Donor-Derived Cell Free DNA: Is It All the Same?
J. Keith Melancon, Ali Khalil, Mark Lerman
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, n =2; T cell–mediated rejection, n =9). Results Prospera demonstrated larger measurements of dd-cfDNA in comparison with AlloSure, but this was NS ( P =0.12). 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 ( P =0.01) 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.