%dd-cfDNA: The New Frontier for Heart/Lung Transplant Surveillance?

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.