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

Clin Transplant. 2023 Sep;37(9):e15078. doi: 10.1111/ctr.15078. Epub 2023 Jul 25.

Abstract

Introduction: Donor-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.

Methods: Twenty-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.

Results: In 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 ≥.25% dd-cfDNA, EMB was performed. There was no missed rejection.

Conclusion: Our 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.

Keywords: allograft injury; donor-derived cell-free DNA; heart transplantation; local laboratory-run assay; next-generation sequencing; rejection.

MeSH terms

  • Biomarkers
  • Cell-Free Nucleic Acids*
  • Graft Rejection / diagnosis
  • Graft Rejection / etiology
  • Heart Transplantation*
  • Humans
  • Tissue Donors

Substances

  • Cell-Free Nucleic Acids
  • Biomarkers