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


METHODS
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.
Steiner
M
M
St. Anna Children's Hospital, Vienna, Austria. manuel.steiner@stanna.at
Attarbaschi
A
A
Kastner
U
U
Dworzak
M
M
Haas
O A
OA
Gadner
H
H
Mann
G
G
D000293:Adolescent; D000641:Ammonia / Q000097:blood*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001215:Asparaginase / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy*
D000970:Antineoplastic Agents; D000641:Ammonia; D001215:Asparaginase