Donor-derived cell-free DNA as a composite marker of acute lung allograft dysfunction in clinical care

Michael Keller, Junfeng Sun, Cedric Mutebi, Pali Shah, Deborah Levine, Shambhu Aryal, Aldo Iacono, Irina Timofte, Joby Mathew, Anu Varghese, Cassandra Giner, Sean Agbor-Enoh

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Background: As a marker of underlying lung allograft injury, donor-derived cell-free DNA (dd-cfDNA) may be used to identify episodes of acute allograft injury in lung transplant recipients. We investigated the utility of dd-cfDNA to monitor subjects at risk of acute rejection or infection in routine clinical practice. Methods: This multicenter, retrospective cohort study collected data from lung transplant recipients within 3 years of transplant at 4 centers between March 24, 2020 and September 1, 2020. During this period, as part of routine care during the COVID-19 pandemic, these centers implemented a home-based surveillance program using plasma dd-cfDNA in preference to surveillance bronchoscopy. Dd-cfDNA was used to detect acute lung allograft dysfunction (ALAD) – a composite endpoint of acute rejection and infection. dd-cfDNA levels in patients with ALAD were compared to stable patients. The performance characteristics of dd-cfDNA ≥ 1.0% to detect ALAD were estimated. Results: A total of 175 patients underwent 380 dd-cfDNA measurements, of which 290 were for routine surveillance purposes. dd-cfDNA was higher in patients with ALAD than stable patients (Median (IQR) 1.7% (0.63, 3.1) vs 0.35% (0.22, 0.79), p < 0.001). As an indication of underlying ALAD during surveillance testing, the estimated sensitivity of dd-cfDNA ≥1% was 73.9%, specificity of 87.7%, positive predictive value of 43.4% and negative predictive value of 96.5%. Conclusions: dd-cfDNA identified acute lung allograft dysfunction in asymptomatic lung transplant patients that may not have been identified by using a clinically indicated biopsy strategy alone. dd-cfDNA <1.0% may be useful in ruling out acute rejection and infection, supporting its use as a potential noninvasive marker for surveillance monitoring.

Original languageEnglish (US)
Pages (from-to)458-466
Number of pages9
JournalJournal of Heart and Lung Transplantation
Issue number4
StatePublished - Apr 2022
Externally publishedYes


  • acute lung allograft injury
  • dd-cfDNA
  • lung transplant

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation


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