Longitudinal Monitoring of Donor Derived Cell Free DNA in Lung Transplant Recipients

Purpose The purpose of this study is to evaluate whether 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. Methods 24 subjects were enrolled in this study measuring dd-cfDNA levels on a monthly basis in the first year after bilateral lung transplant. Blinded clinical adjudications were 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 was elicited based on available clinical data. We then evaluated correlation between dd-cfDNA results and the clinical impression of allograft function. Results Median dd-cfDNA levels in those with clinically stable graft function was 0.28 (IQR 0.16, 0.65), and unstable graft function was 0.35 (IQR 0.22, 0.90) (Figure 1.). In those with stable graft function, the change in dd-cfDNA decreased over time with a median change of -0.08 (IQR -0.27, +0.08) whereas those with unstable graft function had increases in dd-cfDNA over time with a median change of +0.09 (IQR -0.01, +0.17) (Figure 2.). Conclusion dd-cfDNA does not have sufficient precision to be used as an independent monitor of allograft function using a threshold value in the absence of clinical correlation. Serial trends in dd-cfDNA may identify an unstable graft that is vulnerable. Further analysis of the dataset regarding development of CLAD will refine the utility of this clinical tool. The purpose of this study is to evaluate whether 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. 24 subjects were enrolled in this study measuring dd-cfDNA levels on a monthly basis in the first year after bilateral lung transplant. Blinded clinical adjudications were 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 was elicited based on available clinical data. We then evaluated correlation between dd-cfDNA results and the clinical impression of allograft function. Median dd-cfDNA levels in those with clinically stable graft function was 0.28 (IQR 0.16, 0.65), and unstable graft function was 0.35 (IQR 0.22, 0.90) (Figure 1.). In those with stable graft function, the change in dd-cfDNA decreased over time with a median change of -0.08 (IQR -0.27, +0.08) whereas those with unstable graft function had increases in dd-cfDNA over time with a median change of +0.09 (IQR -0.01, +0.17) (Figure 2.). dd-cfDNA does not have sufficient precision to be used as an independent monitor of allograft function using a threshold value in the absence of clinical correlation. Serial trends in dd-cfDNA may identify an unstable graft that is vulnerable. Further analysis of the dataset regarding development of CLAD will refine the utility of this clinical tool.