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.

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.

Keywords: ALL; Asparaginase; hepatic injury; hyperbilirubinemia; leukemia; levocarnitine.

Publication types

  • Case Reports
  • Multicenter Study
  • Review

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Asparaginase / adverse effects*
  • Carnitine / therapeutic use*
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / diagnosis
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / etiology
  • Child
  • Female
  • Humans
  • Hyperbilirubinemia / blood
  • Hyperbilirubinemia / diagnosis
  • Hyperbilirubinemia / drug therapy*
  • Hyperbilirubinemia / etiology
  • Liver / diagnostic imaging
  • Liver / drug effects
  • Liver Function Tests
  • Male
  • Polyethylene Glycols / adverse effects*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Remission Induction / methods
  • Treatment Outcome
  • Ultrasonography
  • Young Adult

Substances

  • Polyethylene Glycols
  • pegaspargase
  • Asparaginase
  • Carnitine