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E.R. Finch et al.
marily in individuals with familial lipid disorders.20,48-50 Fibrates have been shown to reduce triglycerides effectively in children, by between 39% and 54%.49,51 As seen in adults, data suggest that fibrates are well tolerated in children, with the most frequently reported adverse reactions being gas- trointestinal disturbances and muscle cramps.13,14,20,49 However, transient increases in liver function tests have been reported in a small number of cases,48,51 indicating a potential for hepatotoxicity when used in combination with other hepatotoxic chemotherapeutic agents.
Although fibrates have been included in a case-by-case basis to manage hypertriglyceridemia during ALL thera- py,3,5,47 there has been no systematic analysis of the effect of lipid-lowering interventions and long-term outcomes in ALL survivors. Our proof-of-principle preclinical experi- ments show that fenofibrate treatment is a potential inter- vention to reduce dexamethasone-induced osteonecrosis in ALL, without carrying the risk of substantial drug interac- tions and without any untoward effect on the efficacy of ALL therapy. Our findings support the rationale for con- trolled clinical trials with fenofibrate in chemotherapy- related hypertriglyceridemia.
Disclosures
No conflicts of interest to disclose.
Contributions
ERF: conceptualization of experiments; ERF, MAP, DAJ, XC, LL, SEK, MVR and LJJ: methodology and data collection; ERF, MVR and LJJ: formal analysis; ERF, MVR and LJJ wrote the original manuscript. All authors reviewed and approved the manuscript.
Acknowledgments
We are grateful to St. Jude’s Animal Resource Center and Veterinary Pathology Core for technical assistance.
Funding
This research was supported by the National Institutes of Health (CA142665, CA21765, and GM115279) and ALSAC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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