<smlcap>L</smlcap>-Carnitine for Treatment of Pegasparaginase-Induced Hepatotoxicity

Abstract

Introduction: Similar to pediatric regimens, multiple doses of <smlcap>L</smlcap>-asparaginase (PEG-Asp) are being increasingly used in adults with newly diagnosed acute lymphoblastic leukemia (ALL) with promising results. One of the most common side effects of the drug in adults is high-grade hyperbilirubinemia and transaminitis. Despite being almost always reversible and may not recur, clinicians may still be reluctant to continue with PEG-Asp in patients with liver toxicity, losing the benefit from multiple doses of the drug. Case Report: We describe a case of adult ALL who developed PEG-Asp-related high grade liver toxicity. The rising hyperbilirubinemia and transaminitis rapidly and permanently reversed using the amino-acid derivative <smlcap>L</smlcap>-carnitine. This case goes in line with similar observations in animal models and humans. Conclusion:<smlcap>L</smlcap>-Carnitine may show therapeutic benefit in PEG-Asp-related hepatotoxicity and should be considered in clinical trials of the drug.

Optimizing the use of the hyperCVAD regimen: Clinical vignettes and practical management

“…Although toxicities associated with pegaspargase may be more significant during induction chemotherapy, it is prudent to be mindful of these toxicities, which occur more frequently in adult patients . Avoiding concomitant hepatotoxic medications and using ursodiol, vitamin B, and levocarnitine in patients who develop or are at higher risk of hepatotoxicity may be considered …”

“…Hepatotoxicity associated with pegaspargase can be severe and preclude anticipated chemotherapy. The use of vitamin B complex in combination with levocarnitine at doses of 50‐150 mg/kg/day has been shown to mitigate this toxicity and is currently being studied as a means to shorten the severity and duration of hepatotoxicity in patients receiving pegaspargase . Consensus guidelines for management of additional asparaginase‐associated toxicities should also be referenced .…”

Bortezomib Comes to the Rescue: Comment on the Article by Nachmias et al. Entitled “A Bortezomib-Based Protocol Induces a High Rate of CR with Minor Toxicity in Adult Patients with Relapsed/Refractory ALL”

“…Whether it can be omitted as was done in 2 of the patients who attained remission remains unclear. Notably, carnitine can be used to prevent haptic toxicity in patients with fatty liver disease and it may reduce PEG-asparaginase hepatotoxicity [8]. Additionally, Erwinia asparaginase can be used if a patient has a history of allergy to PEG-asparaginase.…”

Is N-acetylcysteine infusion an effective treatment option in L-asparaginase associated hepatotoxicity?

“…However, the mechanism of L-asparaginase-associated hepatotoxicity is not clear. There are few reports on the treatment of L-asparaginase-associated hepatotoxicity [234]. An experimental study conducted by Roesmann et al [2] reported that when L-carnitine is administered in combination with L-asparaginase for steatosis, carnitine reduces the toxicity associated with L-asparaginase.…”

“…An experimental study conducted by Roesmann et al [2] reported that when L-carnitine is administered in combination with L-asparaginase for steatosis, carnitine reduces the toxicity associated with L-asparaginase. Alshiekh-Nasany and Douer [3] reported that polyethylene glycol (PEG)-asparaginase related high-grade liver toxicity in adult patients could be rapidly and permanently reversed using the amino acid derivate L-carnitine. Al-Nawalki et al [4] reported that histopathological macrovesicular steatosis was detected in 3 adult patients who developed L-asparaginase toxicity, and that the hepatotoxicity resolved after administration of carnitine and a vitamin B complex.…”