Levocarnitine for asparaginase-induced hepatic injury: a multi-institutional case series and review of the literature

Abstract

Asparaginase, an important treatment component for acute lymphoblastic leukemia (ALL), causes severe hepatotoxicity in some patients. Levocarnitine is a mitochondrial co-factor that can potentially ameliorate the mitochondrial toxicity of asparaginase. In this retrospective case series, we describe the clinical presentation and management of six pediatric and young adult patients (mean age 12.7, range 9-24 years) with ALL who developed Grade 3-4 hyperbilirubinemia following administration of asparaginase as part of induction/re-induction therapy. Five of these patients were treated with levocarnitine with subsequent improvement of hyperbilirubinemia, while one patient was given levocarnitine prophylactically during induction and developed Grade 3 hyperbilirubinemia, but did not require therapy adjustments or delays. Increased awareness in the pediatric oncology community regarding asparaginase-associated hepatic toxicity and the potential role of levocarnitine in management is warranted.

Multiple Severe Toxicities of L-Asparaginase and Their Innovative Management during Induction Therapy of Acute Lymphoblastic Leukemia in an Adult Patient

“…L-asparaginase induces mitochondrial dysfunction caused by amino acid depletion, resulting in accumulation of unoxidized fatty acids which are directly responsible for hepatic damages. L-carnitine, through its roles in fatty acids metabolism, helps to maintain normal mitochondrial function and cell viability under these abnormal cellular conditions [11]. Few clinical experiments of L-carnitine in management of hepatic toxicity of L-asparaginase exist, showing some cases of improvement of the liver enzyme counts [12], but there is no prospective or comparative study to affirm the efficacy of L-carnitine in this situation.…”

Acute lymphoblastic leukemia presenting as cholestatic jaundice in a 7-year-old boy

“…There have also been reports of levocarnitine being useful in treating and preventing chemotherapy-related hepatic injury, although it was not used in our patient. 15…”

National Italian Delphi panel consensus: which measures are indicated to minimize pegylated-asparaginase associated toxicity during treatment of adult acute lymphoblastic leukemia?

“…In case of hyperbilirubinemia the use of L-carnitine is recommended as suggested in some reports [ 47 – 49 ]. A suggested L-carnitine schedule is 50 mg/kg daily intravenously in divided doses for 5–8 days until toxicity resolves.…”