Donor-derived cell-free DNA testing for noninvasive monitoring of allograft rejection after lung transplantation.

BACKGROUND

Donor-derived cell-free DNA (dd-cfDNA) is a promising noninvasive marker of graft injury after lung transplantation (LTx), but its real-world value for identifying rejection-associated allograft injury and its interpretation across infection status and transplant procedures remain uncertain.

METHODS

This single-center retrospective study consecutively included LTx recipients undergoing inpatient follow-up and dd-cfDNA testing from February 2024 to March 2026. Analyses used observations obtained ≥1 month after LTx. Diagnostic performance was assessed by ROC analysis, and the association between dd-cfDNA (%) and clinically diagnosed rejection was evaluated by multivariable logistic regression. Single- and double-LTx recipients were compared, and a stable-state correction factor was explored.

RESULTS

Among 161 recipients, 218 dd-cfDNA tests were performed; 196 non-perioperative observations were analyzed, including 64 rejection and 132 non-rejection observations. Both dd-cfDNA (%) and dd-cfDNA (copies/mL) were higher in rejection. dd-cfDNA (%) yielded an AUC of 0.677 (95% CI, 0.600-0.755), with a cutoff of 1.03% (sensitivity, 90.6%; specificity, 40.9%). dd-cfDNA (copies/mL) yielded an AUC of 0.666 (95% CI, 0.584-0.748), with a cutoff of 104.10 copies/mL (sensitivity, 48.4%; specificity, 78.8%). dd-cfDNA (%) remained independently associated with rejection (adjusted OR, 1.36; 95% CI, 1.15-1.62; P<0.001). Single-LTx recipients had lower dd-cfDNA (%) than double-LTx recipients under stable and rejection conditions; this difference was attenuated after correction (CF = 1.54).

CONCLUSIONS

dd-cfDNA may serve as a noninvasive adjunct for identifying rejection-associated allograft injury after LTx. Infection and transplant procedure should be considered during interpretation, and stable-state correction may improve comparability between single- and double-LTx recipients.