Performance of Donor Derived Cell-Free DNA in Routine Clinical Care of Lung Transplant Recipients, a Multi-Center Study

Abstract

Purpose Prior observational data suggest that donor-derived cell-free DNA (dd-cfDNA) increases in lung transplant acute rejection and infection. The performance of dd-cfDNA in routine clinical care remains undefined. In response to the COVID-19 pandemic, to mitigate the risk of exposing patients to infection, four centers used dd-cfDNA for surveillance instead of surveillance bronchoscopy, providing a unique opportunity to assess the performance of dd-cfDNA in routine clinical care. Methods As part of routine care during the COVID-19 pandemic, four lung transplant centers implemented a home-based surveillance program using plasma dd-cfDNA (Allosure®) in preference to surveillance bronchoscopy. Based on prior data, dd-cfDNA > 1% triggered further work-up including bronchoscopy. dd-cfDNA testing was also performed in response to a decline in forced expiratory volume in 1 second (FEV1), symptoms or treatment follow up. Data was retrospectively analyzed from 4/1/2020 - 9/1/2020 to assess the performance of dd-cfDNA in diagnosing a composite of ACR, AMR and/or infection. Results 169 patients underwent 380 dd-cfDNA measurements over the study period. The mean age was 58.5 years, 54% of patients were male and 82% bilateral lung transplants. 99 (58%) patients were 1%. Of these, 19/31 (61%) had evidence of ACR, AMR or infection. 115 patients had surveillance levels that remained 1%). For diagnosis of ACR, AMR or infection in these patients, dd-cfDNA > 1% yielded a sensitivity of 84%, specificity of 77%, positive predictive value of 73% and negative predictive value of 87%. Conclusion In this study, dd-cfDNA identified ACR, AMR and/or infection in asymptomatic lung transplant patients that may not have been identified by clinically indicated biopsy alone. Low levels of dd-cfDNA may also be useful in ruling out AMR, ACR and/or infection, supporting its use as a potential non-invasive marker for surveillance monitoring.