host disease-free, relapse-free survival; GVHD, graft-versus-host disease; HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; LVEF, left ventricular ejection fraction; LVSD, left ventricular systolic dysfunction; PT-Cy, post-transplant cyclophosphamide; allogeneic stem cell transplantation; cardiotoxicity; haploidentical transplantation; left ventricular systolic dysfunction; post-transplant cyclophosphamide.

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Conflict of interest statement

This study was supported by the Association for Training, Education and Research in Hematology, Immunology, and Transplantation (ATERHIT). Drs. Duléry, Mohty, and Malard have received honoraria for lectures from Keocyt and Sanofi, whose drugs were included in this study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Central Illustration
Central Illustration
Impact of Post-Transplant Cyclophosphamide on Early Cardiac Events and Overall Survival According to the Occurrence of These Cardiac Events Post-transplant cyclophosphamide reduces the incidence of acute graft-versus-host disease. However, patients who receive post-transplant cyclophosphamide have a higher incidence of cardiac events within the first 100 days after allogeneic stem cell transplantation compared with patients who do not. Kaplan-Meier estimates (with a landmark analysis on day 100) show the detrimental impact of early cardiac events on overall survival. The 2-year overall survival was 47% in patients who had cardiac events compared with 72% in patients who did not (p = 0.046). CI = confidence interval; HR = hazard ratio.
See this image and copyright information in PMC

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