AUTHOR=Agbor-Enoh Sean , Fraser Ethan , Nadella Nitin , Andargie Temesgen E. , Alnababteh Muhtadi 
  
TITLE=%dd-cfDNA: The New Frontier for Heart/Lung Transplant Surveillance?
  
JOURNAL=Transplant International
  
VOLUME=Volume 38 - 2025
  
YEAR=2025
  
URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2025.15555
  
DOI=10.3389/ti.2025.15555
  
ISSN=1432-2277
  
ABSTRACT=Transplantation improves survival and quality of life, but rejection remains a major threat to allograft longevity. Current surveillance relies heavily on protocols with clinically indicated biopsies, which are invasive, carry procedure-related risks, and have variable sensitivity due to sampling and interpretation limitations. Percent donor-derived cell-free DNA (%dd-cfDNA) has emerged as a noninvasive blood-based biomarker for allograft injury and a potential rule-out test for rejection. Centralized commercial assays are increasingly used in clinical practice; however, published studies report heterogeneous performance and reveal important blind spots and confounders. This review synthesizes the evidence for %dd-cfDNA in thoracic transplantation, delineates its limitations, and outlines emerging cfDNA methodologies that may reduce reliance on invasive biopsies and enable more individualized monitoring strategies.