Plasma Donor-Derived Cell-Free DNA Levels are Not Affected by Prednisone Dose nor Time after Heart Transplant: Pilot Data from DOAR and SHORE

Purpose Gene expression profiling (GEP; AlloMap®) scores can be impacted in the presence of >20 mg/day of prednisone due to effects on steroid-responsive genes (IL-1R2, ITGAM, FLT3) and is not validated for use prior to 55 days post-heart transplant. Donor-derived cell-free DNA (dd-cfDNA) can be used as early as 14 days after heart transplant (HT), but the impact of early use and the impact of steroid dosing has not yet been demonstrated. Methods The dd-cfDNA (AlloSure®) from the Donor-Derived Cell-Free DNA Outcomes AlloMap Registry (D-OAR) and Surveillance Heart Care Outcome Registry (SHORE) registries had 17 visits 5-10, >10-15, >15-20, and >20 mg/day (n=1113, 542, 203, 82, and 30). Results For those = 55 days post-HT the median dd-cfDNA result was 0.15% (IQR: 0.15-0.15%) and 0.15% (0.15-0.19%), respectively (p=NS). When stratified by prednisone doses (0-5], (5-10], (10-15], (15-20], and (>20, there was also no difference in median dd-cfDNA: 0.12%, 0.12%, 0.15%, 0.15%, and 0.15%, respectively, p=0.7. Conclusion This preliminary data suggests that dd-cfDNA levels are not significantly affected when assessed earlier than 55 days post-HT or by varying prednisone dosage. Implementation of dd-cfDNA as an early biomarker of allograft injury and rejection may represent a valuable clinical tool during the early post-HT period.