Initiation of Noninvasive Surveillance for Allograft Rejection in a Cohort of Heart Transplant Patients >1 Year after Transplant: An Exploratory Analysis

Purpose Gene expression profiling (GEP) and donor-derived, cell-free DNA (dd-cfDNA) measurement are alternative methods to endomyocardial biopsy (EMB) to monitor for rejection following heart transplantation. Both tests were individually validated but the utility of the combined use is unclear, especially in patients >1-year post-transplantation. We aim to describe our use of GEP and dd-cfDNA in heart transplant recipients >1-year post-transplantation. Methods This is a retrospective study conducted at The Queen's Medical Center, a non-heart transplant center located in Hawai'i, which cares for heart transplant recipients in a shared-care model with transplant centers located on the mainland. A protocol for GEP and dd-cfDNA for our patients was started in July 2019. For patients who were >1-year post-transplantation and were clinically deemed to be at an elevated risk for rejection, we collected both GEP and dd-cfDNA every 3 months. Baseline characteristics including GEP, dd-cfDNA, rejection episodes, and number of EMB were obtained. Results Since July 2019, there were 18 patients being followed with GEP and dd-cfDNA who were >1-year post-transplantation. The majority were male (72%), the mean age was 57.3±12.8 years, the average time from transplantation was 7.2.±1.6 years. Since then, 9 EMBs had been performed due to reasons as follows; 3 for elevated GEP (≥ 34), 1 for elevated dd-cfDNA ( ≥ 0.20%), 2 for elevations of both GEP and dd-cfDNA, 2 for clinical rejection and 1 to follow up a post-rejection episode. Of the 2 biopsies due to elevations of both GEP and dd-cfDNA, 50% showed evidence of acute rejection (acute cellular rejection grade 2R). None of the other 4 biopsies due to either an elevation in the GEP or dd-cfDNA alone revealed any significant rejection. We also followed 18 patients >1-year post-transplantation without the routine use of GEP or dd-cfDNA. None experienced clinical episodes of rejection or had any EMB performed. Conclusion In this study, the use of both GEP and dd-cfDNA led to an increased number of EMB in patients >1-year post-transplantation. Patients were at higher risk of rejection if they have elevation of both GEP and dd-cfDNA. Further studies are needed to validate these findings and evaluate long-term consequences of these diagnostic tests in patients who are > 1-year post-transplantation.