Plasma Levels of Donor-Derived Cell-Free DNA Increase With Rejection and Often Decrease After Treatment in Organ Transplant Recipients

M. Grskovic,¹ J. Beausang,¹ D. Hiller,¹ R. Sit,¹ B. Christie,¹ J. Elechko,¹ R. Woodward,¹ J. Yee,¹ J. Kobashigawa.²

¹CareDx, Inc, Brisbane, CA
²Cedars-Sinai Medical Center, Los Angeles, CA.

Meeting: 2015 American Transplant Congress

Abstract number: 153

Keywords: Genomic markers, Heart transplant patients

Session Information

Session Name: Plenary Session II

Session Type: Plenary

Date: Monday, May 4, 2015

Session Time: 8:30am-9:30am

Presentation Time: 8:30am-8:45am

Location: Terrace Ballroom 1, 2, 3

Purpose: Donor-derived cell-free DNA (dd-cfDNA) is a potential biomarker of acute cellular rejection (ACR) in organ transplant recipients. dd-cfDNA levels in longitudinal plasma samples from heart transplant recipients with a biopsy-confirmed ACR were compared to plasma levels of dd-cfDNA in non-ACR heart transplant recipients.

Methods: 63 patients (pts) from the CARGO II trial provided 205 plasma samples. For 180 samples, biopsies were conducted and graded by ≤4 independent pathologists. 28 samples assigned a biopsy grade of 2R or 3R, by ≥2 pathologists, were classified as rejection (R). 27 samples assigned a biopsy grade of 0R by 4 pathologists were classified as non-rejection (NR). Samples from up to two prior visits before R and NR events, and up to three visits after R events comprised the remaining 150 samples. cfDNA purified from plasma was sequenced to quantify dd-cfDNA levels. Standard statistical measures of correlation and significance were used.

Results: dd-cfDNA levels were significantly higher (p=0.017) in pts with biopsy-confirmed ACR (R, mean 1.7%) compared to stable pts (NR, mean 0.99%). An ROC curve yielded the AUC of 0.68 (95% CI 0.56-0.80). We analyzed 16 cases with biopsy-confirmed ACR and 2 serial samples preceding ACR, and found that in 10 cases levels of dd-cfDNA were elevated as early as 25 days prior to ACR. In 17 cases with clinically treated biopsy-confirmed ACR and 2 serial samples following the ACR, trends were observed where pts with an improved biopsy grade following treatment often experienced the largest decrease (>2 fold) in dd-cfDNA. Pts with smaller changes (<2 fold) in dd-cfDNA often experienced a grade 1R ACR within 30 days of treatment, suggesting that the initial treatment may have been insufficient.

Conclusion: dd-cfDNA is a useful biomarker of ACR and a quantitative indicator of organ health. Preliminary data suggest that levels of dd-cfDNA increase at the time of ACR and decrease when the rejection resolves, but may stay elevated or increase if rejection persists. This non-invasive test may aid in the long-term monitoring of allograft health and identification of patients with ACR, thereby helping ascertain clinical response to rejection treatment without the need for follow-up biopsy.

To cite this abstract in AMA style:

Grskovic M, Beausang J, Hiller D, Sit R, Christie B, Elechko J, Woodward R, Yee J, Kobashigawa J. Plasma Levels of Donor-Derived Cell-Free DNA Increase With Rejection and Often Decrease After Treatment in Organ Transplant Recipients [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/plasma-levels-of-donor-derived-cell-free-dna-increase-with-rejection-and-often-decrease-after-treatment-in-organ-transplant-recipients/. Accessed October 6, 2024.

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