title: Serum asparaginase activities and asparagine concentrations in the cerebrospinal fluid after a single infusion of 2,500 IU/m(2) PEG asparaginase in children with ALL treated according to protocol COALL-06-97.
abstract: METHODS
  Pharmacological surrogate parameters are considered a useful tool in estimating the treatment intensity of asparaginase (ASNase) preparations. When a pegylated ASNase (single infusion of 2,500 IU/m(2) polyethylene glycol (PEG)-ASNase, Oncaspar) was introduced into the treatment protocols of the German Cooperative Acute Lymphoblastic Leukaemia (COALL) study group, this was accompanied by a drug monitoring programme measuring serum ASNase activity and asparagine (ASN) concentrations in the cerebrospinal fluid (CSF) in 70 children.
  
  
  RESULTS
  Four hundred fifty-nine serum samples from 67 evaluable patients showed medians of ASNase activity of 1,189.5, 824.5, 310.5, 41 and 4 U/l on day 7 +/- 1, 14 +/- 1, 21 +/- 1, 28 +/- 1 and 35 +/- 1 respectively. One hundred eighty-four samples from 59 patients were evaluable for ASN concentrations in the CSF. The medians of ASN concentration were <0.2, 0.2, 0.9 and 3.2 microM on day 14 +/- 1, 21 +/- 1, 28 +/- 1 and 35 +/- 1 respectively. When relating CSF ASN levels to the serum ASNase activity measured on the same day, a median of 1.2 microM CSF ASN was associated with values of serum ASNase activity between > or =2.5 and <100 U/l. Serum ASNase activity values > or =100 U/l were associated with a median CSF ASN of <0.2 microM, with 13/27 samples being incompletely depleted.
  
  
  CONCLUSIONS
  The treatment intensity achieved with PEG ASNase in the present study appears to be acceptable based on the surrogate of serum ASNase activity. However, the pharmacological objective of ASNase treatment, that is, complete CSF ASN depletion with an ASNase activity >100 U/l, was not ensured. Nevertheless, one must also be aware that the minimum ASN concentration required for leukaemic cell growth is yet to be established.
authors.affiliation: University Hospital Muenster, Coordinating Centre for Clinical Trials (KKS), Muenster, Germany.
authors.forename: J P
authors.initials: JP
authors.lastname: Vieira Pinheiro
authors.forename: K
authors.initials: K
authors.lastname: Wenner
authors.forename: G
authors.initials: G
authors.lastname: Escherich
authors.forename: C
authors.initials: C
authors.lastname: Lanvers-Kaminsky
authors.forename: G
authors.initials: G
authors.lastname: Würthwein
authors.forename: G
authors.initials: G
authors.lastname: Janka-Schaub
authors.forename: J
authors.initials: J
authors.lastname: Boos
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage / Q000097:blood* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase