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

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

doi:10.1016/j.jaccao.2021.02.011

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

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

Authors

Rémy Duléry^{1

2

3}, Razan Mohty¹, Myriam Labopin^{1

4}, Simona Sestili¹, Florent Malard^{1

2

3}, Eolia Brissot^{1

2

3}, Giorgia Battipaglia¹, Clémence Médiavilla¹, Anne Banet^{1

2}, Zoé Van de Wyngaert^{1

2}, Annalisa Paviglianiti¹, Ramdane Belhocine¹, Françoise Isnard¹, Simona Lapusan¹, Rosa Adaeva¹, Anne Vekhoff¹, Tounes Ledraa¹, Ollivier Legrand^{1

2}, Ariel Cohen^{2

5}, Agnès Bonnin¹, Stéphane Ederhy⁵, Mohamad Mohty^{1

2

3}

Affiliations

¹ Department of Clinical Hematology and Cellular Therapy, Saint Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
² Department of Hematology, Sorbonne University, Paris, France.
³ National Institute of Health and Medical Research (INSERM) Joint Research Units (UMRs) 938, Saint Antoine Research Center, Paris, France.
⁴ Acute Leukemia Working Party, European Society for Blood and Marrow Transplantation (Paris Study Office/CEREST-TC), Paris, France.
⁵ Department of Cardiology, UNICO-GRECO Cardio-oncology Program, Sorbonne University, Saint Antoine Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.

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.