title: Asparagine concentration in plasma after 2,500 IU/m(2) PEG-asparaginase i.v. in children with acute lymphoblastic leukemia.
abstract: Polyethylene glycol conjugated asparaginase (PEG-ASNase) can be substituted in cases of hypersensitivity to native Escherichia coli asparaginase. We measured asparagine (asn) levels in plasma after a single dose of 2,500 IU/m(2) i.v. PEG-ASNase (Oncaspar) in consolidation treatment of ALL and compared those with data from the previous protocol COALL-05-92. This protocol was similar to COALL-06-97, except that children had been given 45,000 IU/m(2) C-ASNase instead of PEG-ASNase.
  
  
  METHODS
  Between May 2000 and December 2001 seventy-one children (38 boys, 33 girls) with newly diagnosed ALL treated according to the multicenter protocol COALL-06-97 were investigated in this study. Four hundred and seventy-four plasma samples (71 patients) were analysed by ion exchange chromatography after column derivatization with o-phthaldialdehyde. For comparison data (350 plasma samples) from 51 patients treated according to the protocol COALL-05-92 were available. The same method for detection of asn in plasma was used.
  
  
  RESULTS
  The median asparagine level in plasma after 2,500 IU/m(2) PEG-ASNase i.v. was below the limit of detection for at least 5 weeks in 81 % of the patients. When divided into high risk (HR) and low risk (LR) group, HR patients who had previously received one dose more of C-ASNase showed a markedly shorter depletion than the LR patients compatible with a higher risk of antibody formation and consequent silent inactivation after a higher number of exposures to ASNase. In the previous protocol COALL-05-92 median asn levels in plasma after 45,000 IU/m(2) native C-ASNase i.v. were below the limit of detection for at least 5 weeks in 65 % of the patients.
  
  
  CONCLUSIONS
  2,500 IU/m(2) PEG-ASNase led to an equally long depletion of asn in plasma as did 45,000 IU/m(2) native C-ASNase i.v. used in COALL-05-92.
authors.affiliation: University Children's Hospital, Pediatric Hematology and Oncology, University of Hamburg, Germany.
authors.forename: K A
authors.initials: KA
authors.lastname: Wenner
authors.forename: J P
authors.initials: JP
authors.lastname: Vieira Pinheiro
authors.forename: G
authors.initials: G
authors.lastname: Escherich
authors.forename: R
authors.initials: R
authors.lastname: Wessalowski
authors.forename: N
authors.initials: N
authors.lastname: Jorch
authors.forename: J
authors.initials: J
authors.lastname: Wolff
authors.forename: M
authors.initials: M
authors.lastname: Stehn
authors.forename: A
authors.initials: A
authors.lastname: Kohlschütter
authors.forename: J
authors.initials: J
authors.lastname: Boos
authors.forename: G E
authors.initials: GE
authors.lastname: Janka-Schaub
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage*; D001216:Asparagine / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D002852:Chromatography, Ion Exchange; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity / Q000276:immunology / Q000517:prevention & control; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D015337:Multicenter Studies as Topic; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D011092:Polyethylene Glycols; D001216:Asparagine; C042705:pegaspargase; D001215:Asparaginase