title: Pegylated asparaginase (Oncaspar) in children with ALL: drug monitoring in reinduction according to the ALL/NHL-BFM 95 protocols.
abstract: Hypersensitivity reactions are relevant adverse effects of asparaginase therapy. Therefore, children treated with native Escherichia coli asparaginase in induction therapy of acute lymphoblastic leukaemia (ALL) or non-Hodgkin's lymphoma (NHL) were switched to the pegylated enzyme for reinduction under drug monitoring. Seventy children, including four patients with allergic reactions during induction, were given one dose of Oncaspar 1,000 U/m2 intravenously. Activity was determined every third or fourth day until it dropped below the limit of quantification. In current reinduction protocols [ALL/NHL-Berlin-Frankfurt-Münster (BFM) 95 trials], four doses of 10,000 U/m2 E. coli asparaginase deplete asparagine for about 2-3 weeks, therefore activities of >/= 100 U/l up to day 14 and >/= 50 U/l up to day 21 were targeted. In 66 patients without an allergic reaction during induction, the mean activity was 606 +/- 313 U/l, 232 +/- 211 U/l and 44 +/- 50 U/l after 1, 2 and 3 weeks respectively. In 44/66 patients, activity was >/= 100 U/l after 14 d. A rapid decline in activity was seen in the remaining 22 patients, including 8/22 patients who showed no activity after 1 week. Toxicity was low and comparable to the native enzymes but, in contrast to about 30% of hypersensitivity reactions with conventional reinduction therapy, no allergic reaction was seen. Substituting 4 x 10,000 U/m2 asparaginase medac for one dose of 1,000 U/m2 Oncaspar was safe and well tolerated. Comparable pharmacokinetic treatment intensity was achieved in about two-thirds of patients.
authors.affiliation: Department of Paediatric Haematology/Oncology, University of Münster, Germany. hmuller@uni-muenster.de
authors.forename: H J
authors.initials: HJ
authors.lastname: Müller
authors.forename: L
authors.initials: L
authors.lastname: Löning
authors.forename: A
authors.initials: A
authors.lastname: Horn
authors.forename: D
authors.initials: D
authors.lastname: Schwabe
authors.forename: M
authors.initials: M
authors.lastname: Gunkel
authors.forename: M
authors.initials: M
authors.lastname: Schrappe
authors.forename: V
authors.initials: V
authors.lastname: von Schütz
authors.forename: G
authors.initials: G
authors.lastname: Henze
authors.forename: J
authors.initials: J
authors.lastname: Casimiro da Palma
authors.forename: J
authors.initials: J
authors.lastname: Ritter
authors.forename: J P
authors.initials: JP
authors.lastname: Pinheiro
authors.forename: M
authors.initials: M
authors.lastname: Winkelhorst
authors.forename: J
authors.initials: J
authors.lastname: Boos
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000097:blood / Q000627:therapeutic use*; D001215:Asparaginase / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity / Q000209:etiology; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007223:Infant; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D001215:Asparaginase