Plasma asparaginase activity and asparagine depletion in acute lymphoblastic leukemia patients treated with pegaspargase on Children’s Oncology Group AALL07P4
Year: 2019
Type: article
Abstract: The efficacy of asparaginase in acute lymphoblastic leukemia (ALL) is dependent on depletion of asparagine, an essential amino acid for ALL cells. The target level of plasma asparaginase activity to achieve asparagine depletion has been between 0.05 and 0.4 IU/mL. COG AALL07P4 examined the asparaginase activity and plasma and CSF asparagine concentration of pegaspargase when given intravenously in the treatment of NCI high risk ALL. Matched plasma asparaginase/asparagine levels of the clearance of 54 doses of pegaspargase given in induction or consolidation demonstrated that all patients who had a plasma asparaginase level >0.02 IU/mL had undetectable plasma asparagine. No difference was observed in CSF asparagine levels associated with matched plasma asparaginase levels of 0.02–0.049 versus 0.05–0.22 IU/mL (p = .25). Our data suggest that a plasma asparaginase activity level of 0.02 IU/mL can effectively deplete plasma asparagine. The data also indicate that the 95% CI for plasma asparagine depletion after a pegaspargase dose is 22–29 days.Clinical trial registration: clinicaltrials.gov identifier NCT00671034.
Institutions: Children's National, University of Florida Health, University of Florida, St. Charles Medical Center, The University of Texas Southwestern Medical Center, University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, NYU Langone Health, NYU Langone’s Laura and Isaac Perlmutter Cancer Center, New York University, Children's Hospital of Philadelphia, University of Pennsylvania
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2909288016