Donor-Derived Cell-Free DNA Across the Spectrum of Solid Organ Transplantation

S. R. Potter¹, J. Miles², K. Qu², R. Woodward², S. Dholakia²

¹Baylor Scott & White Health, Temple, TX, ²CareDx, Inc, Brisbane, CA

Meeting: 2022 American Transplant Congress

Abstract number: 562

Keywords: Heart, Kidney, Liver, Lung

Topic: Basic Science » Basic Clinical Science » 17 - Biomarkers: Clinical Outcomes

Session Information

Session Name: Biomarkers: Clinical Outcomes II

Session Type: Rapid Fire Oral Abstract

Date: Tuesday, June 7, 2022

Session Time: 5:30pm-7:00pm

Presentation Time: 5:30pm-5:40pm

Location: Hynes Ballroom A

*Purpose: Donor-derived cell-free DNA (dd-cfDNA) is a robust and clinically useful analyte initially validated for kidney allograft surveillance. Emerging data support the utility of dd-cfDNA in recipients of multiple types of solid organ transplants (SOT). Understanding and calibrating the baseline characteristics of dd-cfDNA across SOT recipients of various organs is important in guiding assay interpretation and clinical decision making. Results may vary based on analytical methodology and sequencing, making consistency in the method of dd-cfDNA assessment critical to result interpretation. We evaluated the cumulative data for the dd-cfDNA test by AlloSure (CareDx, Brisbane) across kidney (K), heart (H), lung (LU) and liver (LI) transplant recipients.

*Methods: The cumulative K [DART: NCT02424227; K-OAR: NCT03326076; OKRA: NCT03326076] (9/15/16-7/24/20), H [D-OAR: NCT01833195; SHORE: NCT03695601](5/21/18-7/24/20) and LU [LARGO: NCT00751309; ALARM/GTD: NCT02423070](5/10/19-7/8/20) and LI transplant (MAPLE: NCT04793360) recipient dd-cfDNA results were analyzed.

*Results: Evaluation of 68,023 samples in 24,753 unique K recipients yielded a median dd-cfDNA level of 0.25% (IQR 0.17-0.48%). Evaluation of 13,847 samples in 4,384 unique H recipients yielded a median dd-cfDNA level of 0.14% (IQR 0.12-0.16%). Evaluation of 673 samples in 407 unique LU recipients yielded a median dd-cfDNA level of 0.63% (IQR 0.280-1.30%). Evaluation of 83 samples from 31 unique LI recipients yielded a median of 2.5% (IQR 1.19-6.67%). Violin plot distributions are depicted by SOT type [FIGURES: 1A-D]. All distributions are left skewed, with most recipients having low levels of dd-cfDNA relative to the assay reference ranges.

*Conclusions: With over 82,500 samples analyzed in 29,500 SOT recipients, these data represent the largest experience implementing dd-cfDNA described to date. The skewed distributions across populations support the use of nonparametric tests and median values for assay interpretation. The reference ranges vary by SOT type, indicating that dd-cfDNA levels are not linearly related to organ mass. The continuous distribution suggests that relative change, rather than cut-points alone, may be important in the analysis of dd-cfDNA results and the clinical decision making based on those results.

To cite this abstract in AMA style:

Potter SR, Miles J, Qu K, Woodward R, Dholakia S. Donor-Derived Cell-Free DNA Across the Spectrum of Solid Organ Transplantation [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-across-the-spectrum-of-solid-organ-transplantation/. Accessed November 21, 2024.

« Back to 2022 American Transplant Congress