Pharmacoepidemiol Risk Manage.  2024 Sep;16(2):146-155. 10.56142/perm.24.0014.

Incidence and Risk Factors of Hyperammonemia Secondary to L-asparaginase in Children with Leukemia or Lymphoma

• Lee SY
• Song SJ
• Yoon J
• Kim HJ
• Ahn KM
• Suh DI
• Kang HR
• Hong KT

• KMID: 2564479
• DOI: http://doi.org/10.56142/perm.24.0014

Abstract

Objective
Ammonia generated during breakdown of L-asparaginase is elevated due to excessive production or hindrance of ammonia conversion to urea. While children are in condition of growth and have faster metabolic rate compared to adults, hyperammonemia is more critical and can potentially lead to neurotoxicity. We aimed to assess the incidence and risk factors of hyperammonemia in pediatric patients with leukemia or lymphoma during hospitalization after L-asparaginase administration.
Methods
Electronic medical records of pediatric patients with leukemia or lymphoma who were hospitalized at Seoul National University Children's Hospital and received L-asparaginase between 2013 and 2022, were retrospectively reviewed. Ammonia level ≥ 200 μmol/L were defined as hyperammonemia. Risk factors for hyperammonemia were analyzed using chi-square tests.
Results
Among 110 patients whose ammonia levels were measured after L-asparaginase administration, hyperammonemia was observed in 70 patients (63.6%). Among them, 32 patients (45.7%) experienced neurological symptoms including nausea, vomiting, dizziness, confusion, seizure.Ideal body weight percentage, acute lymphoblastic leukemia (ALL) standard risk group and 1952 induction regimen (p = 0.019, 0.018, 0.038) were found as risk factors. Patients classified as high-risk for leukemia treatment had a higher risk of neurological symptoms (p = 0.005).
Conclusion
Hyperammonemia occurred in 63.6% of pediatric hospitalized patients administered L-asparaginase. Patients with overweight or in the standard risk group for ALL were more likely to develop hyperammonemia. The risk of developing neurological symptoms in the high-risk group for ALL was higher and treatment was necessary. Thus, consistent monitoring of ammonia levels in pediatric patients administered L-asparaginase is necessary to detect hyperammonemia.

Keyword

Asparaginase; Hyperammonemia; Drug-related side effects and adverse reactions; Risk factors