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Cerebrospinal fluid asparagine depletion during pegylated asparaginase therapy in children with acute lymphoblastic leukaemia
Author(s) -
Henriksen Louise T.,
Nersting Jacob,
Raja Raheel A.,
Frandsen Thomas L.,
Rosthøj Steen,
Schrøder Henrik,
Albertsen Birgitte K.
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12865
Subject(s) - asparaginase , medicine , cerebrospinal fluid , lymphoblastic leukemia , leukemia
Summary 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 N ordic S ociety of P aediatric H aematology and O ncology ALL 2008 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.