Evidence map›Paper›PMID 41619918›Full record

Observational studyThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation2026

Donor-derived cell-free DNA associated with increased risk of chronic lung allograft dysfunction and mortality: Are absolute levels better than percentage?

Kellie Phipps, Hyesik Kong, Han Su, Auriel Sanders, Michael Keller, Muhtadi Alnababteh, Pali Shah, Shambhu Aryal, GRAfT Investigators, Moon Kyoo Jang and 6 more

Registry-linked trialAbstract readMulticenter StudyObservational Study
In one paragraph

Observational study in The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02423070 (Genome Transplant Dynamics), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02423070 recruitingnot on this map

Genome Transplant Dynamics

TypeobservationalSponsorNational Heart, Lung, and Blood Institute (NHLBI)Ran2015 to 2034Enrolled991ConditionsThoracic Organ Transplantation
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Utility of donor-derived cell-free DNA testing after lung transplantation in the precision medicine era.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2026
    Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Kellie PhippsGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laboratory of Applied Precision Omics (APO), Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Albert Einstein College of Medicine, Bronx, New York.
Hyesik KongGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laboratory of Applied Precision Omics (APO), Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Han SuOffice of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Statistics, George Washington University, Washington, District of Columbia.
Auriel SandersGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laboratory of Applied Precision Omics (APO), Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Michael KellerGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laboratory of Applied Precision Omics (APO), Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Critical Care Medicine and Pulmonary Department, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Medicine, University of Maryland Medical Center, Baltimore, Maryland.
Muhtadi AlnababtehGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laboratory of Applied Precision Omics (APO), Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Critical Care Medicine and Pulmonary Department, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Medicine, University of Maryland Medical Center, Baltimore, Maryland.
Pali ShahGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Department of Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland.
Shambhu AryalGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Department of Medicine, Inova Medical Group, Transplant Specialists, Fairfax, Virginia.
GRAfT Investigators
Moon Kyoo JangGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laboratory of Applied Precision Omics (APO), Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Woojin ParkGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laboratory of Applied Precision Omics (APO), Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Temesgen AndargieGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laboratory of Applied Precision Omics (APO), Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Jonathan OrensDepartment of Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland.
Steven D NathanGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Department of Medicine, Inova Medical Group, Transplant Specialists, Fairfax, Virginia.
Xin TianGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Sean Agbor-EnohGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laboratory of Applied Precision Omics (APO), Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Critical Care Medicine and Pulmonary Department, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland. Electronic address: sean.agbor-enoh@nih.gov.

Funding

Cell-free DNA to detect transplant rejectionZIAHL006268 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI AGBOR-ENOH, SEAN · 2021 to 2025
$8.8M
Use of donor-derived cell-free DNA for risk stratification and post-treatment monitoring of lung transplant patients at risk for chronic lung allograft dysfunctionK22HL166368 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI Michael Keller · 2025 to 2026
$498k
Intramural NIH HHS ZIA HL006268NHLBI NIH HHS K22 HL166368
6 · The paper itself

Abstract

backgroundThere is a need for reliable methods to risk-stratify patients for chronic lung allograft dysfunction (CLAD) and death. A proof-of-concept study reported the predictive utility of early post-transplant levels of percent donor-derived cell-free DNA (dd-cfDNA), a measure affected by host cell-free DNA changes. This study assesses the predictive utility of dd-cfDNA in and beyond the early post-transplant period using absolute dd-cfDNA, a measure not affected by host cell-free DNA changes.

methodsThis multicenter study (Genome Research Alliance for Transplantation, NCT02423070) of lung transplant patients measured serial absolute dd-cfDNA in copies/ml and percent dd-cfDNA. We performed multivariable Cox regression analyses to determine the association between dd-cfDNA and the composite outcome of moderate-to-severe CLAD and/or death; the early post-transplant model used mean dd-cfDNA levels within days 30 to 91. A time-dependent model used dd-cfDNA values beyond the early post-transplant period.

resultsThe cohort included 242 patients and 2,838 serial dd-cfDNA assessments. Absolute dd-cfDNA had similar or better performance than percent dd-cfDNA to risk-stratify patients for moderate-to-severe CLAD/death. High absolute dd-cfDNA levels in the early post-transplant period (hazard ratio 1.29, 95% confidence interval 1.04-1.60, p = 0.018) or at any time post-transplant (hazard ratio 1.51, 95% confidence interval 1.32-1.73, p < 0.001) were associated with an increased risk of moderate-to-severe CLAD/death, and absolute dd-cfDNA levels >250 copies/ml were associated with an elevated risk of moderate-to-severe CLAD/death.

conclusionsThe study reports dd-cfDNA risk assessment models for moderate-to-severe CLAD/death; absolute values showed similar or better predictive performance than percent.

Indexed as

Cell-Free Nucleic AcidsLung TransplantationPrimary Graft DysfunctionTissue DonorsAllograftsChronic DiseaseFemaleFollow-Up StudiesHumansMaleMiddle AgedRisk AssessmentRisk FactorsSurvival RateCell-Free Nucleic Acidschronic lung allograft dysfunctiondonor–derived cell-free DNAhigh allograft injurylung transplantrisk stratification

Identifiers

PMID41619918
PMCPMC13222714

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.