Donor-Derived Cell-Free DNA-Guided Rejection Surveillance in Medium- and High-Risk Pediatric Heart Transplant Recipients: A Single-Center Experience.

Abstract

Background: Allograft rejection remains a leading cause of morbidity in pediatric heart transplant (HT) recipients. Endomyocardial biopsy (EMB), the standard for surveillance, is invasive and resource-intensive. Donor-derived cell-free DNA (dd-cfDNA) is a promising noninvasive biomarker, though pediatric data remain limited.

Methods: We performed a retrospective cohort study of 50 pediatric HT recipients (< 18 years) at a single quaternary center. Medium- and high-risk patients managed with a dd-cfDNA-guided protocol (n = 25) were compared with a historical biopsy-based cohort (n = 25). Primary outcomes included biopsy frequency and incidence of clinically significant rejection (ACR ≥ 2R, pAMR ≥ 2, or treated rejection) over the first year post-HT.

Results: The dd-cfDNA group underwent fewer biopsies (p = 0.005), with only 4% requiring ≥ 5 biopsies versus 16% in controls. There was no difference in 12-month rejection incidence (39% vs. 25%, p = 0.99). Biopsy yield was higher in the dd-cfDNA group (p = 0.053). Among rejection episodes, 88% were preceded by increased dd-cfDNA, with a significant relative rise within 30 days (104%, p = 0.021).

Conclusion: In medium- and high-risk pediatric HT recipients, dd-cfDNA-guided surveillance reduced biopsy utilization without increasing rejection. These findings support dd-cfDNA as a clinically useful adjunct to optimize surveillance strategies in pediatric transplantation.