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

Abstract

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 2-step platform. The 2-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/d for 2 d (Day-3, Day-2). On day 0, patients receive CD34⁺ selected donor stem cells (Step 2). We examined cardiac AEs in recipients of HSCT with PT-Cy across 7 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 nonmyeloablative (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 d and 8.12% at 100 d. 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 1-year OS was 71.1% for patients without G ≥3 cardiac event vs 36.4% for patients with G ≥3 AEs (P = .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 = .0375). 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 d 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.

Keywords: Allogenic transplant; Cardiotoxicity; Cyclophosphamide; Toxicities.