Date: Monday, May 4, 2015
Session Time: 2:15pm-3:45pm
Presentation Time: 2:51pm-3:03pm
Location: Room 118-C
Purpose: An elevated fraction of donor-derived cell-free DNA (dd-cfDNA) detected in the venous blood of recipients has been shown to be correlated to rejection of heart transplant allografts. We examined the characteristics of dd-cfDNA in longitudinal samples from non-rejecting patients (pts) to assess the range and components of normal variability in dd-cfDNA.
Methods: From the CARGO II, 17-center, observational study of 737 heart transplant recipients, a subset of 24 pts was selected that did not have ≥2R acute cellular rejection detected at any time while on study. A novel approach for quantifying dd-cfDNA using targeted amplification and next-generation sequencing was used to quantify dd-cfDNA on 109 plasma samples from these 24 pts. 3 to 10 samples were collected between 2 months and 1 year post-transplantation for each patient. Most plasma samples had endomyocardial biopsy rejection grades and gene-expression profiling (GEP) test scores available from the same clinic visits.
Results: Median dd-cfDNA was 0.79% (interquartile range [0.38%, 1.30%]). Total between-patient variability (51% CV) was similar to within-patient variability (45% CV). Analytical variability was 17%. The ratio of between-patient variability to within-patient variability was 1.6 times lower for dd-cfDNA than for GEP. No effect of recipient gender, age, CMV serologic status, or time post-transplantation was seen on % dd-cfDNA measurements.
Conclusion: In this longitudinal study of non-rejecting heart transplant recipients, the within-patient and between-patient variabilities of dd-cfDNA were shown to be of similar size, and significantly larger than the analytical variability of the assay. The ratio of between-patient variability to within-patient variability was significantly less than in GEP, suggesting that dd-cfDNA does not depend as strongly on patient-specific factors as does GEP. dd-cfDNA showed no dependence on patient age, gender, CMV serologic status, or time since transplant in this cohort. Taken together, these characteristics indicate that dd-cfDNA is a stable analyte in non-rejecting pts.
To cite this abstract in AMA style:Hiller D, Grskovic M, Beausang J, Sit R, Christie B, Elechko J, Woodward R, Yee J, Eisen H. Donor-Derived Cell-Free DNA Is Stable in Non-Rejecting Heart Transplant Recipients in the CARGO II Multicenter Trial [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-is-stable-in-non-rejecting-heart-transplant-recipients-in-the-cargo-ii-multicenter-trial/. Accessed July 4, 2020.
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