ReviewCancers2021
Systematic Review of Pharmacogenetic Factors That Influence High-Dose Methotrexate Pharmacokinetics in Pediatric Malignancies.
Review in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Factors influencing methotrexate pharmacokinetics highlight the need for individualized dose adjustment: a systematic review.European journal of clinical pharmacology · 2024Pooled it
- Pharmacological assessment of drugs retained in the 1Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Successful re-exposure to high-dose methotrexate after severely delayed methotrexate elimination and renal toxicity in children with acute lymphoblastic leukemia.Haematologica · 2026Article
- A Model-Informed Early Prediction of Methotrexate-Induced Acute Kidney Injury in Pediatric Patients with Osteosarcoma Using Real-World Data: A Multi-center Pharmacokinetic Study.Clinical pharmacokinetics · 2026Article
- Pharmacogenomics and Epigenetic Regulation Transforming Pediatric Precision Therapeutics.Journal of personalized medicine · 2026Review
- Methotrexate-induced myelopathy: a great imitator of relapsed malignant lymphoma.BMC neurology · 2026Article
- Development of a web-based machine learning model for early prediction of delayed high-dose methotrexate clearance in pediatric osteosarcoma.Frontiers in pediatrics · 2026Article
- Review
- Genetic Markers of Methotrexate Treatment Failure in Psoriasis.Journal of personalized medicine · 2025Article
- The Role of miRNAs as Predictors of Acute Lymphoblastic Leukemia Chemotherapy Toxicity in Children: A Systematic Review.Journal of clinical medicine · 2025Review
- Genetics and Epigenetics of Chemoinduced Oral Mucositis in Paediatric Patients with Haematological Malignancies-A Review.Epigenomes · 2025Review
- Impact of Pharmacogenetics on High-Dose Methotrexate Toxicity in Pediatric Oncology.Pharmaceutics · 2025Article
- DHFR2 RNA directly regulates dihydrofolate reductase and its expression level impacts folate one carbon metabolism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Dose adjustment strategy for high-dose methotrexate-induced toxicities in pediatric acute lymphoblastic leukemia: based on population PK analysis and exposure-toxicity relationship.Cancer chemotherapy and pharmacology · 2025Article
- 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
- Delayed excretion of high-dose methotrexate in pediatric acute leukemia correlates with laxative and constipation management.Pediatric blood & cancer · 2025Article
- Prediction of High-Dose Methotrexate Blood Concentration in Osteosarcoma Patients Using Machine Learning.Drug design, development and therapy · 2025Article
- Hypoalbuminemia in children with acute lymphoblastic leukemia: relation to asparaginase therapy and impact on high dose methotrexate elimination.Cancer chemotherapy and pharmacology · 2024Article
- Association ofCurrent issues in molecular biology · 2024Article
- Novel genomic variants influencing methotrexate delayed clearance in pediatric patients with acute lymphoblastic leukemia.Frontiers in pharmacology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Methotrexate (MTX) is a mainstay therapeutic agent administered at high doses for the treatment of pediatric and adult malignancies, such as acute lymphoblastic leukemia, osteosarcoma, and lymphoma. Despite the vast evidence for clinical efficacy, high-dose MTX displays significant inter-individual pharmacokinetic variability. Delayed MTX clearance can lead to prolonged, elevated exposure, causing increased risks for nephrotoxicity, mucositis, seizures, and neutropenia. Numerous pharmacogenetic studies have investigated the effects of several genes and polymorphisms on MTX clearance in an attempt to better understand the pharmacokinetic variability and improve patient outcomes. To date, several genes and polymorphisms that affect MTX clearance have been identified. However, evidence for select genes have conflicting results or lack the necessary replication and validation needed to confirm their effects on MTX clearance. Therefore, we performed a systematic review to identify and then summarize the pharmacogenetic factors that influence high-dose MTX pharmacokinetics in pediatric malignancies. Using the PRISMA guidelines, we analyzed 58 articles and 24 different genes that were associated with transporter pharmacology or the folate transport pathway. We conclude that there is only one gene that reliably demonstrates an effect on MTX pharmacokinetics:
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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.