A Longitudinal Assessment Of Donor Derived Cell Free Dna In Lung Transplant Recipients

PurposeThe purpose of this study is to determine to what extent longitudinal monitoring of donor-derived cell free DNA (dd-cfDNA) in lung transplant recipients can be used as a marker of lung injury and stability.Methods21 out of a planned cohort of 24 subjects have been enrolled in this study measuring dd-cfDNA levels on a monthly basis in the first year after bilateral lung transplant. A blinded clinical adjudication is performed at the same timepoints to categorize allograft function as stable (FEV1 within 10% of prior value) or unstable. When deemed unstable, etiology of unstable graft function is elicited. We then evaluate correlation between dd-cfDNA results and the clinical impression of allograft function.ResultsAt present, we have 5 months of data on 6 patients. Median dd-cfDNA levels in those with clinically stable graft function was 0.41 (IQR 0.6), and unstable graft function was 0.88 (IQR 1.0). There was little within patient variability with the exception of one subject who experienced an A2 rejection at month 3. There also did not appear to be a consistent increase in dd-cfDNA levels in the time directly before recording unstable graft function.ConclusionDecreasing dd-cfDNA values post-transplant may relate to delayed resolution of graft injury due to ischemia-reperfusion. The sample median dd-cfDNA value was 2X higher during adjudicated “unstable graft function” versus “stable”. We speculate that serial trends in dd-cfDNA may detect unstable graft function with higher precision than a dd-cfDNA threshold. Further analysis with ongoing patient enrollment and utilization of the enriched dataset regarding etiology of “unstable graft function” will further refine the utility of this clinical tool. The purpose of this study is to determine to what extent longitudinal monitoring of donor-derived cell free DNA (dd-cfDNA) in lung transplant recipients can be used as a marker of lung injury and stability. 21 out of a planned cohort of 24 subjects have been enrolled in this study measuring dd-cfDNA levels on a monthly basis in the first year after bilateral lung transplant. A blinded clinical adjudication is performed at the same timepoints to categorize allograft function as stable (FEV1 within 10% of prior value) or unstable. When deemed unstable, etiology of unstable graft function is elicited. We then evaluate correlation between dd-cfDNA results and the clinical impression of allograft function. At present, we have 5 months of data on 6 patients. Median dd-cfDNA levels in those with clinically stable graft function was 0.41 (IQR 0.6), and unstable graft function was 0.88 (IQR 1.0). There was little within patient variability with the exception of one subject who experienced an A2 rejection at month 3. There also did not appear to be a consistent increase in dd-cfDNA levels in the time directly before recording unstable graft function. Decreasing dd-cfDNA values post-transplant may relate to delayed resolution of graft injury due to ischemia-reperfusion. The sample median dd-cfDNA value was 2X higher during adjudicated “unstable graft function” versus “stable”. We speculate that serial trends in dd-cfDNA may detect unstable graft function with higher precision than a dd-cfDNA threshold. Further analysis with ongoing patient enrollment and utilization of the enriched dataset regarding etiology of “unstable graft function” will further refine the utility of this clinical tool.