Cardiac Toxicity in Recipients of Hematopoietic Stem Cell Transplant with Post Transplant Cyclophosphamide

Background: Cardiac adverse events (AEs) are a significant concern in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), particularly after the adoption of post-transplant cyclophosphamide (PTCY). We examined the incidence and characterization of cardiac AEs in recipients of HSCT with PTCY at our center. Patients were treated on seven prospective clinical trials utilizing PTCY. The majority of patients were treated with the previously described two-step platform. The two-step HSCT approach isolates the graft's lymphoid and myeloid components, enabling a constant T cell dosage and protects the stem cells from cyclophosphamide's effects. Patients receive conditioning regimen, followed by 2 x 10*8/kg DLI (step 1). After 2 days, patients receive cyclophosphamide 60 mg/kg/day for 2 days. Finally, patients receive a CD34 selected stem cell graft (step 2) Methods: We examined cardiac AEs in recipients of HSCT with PTCY across seven prospective clinical trials conducted at Thomas Jefferson University Hospital from 2012 to 2023. Adverse events were graded per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: Two hundred eighty-six patients were included in the study. All patients had adequate cardiac function prior to HSCT. The median age of patients was 58 years (range 19-76 years). The patients were 61% male and 75% were Caucasian. The HCT co-morbidity index was >=3 in 59% of patients. The most common diagnoses were AML (n=106, 37%), MDS (n=56, 20%), and B-ALL (n=20, 7%). Most patients received haploidentical (HI) HSCT (n=197, 69%), 24 (8.4%) had matched related donors, and 60 (21%) had matched unrelated donors. Patients received myeloablative (n=131, 46%), reduced intensity (n=121, 25%), or non-myeloablative (n=34, 12%) conditioning regimens. Approximately half of the patients (n=146, 51%) experienced grade 1-4 cardiac AEs from time of receiving donor cells to day 100. Twenty-two patients experienced grade 3-4 events, with a cumulative incidence of 7.38% at 50 days and 8.12% at 100 days. Twenty-three Grade 3-4 cardiac AEs were recorded. The vast majority of grade 3-4 cardiac AEs occurred through day 30 (n=20, 87%) and 13% (n=3) from Day 30 to Day 100. The most common grade 3-4 cardiac AE was heart failure (n=10, 43%), followed by arrhythmia (n=6, 26%), pericardial effusion (n=5, 22%), chest pain (n=1, 4%) and cardiac arrest (n=1, 4%). Conclusion: Cardiac toxicity is common after HSCT with PTCY, however severe cardiac AEs are uncommon, and mortality is rare. Most cardiac AEs occur in the first 30 days post HSCT. Heart failure, arrhythmias and pericardial effusion constitute the majority of severe cardiac AEs. Measure to mitigate cardiac toxicities such as careful patient selection, strict fluid balance and meticulous central venous pressure should be adopted in patients receiving PTCY.

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