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Allogeneic Hematopoietic Cell Transplantation with Non-Myeloablative Conditioning and Post-Transplant Cyclophosphamide Prophylaxis in Patients with Reduced Systolic Function
LeMaistre, F. I., Tsai, H. L., Varadhan, R., Al-Talib, T., Jones, R., Ambinder, A.
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Post-transplant cyclophosphamide (PTCy) has become standard-of-care for graft-vs-host disease (GVHD) prophylaxis, including allowing expanded donor options. However, there is little literature examining outcomes of patients with reduced systolic function receiving PTCy. OBJECTIVES This study aims to describe our experience in transplanting patients with reduced systolic function, including their non-relapse related mortality (NRM), overall survival (OS), and cumulative incidence of early cardiac events (ECE). STUDY DESIGN This study is a retrospective descriptive analysis using the Johns Hopkins Hematologic Malignancy database. From 2017 through 2021, 1118 consecutive patients underwent allogeneic transplantation with a non-myeloablative (NMA) conditioning and PTCy. A total of 43 of those patients were found to have a pretransplant left ventricular ejection fraction (LVEF) ≤ 45% measured by transthoracic echocardiography. Patients whose LVEF improved on treatment prior to transplant were also included. These two cohorts were stratified into heart failure with reduced ejection fraction (HFrEF) and heart failure with recovered ejection fraction (HFrecEF), and subgroup analysis compared NRM, OS, and cumulative incidence of ECE. ECE was defined as arrhythmia, coronary artery disease, reduction in LVEF, or pericardial effusion within 100 days post-transplant. RESULTS The median LVEF for 31 patients undergoing transplant with HFrEF was 40-45% (range 30-45%) and 35-40% (range 20-45%) for the 12 patients with HFrecEF. The NRM for all 43 patients was 16% (5-27%) at 100 days and 23% (11-36%) at 2 years. The NRM was 23% (8-38%) and 26% (10-42%) at 100 days and 2 years for the HFrEF cohort and 0 and 18% (0-41%) at 100 days and 2 years for the HFrecEf cohort. The OS at 3 years was 41% (26-62%), 40% (25-65%) and 38% (14-100%) in combined, HFrEF, and HFrecEF cohorts, respectively. The cumulative incidence of any ECE was 37.2% (22-51.9%), including 39% of HFrEF subjects and 33% of HFrecEF subjects. Grade 3 or higher toxicities were seen in 56% of patients. A reduction in ejection fraction was the most common ECE. One death was attributable to a cardiac etiology. CONCLUSIONS Cardiac toxicities seemed to frequent and severe in patients with a history of systolic dysfunction, but these do not lead to worse survival outcomes. This study adds to and extends existing literature supporting NMA conditioning and PTCy in patients with systolic dysfunction.