Work

The Heart of the Matter: Cardiac Toxicity in Allogenic Stem Cell Transplant with Post-Transplant Cyclophosphamide

Year: 2025

Type: article

Abstract: 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 (PT-Cy). We examined the incidence and characterization of cardiac AEs in recipients of HSCT with PT-Cy at our center. Most patients were treated with the 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 a fixed dose of donor CD3 + T cells, 2 × 10*8/kg DLI (Day -6, Step 1). Then, patients receive PT-Cy 50 or 60 mg/kg/day for two days (Day -3, Day -2). On day 0, patients receive CD34 + selected donor stem cells (Step 2). Methods We examined cardiac AEs in recipients of HSCT with PT-Cy 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. Most patients received haploidentical (HI) HSCT (n=197, 69%), 24 (8.4%) had matched related donors (MRD), and 60 (21%) had matched unrelated donors (MUD). 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 cardiac events, with a cumulative incidence of 7.38% at 50 days and 8.12% at 100 days. Twenty-three Grade ≥3 cardiac AEs were recorded. The vast majority of grade ≥3 cardiac AEs occurred through day 30 (n=20, 87%) and 13% (n=3) from Day 30 to Day 100. The most common grade ≥3 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%). The one-year OS was 71.1% for patients without G ≥3 cardiac event vs 36.4% for patients with G ≥3 AEs (p = 0.0001). The presence of having any cardiac risk factors (arrhythmia, CAD, CHF, and other) increase risks of having G3 or more cardiac toxicity (OR = 2.65, p = 0.0375). Conclusion Cardiac toxicity is common after HSCT with PT-Cy, however severe cardiac AEs are uncommon, and mortality is rare. Most cardiac AEs occurred in the first 30 days post donor cells infusion. Heart failure, arrhythmias and pericardial effusion constituted most severe cardiac AEs. Patients who experienced grade ≥3 cardiac events had worse OS than patients that did not.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.09.009