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Browsing by Author "Wells, Elizabeth"
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Item A Metabolomics Approach for Early Prediction of Vincristine-Induced Peripheral Neuropathy(Springer, 2020-04-15) Verma, Parul; Devaraj, Jayachandran; Skiles, Jodi L.; Sajdyk, Tammy; Ho, Richard H.; Hutchinson, Raymond; Wells, Elizabeth; Li, Lang; Renbarger, Jamie; Cooper, Bruce; Ramkrishna, Doraiswami; Pediatrics, School of MedicineVincristine 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.Item Obesity as a Potential Risk Factor for Vincristine Induced Peripheral Neuropathy(Wolters Kluwer, 2020-10) Sajdyk, Tammy J.; Boyle, Frances A.; Foran, Kaitlin S.; Tong, Yan; Pandya, Pankita; Smith, Ellen M.L.; Ho, Richard H.; Wells, Elizabeth; Renbarger, Jamie L.; Pediatrics, School of MedicineAcute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Vincristine is a core chemotherapeutic agent for patients with ALL; unfortunately, approximately 78% will develop vincristine-induced peripheral neuropathy (VIPN). VIPN can result in vincristine dose reductions that decrease therapeutic efficacy: making it important to understand which children are at highest risk for VIPN. We hypothesized that pediatric ALL patients who were obese at diagnosis would develop worse VIPN than healthy weight children with ALL within the first year. Our results confirmed that obese pediatric patients have significantly (p=0.03) worse VIPN than patients of healthy weight.