Henriksen, Louise T5; Nersting, Jacob6; Raja, Raheel A6; Frandsen, Thomas L6; Rosthøj, Steen1; Schrøder, Henrik6; Albertsen, Birgitte K6
1 Klinik Kvinde-Barn og Urinvejskirurgi, The Faculty of Medicine, Aalborg University, VBN2 Børn og Unge (Pædiatri), The Faculty of Medicine, Aalborg University, VBN3 Aalborg University Hospital, The Faculty of Medicine, Aalborg University, VBN4 The Faculty of Medicine, Aalborg University, VBN5 Department of Paediatrics, Aarhus University Hospital, Aarhus N, Denmark.6 unknown
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.
British Journal of Haematology, 2014, Vol 166, Issue 2, p. 213-220