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Antithrombin III as the Indicator of L-Asparaginase Activity in Children Treated for Acute Lymphoblastic Leukemia
Małgorzata Czogała1, Walentyna Balwierz, Krystyna Sztefko
1Departments of *Pediatric Oncology and Hematology ‡Clinical Biochemistry, Institute of Pediatrics, Jagiellonian University Medical College †Department of Pediatric Oncology and Hematology, Children's University Hospital of Krakow, Krakow, Poland.
Insights
Monitoring L-asparaginase (ASP) activity in children with acute lymphoblastic leukemia (ALL) is crucial. Antithrombin III (ATIII) activity can serve as a surrogate marker for ASP activity when direct measurement is unavailable.
Area of Science:
- Biochemistry
- Pediatric Oncology
- Pharmacology
Background:
- L-asparaginase (ASP) is a key therapeutic agent for childhood acute lymphoblastic leukemia (ALL).
- Drug inactivation due to immune responses and side effects like coagulopathy, specifically antithrombin III (ATIII) deficiency, necessitate activity monitoring.
- Understanding the relationship between ASP and ATIII levels is important for optimizing ALL treatment.
Purpose of the Study:
- To investigate the correlation between L-asparaginase (ASP) and antithrombin III (ATIII) activities in children with ALL.
- To evaluate the potential of using ATIII activity as an indirect measure of ASP activity.
Main Methods:
- ASP and ATIII activities were measured in 76 children with ALL undergoing treatment.
- Statistical analysis, including correlation and Receiver Operating Characteristic (ROC) curve analysis, was performed.
Main Results:
- A significant negative correlation was observed between ASP and ATIII activities (R=-0.43, P=0.0001).
- ROC curve analysis indicated that ATIII levels could effectively identify patients with low or undetectable ASP activity (AUC=0.87 and 0.93).
- Higher ATIII activity was associated with a greater likelihood of decreased ASP activity.
Conclusions:
- Antithrombin III (ATIII) activity shows a significant association with L-asparaginase (ASP) activity in pediatric ALL patients.
- ATIII activity can serve as a valuable surrogate marker for assessing ASP activity, particularly when direct measurement is not feasible.
- While not a replacement for direct ASP activity testing, ATIII monitoring offers a practical approach to gauge drug efficacy and manage treatment.
Abstract:
L-asparaginase (ASP) is widely used in the treatment of acute lymphoblastic leukemia (ALL) in children. Monitoring its activity is necessary because of the risk of drug inactivation as the result of an immune reaction. Besides allergic reactions, another frequent side effect of ASP treatment is coagulopathy, especially deficiency of antithrombin III (ATIII). The aim of this study was to analyze the relationship between ASP and ATIII activities and the possibility of ATIII activity use in an indirect ASP activity assessment. ASP and ATIII activity was measured in 76 children with ALL treated according to the ALL IC BFM 2002 protocol. A correlation between ASP and ATIII activities was found (R=-0.43, P=0.0001). ROC curve analysis revealed some utility regarding the determination of ATIII in identifying patients with low or undetectable ASP activity (area under the curve=0.87 [95% confidence interval, 0.77-0.96], P<0.0001 and 0.93 [95% confidence interval, 0.85-1.0], P<0.0001, respectively). Higher ATIII activity is associated with a higher probability of a decline in ASP activity. Examination of ATIII activity cannot replace a direct determination of ASP activity, but in the case of unavailability of the direct test, it can be a helpful surrogate parameter of drug activity.
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