Donor Fraction Cell-Free DNA and Rejection in Adult and Pediatric Heart Transplantation

Abstract Purpose Endomyocardial biopsy (EMB) is the current standard for rejection surveillance in heart transplant recipients. Quantification of donor-specific cell-free DNA (cfDNA) may be an appropriate biomarker for non-invasive rejection surveillance. A multi-center prospective blinded study (DNA-based Transplant Rejection Test, DTRT) investigated the value of donor fraction (DF), defined as the ratio of cfDNA specific to the transplanted organ to total amount of cfDNA present in a blood sample. Methods 241 heart transplant patients were recruited from seven centers. Age at transplant ranged from 8 days to 73 years, with 146 subjects Results DF in ACR 1R/2R (n=15) was higher than ACR 0R (n=42) (p=0.02); DF in pAMR1 (n=8) and pAMR2 (n=12) (p=0.05) were higher than pAMR0 (n=466) (p=0.04 and p=0.05 respectively). By ROC analysis an optimal DF threshold was determined which ruled out the presence of either ACR or AMR. Conclusion Cell-free DNA donor fraction holds promise as a non-invasive diagnostic test to rule out acute rejection in both adult and pediatric heart transplant populations.