Abstract 17052: Are Sex-Specific Thresholds Needed for Donor-Derived Cell-Free DNA in Rejection Surveillance? An Analysis From the Genomic Research Alliance for Transplantation

Abstract

Introduction: Non-invasive methods for surveillance of rejection are increasingly used among heart transplant (HT) recipients, including donor-derived cell-free DNA (dd-cfDNA). The purpose of the current study was to examine patterns of dd-cfDNA seen in quiescence and acute rejection in males and females. Hypothesis: As other cardiac biomarkers differ by sex, we hypothesized that there may be sex-specific differences in performance for detection of acute rejection. Methods: Patients previously enrolled in GRAfT who were ≥18 years at the time of HT were included. Rejection was defined by endomyocardial biopsy with ISHLT acute cellular rejection (ACR) grade ≥2R and/or antibody-mediated rejection ≥ pAMR 1. Median dd-cfDNA levels were compared between sexes during quiescence and rejection. The performance of dd-cfDNA by sex at or after Day 28 was assessed using AUROC. Allograft injury was defined as dd-cfDNA ≥0.25%. Results: After exclusions, 148 patients were included with 1109 dd-cfDNA measurements. Baseline characteristics including demographics and comorbidities were not significantly different between sexes. During quiescence, there were no significant sex differences in median dd-cfDNA (0.038% [IQR 0.001-0.167] in females vs 0.029% [IQR 0.001-0.125] in males, p = 0.21). There were no significant sex differences in median dd-cfDNA for ACR (0.33% [0.210-0.356] in females vs 0.32% [0.210-1.103] in males, p = 0.57). Overall, median dd-cfDNA levels were higher in AMR than ACR but did not significantly differ by sex (0.50% [IQR 0.180-0.820] in females vs 0.63% [IQR 0.316-1.945] in males, p = 0.51). Elevated dd-cfDNA detected ACR/AMR with an AUROC of 0.83 in females and 0.89 in males (Figure). Conclusions: There were no significant sex differences between dd-cfDNA levels during quiescence and rejection. Performance characteristics were similar, suggesting that similar thresholds can be used in men and women for rejection surveillance.