Clinical Utility of Ammonia Concentration as a Diagnostic Test in Monitoring of the Treatment with L-Asparaginase in Children with Acute Lymphoblastic Leukemia

Abstract

L-asparaginase (ASP) is an enzyme used as one of the basic regimens in the acute lymphoblastic leukemia (ALL) therapy. Because of the possibility of the enzyme inactivation by antibodies, monitoring of ASP activity is essential. The aim of the study was to examine if plasma concentration of ammonia, a direct product of the reaction catalyzed by ASP, can be used in the assessment of ASP activity. A group of 87 patients with acute lymphoblastic leukemia treated in the Department of Pediatric Oncology and Hematology in Krakow was enrolled to the study. ASP activity and ammonia concentration were measured after ASP administrations during induction. A positive correlation was found between the ammonia concentration and ASP activity (R = 0.44; P < 0.0001) and between the medium values of ammonia concentration and ASP activity (R = 0.56; P < 0.0001). The analysis of ROC curves revealed the moderate accuracy of the ammonia concentration values in the ASP activity assessment. It was also found that the medium value of ammonia concentrations can be useful in identification of the patients with low (<100 IU/L) and undetectable (<30 IU/L) ASP activity. The plasma ammonia concentration may reflect ASP activity and can be useful when a direct measurement of the activity is unavailable.

Reactions related to asparaginase infusion in a 10-year retrospective cohort

“…The analysis of the descriptions of the suspected adverse reactions suggests that, in some of the cases, hyperammonemia reactions may have occurred, whose management is possible. The increase in serum ammonia levels after the intravenous administration of asparaginase occurs in children at concentrations of 260–700 μmol/L 17 (reference value up to 30 μmol/L). Hyperammonemia can cause nausea, vomiting, headache, restlessness, dizziness and rash, 8 , 25 which were observed in 13 cases of this study.…”

“…The data related to the characterization of the patient (age at diagnosis and sex), leukemia (type of ALL, risk classification), treatment (treatment phase, prescribed medication, posology, route of administration) and description of suspicions of adverse reactions to EcA 13 , 17 were collected on a specific form designed for this study and later organized on spreadsheets of the Microsoft Excel ® program.…”

Ammonia Levels Should Not Be Used as a Surrogate Marker of Levels of Asparaginase Activity in Acute Lymphoblastic Leukemia Patients

“…Recently, a Polish study group published ammonia levels of 87 children during acute lymphoblastic leukemia (ALL) induction therapy. They concluded that the ammonia concentration reflects the levels of asparaginase activity and could be useful when asparaginase activity assays are not available . We evaluated if ammonia levels could be used as a surrogate marker of levels of asparaginase activity.…”

Pegylated asparaginase as cause of fatal hyperammonemia in patients with latent urea cycle disorder

“…7 Studies suggest monitoring ammonia levels as a marker for PEG-ASNase activity, but not toxicity. 8 Our case highlights the need for routine ammonia monitoring with drug administration.…”

“…The only intervention for dosage monitoring in response to hyperammonemia is with fatigue, known as “ASNase blues,” where a 25% reduced dose is recommended . Studies suggest monitoring ammonia levels as a marker for PEG‐ASNase activity, but not toxicity . Our case highlights the need for routine ammonia monitoring with drug administration.…”