Clinically viable blood test for donor-derived cell-free DNA

A new study, presented today at the AATS 101st Annual Meeting, shows that non-invasive cell-free DNA tests can reduce the need for regular surveillance biopsies to detect early rejection in heart transplant patients. The study was the first of its kind to be performed on both adult and pediatric patients.

Pediatric and adult heart transplant recipients were recruited prospectively from eight participating sites and followed longitudinally for at least 12 months with serial plasma samples collected immediately prior to all endomyocardial biopsies. Structured biopsy results and clinical data were collected and monitored by an independent clinical research organization (CRO).

For all patients taken together in comparison to the composite biopsy outcome using repeated measures, donor fraction (DF) cfDNA at a pre-defined cut point of 0.14 had a sensitivity of 67%, a specificity of 79%, a PPV of 34% and a NPV of 94% with an area under the curve (AUC) of 0.78 (p<0.0001) for detecting rejection. Using this threshold as a guide, DF cfDNA holds promise as a non-invasive biomarker to assess for risk of rejection following heart transplantation in both pediatrics and adults for both acute cellular and antibody-mediated rejection (ACR and AMR). For pediatric patients at an optimal cutpoint slightly lower than adults, DF cfDNA had a sensitivity of 86%, specificity of 61%, PPV of 25%, NPV of 97% and AUC of 0.79 ( p= 0.002).

“Our multicenter group has demonstrated the utility of a clinically viable test for the donor-derived fraction of cell-free DNA, which can vastly reduce the need for routine surveillance biopsies,” explained Marc Richmond, MD, MS, Associate Professor of Pediatrics at Columbia University Medical Center, and the Associate Medical Director of the Program for Pediatric Cardiomyopathy, Heart Failure and Transplantation. “Our consortium of eight centers is continuing to analyze additional data and put forth new studies using this technology.” This assay is clinically usable at any time point after seven days post-transplant and can have a turnaround time of as little as 24 hours. Future studies will include clinical protocols that further assess how this method compares to current practice standards.