Abstract
(748) - Donor Derived Cell-Free DNA is Elevated during Rejection in Pediatric Heart Transplant Recipients
The Journal of heart and lung transplantation, Vol.44(4 Supplement), pp.S354-S354
04/2025
DOI: 10.1016/j.healun.2025.02.756
Abstract
Purpose: Donor derived cell-free DNA (dd-cfDNA) has been shown to distinguish between acute rejection (AR) and no rejection (NR) in heart transplant (HT) recipients ≥15 years old; however, the performance of dd-cfDNA in recipients <15 has not been studied. Our goal was to assess the relationship between dd-cfDNA levels during AR and NR in pediatric HT recipients.
Methods: This 4-center analysis included single-organ HT recipients <15 years old at the time of dd-cfDNA testing with ≥1 paired dd-cfDNA and endomyocardial biopsy (EMB) performed on the same day. A second analysis using a dd-cfDNA window of 0-30 days before EMB was also performed. AR was defined as EMB-proven acute cellular rejection (ACR) grade ≥2R and/or antibody mediated rejection (AMR) grade ≥pAMR1. NR was defined as an ACR grade <2R and pAMR0 on EMB.
Results: This analysis included 126 HT recipients <15 years old. Amongst patients with complete demographic data, the cohort was 61% white and 50% male, with a median age at HT of 3 (IQR 1-9) years. There were 207 dd-cfDNA paired on the same day as EMB, of which 175 (85%) across 121 patients showed NR and 32 (15%) from 21 patients had AR. AMR-alone accounted for 81% (n=26) of AR, with ACR-alone representing 16% (n=5) of AR cases. One (3%) EMB had both ACR and AMR. The median time post-HT of dd-cfDNA for AR and NR were 3.2 and 1.8 years, respectively. Median age at EMB was 8 years old in the AR group and 6 years old in NR. Median same day dd-cfDNA levels were significantly higher during AR than NR (1.55% vs 0.16%, p<0.001, Figure A). Similar results were observed in 50 AR (35 AMR, 14 ACR, 1 mixed) dd-cfDNA samples in the dd-cfDNA pairing window 0-30 days before EMB (Figure B). At a dd-cfDNA threshold of 0.20%, the sensitivity for AR was 84.7%, specificity was 59.1%, PPV was 19.6%, NPV was 97.1%, and the positive likelihood ratio was 2.08.
Conclusion: dd-cfDNA can successfully distinguish between AR and NR in HT recipients <15 years old, suggesting dd-cfDNA can be used to identify patients at higher risk for AR in this population.
Details
- Title: Subtitle
- (748) - Donor Derived Cell-Free DNA is Elevated during Rejection in Pediatric Heart Transplant Recipients
- Creators
- B. Feingold - Children's Hospital of PittsburghD. Mokshagundam - Washington University in St. LouisG. Beasley - University of Iowa Stead Family Children's Hospital, Iowa City, IAM. Everitt - Children's Hospital ColoradoK. Oreschak - CareDx, Brisbane, CAS. Wang - CareDx, Brisbane, CAJ. Kobulnik - CareDx, Brisbane, CAD. Magnetta - Lurie Children's Hospital
- Resource Type
- Abstract
- Publication Details
- The Journal of heart and lung transplantation, Vol.44(4 Supplement), pp.S354-S354
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.healun.2025.02.756
- ISSN
- 1053-2498
- Language
- English
- Date published
- 04/2025
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics
- Record Identifier
- 9984816017902771
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