title: Thrombotic effects of asparaginase in two acute lymphoblastic leukemia protocols (NOPHO ALL-1992 versus NOPHO ALL-2000): a single-institution study.
abstract: Asparaginase is essential in the treatment of lymphoproliferative malignancies, but it is associated with several side effects. The objective of this study was to compare asparaginase-induced alterations of the coagulation inhibitors and the impact on central line-associated thrombosis in children treated according to 2 different asparaginase regimens. The study enrolled 30 children treated for acute lymphoblastic leukemia, and they were divided into 2 groups with respect to asparaginase preparation and protocol (NOPHO ALL-1992 versus NOPHO ALL-2000). The coagulation inhibitors antithrombin, protein C, and proteins S were measured prior to and during asparaginase therapy, and incidence of central line-associated thromboses was compared to evaluate the protocols' thrombogenicity. Thirteen children received Erwinia asparaginase and 17 children received E. coli asparaginase. Independent of protocol, the coagulation inhibitors were significantly reduced during asparaginase therapy (p < .001), and central line-associated thromboses were frequent. Four children developed thrombosis in the course of asparaginase therapy, and there was a correlation between asparaginase-induced fall of antithrombin and occurrence of new thromboses (p = .01).
authors.affiliation: Department of Paediatrics, National Hospital, Oslo, Norway. ellen.ruud@rikshospitalet.no
authors.forename: Ellen
authors.initials: E
authors.lastname: Ruud
authors.forename: Henrik
authors.initials: H
authors.lastname: Holmstrøm
authors.forename: Charlotte
authors.initials: C
authors.lastname: de Lange
authors.forename: Solveig
authors.initials: S
authors.lastname: Natvig
authors.forename: Birgitte Klug
authors.initials: BK
authors.lastname: Albertsen
authors.forename: Finn
authors.initials: F
authors.lastname: Wesenberg
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000991:Antithrombins / Q000032:analysis; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects*; D002405:Catheterization, Central Venous / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004885:Erwinia / Q000201:enzymology; D004926:Escherichia coli / Q000201:enzymology; D005260:Female; D006801:Humans; D007223:Infant; D007601:Jugular Veins; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy; D011486:Protein C / Q000032:analysis; D017293:Protein S / Q000032:analysis; D019851:Thrombophilia / Q000139:chemically induced*; D020246:Venous Thrombosis / Q000139:chemically induced*
chemical_list: D000991:Antithrombins; D011486:Protein C; D017293:Protein S; D001215:Asparaginase