Transpl Int. 2025 Dec 29;38:15555. doi: 10.3389/ti.2025.15555. eCollection 2025.

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.

PMID:41531497 | PMC:PMC12791046 | DOI:10.3389/ti.2025.15555

JACC Heart Fail. 2025 Nov 21:102782. doi: 10.1016/j.jchf.2025.102782. Online ahead of print.

NO ABSTRACT

PMID:41273317 | DOI:10.1016/j.jchf.2025.102782

Chest. 2025 Sep;168(3):581-583. doi: 10.1016/j.chest.2025.04.023.

NO ABSTRACT

PMID:40935546 | DOI:10.1016/j.chest.2025.04.023

Eur Respir J. 2025 Jul 31:2402537. doi: 10.1183/13993003.02537-2024. Online ahead of print.

ABSTRACT

BACKGROUND: Allograft injury in the early post-transplant period is a known risk factor of death after lung transplantation. However, the recipient tissue injury profile and its association with outcomes remain unexplored. This study leverages cell-free DNA (cfDNA) to test this association.

METHODS: The prospective cohort multicenter study included lung transplant recipients (GRAfT, NCT02423070) with serial plasma measurements of recipient-derived (rd)-cfDNA using digital droplet PCR. Non-transplant healthy controls were recruited as the comparator. Whole-genome bisulfite sequencing identified tissue sources of cfDNA. Mean rd-cfDNA levels within 30 days post-transplant was computed. Multivariable regression models were used to assess the association between rd-cfDNA tertiles and the primary outcome of death and secondary outcomes.

RESULTS: The study included 215 patients with 2530 cfDNA values, including 675 cfDNA assessments in the first 30 days. Median rd-cfDNA levels in the first 30 days post-transplant were ∼16-fold higher than cfDNA for healthy controls. Patients in the highest tertile rd-cfDNA group had lower lung function post-transplant, and increased risk of death (HR: 3.15, 95% CI: 1.59-6.24, p<0.001) and acute rejection (HR 2.33, 95% CI: 1.33-4.08, p=0.03), compared to the low/middle tertile group. Tissue-specific cfDNA sources were also distinct cfDNA in the highest versus lowest rd-cfDNA tertiles, with cfDNA from innate immune cells serving as the strongest predictor of mortality.

CONCLUSION: Post-transplant recipient tissue injury varies between lung transplant patients and is associated with increased risk of acute rejection and mortality.

PMID:40744691 | DOI:10.1183/13993003.02537-2024