title: Antithrombin III as the Indicator of L-Asparaginase Activity in Children Treated for Acute Lymphoblastic Leukemia.
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.
authors.affiliation: Departments 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.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Czogała
authors.forename: Walentyna
authors.initials: W
authors.lastname: Balwierz
authors.forename: Krystyna
authors.initials: K
authors.lastname: Sztefko
authors.forename: Iwona
authors.initials: I
authors.lastname: Rogatko
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000990:Antithrombin III / Q000032:analysis*; D019540:Area Under Curve; D001215:Asparaginase / Q000008:administration & dosage / Q000097:blood*; D015415:Biomarkers; D001780:Blood Coagulation Tests; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy*; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D000990:Antithrombin III; D005340:Fibrinogen; D001215:Asparaginase