Joseph K Melancon1, Ali Khalil2, Mark J Lerman2. 1. Department of Surgery, The George Washington University Hospital, Washington, D.C. 2. Dallas Nephrology Associates, Dallas, Texas.
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.
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.
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