title: Therapeutic drug monitoring of asparaginase in the ALL-BFM 2000 protocol between 2000 and 2007.
abstract: BACKGROUND
  On a voluntary basis therapeutic drug monitoring (TDM) was implemented in the ALL-BFM 2000 protocol for the three currently used asparaginase (ASNase) preparations (first line: native Escherichia coli ASNase; second line: pegylated ASNase and third line: Erwinia chrysanthemi ASNase).
  
  
  METHODS
  Between 2000 and 2007, 2,074 ASNase samples from 763 patients out of 114 hospitals were evaluated (5,000 U/m2 E. coli ASNase (n = 318), 1,000 U/m2 pegylated ASNase (n = 416) and 10,000 U/m2 Erwinia chrysanthemi ASNase (n = 29)).
  
  
  RESULTS
  First-line therapy with 5,000 U/m2 E. coli ASNase resulted in an ASNase activity of <100 U/L in 10% of all samples from day +3 after administration. Second-line treatment with 1,000 U/m2 PEG ASNase led to activity values below 100 U/L in approximately 30% of all samples taken +7 days. Relating ASNase activity to route of administration, 10,000 U/m2 Erwinia ASNase IM compared to IV as third-line treatment, led to a higher median activity (IM: median 151.5 U/L, range (0-750 U/L); IV: median 115 U/L, range (0-884 U/L), P = 0.3) and fewer samples below 100 U/L (IM: 15% vs. IV: 45%) at day +2.
  
  
  CONCLUSIONS
  The reduced dose of 5,000 U/m2 E. coli ASNase for induction treatment succeeded to achieve an activity level above 100 U/L in more than 90% of all samples. They confirm that dose reduction is reasonable and provide the basis for future treatment strategies employing ASNase.
authors.affiliation: Department of Paediatric Haematology and Oncology, University Hospital Muenster, Muenster, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Schrey
authors.forename: Stephan
authors.initials: S
authors.lastname: Borghorst
authors.forename: Claudia
authors.initials: C
authors.lastname: Lanvers-Kaminsky
authors.forename: Georg
authors.initials: G
authors.lastname: Hempel
authors.forename: Joachim
authors.initials: J
authors.lastname: Gerss
authors.forename: Anja
authors.initials: A
authors.lastname: Möricke
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Joachim
authors.initials: J
authors.lastname: Boos
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D016974:Dickeya chrysanthemi / Q000201:enzymology; D004342:Drug Hypersensitivity / Q000453:epidemiology / Q000209:etiology; D016903:Drug Monitoring; D004926:Escherichia coli / Q000201:enzymology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D001215:Asparaginase