Use of dd-cfDNA in Multiorgan Transplantation

Purpose Gene expression profiling testing (GEP; AlloMap) and donor-derived cell free DNA (dd-cfDNA; AlloSure) each provide non-invasive means to detect possible heart allograft rejection, including acute cellular rejection (ACR). Use of dd-cfDNA in multiorgan transplantation has not previously been reported. This report describes the largest single center use of dd-cfDNA to date in this population. Methods Post heart transplant (HT) management is standardized at our center such that endomyocardial biopsy is used for rejection surveillance in the early period with crossover to GEP testing at day 56. Elevated GEP (≥34) prompts biopsy. dd-cfDNA was utilized in conjunction with biopsy or in lieu of biopsy (barrier to biopsy). A cohort of 26 HT patients underwent dd-cfDNA testing, including 3 multiorgan (same donor) and 5 retransplant patients. The dd-cfDNA (%, AlloSure) and GEP (AlloMap, score 0-40) results were correlated patient survival. Results Among 26 HT patients, there were 3 multiorgan transplant recipients (2 heart-kidney & 1 heart-lung). Mean dd-cfDNA was 0.9 ± 0.5%. Mean GEP score was 32.8 ± 4.0. dd-cfDNA usage was due to inability to biopsy (33.3%), anticoagulation (33.3%) & elevated Allomap (33.3%). Mean LVEF was 55 ± 1%. Mean day post transplant for first dd-cfDNA was 153 (IQR 119-347). There were no deaths. Of the heart-kidney recipients, mean ACR & AMR biopsy grade was 0.67 & 0, respectively. The heart-lung recipient underwent 2 lung biopsies with mean grade of 0. Conclusion In surveillance of heart allograft recipients for rejection, consideration of dd-cfDNA levels may improve patient management decisions particularly when endomyocardial biopsy may not be feasible. This is the first report of use of dd-cfDNA in multiorgan transplantation. Baseline levels of dd-cfDNA appear to be higher than that of heart-only recipients. Further study is warranted to assess the utilization of dd-cfDNA in multiorgan transplantation.