Tale of two assays: Comparison of modern donor-derived cell-free DNA technologies

Abstract

Little is known about the comparative differences between the Allosure (CareDx) and Prospera (Natera) donor-derived cell-free DNA (dd-cfDNA) assays following heart transplantation. We retrospectively analyzed 248 consecutive samples that had both dd-cfDNA assays simultaneously performed. Twenty-six biopsy specimens were available within 7 days from dd-cfDNA assays. Both dd-cfDNA assays were correctly suggestive of rejection when biopsy was available. However, discordant classifications were present in 23/248 samples when utilizing respective recommended cutoff values for each assay (0.12% for Allosure and 0.15% for Prospera). Discordance was due to increased classification as abnormal results with Allosure (McNemar’s p = 0.004). However, there were no significant differences between assays when identical thresholds of 0.12% or 0.15% were implemented for both assays (McNemar’s, p = non-significant). We conclude that both dd-cfDNA assays can be utilized interchangeably for surveillance of rejection following heart transplantation.

Keywords

• heart transplantation
• acute allograft rejection
• acute cellular rejection
• antibody-mediated rejection
• donor-derived cell-free DNA