Evidence map›Paper›PMID 25425682›Full record

ArticleHaematologica2015

Cyclosporine and methotrexate-related pharmacogenomic predictors of acute graft-versus-host disease.

Isabelle Laverdière, Chantal Guillemette, Ryad Tamouza, Pascale Loiseau, Regis Peffault de Latour, Marie Robin, Félix Couture, Alain Filion, Marc Lalancette, Alan Tourancheau and 3 more

Open access · goldAbstract read
In one paragraph

Article in Haematologica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 2 pooled it
0.4field-weighted citation impact, top 36% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 2 syntheses or guidelines pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Polymorphisms inFrontiers in pharmacology · 2025
    Pooled it
  3. Article
  4. Impact of genetic variants in the solute carrier (Cancer drug resistance (Alhambra, Calif.) · 2024
    Review
  5. Review
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

13 authors at 8 institutions in 2 countries.

Isabelle LaverdièrePharmacogenomics Laboratory, Centre Hospitalier de l'Université Laval (CHU de Québec) Research Center, Faculty of Pharmacy, Laval University, Québec, Canada.
Chantal GuillemettePharmacogenomics Laboratory, Centre Hospitalier de l'Université Laval (CHU de Québec) Research Center, Faculty of Pharmacy, Laval University, Québec, Canada.
Ryad TamouzaINSERM UMRS 940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint Louis, CIB-HOG, AP-HP, Paris, France.
Pascale LoiseauINSERM UMRS 940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint Louis, CIB-HOG, AP-HP, Paris, France.
Regis Peffault de LatourInserm UMRS 940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Service d'Hématologie-Greffe de Moelle, Hôpital Saint-Louis, AP-HP, Paris, France.
Marie RobinInserm UMRS 940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Service d'Hématologie-Greffe de Moelle, Hôpital Saint-Louis, AP-HP, Paris, France.
Félix CoutureCHU de Québec Research Center; Faculty of Medicine, Laval University, Québec, Canada.
Alain FilionCHU de Québec Research Center; Faculty of Medicine, Laval University, Québec, Canada.
Marc LalancetteCHU de Québec Research Center; Faculty of Medicine, Laval University, Québec, Canada.
Alan TourancheauPharmacogenomics Laboratory, Centre Hospitalier de l'Université Laval (CHU de Québec) Research Center, Faculty of Pharmacy, Laval University, Québec, Canada.
Dominique CharronINSERM UMRS 940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint Louis, CIB-HOG, AP-HP, Paris, France.
Gérard SociéInserm UMRS 940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Service d'Hématologie-Greffe de Moelle, Hôpital Saint-Louis, AP-HP, Paris, France.
Éric LévesqueCHU de Québec Research Center; Faculty of Medicine, Laval University, Québec, Canada eric.levesque@crchuq.ulaval.ca gerard.socie@paris7.jussieu.fr.
Centre hospitalier de l'Université Laval · CAAssistance Publique – Hôpitaux de Paris · FRUniversité Laval · CACentre hospitalier universitaire de Québec · CADélégation Paris 7 · FRHôpital Saint-Louis · FRInserm · FRUniversité Paris Cité · FR

Funding

Canadian Institutes of Health Research MOP-89954
6 · The paper itself

Abstract

Effective immunosuppression is mandatory to prevent graft-versus-host disease and to achieve a successful clinical outcome of hematopoietic stem cell transplantation. Here we tested whether germline single nucleotide polymorphisms in 20 candidate genes related to methotrexate and cyclosporine metabolism and activity influence the incidence of graft-versus-host disease in patients who undergo stem cell transplantation for hematologic disorders. Recipient genetic status of the adenosine triphosphate-binding cassette sub-family C1 and adenosine triphosphate-binding cassette sub-family C2 transporters, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/ inosine monophosphate cyclohydrolase within the methotrexate pathway, and nuclear factor of activated T cells (cytoplasmic 1) loci exhibit a remarkable influence on severe acute graft-versus-host disease prevalence. Indeed, an increased risk of acute graft-versus-host disease was observed in association with single nucleotide polymorphisms located in 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (hazard ratio=3.04; P=0.002), nuclear factor of activated T cells (cytoplasmic 1) (hazard ratio=2.69; P=0.004), adenosine triphosphate-binding cassette sub-family C2 (hazard ratio=3.53; P=0.0018) and adenosine triphosphate-binding cassette sub-family C1 (hazard ratio=3.67; P=0.0005). While donor single nucleotide polymorphisms of dihydrofolate reductase and solute carrier family 19 (member 1) genes are associated with a reduced risk of acute graft-versus-host disease (hazard ratio=0.32-0.41; P=0.0009-0.008), those of nuclear factor of activated T cells (cytoplasmic 2) are found to increase such risk (hazard ratio=3.85; P=0.0004). None of the tested single nucleotide polymorphisms was associated with the occurrence of chronic graft-versus-host disease. In conclusion, by targeting drug-related biologically relevant genes, this work emphasizes the potential role of germline biomarkers in predicting acute graft-versus-host disease. Further investigations are warranted to improve our understanding of these relationships to personalize immunosuppressive therapy and optimize outcomes.

Indexed as

PharmacogeneticsAcute DiseaseAdultBiomarkers, TumorCanadaChronic DiseaseCohort StudiesCyclosporineFemaleFollow-Up StudiesGraft vs Host DiseaseHematologic NeoplasmsHematopoietic Stem Cell TransplantationHumansImmunosuppressive AgentsIncidenceBiomarkers, TumorCyclosporineImmunosuppressive AgentsMethotrexate

Identifiers

PMID25425682
PMCPMC4803136
OpenAlexW2107224115

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.