A Metabolomics Approach for Early Prediction of Vincristine-Induced Peripheral Neuropathy

Parul Verma, Jayachandran Devaraj, Jodi L. Skiles, Tammy Sajdyk, Richard H. Ho, Raymond Hutchinson, Elizabeth Wells, Lang Li, Jamie Renbarger, Bruce Cooper, Doraiswami Ramkrishna

Research output: Contribution to journalArticle

Abstract

Vincristine is a core chemotherapeutic drug administered to pediatric acute lymphoblastic leukemia patients. Despite its efficacy in treating leukemia, it can lead to severe peripheral neuropathy in a subgroup of the patients. Peripheral neuropathy is a debilitating and painful side-effect that can severely impact an individual's quality of life. Currently, there are no established predictors of peripheral neuropathy incidence during the early stage of chemotherapeutic treatment. As a result, patients who are not susceptible to peripheral neuropathy may receive sub-therapeutic treatment due to an empirical upper cap on the dose, while others may experience severe neuropathy at the same dose. Contrary to previous genomics based approaches, we employed a metabolomics approach to identify small sets of metabolites that can be used to predict a patient's susceptibility to peripheral neuropathy at different time points during the treatment. Using those identified metabolites, we developed a novel strategy to predict peripheral neuropathy and subsequently adjust the vincristine dose accordingly. In accordance with this novel strategy, we created a free user-friendly tool, VIPNp, for physicians to easily implement our prediction strategy. Our results showed that focusing on metabolites, which encompasses both genotypic and phenotypic variations, can enable early prediction of peripheral neuropathy in pediatric leukemia patients.

Original languageEnglish (US)
Pages (from-to)9659
Number of pages1
JournalScientific reports
Volume10
Issue number1
DOIs
StatePublished - Jun 15 2020

ASJC Scopus subject areas

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    Verma, P., Devaraj, J., Skiles, J. L., Sajdyk, T., Ho, R. H., Hutchinson, R., Wells, E., Li, L., Renbarger, J., Cooper, B., & Ramkrishna, D. (2020). A Metabolomics Approach for Early Prediction of Vincristine-Induced Peripheral Neuropathy. Scientific reports, 10(1), 9659. https://doi.org/10.1038/s41598-020-66815-y