L-carnitine for L-asparaginase Induced Hepatotoxicity

Sumant Arora; Jagpal Klair; Andrew Bellizzi; Tomohiro Tanaka

doi:10.14309/00000434-201810001-02228

Asparaginase is used as part of combination chemotherapy for ALL and common adverse effects include hypersensitivity reactions and pancreatitis. Asparaginase-induced hepatotoxicity, characterized by hyperbilirubinemia and transaminase elevation, is common (30-60%), with the severity depending on the dose and duration of therapy. A 58-year-old female with refractory B-cell acute lymphoblastic leukemia (ALL) received chemotherapy including prednisone, intravenous PEG-L-asparaginase, vincristine, and intrathecal cytarabine. After 18 days of chemotherapy, she developed jaundice with total bilirubin 5 mg/dL, AST 132 IU/L, and ALT 170 IU/L. Hepatology recommended starting L-carnitine 50 mg/kg every 6 hours and vitamin B-complex; PEG-L-asparaginase was discontinued. Transaminases initially improved before trending up again to peak at AST 231 IU/L, ALT 276 IU/L, bilirubin 12.7 (direct 10.3) mg/dL and ALP 1053 IU/L. Work up was negative for cytomegalovirus, Epstein-Barr virus, herpes simplex virus and hepatitis B. Bone marrow biopsy revealed B-ALL under therapy with no increase in blasts. Transjugular liver biopsy showed concomitant severe steatohepatitis with marked ballooning degeneration/foamy change, as well as biliary injury in the form of moderate bile stasis, severe bile duct epithelial injury, with no evidence of leukemic infiltration of the hepatic parenchyma. We diagnosed drug-induced liver injury due to PEG-L-asparaginase and continued L-carnitine and vitamin B-complex until day 44. Transaminases and bilirubin improved on follow up and remained normal at day 98. Hepatic dysfunction due to asparaginase is attributed to depletion of L-asparagine and glutamine, which impairs mitochondrial ß-oxidation and induces steatosis. Previously reported cases of asparaginase toxicity did not mention biliary injury as a prominent feature. It is possible in our case that this represented an unusual histologic presentation of asparaginase toxicity. We reiterate the role of L-carnitine and vitamin B-complex as mitochondrial ß-oxidation co-factors for treatment of asparaginase induced hepatotoxicity. We further reinforce the fact that such patients may be able to receive additional dose of asparaginase following the recovery of hepatic function. Future prospective studies are needed to confirm the efficacy of L-carnitine and vitamin B-complex.

L-carnitine for L-asparaginase Induced Hepatotoxicity

View Online

Abstract

Details

Metrics