TIBURON study: Donor-derived and total cfDNA across lung allograft injury states

Results from TIBURON (Transplant Investigation of Biomarker Utility in Rejection), a multicenter, cross-sectional, observational pilot study evaluating donor-derived cfDNA (dd-cfDNA) and total cfDNA (TcfDNA) across lung allograft injury states in adult lung transplant recipients, were published in The Journal of Molecular Diagnostics by Betensley et al. The study analyzed 354 plasma samples from 66 lung transplant recipients; stratified into stable, acute rejection (AR), infectious disease (ID), and chronic lung allograft dysfunction (CLAD) cohorts, with stable double lung transplant recipients further stratified as baseline lung allograft dysfunction (BLAD) and non-BLAD. 

Key data: Median dd-cfDNA was higher in the AR vs the stable cohort (2.08% vs 0.60% p = 0.019), with trends toward elevation in the ID (1.19%; p = 0.066) and CLAD cohorts (1.38%; p = 0.111). No significant differences in dd-cfDNA levels were observed between the AR cohort and either the ID or CLAD cohorts. TcfDNA was elevated only in the ID cohort (p = 0.043), and levels did not differentiate ID from AR (p = 0.234). Following AR treatment, median dd-cfDNA decreased from 2.41% at baseline to 0.80% at Day 7 (p = 0.004). Beyond 12 months post-transplant, TcfDNA was higher in BLAD vs non-BLAD (13,843 cp/mL vs 7,768 cp/mL; p = 0.005). 

Key learning: dd-cfDNA and TcfDNA show value in assessing lung allograft dysfunction beyond AR, including monitoring infection, treatment response, and BLAD.