title: L-asparagine depletion and L-asparaginase activity in children with acute lymphoblastic leukemia receiving i.m. or i.v. Erwinia C. or E. coli L-asparaginase as first exposure.
abstract: OBJECTIVE
  The present study was aimed at investigating L-asparaginase (L-ASE) activity (in plasma) and L-asparagine (L-ASN) depletion (in plasma and CSF) in children with newly diagnosed acute lymphoblastic leukemia (ALL) exposed for the first time to different L-ASE products.
  
  
  METHODS
  During the induction treatment of the AIEOP ALL 95 study, 62 patients were treated with either Erwinase (n = 15), or E. coli medac (n = 47) L-ASE products, given either i.m. or i.v., at the standard dosage of 10,000 IU/m2, q 3 days x 8 (first exposure).
  
  
  RESULTS
  Plasma and CSF L-ASN trough levels were undetectable in all cases, including those with L-ASE trough activity < 50 mU/ml. L-ASE trough activity during the administration of medac was however significantly higher when compared with that of Erwinase.
  
  
  CONCLUSIONS
  L-ASN depletion after a first exposure to standard doses of Erwinase or medac is obtained in virtually all patients. No differences are seen between the I.M. or I.V. administration routes but the medac product is associated with a significantly higher enzyme activity in respect of Erwinase. L-ASN levels may be undetectable also in patients with L-ASE trough activity levels < 50 mU/ml, challenging the current opinion that an activity level of 100 mU/ml is needed to obtain L-ASN depletion.
authors.affiliation: Department of Pediatrics, San Gerardo Hospital, Monza, Italy. masera@xquasar.it
authors.forename: C
authors.initials: C
authors.lastname: Rizzari
authors.forename: M
authors.initials: M
authors.lastname: Zucchetti
authors.forename: V
authors.initials: V
authors.lastname: Conter
authors.forename: L
authors.initials: L
authors.lastname: Diomede
authors.forename: A
authors.initials: A
authors.lastname: Bruno
authors.forename: L
authors.initials: L
authors.lastname: Gavazzi
authors.forename: M
authors.initials: M
authors.lastname: Paganini
authors.forename: P
authors.initials: P
authors.lastname: Sparano
authors.forename: L
authors.initials: L
authors.lastname: Lo Nigro
authors.forename: M
authors.initials: M
authors.lastname: Aricò
authors.forename: M
authors.initials: M
authors.lastname: Milani
authors.forename: M
authors.initials: M
authors.lastname: D'Incalci
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001215:Asparaginase / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D001216:Asparagine / Q000187:drug effects* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004926:Escherichia coli / Q000201:enzymology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001216:Asparagine; D001215:Asparaginase