Cerebrospinal fluid asparagine concentrations after Escherichia coli asparaginase in children with acute lymphoblastic leukemia

Purpose: The CNS is an important sanctuary site in childhood acute lymphobl astic leukemia (ALL). CSF asparagine concentration reflects asparaginase sy stemic pharmacodynamics. We evaluated the time course of CSF asparagine dep letion in children with ALL during and after a course of Escherichia coli a sparaginase. Patients and Methods: Thirty-one children (24 newly diagnosed and seven at relapse) received E coli asparaginase 10,000 IU/m(2) intramuscularly three times weekly for six and nine doses, respectively, as part of multiagent in duction chemotherapy. CSF asparagine levels were measured before, during, a nd after asparaginase dosing. Results: The percentage of patients with undetectable (< 0.04 mu mol/L) CSF asparagine was 3.2% tone of 31 patients) at baseline, 73.9%(17 of 23) duri ng asparaginase therapy and 56.3% (nine of 16) 1 to 5 days, 43.8% (seven of 16) 6 to 10 days, 20.0% (two of 10) 1 1 to 30 days and 0% (zero of 21) mor e than 30 days after asparaginase therapy The proportion of patients with d epleted CSF asparagine was higher during asparaginase therapy than at basel ine (P <.001), 11 to 30 days (P =.003), and more than 30 days after asparag inase therapy (P <.001]. Median CSF asparagine concentrations were 4.42 mu mol/L before, less than 0.04 mu mol/L during, and less than 0.04 mu mol/L a t 1 to 5 days, 1.63 mu mol/L at 6 ta 10 days, 1.70 mu mol/L at 11 to 30 day s, and 5.70 mu mol/L at more than 30 days after asparaginase therapy respec tively. CSF depletion was more common in patients with low baseline CSF asp aragine concentrations (P=.003). Conclusion: CSF asparagine concentrations are depleted by conventional dose s of E call asparaginase in the majority of patients, bur they rebound once asparaginase therapy is completed. J Clin Oncol 17:1568-1573. (C) 1999 by American Society of Clinical Oncology.