Cardiac Toxicities after HLA-Matched Allogeneic Hematopoietic Cell Transplantation (Allo-HCT): Post-Transplant Cyclophosphamide (PTCy) Is Not Associated with Higher Incidence of Cardiotoxicity

Abstract

<h3>Introduction</h3> PTCy-based GVHD prophylaxis has emerged as an effective method in Allo-HCT. Cyclophosphamide has historically been associated with increased rates of cardiac toxicities. This potential complication plays a role in the choice of optimal GVHD prophylaxis. The cardiac toxicity profile of PTCy compared with non-PTCy GVHD prophylaxis in HLA-matched Allo-HCT setting is unclear. <h3>Methods</h3> We performed a retrospective analysis to evaluate cardiac toxicities after HLA-matched Allo-HCT between October 1, 2016 and April 1, 2019. Cardiac toxicity was defined as any documented arrhythmia, heart failure, cardiac event (cardiac arrest or myocardial infarction), pericarditis, or pericardial effusion that occurred between Day 0 and 100. <h3>Results</h3> A total of 585 consecutive adult patients met eligibility (Table 1). 38 unique patients developed a total of 52 cardiac toxicities. The median time to cardiac toxicity was 20 days in the PTCy and 15 days in the non-PTCy groups. Toxicities (Table 2) included arrhythmias (40%), heart failure (27%), pericardial effusions (19%), and cardiac events (13%). This distribution and severity of toxicity was comparable between groups. Similarly the cumulative incidence of cardiac toxicity was comparable between the PTCy and non-PTCy groups (7 vs. 6%, p=0.4). Predictors of cardiac toxicity are shown in table 1. In univariate analysis, the cardiac comorbidity composite (defined as the presence of arrhythmia, cardiac, or heart valve comorbidities obtained via HCT-CI score) was found to be the most significant predictor for the development of cardiac toxicity (p<0.001). This effect was consistent in the PTCy (5 vs 19%, p=0.006) and non-PTCy (3 vs 18%, p<0.001) groups. In multivariate analysis, the cardiac comorbidity composite maintained significance and this effect was augmented by the presence of diabetes and infection. Patients with the cardiac comorbidity composite who also had diabetes or infection had the highest incidence (37%, p<0.001) of toxicity compared with those who only had cardiac comorbidities (7%). In patients without the cardiac comorbidity composite, a matched unrelated donor (MUD) was associated with higher incidence of cardiac toxicity (6 vs 1%, p=0.02). One year survival since the development of toxicity was superior (62 vs 33%, p=0.04) for the PTCy group (Figure 1). <h3>Conclusion</h3> Our results demonstrate a low incidence of cardiac toxicity. Baseline cardiac comorbidities are associated with higher incidence of developing cardiac toxicities after Allo-HCT. PTCy-based GVHD prophylaxis does not appear to impact the development of cardiac toxicities after HLA-matched Allo-HCT and may be associated with survival benefit in patients who do experience toxicity.