Donor-Derived Cell Free DNA: Is It All the Same?

Abstract

Background Clinical utility of donor-derived, cellfree DNA (dd-cfDNA) in transplantation has been extensively reviewed, supporting its use as a surveillance tool for the early and accurate detection of allograft injury. Yet studies comparing different assay methods have been lacking. Methods Paired sampling of commercially available dd-cfDNA (AlloSure and Prospera) was compared and examined against histology and manufacturer guidance. A total of 76 patients were prospectively assessed, with 11 biopsy sample-proven rejections (antibody-mediated rejection, n2; T cell-mediated rejection, n9). Results Prospera demonstrated larger measurements of dd-cfDNA in comparison with AlloSure, but this was NS (P0.12). At current manufacturer recommended diagnostic cutoffs, there was no significant difference in sensitivity, specificity, negative predictive value, or positive predictive value of AlloSure versus Prospera in detecting rejection. AlloSure demonstrated a significantly shorter turnaround time (P0.01) from blood draw to patient result. Conclusions Although dd-cfDNAs are similar, they are not the same. Extensive evidence for dd-cfDNA interpretation remains the key to building clinical utility when considering clinical implementation, and remaining consistent to a single platform is important when creating data comparisons.