Levocarnitine does not impair chemotherapy cytotoxicity against acute lymphoblastic leukemia

Abstract

Asparaginase (ASNase) is an integral part of pediatric induction chemotherapy that has also been shown to improve adult survival rates; however, pegylated (PEG)-ASNase induces severe hepatotoxicity in this population. Recent case reports describe the incorporation of levocarnitine (LC) supplementation into PEG-ASNase-containing induction regimens to prevent or treat hepatotoxicity. Because LC facilitates the metabolism of free fatty acids (FFA), a primary fuel source for ALL cells, LC could potentially interfere with ALL chemotherapy efficacy. To test this, we employed in vitro and in vivo models of ALL. We show in vitro that LC supplementation does not impact cytotoxicity from vincristine, daunorubicin, dexamethasone, or ASNase on human ALL cells nor lead to an increase in ALL cell metabolic rate. In vivo, we demonstrate LC does not impair PEG-ASNase monotherapy in mice with syngeneic ALL. Together, our findings show that LC supplementation is a safe strategy to prevent/reverse ASNase-induced toxicities in preclinical models.

Keywords:

• Acute lymphoblastic leukemia (ALL)
• levocarnitine (L-carnitine)
• PEG-asparaginase
• hepatotoxicity

Acknowledgements

We thank the UCLA Mitochondrial and Metabolism Core, and the UCLA Flow Cytometry Core.

Disclosure statement

The authors have no conflicts of interest to report.

Additional information

Funding

The corresponding author is funded by an R01 from the National Institutes of Health National Cancer Institute (NIH/NCI) [Award number R01 CA201444-04].