542 The association between cell-free DNA and lung transplant survival

Objectives/Goals: Lung transplant is a life-saving surgery for patients with advanced lung diseases yet long-term survival remains poor. The clinical features and lung injury patterns of lung transplant recipients who die early versus those who survive longer term remain undefined. Here, we use cell...

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Main Authors: Rohan Meda, Yi-Ping Fu, Hyesik Kong, Moon Kyoo Jang, Temesgen Andargie, Woojin Park, Jae Lee, Ilker Tunc, Gerald J Berry, Charles C Marboe, Pali D Shah, Steven D Nathan, Michael B Keller, Sean Agbor-Enoh
Format: Article
Language:English
Published: Cambridge University Press 2025-04-01
Series:Journal of Clinical and Translational Science
Online Access:https://www.cambridge.org/core/product/identifier/S2059866124011142/type/journal_article
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Summary:Objectives/Goals: Lung transplant is a life-saving surgery for patients with advanced lung diseases yet long-term survival remains poor. The clinical features and lung injury patterns of lung transplant recipients who die early versus those who survive longer term remain undefined. Here, we use cell-free DNA and rejection parameters to help elucidate this further. Methods/Study Population: Lung transplant candidacy prioritizes patients who have a high mortality risk within 2 years and will likely survive beyond 5 years. We stratified patients who died within 2 years of transplant as early death (n = 50) and those who survived past 5 years as long-term survivors (n = 53). Lung transplant recipients had serial blood collected as part of two prospective cohort studies. Cell-free DNA (cfDNA) was quantified using relative (% donor-derived cfDNA {%ddcfDNA}) and absolute (nuclear-derived {n-cfDNA}, mitochondrial-derived {mt-cfDNA}) measurements. As part of routine posttransplant clinical care, all patients underwent pulmonary function testing (PFT), surveillance bronchoscopy with bronchoalveolar lavage (BAL), transbronchial biopsy (TBBx), and donor-specific antibody testing (DSA). Results/Anticipated Results: Over the first 2 years after transplant, the number of episodes of antibody-mediated rejection (p) Discussion/Significance of Impact: Clinically, early-death patients perform worse on routine surveillance PFTs and experience a worse degree of CLAD. These patients also have higher levels of cfDNA as quantified by n-cfDNA and mt-cfDNA. These results provide preliminary evidence that early-death patients have worse allograft rejection, dysfunction, and molecular injury.
ISSN:2059-8661