Plasma asparaginase activity and asparagine depletion in acute lymphoblastic leukemia patients treated with pegaspargase on Children’s Oncology Group AALL07P4*

Reuven J. Schore, Meenakshi Devidas, Archie Bleyer, Gregory H. Reaman, Naomi J Winick, Mignon L. Loh, Elizabeth A. Raetz, William L. Carroll, Stephen P. Hunger, Anne L. Angiolillo

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
JournalLeukemia and Lymphoma
DOIs
StateAccepted/In press - Jan 1 2018

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Asparaginase
Asparagine
Precursor Cell Lymphoblastic Leukemia-Lymphoma
pegaspargase
Essential Amino Acids
Clinical Trials

Keywords

  • asparaginase
  • asparagine depletion
  • Lymphoid Leukemia
  • pharmacodynamics
  • pharmacokinetics

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Plasma asparaginase activity and asparagine depletion in acute lymphoblastic leukemia patients treated with pegaspargase on Children’s Oncology Group AALL07P4* . / Schore, Reuven J.; Devidas, Meenakshi; Bleyer, Archie; Reaman, Gregory H.; Winick, Naomi J; Loh, Mignon L.; Raetz, Elizabeth A.; Carroll, William L.; Hunger, Stephen P.; Angiolillo, Anne L.

In: Leukemia and Lymphoma, 01.01.2018.

Research output: Contribution to journalArticle

Schore, Reuven J. ; Devidas, Meenakshi ; Bleyer, Archie ; Reaman, Gregory H. ; Winick, Naomi J ; Loh, Mignon L. ; Raetz, Elizabeth A. ; Carroll, William L. ; Hunger, Stephen P. ; Angiolillo, Anne L. / Plasma asparaginase activity and asparagine depletion in acute lymphoblastic leukemia patients treated with pegaspargase on Children’s Oncology Group AALL07P4* In: Leukemia and Lymphoma. 2018.
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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.",
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