Trial reportBlood2013
Genome-wide study of methotrexate clearance replicates SLCO1B1.
Trial report in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 97 papers, 5 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.
ALINC #17 Treatment for Patients With Low Risk Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Phase III Study
ALinC 17: Protocol for Patients With Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia (ALL): A Phase III Study
Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
Who cites it
97 citing papers in PubMed, 5 syntheses or guidelines pooled it, 210 citations in OpenAlex.
- Systematic review: genetic polymorphisms in the pharmacokinetics of high-dose methotrexate in pediatric acute lymphoblastic leukemia patients.Cancer chemotherapy and pharmacology · 2024Pooled it
- The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms.Clinical pharmacology and therapeutics · 2022Guideline
- Genetic markers in methotrexate treatments.The pharmacogenomics journal · 2018Pooled it
- Human Ontogeny of Drug Transporters: Review and Recommendations of the Pediatric Transporter Working Group.Clinical pharmacology and therapeutics · 2015Pooled it
- The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update.Clinical pharmacology and therapeutics · 2014Guideline
- Association of GATA3 Polymorphisms With Minimal Residual Disease and Relapse Risk in Childhood Acute Lymphoblastic Leukemia.Journal of the National Cancer Institute · 2021Trial
- Urinary coproporphyrin I/(I + III) ratio as a surrogate for MRP2 or other transporter activities involved in methotrexate clearance.British journal of clinical pharmacology · 2014Trial
- Association of Variants in Candidate Pharmacogenes with Response to Mercaptopurine and Methotrexate in Pediatric Acute Lymphoblastic Leukemia: A Single-Center Experience from Croatia.Oncology and therapy · 2026Article
- From Genotype to Functional Risk: A Multi-Omic Approach to Predicting Thiopurine and Methotrexate Co-Therapy-Induced Liver Injury.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Potential of pharmacogenetics in treatment of chronic inflammatory diseases - a danish report overview from 2000 - 2024.The pharmacogenomics journal · 2026Review
- Pathway-Informed Machine Learning Identifies Genetic Predictors of High-Dose Methotrexate-Induced Mucositis in Pediatric Acute Lymphoblastic Leukemia.Clinical pharmacology and therapeutics · 2026Article
- Review
- Pharmacogenetic hSLCO1B1*14-Guided Dosing of Methotrexate in Transgenic Arthritic Mice Normalizes Exposure and Response.Clinical and translational science · 2026Article
- Pharmacogenomics Applied to Acute Leukemias: Identifying Clinically Relevant Genetic Variants.Biomedicines · 2025Review
- The Role of Candidate Polymorphisms in Drug Transporter Genes on High-Dose Methotrexate in the Consolidation Phase of the AIEOP-BFM ALL 2009 Protocol.Clinical and translational science · 2025Article
- Population Pharmacokinetic and Toxicity Analysis of High-Dose Methotrexate in Patients with Central Nervous System Lymphoma.Clinical pharmacokinetics · 2025Article
- Evaluation of methotrexate Pharmacogenomic variation to predict acute neurotoxicity in children with acute lymphoblastic leukemia.Pharmacotherapy · 2025Article
- Hypoalbuminemia in children with acute lymphoblastic leukemia: relation to asparaginase therapy and impact on high dose methotrexate elimination.Cancer chemotherapy and pharmacology · 2024Article
- Relationship between SLCO1B1 polymorphisms and methotrexate intolerance in Mexican children with juvenile idiopathic arthritis.Clinical rheumatology · 2024Observational
- Clinical Risk Factors for High-Dose Methotrexate-Induced Oral Mucositis Following Individualized Dosing.Cancer medicine · 2024Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
Methotrexate clearance can influence the cure of and toxicity in children with acute lymphoblastic leukemia (ALL). We estimated methotrexate plasma clearance for 1279 patients with ALL treated with methotrexate (24-hour infusion of a 1 g/m2 dose or 4-hour infusion of a 2 g/m2 dose) on the Children’s Oncology Group P9904 and P9905 protocols. Methotrexate clearance was lower in older children (P = 7 x 10(-7)), girls (P = 2.7 x 10(-4)), and those who received a delayed-intensification phase (P = .0022). A genome-wide analysis showed that methotrexate clearance was associated with polymorphisms in the organic anion transporter gene SLCO1B1 (P = 2.1 x 10(-11)). This replicates findings using different schedules of high-dose methotrexate in St Jude ALL treatment protocols; a combined meta-analysis yields a P value of 5.7 x 10(-19) for the association of methotrexate clearance with SLCO1B1 SNP rs4149056. Validation of this variant with 5 different treatment regimens of methotrexate solidifies the robustness of this pharmacogenomic determinant of methotrexate clearance. This study is registered at http://www.clinicaltrials.gov as NCT00005585 and NCT00005596.
Indexed as
Identifiers
What OpenQuestion holds
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.