Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Elevations in donor-derived cell-free DNA (dd-cfDNA) ≥0.20 % in heart transplant recipients (HTR) has been shown to be associated with a probability of acute rejection (AR). Characterizing the normal biological variation of this biomarker in HTR is essential to better define the dd-cfDNA levels that are associated with AR and/or allograft injury.
*Methods: dd-cfDNA (AlloSure®) reference ranges were characterized in peripheral blood samples obtained from a HTR population participating in the D-OAR study between 2014 and 2016. Inclusion criteria: patients who had no clinical signs/symptoms of AR during regular surveillance visits. Patients with endomyocardial biopsy-based diagnoses of ≥1 acute cellular rejection (ACR); grade ≥1R) or antibody mediated rejection (AMR; grade ≥pAMR1) were excluded.
*Results: 352 HTR contributed 1038 dd-cfDNA samples, obtained at surveillance visits. Patients were enrolled at a median of 239 days post-transplant (inter-quartile range, (IQR) 164 – 318). 74% of patients were male, 68% were Caucasian, mean age was 55 years, and the most common indications for transplant were dilated cardiomyopathy (50%) and ischemic cardiomyopathy (30%). These demographics are similar to those for Organ Procurement and Transplantation Network HTR 2016 cohort. Reference ranges of dd-cfDNA: Median dd-cfDNA = 0.06% (IQR 0.02%-0.12%, 97.5th percentile 1.46%). A subset of 107 HTR with negative EMB (ACR grade 0R or AMR grade pAMR0 had no significant difference in median dd-cfDNA value: 0.07% (IQR 0.03%-0.13%); 168 samples, (p=0.31, K-S test). The dd-cfDNA intra-patient (CVI) = 74%, and the inter-patient Coefficient of Variation CVG = 94%, based on an average of 3 tests result/patients.
*Conclusions: The range of dd-cfDNA levels in this HTR population reflects the biological variation in rate and mass of of cell turnover within the allograft relative to the recipient’s cell mass and turnover. The median dd-cfDNA levels (0.06%) in this reference heart transplant population are significantly lower than the median reference value observed in kidney transplant recipients (KTR) 0.21% (IQR 0.12-0.39%), but the upper 97.5%tile of 1.46% in HRT is similar to outlier values observed in KTR (1.20%).
To cite this abstract in AMA style:Kao A, Dholakia S, Deng M. Reference Ranges Donor-Derived Cell-Free DNA in a Heart Transplant Population [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/reference-ranges-donor-derived-cell-free-dna-in-a-heart-transplant-population/. Accessed May 7, 2021.
« Back to 2019 American Transplant Congress