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.
Highlights
L-asparaginase (ASP), an enzyme catalyzing hydrolysis of asparagine to aspartic acid and ammonia, is one of the basic regimens used in the treatment of acute lymphoblastic leukemia (ALL)
The treatment efficacy is related to the duration and grade of the reduction of the asparagine concentration in plasma and cerebrospinal fluid, which depends on the ASP activity
The mean value of the ammonia concentration measured 3 days after ASP administration account the risk of ASP inactivation by antibodies, the therapy monitoring with ASP activity measurements is very important [5, 6, 8]
Summary
L-asparaginase (ASP), an enzyme catalyzing hydrolysis of asparagine to aspartic acid and ammonia, is one of the basic regimens used in the treatment of acute lymphoblastic leukemia (ALL). ASP causes asparagine depletion from plasma, leading to inhibition of protein biosynthesis in blast cells, cell cycle arrest, and cellular death [2]. The treatment efficacy is related to the duration and grade of the reduction of the asparagine concentration in plasma and cerebrospinal fluid, which depends on the ASP activity. It is considered that the therapeutic ASP activity is above 100 IU/L [3,4,5,6] but a complete asparagine depletion was observed in some patients with lower enzyme activity [3, 5, 6]. Distinct treatment schedules are used for each preparation to assure the optimal efficacy in most of the patients
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