ArticlePediatric blood & cancer2011
Increased risk of vincristine neurotoxicity associated with low CYP3A5 expression genotype in children with acute lymphoblastic leukemia.
Article in Pediatric blood & cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 5 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
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Who cites it
97 citing papers in PubMed, 5 syntheses or guidelines pooled it, 186 citations in OpenAlex.
- Why pharmacogenomic biomarkers for chemotherapy-induced peripheral neuropathy fail: a systematic review of genetic associations, replication, and clinical translation.Frontiers in pharmacology · 2026Pooled it
- Vincristine-induced ptosis in pediatric patients: a systematic review and practice recommendations.European journal of pediatrics · 2025Pooled it
- Approaches to measure paediatric chemotherapy-induced peripheral neurotoxicity: a systematic review.The Lancet. Haematology · 2020Pooled it
- Aspects of vincristine-induced neuropathy in hematologic malignancies: a systematic review.Cancer chemotherapy and pharmacology · 2019Pooled it
- Neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on contemporary treatment protocols: A systematic review.Neuroscience and biobehavioral reviews · 2015Pooled it
- Benefits of risk-adapted and mould-specific antifungal prophylaxis in childhood leukaemia.British journal of haematology · 2020Trial
- CYP3A5 genotype and its impact on vincristine pharmacokinetics and development of neuropathy in Kenyan children with cancer.Pediatric blood & cancer · 2018Trial
- Glutamic acid not beneficial for the prevention of vincristine neurotoxicity in children with cancer.Pediatric blood & cancer · 2015Trial
- Extrapolating Vincristine-Induced Peripheral Neuropathy From Caucasian to Kenyan Populations: Impact of Type I and Type II Selection Bias.CPT: pharmacometrics & systems pharmacology · 2026Article
- The role of pharmacogenetics in the therapy regimen of acute lymphoblastic leukemia in children: recent discoveries and future perspectives.Pharmacological reports : PR · 2026Review
- Pharmacogenomic variation and chemotherapy-related toxicity profiles in pediatric patients with cancer in Tanzania: a cross-sectional study.Frontiers in pharmacology · 2026Article
- Insect Lipidomics: Advances, Applications, and Physiological Insights.Advances in experimental medicine and biology · 2026Review
- Pharmacogenomic impact and genetic architecture of toxicity in pediatric acute lymphoblastic leukemia induction therapy: an exploratory modeling approach.Frontiers in pharmacology · 2026Article
- Pharmacogenomics of treatment toxicities in pediatric B-Cell ALL: toward safer precision therapy.Frontiers in pharmacology · 2026Review
- Impact of Population Pharmacogenomics on Cisplatin-Induced Neurotoxicities in Testicular Cancer Survivors.Cancer medicine · 2025Article
- Decoding the selective chemical modulation of CYP3A4.Nature communications · 2025Article
- Review of Personalized Medicine and Pharmacogenomics of Anti-Cancer Compounds and Natural Products.Genes · 2024Review
- Efficacy and Toxicity of Vincristine and CYP3A5 Genetic Polymorphism in Rhabdomyosarcoma Pediatric Egyptian Patients.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Vincristine Disposition and Neurotoxicity Are Unchanged in Humanized CYP3A5 Mice.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Influence of CYP3A5 and ABCB1 polymorphisms on the pharmacokinetics of vincristine in adult patients receiving CHOP therapy.Cancer chemotherapy and pharmacology · 2023Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThis study evaluates the relationship between cytochrome P450 (CYP) 3A5 genotype and vincristine-induced peripheral neuropathy (VIPN) in children with precursor B cell acute lymphoblastic leukemia (preB ALL). We have shown in vitro that vincristine is metabolized significantly more efficiently by CYP3A5 than by CYP3A4. We also found that vincristine neurotoxicity is less common in African-Americans (70% express CYP3A5) than in Caucasians. We test the hypothesis that CYP3A5 expressers experience less vincristine neuropathy than do CYP3A5 non-expressers. PROCEDURE: This study of pharmacogenetics of vincristine neuropathy in children with preB ALL was completed at Indiana University Simon Cancer Center. Whole blood for DNA extraction and genotyping was collected as well as plasma from a single time-point for analysis of vincristine and primary metabolite (M1) concentrations. Vincristine neuropathy was captured via chart review and graded per the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0.
resultsEighty-nine percent of CYP3A5 expressers experienced neurotoxicity versus 100% of non-expressers (P = 0.03). The proportion of treatment months with neurotoxicity was significantly different between the expressers and non-expressers (16% vs. 27%, P = 0.0007). Limited pharmacokinetic data suggest different rates of vincristine metabolism between CYP3A5 genotype groups with higher primary metabolite (M1) plasma concentrations (P = 0.0004) and lower metabolic ratios ([vincristine]/[M1]) (P = 0.036) in the CYP3A5 expressers compared to the CYP3A5 non-expressers. M1 concentration was also inversely related to severity of neuropathy (P = 0.0316).
conclusionsIn children with preB ALL, CYP3A5 expressers experience less VIPN, produce more M1, and have lower metabolic ratios compared to CYP3A5 non-expressers.
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Registered trials
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