Trial reportLeukemia2009
Thiopurine methyltransferase activity is related to the risk of relapse of childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study.
Trial report in Leukemia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02912676 (A Phase 1-2 Study of 6-Thioguanine in Combination With Methotrexate and 6-Mercaptopurine During Maintenance Therapy of Childhood, Adolescent, and Adult Lymphoblastic Non-Hodgkin's Lymphoma and Acute Lymphoblastic Leukemia), which is not on this map. Cited by 55 papers, 7 of them syntheses that pooled 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.
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.
A Phase 1-2 Study of 6-Thioguanine in Combination With Methotrexate and 6-Mercaptopurine During Maintenance Therapy of Childhood, Adolescent, and Adult Lymphoblastic Non-Hodgkin's Lymphoma and Acute Lymphoblastic Leukemia
Who cites it
55 citing papers in PubMed, 7 syntheses or guidelines pooled it, 123 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
- Association ofHaematologica · 2024Pooled it
- Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update.Clinical pharmacology and therapeutics · 2019Guideline
- Association between the c.415C > T, c.52G > A, and 36_37insGGAGTC polymorphisms ofDrug design, development and therapy · 2019Pooled it
- Thiopurine S-methyltransferase testing for averting drug toxicity in patients receiving thiopurines: a systematic review.Pharmacogenomics · 2016Pooled it
- NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity.Nature genetics · 2016Pooled it
- Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing.Clinical pharmacology and therapeutics · 2011Guideline
- Association of GATA3 Polymorphisms With Minimal Residual Disease and Relapse Risk in Childhood Acute Lymphoblastic Leukemia.Journal of the National Cancer Institute · 2021Trial
- DNA-thioguanine nucleotide as a treatment marker in acute lymphoblastic leukemia patients with NUDT15 variant genotypes.PloS one · 2021Trial
- Thiopurine methyltransferase and treatment outcome in the UK acute lymphoblastic leukaemia trial ALL2003.British journal of haematology · 2015Trial
- Thiopurine pharmacogenomics: association of SNPs with clinical response and functional validation of candidate genes.Pharmacogenomics · 2014Trial
- Trial
- Long-term results of St Jude Total Therapy Studies 11, 12, 13A, 13B, and 14 for childhood acute lymphoblastic leukemia.Leukemia · 2010Trial
- Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia.Leukemia · 2010Trial
- Trial
- Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia, 1984-1999.Leukemia · 2010Trial
- Pharmacogenetic Predictors of Chemotherapy Treatment-Related Toxicities in Paediatric and Adolescent Acute Lymphoblastic Leukemia: A Systematic Review, Meta-Analysis and Literature-Based Candidate Prioritization.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Maintenance therapy for acute lymphoblastic leukemia: basic science and clinical translations.Leukemia · 2022Review
- Bayesian hierarchical lasso Cox model: A 9-gene prognostic signature for overall survival in gastric cancer in an Asian population.PloS one · 2022Article
- Increments in DNA-thioguanine level during thiopurine-enhanced maintenance therapy of acute lymphoblastic leukemia.Haematologica · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 6 institutions in 5 countries.
Funding
Abstract
Myelotoxicity during thiopurine therapy is enhanced in patients, who because of single nucleotide polymorphisms have decreased activity of the enzyme thiopurine methyltransferase (TPMT) and thus more thiopurine converted into 6-thioguanine nucleotides. Of 601 children with acute lymphoblastic leukemia (ALL) who were treated by the NOPHO ALL-92 protocol, 117 had TPMT genotype determined, whereas for 484 patients only erythrocyte TPMT activity was available. The latter were classified as heterozygous, if TPMT activity was <14 IU/ml, or deficient (<1.0 IU/ml). 526 patients had TPMT wild type, 73 were presumed heterozygous, and two were TPMT deficient. Risk of relapse was higher for the 526 TPMT wild type patients than for the remaining 75 patients (18 vs 7%, P=0.03). In Cox multivariate regression analysis, sex (male worse; P=0.06), age (higher age worse, P=0.02), and TPMT activity (wild type worse; P=0.02) were related to risk of relapse. Despite a lower probability of relapse, patients in the low TPMT activity group did not have superior survival (P=0.82), possibly because of an excess of secondary cancers among these 75 patients (P=0.07). These data suggest that children with ALL and TPMT wild type might have their cure rate improved, if the pharmacokinetics/-dynamics of TPMT low-activity patients could be mimicked without a concurrent excessive risk of second cancers.
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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.