Distinct fluctuations of ammonia levels during asparaginase therapy for childhood acute leukemia

Pediatr Blood Cancer. 2007 Oct 15;49(5):640-2. doi: 10.1002/pbc.21022.


Background: The enzyme asparaginase (L-Asp) catalyses the hydrolysis of the non-essential amino acids asparagine and glutamine to aspartic and glutamic acid and ammonia. Ammonia therefore represents a direct metabolite of the biochemical reaction induced by this enzyme. However, data regarding the dynamics and clinical relevance of ammonia levels during L-Asp therapy are lacking.

Procedure: We prospectively followed the dynamics of ammonia levels during L-Asp containing induction therapy according to the ALL-BFM 2000 protocol in 10 pediatric patients with acute lymphoblastic leukemia (ALL), in order to assess the possible relevance of ammonia levels for clinical practice and its use as a possible surrogate parameter of L-Asp enzyme activity.

Results: We observed a significant elevation of ammonia levels 1 day after intravenous L-Asp administration with ammonia levels reaching up to the seventh fold of normal values, followed by a steep decline to basal values within another 2 days, resulting in an undulating course of ammonia concentrations during L-Asp containing induction treatment.

Conclusions: Although there are potential neurotoxic properties of ammonia, central nervous system (CNS) toxicity has not been observed in our study and is generally not seen as a common side effect of L-Asp therapy. Furthermore, due to the characteristic fluctuation profile, ammonia levels may represent a suitable surrogate parameter of L-Asp enzyme activity and may enable the monitoring of silent inactivation of L-Asp.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Ammonia / blood*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Asparaginase / pharmacology
  • Asparaginase / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Monitoring
  • Female
  • Humans
  • Infant
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*


  • Antineoplastic Agents
  • Ammonia
  • Asparaginase