Evidence map›Paper›PMID 37971879›Full record

ArticleThe Journal of clinical investigation2024

Chronic graft-versus-host disease detected by tissue-specific cell-free DNA methylation biomarkers.

Batia Avni, Daniel Neiman, Elior Shaked, Ofer Gal-Rosenberg, Sigal Grisariu, Mona Kuzli, Ilai Avni, Andrea Fracchia, Polina Stepensky, Tsila Zuckerman and 8 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06715046 (Cell Free DNA Profiling As a Tool to Monitor Clinically-Relevant Events in Allogeneic Hematopoietic Stem Cell Transplantation), which is not on this map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
3.2field-weighted citation impact, top 8% of its field
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.

NCT06715046 recruitingnot on this map

Cell Free DNA Profiling As a Tool to Monitor Clinically-Relevant Events in Allogeneic Hematopoietic Stem Cell Transplantation

TypeobservationalSponsorUniversity of Turin, ItalyRan2024 to 2026Enrolled30ConditionsGVHD - Graft-Versus-Host Disease, Infections After HSCT, Transplant Associated Microangiopathy TAM, Sinusoidal Obstruction Syndrome (SOS)ArmsSample collation for cfDNA methylation analysis, Sample collection for EV phenotype analysis
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 11 citations in OpenAlex.

  1. A multi-analyte blood test for acute spinal cord injury.The Journal of clinical investigation · 2025
    Trial
  2. Article
  3. Chronic graft-versus-host disease.Nature reviews. Disease primers · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. 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

18 authors at 3 institutions in 1 country.

Batia AvniBone Marrow Transplantation and Cancer Immunotherapy Department, Hadassah University Medical Center and Faculty of Medicine, the Hebrew University, Jerusalem, Israel.
Daniel NeimanDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Elior ShakedDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Ofer Gal-RosenbergDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Sigal GrisariuBone Marrow Transplantation and Cancer Immunotherapy Department, Hadassah University Medical Center and Faculty of Medicine, the Hebrew University, Jerusalem, Israel.
Mona KuzliBone Marrow Transplantation and Cancer Immunotherapy Department, Hadassah University Medical Center and Faculty of Medicine, the Hebrew University, Jerusalem, Israel.
Ilai AvniFaculty of Data and Decision Sciences, Institute of Technology - Technion, Haifa, Israel.
Andrea FracchiaBone Marrow Transplantation and Cancer Immunotherapy Department, Hadassah University Medical Center and Faculty of Medicine, the Hebrew University, Jerusalem, Israel.
Polina StepenskyBone Marrow Transplantation and Cancer Immunotherapy Department, Hadassah University Medical Center and Faculty of Medicine, the Hebrew University, Jerusalem, Israel.
Tsila ZuckermanHematology Institute and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel.
Ahinoam Lev-SagieDepartment of Obstetrics and Gynecology, Hadassah University Medical Center and Faculty of Medicine, the Hebrew University, Jerusalem, Israel.
Ilana Fox-FisherDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Sheina PiyanzinDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Joshua MossDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Seth J SalpeterDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Benjamin GlaserEndocrinology and Metabolism Service, Hadassah University Medical Center and Faculty of Medicine, the Hebrew University, Jerusalem, Israel.
Ruth ShemerDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Yuval DorDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Hadassah Medical Center · ILRambam Health Care Campus · ILTechnion – Israel Institute of Technology · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAccurate detection of graft-versus-host disease (GVHD) is a major challenge in the management of patients undergoing hematopoietic stem cell transplantation (HCT). Here, we demonstrated the use of circulating cell-free DNA (cfDNA) for detection of tissue turnover and chronic GVHD (cGVHD) in specific organs.

methodsWe established a cocktail of tissue-specific DNA methylation markers and used it to determine the concentration of cfDNA molecules derived from the liver, skin, lungs, colon, and specific immune cells in 101 patients undergoing HCT.

resultsPatients with active cGVHD showed elevated concentrations of cfDNA, as well as tissue-specific methylation markers that agreed with clinical scores. Strikingly, transplanted patients with no clinical symptoms had abnormally high levels of tissue-specific markers, suggesting hidden tissue turnover even in the absence of evident clinical pathology. An integrative model taking into account total cfDNA concentration, monocyte/macrophage cfDNA levels and alanine transaminase was able to correctly identify GVHD with a specificity of 86% and precision of 89% (AUC of 0.8).

conclusioncfDNA markers can be used for the detection of cGVHD, opening a window into underlying tissue dynamics in patients that receive allogeneic stem cell transplants.

fundingThis work was supported by grants from the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine, The Israel Science Foundation, the Waldholtz/Pakula family, the Robert M. and Marilyn Sternberg Family Charitable Foundation and the Helmsley Charitable Trust (to YD).

Indexed as

Bronchiolitis Obliterans SyndromeCell-Free Nucleic AcidsGraft vs Host DiseaseHematopoietic Stem Cell TransplantationBiomarkersChronic DiseaseDNA MethylationGenetic MarkersHumansBiomarkersCell-Free Nucleic AcidsGenetic MarkersStem cell transplantationTransplantation

Identifiers

PMID37971879
PMCPMC10786696
OpenAlexW4388722726

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.