Clinical utility of plasma percent donor-derived cell-free DNA for lung allograft surveillance: A real-world single-center experience

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BackgroundPlasma percent donor-derived cell-free DNA (%dd-cfDNA) has been investigated as a biomarker of allograft injury after lung transplantation (LT). We sought to determine the clinical utility of plasma percent donor-derived cell-free DNA (%dd-cfDNA) as a screening tool for acute cellular rejection (ACR) and respiratory infections (RIs) among LT recipients (LTRs). MethodsWe retrospectively analyzed %dd-cfDNA results from 95 plasma samples collected from 81 bilateral LTRs at our center with a paired transbronchial biopsy within 24 hours after sample collection. We calculated sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of %dd-cfDNA to detect ACR and RIs and used a generalized estimating equation model to compare %dd-cfDNA between groups. ResultsA dd-cfDNA threshold of 0.5% had low sensitivity to detect ACR among LTRs >45 days after LT (41.67%), as did a 70% increase in %dd-cfDNA (50.00%). The NPV was high (88.89% and 87.50%, respectively) but driven by the low prevalence of ACR (12/95 [12.6%]). The area under the receiver operating characteristic curve (AUC) was 0.499 (95%CI [0.326-0.672]) and 0.360 (95%CI [0.132-0.588]) for the detection of ACR and ACR grade ≥A2, respectively. The adjusted mean %dd-cfDNA trended higher in LTRs with a definite or possible RI (1.218, 95%CI [0.671-2.212]) than in LTRs without microbial isolation (0.731, 95%CI [0.525-1.017], p=0.059), but was not significantly different from those with microbial colonization (0.873, 95%CI [0.538-1.415], p=0.390). There was no significant difference in the adjusted mean %dd-cfDNA between patients with microbial colonization and those without microbial isolation (p=0.464). %dd-cfDNA testing had an AUC of 0.573 (95%CI [0.431-0.716]) for the detection of lung allograft dysfunction due to ACR and/or infection. Conclusions%dd-cfDNA may have limited utility as a screening tool to detect ACR among LTRs.