Evidence map›Paper›PMID 23292236›Full record

Trial reportBone marrow transplantation2013

Glutathione S-transferase gene variations influence BU pharmacokinetics and outcome of hematopoietic SCT in pediatric patients.

M Ansari, M A Rezgui, Y Théoret, C R S Uppugunduri, S Mezziani, M-F Vachon, C Desjean, J Rousseau, M Labuda, C Przybyla and 6 more

Registry-linked trialAbstract readClinical Trial
PubMed Publisher
In one paragraph

Trial report in Bone marrow transplantation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01257854 (Polymorphisms and Busulfan Pharmacokinetic Study in Pediatric Transplnatation), which is not on this map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
3.6field-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.

NCT01257854 unknown statusnot on this map

Polymorphisms and Busulfan Pharmacokinetic Study in Pediatric Transplnatation

TypeobservationalSponsorUniversity Hospital, GenevaRan2008 to 2023Enrolled200ConditionsChildren Who Receive a Stem Cell Transplantation With Busulfan IV
3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Pooled it
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  6. Review
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  16. Busulfan Pharmacokinetics in Adenosine Deaminase-Deficient Severe Combined Immunodeficiency Gene Therapy.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2020
    Article
  17. Article
  18. Impact ofPharmaceutics · 2019
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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 at 4 institutions in 3 countries.

M AnsariDepartment of Pediatrics, Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada.
M A Rezgui
Y Théoret
C R S Uppugunduri
S Mezziani
M-F Vachon
C Desjean
J Rousseau
M Labuda
C Przybyla
M Duval
M Champagne
C Peters
H Bittencourt
M Krajinovic
Pediatric Disease Working Parties of the European Blood and Marrow Transplant Group
Centre Hospitalier Universitaire Sainte-Justine · CAUniversité de Montréal · CASt Anna Children's Hospital · ATUniversity Hospital of Geneva · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BU is a key compound of conditioning regimens in children undergoing hematopoietic SCT (HSCT). Inter-individual differences in BU pharmacokinetics (PKs) might affect BU efficacy and toxicity. As BU is mainly metabolized by glutathione S-transferase (GST), we investigated the relationship between GSTA1, GSTM1 and GSTP1 genotypes with first-dose BU PKs, and the relationship with HSCT outcomes in 69 children receiving myeloablative conditioning regimen. GSTM1 null genotype correlated with higher BU exposure and lower clearance in patients older than 4 years (P ≤ 0.04). In accordance with the suggested functional role, GSTA1*A2 haplotype was associated with lower drug levels and higher drug clearance (P ≤ 0.03). Gene-dosage effect was also observed (P ≤ 0.007). GSTA1 haplotypes were associated with HSCT outcomes. Patients with two copies of haplotype *A2 had better event free survival (P=0.03). In contrast, homozygous individuals for haplotypes *B and *B1 had higher occurrence of veno-occlusive disease (P=0.009). GSTM1 null individuals older than 4 years had more frequently graft versus host disease (P=0.03). In conclusion, we showed that GST gene variants influence BU PK and outcomes of HSCT in children. A model for the dosage adjustment with the inclusion of genetic and non-genetic factors should be evaluated in a future prospective validation cohort.

Indexed as

BusulfanHematopoietic Stem Cell TransplantationMyeloablative AgonistsTransplantation ConditioningAdultAge FactorsAllograftsChildChild, PreschoolFemaleGene DosageGlutathione TransferaseHaplotypesHumansInfantMaleBusulfanGlutathione TransferaseMyeloablative Agonists

Identifiers

PMID23292236
OpenAlexW2083918798

What OpenQuestion holds

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Read underepoch 390

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.