Trial reportBritish journal of clinical pharmacology2013
Thiopurine methyltransferase genotype-phenotype discordance and thiopurine active metabolite formation in childhood acute lymphoblastic leukaemia.
Trial report in British journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 8 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
31 citing papers in PubMed, 8 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2025 Update.Clinical pharmacology and therapeutics · 2026Guideline
- British Society of Gastroenterology guidelines for diagnosis and management of autoimmune hepatitis.Gut · 2025Guideline
- Adherence to Oral Chemotherapy in Acute Lymphoblastic Leukemia during Maintenance Therapy in Children, Adolescents, and Young Adults: A Systematic Review.Current oncology (Toronto, Ont.) · 2023Pooled it
- Polymorphic variation in TPMT is the principal determinant of TPMT phenotype: A meta-analysis of three genome-wide association studies.Clinical pharmacology and therapeutics · 2017Pooled it
- Thiopurine S-methyltransferase testing for averting drug toxicity: a meta-analysis of diagnostic test accuracy.The pharmacogenomics journal · 2016Pooled it
- Thiopurine S-methyltransferase testing for averting drug toxicity in patients receiving thiopurines: a systematic review.Pharmacogenomics · 2016Pooled it
- Pooled it
- Pooled it
- Thiopurine methyltransferase and treatment outcome in the UK acute lymphoblastic leukaemia trial ALL2003.British journal of haematology · 2015Trial
- Methotrexate binds to recombinant thiopurine S-methyltransferase and inhibits enzyme activity after high-dose infusions in childhood leukaemia.European journal of clinical pharmacology · 2013Trial
- Relationship Between Thiopurine S-Methyltransferase Genotype and Phenotype in Pediatric Acute Lymphoblastic Leukemia in Addis Ababa, Ethiopia.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2025Article
- The evaluation of the impact of NUDT15 variants on thiopurine metabolism in Japanese children with acute lymphoblastic leukemia.Cancer chemotherapy and pharmacology · 2025Article
- Competing Benefits and Competing Hazards: The Benefit to Harm Balance in Individual Patients in Rational Therapeutics.Drug safety · 2024Article
- Article
- A bioinformatics approach to the identification of novel deleterious mutations of human TPMT through validated screening and molecular dynamics.Scientific reports · 2022Article
- Pharmacogenomic testing in paediatrics: Clinical implementation strategies.British journal of clinical pharmacology · 2022Review
- Biomarkers for gastrointestinal adverse events related to thiopurine therapy.World journal of gastroenterology · 2021Article
- Thiopurine pharmacogenomics and pregnancy in inflammatory bowel disease.Journal of gastroenterology · 2021Review
- Article
- Modeling the Outcome of Systematic TPMT Genotyping or Phenotyping Before Azathioprine Prescription: A Cost-Effectiveness Analysis.Molecular diagnosis & therapy · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsIn children with acute lymphoblastic leukaemia (ALL) bone marrow activity can influence red blood cell (RBC) kinetics, the surrogate tissue for thiopurine methyltransferase (TPMT) measurements. The aim of this study was to investigate TPMT phenotype-genotype concordance in ALL, and the influence of TPMT on thiopurine metabolite formation.
methodsWe measured TPMT (activity, as units ml(-1) packed RBCs and genotype) at diagnosis (n = 1150) and TPMT and thioguanine nucleotide (TGN) and methylmercaptopurine nucleotide (MeMPN) metabolites (pmol/8 × 10(8) RBCs) during chemotherapy (n = 1131) in children randomized to thioguanine or mercaptopurine on the United Kingdom trial ALL97.
resultsMedian TPMT activity at diagnosis (8.5 units) was significantly lower than during chemotherapy (13.8 units, median difference 5.1 units, 95% confidence interval (CI) 4.8, 5.4, P < 0.0001). At diagnosis genotype-phenotype was discordant. During chemotherapy the overall concordance was 92%, but this fell to 55% in the intermediate activity cohort (45% had wild-type genotypes). For both thiopurines TGN concentrations differed by TPMT status. For mercaptopurine, median TGNs were higher in TPMT heterozygous genotype (754 pmol) than wild-type (360 pmol) patients (median difference 406 pmol, 95% CI 332, 478, P < 0.0001), whilst median MeMPNs, products of the TPMT reaction, were higher in wild-type (10 650 pmol) than heterozygous patients (3868 pmol) (P < 0.0001). In TPMT intermediate activity patients with a wild-type genotype, TGN (median 366 pmol) and MeMPN (median 8590 pmol) concentrations were similar to those in wild-type, high activity patients.
conclusionsIn childhood ALL, TPMT activity should not be used to predict heterozygosity particularly in blood samples obtained at disease diagnosis. Genotype is a better predictor of TGN accumulation during chemotherapy.
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