Evaluating threshold for donor fraction cell‐free DNA using clinically available assay for rejection in pediatric and adult heart transplantation

Abstract

BackgroundThe aims of the study were to assess the performance of a clinically available cell‐free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection.MethodsObservational, non‐interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy‐associated plasma samples were used for cfDNA measurements. Pre‐determined cut points were tested for analytic performance.ResultsA total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df‐cfDNA values between rejection [0.21% (IQR 0.12–0.69)] and healthy samples [0.05% (IQR 0.01–0.14), p < .0001]. The pediatric rejection group had a median df‐cfDNA value of 0.93% (IQR 0.28–2.84) compared to 0.09% (IQR 0.04–0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection.ConclusionThe study suggests that pediatric patients with rejection show higher levels of circulating df‐cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance.