(514) Clinical Utility of Donor Derived Cell-Free DNA in the Multiorgan Transplantation

PurposeDonor-derived cell-free DNA (dd-cfDNA) has emerged as a reliable, noninvasive method for the detection of allograft rejection in heart transplantation (HT) patients. dd-cfDNA is widely used in HT, but its utility in multiorgan transplants (HT + another organ) is unknown. We describe the experience using dd-cfDNA in multiorgan transplant patients.MethodsRetrospective review of all HT patients transplanted between 1998-2022 at our center that had at least one dd-cfDNA collected between 5/2020 and 8/2022. Patients that had multiorgan transplant were identified and enrolled to this study. dd-cfDNA percentages were quantified and correlated with allograft rejection. The dd-cfDNA variability score was calculated by the variance/mean test value per person. Acute cellular rejection (ACR) was defined as ISHLT grade ≥ 2R and antibody mediated rejection (AMR) > pAMR0.ResultsOf 654 HT patients with dd-cfDNA levels, 35 patients had multiorgan transplant. Median age was 55 years, 37.1% were female; median time from HT was 554 days [264, 1660]. 22 patients had heart-kidney (H-K), 8 patients had heart-liver (H-Li) and 5 patients had heart-lung (H-Lu). Of 153 samples, the average dd-cfDNA levels per patient were 0.243 % [0.149, 0.431], 1.49 % [1.02, 2.33] and 0.727% [0.653, 0.790] in the H-K, H-Li and H-Lu group, respectively. No patients had ACR or AMR. 31 patients had multiple levels drawn with a median of 4 samples [2, 6]. The median variability score for each patient was 0.009, 0.263 and 0.0516 in the H-K, H-Li and H-Lu group, respectively.Conclusiondd-cfDNA is chronically elevated in most multiorgan transplant recipients. There is a high degree of variability in levels (particularly for H-Li and H-Lu recipients), which may limit the utility of this assay in multiorgan transplant recipients. Donor-derived cell-free DNA (dd-cfDNA) has emerged as a reliable, noninvasive method for the detection of allograft rejection in heart transplantation (HT) patients. dd-cfDNA is widely used in HT, but its utility in multiorgan transplants (HT + another organ) is unknown. We describe the experience using dd-cfDNA in multiorgan transplant patients. Retrospective review of all HT patients transplanted between 1998-2022 at our center that had at least one dd-cfDNA collected between 5/2020 and 8/2022. Patients that had multiorgan transplant were identified and enrolled to this study. dd-cfDNA percentages were quantified and correlated with allograft rejection. The dd-cfDNA variability score was calculated by the variance/mean test value per person. Acute cellular rejection (ACR) was defined as ISHLT grade ≥ 2R and antibody mediated rejection (AMR) > pAMR0. Of 654 HT patients with dd-cfDNA levels, 35 patients had multiorgan transplant. Median age was 55 years, 37.1% were female; median time from HT was 554 days [264, 1660]. 22 patients had heart-kidney (H-K), 8 patients had heart-liver (H-Li) and 5 patients had heart-lung (H-Lu). Of 153 samples, the average dd-cfDNA levels per patient were 0.243 % [0.149, 0.431], 1.49 % [1.02, 2.33] and 0.727% [0.653, 0.790] in the H-K, H-Li and H-Lu group, respectively. No patients had ACR or AMR. 31 patients had multiple levels drawn with a median of 4 samples [2, 6]. The median variability score for each patient was 0.009, 0.263 and 0.0516 in the H-K, H-Li and H-Lu group, respectively. dd-cfDNA is chronically elevated in most multiorgan transplant recipients. There is a high degree of variability in levels (particularly for H-Li and H-Lu recipients), which may limit the utility of this assay in multiorgan transplant recipients.