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Rigshospitalet - a part of Copenhagen University Hospital
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Cerebrospinal fluid asparagine depletion during pegylated asparaginase therapy in children with acute lymphoblastic leukaemia

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  • Ann Louise Henriksen
  • Jacob Nersting
  • Raheel A Raja
  • Thomas L Frandsen
  • Steen Rosthøj
  • Henrik Schrøder
  • Birgitte K Albertsen
  • Nordic Society of Paediatric Haematology and Oncology (NOPHO) group
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L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Cerebrospinal fluid (CSF) asparagine depletion is considered a marker of asparaginase effect in the central nervous system (CNS) and may play a role in CNS-directed anti-leukaemia therapy. The objective of this study was to describe CSF asparagine depletion during 30 weeks of pegylated asparaginase therapy, 1000 iu/m(2) i.m. every second week, and to correlate CSF asparagine concentration with serum L-asparaginase enzyme activity. Danish children (1-17 years) with ALL, treated according to the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol, standard and intermediate risk, were included. CSF samples were obtained throughout L-asparaginase treatment at every scheduled lumbar puncture. A total of 128 samples from 31 patients were available for analysis. Median CSF asparagine concentration decreased from a pre-treatment level of 5·3 μmol/l to median levels ≤1·5 μmol/l. However, only 4/31 patients (five samples) had CSF asparagine concentrations below the limit of detection (0·1 μmol/l). In 11 patients, 24 paired same day serum and CSF samples were obtained. A decrease in CSF asparagine corresponded to serum enzyme activities above 50 iu/l. Higher serum enzyme activities were not followed by more extensive depletion. In conclusion, pegylated asparaginase 1000 iu/m(2) i.m. every second week effectively reduced CSF asparagine levels.

Original languageEnglish
JournalBritish Journal of Haematology
Volume166
Issue number2
Pages (from-to)213-20
Number of pages8
ISSN0007-1048
DOIs
Publication statusPublished - Jul 2014

    Research areas

  • Adolescent, Antineoplastic Agents, Asparaginase, Asparagine, Child, Child, Preschool, Drug Administration Schedule, Drug Monitoring, Female, Glutamine, Humans, Infant, Injections, Intramuscular, Male, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Specimen Handling

ID: 45093769