Comparison of donor-derived cell-free DNA fractions between combined heart-lung vs isolated heart or lung transplant recipients.

Abstract

Donor-derived cell-free DNA (dd-cfDNA) is a validated marker of graft injury following isolated heart or lung transplantation. However, no such studies exist for heart-lung transplant (HLTx) recipients.HLTx recipients at a single center were screened for enrollment between August 2022 and September 2024. Heart transplant (HTx) and lung transplant (LTx) recipients from the same center served as comparison groups. Plasma dd-cfDNA samples were collected before surveillance bronchoscopies and clinically indicated evaluation for graft dysfunction during the first-year post-transplant. Stable patients demonstrated no evidence of rejection, infection, or injury at any time. Pulmonary function test results (PFTs) were monitored and compared.In total, 92 HTx, 39 LTx, and 10 HLTx recipients were enrolled. The HLTx cohort had a significantly different dd-cfDNA profile compared to LTx and HTx (median dd-cfDNA in HLTx: 0.14, LTx: 0.34, and HTx: 0.06, p<0.001), with values lower than LTx in both stable and unstable groups. One-year post-transplant, 31% of HLTx patients were unstable, compared to 84% of LTx recipients. Acute rejection occurred in 10%, 10.5%, and 22.3%, of the HLTx, HTx, and LTx cohorts, respectively. PFTs at 1-year were also significantly different; in the HLTx group, percent predicted FEV1 values were increasing, but these parameters were decreasing in the LTx cohort.This study indicates that dd-cfDNA could be a useful tool for monitoring allograft health following HLTx, though sample size was limited. Further research is underway to elucidate the mechanisms that account for these findings and to establish thresholds for detecting graft injury in this distinct cohort.

View details for DOI 10.1016/j.jhlto.2026.100569

View details for PubMedID 42220978

View details for PubMedCentralID PMC13218254