2. Academic Validation
  3. Levocarnitine does not impair chemotherapy cytotoxicity against acute lymphoblastic leukemia

Levocarnitine does not impair chemotherapy cytotoxicity against acute lymphoblastic leukemia

  • Leuk Lymphoma. 2020 Feb;61(2):420-428. doi: 10.1080/10428194.2019.1666379.
Jessica L Sea 1,  Etan Orgel 2 3,  Ting Chen 1,  Rebecca L Paszkiewicz 1,  Abigail S Krall 4,  Matthew J Oberley 3 5,  Linsey Stiles 6,  Steven D Mittelman 1
Affiliations

Affiliations

  • 1 Division of Pediatric Endocrinology, UCLA Children's Discovery and Innovation Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • 2 Division of Hematology, Oncology, Blood and Marrow Transplantation, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • 3 Department of Pediatrics, University of Southern California, Los Angeles, CA, USA.
  • 4 Department of Biological Chemistry and the Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA.
  • 5 Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine, Los Angeles, CA, USA.
  • 6 Division of Endocrinology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
PMID: 31526067 DOI: 10.1080/10428194.2019.1666379
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); PEG-asparaginase; hepatotoxicity; levocarnitine (L-carnitine).

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