Use of Levocarnitine to Reduce Asparaginase Hepatotoxicity in Patients With Acute Lymphoblastic Leukemia

Summary

Acute lymphoblastic leukemia (ALL) is the most common cancer seen in pediatric oncology. The necessary chemotherapy for pediatric and adolescent and young adult (AYA) patients with ALL includes steroids, anthracyclines, asparaginase, and vincristine. One of the most hepatotoxic chemotherapy agents is asparaginase, with treatment-associated hepatotoxicity (TAH) observed in up to 60% of patients. The frequency of TAH is increased in overweight or obese patients of Latino heritage. Carnitine is a naturally-derived compound that is produced in the liver and kidneys; it is found in certain foods, such as meat, poultry, fish, and some dairy products. Endogenous carnitine transports long-chain fatty acids into the mitochondria, where they are oxidized to produce energy, and acts as scavengers of oxygen free radicals. Thus, carnitine can reduce oxidative stress and modulate inflammatory response. Levocarnitine is a supplement form of carnitine used typically in the care and management of patients with carnitine deficiency. Pediatric and AYAs with ALL will be given oral levocarnitine as a supplement during their initial phases of treatment, when the most hepatotoxic agents are administered, to determine if the incidence of liver toxicity can be reduced or eliminated.

Timeline

Start

2023-03-03

Primary completion

2024-12-31

Completion

2024-12-31

Publications

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• Background Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA. 2014 Feb 26;311(8):806-14. doi: 10.1001/jama.2014.732.
• Background van der Sluis IM, Vrooman LM, Pieters R, Baruchel A, Escherich G, Goulden N, Mondelaers V, Sanchez de Toledo J, Rizzari C, Silverman LB, Whitlock JA. Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation. Haematologica. 2016 Mar;101(3):279-85. doi: 10.3324/haematol.2015.137380.
• Background Romano M, Vacante M, Cristaldi E, Colonna V, Gargante MP, Cammalleri L, Malaguarnera M. L-carnitine treatment reduces steatosis in patients with chronic hepatitis C treated with alpha-interferon and ribavirin. Dig Dis Sci. 2008 Apr;53(4):1114-21. doi: 10.1007/s10620-007-9983-1. Epub 2007 Oct 16.
• Background Schulte RR, Madiwale MV, Flower A, Hochberg J, Burke MJ, McNeer JL, DuVall A, Bleyer A. Levocarnitine for asparaginase-induced hepatic injury: a multi-institutional case series and review of the literature. Leuk Lymphoma. 2018 Oct;59(10):2360-2368. doi: 10.1080/10428194.2018.1435873. Epub 2018 Feb 12.
• Background Aldoss I, Douer D. How I treat the toxicities of pegasparaginase in adults with acute lymphoblastic leukemia. Blood. 2020 Mar 26;135(13):987-995. doi: 10.1182/blood.2019002477.
• Background Schulte R, Hinson A, Huynh V, Breese EH, Pierro J, Rotz S, Mixon BA, McNeer JL, Burke MJ, Orgel E. Levocarnitine for pegaspargase-induced hepatotoxicity in older children and young adults with acute lymphoblastic leukemia. Cancer Med. 2021 Nov;10(21):7551-7560. doi: 10.1002/cam4.4281. Epub 2021 Sep 16.

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