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Cerebrospinal fluid asparagine concentrations after Escherichia coli asparaginase in children with acute
1Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, and College of Pharmacy, University of Tennessee, Memphis 38105, USA.
Insights
Asparagine levels in cerebrospinal fluid (CSF) are significantly depleted by E. coli asparaginase therapy in children with acute lymphoblastic leukemia (ALL). However, these levels rebound after treatment cessation.
Area of Science:
- Pediatric Oncology
- Pharmacodynamics
- Leukemia Research
Background:
- The central nervous system (CNS) is a critical sanctuary site for childhood acute lymphoblastic leukemia (ALL).
- Cerebrospinal fluid (CSF) asparagine concentration serves as a marker for systemic asparaginase pharmacodynamics.
- Understanding CSF asparagine dynamics is crucial for optimizing ALL treatment strategies.
Purpose of the Study:
- To investigate the time course of CSF asparagine depletion during and after a course of Escherichia coli asparaginase in pediatric ALL patients.
- To assess the impact of asparaginase therapy on asparagine levels within the CNS.
Main Methods:
- Thirty-one children with ALL (newly diagnosed or relapsed) received intramuscular E. coli asparaginase (10,000 IU/m2) three times weekly.
- CSF asparagine levels were meticulously measured at baseline, during, and at various time points after asparaginase administration.
Main Results:
- A significant majority of patients (73.9%) achieved undetectable CSF asparagine levels during asparaginase therapy.
- CSF asparagine levels remained depleted for up to 5 days post-therapy in many patients, with a notable rebound observed after 30 days.
- Lower baseline CSF asparagine concentrations correlated with more effective depletion during therapy.
Conclusions:
- Conventional doses of E. coli asparaginase effectively deplete CSF asparagine in most children with ALL.
- Asparagine levels in the CSF rebound after the completion of asparaginase treatment.
Purpose:
The CNS is an important sanctuary site in childhood acute lymphoblastic leukemia (ALL). CSF asparagine concentration reflects asparaginase systemic pharmacodynamics. We evaluated the time course of CSF asparagine depletion in children with ALL during and after a course of Escherichia coli asparaginase.
Patients And Methods:
Thirty-one children (24 newly diagnosed and seven at relapse) received E coli asparaginase 10,000 IU/m2 intramuscularly three times weekly for six and nine doses, respectively, as part of multiagent induction chemotherapy. CSF asparagine levels were measured before, during, and after asparaginase dosing.
Results:
The percentage of patients with undetectable (< 0.04 micromol/L) CSF asparagine was 3.2% (one of 31 patients) at baseline, 73.9% (17 of 23) during 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) 11 to 30 days and 0% (zero of 21) more than 30 days after asparaginase therapy. The proportion of patients with depleted CSF asparagine was higher during asparaginase therapy than at baseline (P < .001), 11 to 30 days (P = .003), and more than 30 days after asparaginase therapy (P < .001). Median CSF asparagine concentrations were 4.42 micromol/L before, less than 0.04 micromol/L during, and less than 0.04 micromol/L at 1 to 5 days, 1.63 micromol/L at 6 to 10 days, 1.70 micromol/L at 11 to 30 days, and 5.70 micromol/L at more than 30 days after asparaginase therapy, respectively. CSF depletion was more common in patients with low baseline CSF asparagine concentrations (P = .003).
Conclusion:
CSF asparagine concentrations are depleted by conventional doses of E coli asparaginase in the majority of patients, but they rebound once asparaginase therapy is completed.
