Levocarnitine for pegasparaginase-induced hepatotoxicity in acute lymphoblastic leukemia

Abstract

Pegasparaginase (PEG-Asp), commonly used in acute lymphoblastic leukemia (ALL), is associated with hyperbilirubinemia and elevated transaminases. Treatment of acute hepatotoxicity is limited to case studies reporting success with levocarnitine (LC). In a retrospective analysis, 25 ALL patients experienced Grade ≥3 hyperbilirubinemia and/or elevated transaminases following a single dose of PEG-Asp where 12 patients received LC compared to 13 patients with no intervention. Median LC dose was 50 mg/kg/day for a median of 11 days. Median values were greater in the LC group: total bilirubin 5.2 mg/dL vs 4.5 mg/dL (p = 0.19), AST 75.5 units/L vs. 30 units/L (p = 0.05), and ALT 263.5 units/L vs 47 units/L (p = 0.003). Time to resolution (TTR) did not significantly differ between LC and control (p = 0.08), however, patients on LC did resume therapy sooner (p = 0.17). Although significant limitations exist in the study, LC did not result in a clinically significant impact when used to treat PEG-Asp-induced hepatotoxicity.

Keywords:

• Asparaginase
• hepatotoxicity
• levocarnitine
• acute lymphoblastic leukemia

Disclosure statement

Ibrahim Aldoss is a member of the Speakers’ Bureau for Jazz Pharmaceuticals. Amandeep Salhotra is an advisor for Kadmon corporation and receives funding from Celgene Corporation. Vinod Pullarkat is a member of the Advisory Board for Shire. There are no other potential conflicts of interest to disclose.