Local laboratory-run donor-derived cell-free DNA assay for rejection surveillance in heart transplantation-first six months of clinical experience

IntroductionDonor-derived cell-free DNA (dd-cfDNA) is a blood biomarker detecting graft injury with high negative predictive value. While non-invasive strategies for heart transplant (HTx) rejection surveillance are widely adopted in the United States with centralized testing, data on the feasibility of dd-cfDNA assay at the local level are lacking. Here, we report the first 6 months of experience with a local laboratory-run dd-cfDNA assay in the routine clinical surveillance setting. MethodsTwenty-six HTx patients with stable graft function were transitioned from endomyocardial biopsy-based (EMB) to dd-cfDNA-led rejection surveillance using a commercially available next-generation sequencing-based assay. ResultsIn the 90 samples analyzed, dd-cfDNA fraction remained continuously low in most patients, thus 88% of surveillance EMBs could be safely avoided. In the case of & GE;.25% dd-cfDNA, EMB was performed. There was no missed rejection. ConclusionOur data show the feasibility to analyze dd-cfDNA at the local level and successful implementation of this non-invasive surveillance method into clinical practice, thus considerably reducing the frequency of invasive surveillance EMBs.

Automated summary

This study reports the first 6 months of experience with a local laboratory-run dd-cfDNA assay in the routine clinical surveillance setting. The results show that most patients had continuously low dd-cfDNA fractions, allowing safe avoidance of the majority of surveillance endomyocardial biopsies (EMBs). EMBs were only performed when the dd-cfDNA fraction was ≥0.25%, and there were no missed rejections.