Cerebrospinal fluid asparagine depletion during pegylated asparaginase therapy in children with acute lymphoblastic leukaemia.
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.
Department of Paediatrics, Aarhus University Hospital, Aarhus N, Denmark.
Louise T
LT
Henriksen
Jacob
J
Nersting
Raheel A
RA
Raja
Thomas L
TL
Frandsen
Steen
S
Rosthøj
Henrik
H
Schrøder
Birgitte K
BK
Albertsen
D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D001216:Asparagine / Q000134:cerebrospinal fluid* / Q000172:deficiency; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005973:Glutamine / Q000134:cerebrospinal fluid; D006801:Humans; D007223:Infant; D007273:Injections, Intramuscular; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D013048:Specimen Handling / Q000379:methods
D000970:Antineoplastic Agents; D005973:Glutamine; D001216:Asparagine; D001215:Asparaginase
acute lymphoblastic leukaemia; asparagine; central nervous system; cerebrospinal fluid; pegylated asparaginase