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

Abstract

<h3>Purpose</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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) (<i>Figure 1.)</i>. 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) <i>(Figure 2.)</i>. <h3>Conclusion</h3> 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.