Cardiac toxicity after matched allogeneic hematopoietic cell transplant in the posttransplant cyclophosphamide era

Abstract

Graft-versus-host-disease (GVHD) is one of the leading causes of non-relapse mortality (NRM) following allogeneic hematopoietic cell transplantation (alloHCT). Post-transplant cyclophosphamide (PTCy) has shown promise in managing GVHD. However, cyclophosphamide has known cardiac toxicities and few studies have evaluated the cardiac toxicities that arise following PTCy. Here, we completed a retrospective analysis of matched alloHCT patients at our institution who received PTCy or non-PTCy-based GVHD prophylaxis, with the goal of determining the incidence of cardiac toxicities up to 100 days after alloHCT. We included 585 patients in our analysis and found that 38 patients (6.5%) experienced cardiac toxicities after alloHCT. The toxicities observed included arrhythmias (n=21), heart failure (n=14), pericardial effusions (n=10), and myocardial infarction or ischemia (n=7). Patients who received PTCy had a 7.4% incidence of cardiac toxicities, while non-PTCy patients had an incidence of 5.8% (p=0.4). We found that age > 55 years (p=0.02), history of hypertension (p=0.01), arrhythmia (p=0.003), diabetes (p=0.04), and cardiac comorbidities (p<0.001) were significant predictors of cardiac toxicity, while none of the preparative and GVHD prophylaxis regimens used were predictive of cardiac toxicity. From these findings, we proposed the use of a Cardiac Risk Stratification Score to quantify the risk of cardiac toxicity following alloHCT and found that a higher score correlated with cardiac toxicity incidence. Furthermore, the development of cardiac toxicity was associated with worse 1-yr overall survival (OS) and NRM while the use of PTCy was associated with improvements in 1-year OS and NRM rates.

Posttransplant cyclophosphamide versus antithymocyte globulin in patients with acute lymphoblastic leukemia treated with allogeneic hematopoietic cell transplantation from matched unrelated donors: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…Longer follow‐up is needed to evaluate potential late events; however, it appears that PTCY is at least equally as effective as ATG in the prevention of GVHD‐related deaths. In contrast to ATG, the use of high doses of cyclophosphamide may be associated with severe organ complications, including cardiotoxicity and hemorrhagic cystitis 37,38 . However, in our study population, such events have not been reported as reasons for death.…”

Prediction of Nonrelapse Mortality in Patients With Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia Receiving Allogeneic Stem Cell Transplantation With Posttransplantation Cyclophosphamide-based Graft Versus Host Disease Prophylaxis

“…Pretransplant cardiac toxicity was reported to be associated with age >55 years, history of hypertension, arrhythmia, and diabetes, but this association was independent of GVHD prophylaxis used, contradicting earlier reported PTCY-based cardiac toxicity. 31 These findings are in contrast to the retrospective observation that patients treated with PTCY developed more cardiac events during the first 100 days posttransplant than patients in the non-PTCY group. 32 Using a composite risk model of cardiovascular comorbidities might further improve prediction of NRM, which has been reported recently.…”

Long-Term Health Effects of Curative Therapies on Heart, Lungs, and Kidneys for Individuals with Sickle Cell Disease Compared to Those with Hematologic Malignancies

“…Long-term HSCT survivors are also at increased risk for multiple cardiovascular risk factors such as hypertension, obesity, dyslipidemia, constrictive pericarditis, congestive heart failure, cardiomyopathy, conduction abnormalities, and valvular heart disease; prior chest radiotherapy increases the risk for many of these complications [ 43 , 55 ]. Recently, Yeh and colleagues reported cardiac comorbidities, older age, hypertension, diabetes, and arrhythmia were associated with increased risk for cardiac toxicity following HSCT; on the other hand, post-transplant cyclophosphamide was not [ 56 ].…”