A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: A Children's Cancer Group study

Vassilios I. Avramis, Susan Sencer, Antonia P. Periclou, Harland Sather, Bruce C. Bostrom, Lewis J. Cohen, Alice G. Ettinger, Lawrence J. Ettinger, Janet Franklin, Paul S. Gaynon, Joanne M. Hilden, Beverly Lange, Fataneh Majlessipour, Pracad Mathew, Michael Needle, Joseph P Neglia, Gregory Reaman, John S. Holcenberg

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Abstract

For this study, 118 children with standard-risk acute lymphoblastic leukemia (ALL) were given randomized assignments to receive native or pegylated Escherichia coli asparaginase as part of induction and 2 delayed intensification phases. Patients treated with pegaspargase had more rapid clearance of lymphoblasts from day 7 and day 14 bone marrow aspirates and more prolonged asparaginase activity than those treated with native asparaginase. In the first delayed intensification phase, 26% of native asparaginase patients had high-titer antibodies, whereas 2% of pegaspargase patients had those levels. High-titer antibodies were associated with low asparaginase activity in the native arm, but not in the pegaspargase arm. Adverse events, infections, and hospitalization were similar between arms. Event-free survival at 3 years was 82%. A population pharmacodynamic model using the nonlinear mixed effects model (NONMEM) program was developed that closely fit the measured enzyme activity and asparagine concentrations. Half-lives of asparaginase were 5.5 days and 26 hours for pegaspargase and native asparaginase, respectively. There was correlation between asparaginase enzymatic activity and depletion of asparagine or glutamine in serum. In cerebrospinal fluid asparagine, depletion was similar with both enzyme preparations. Intensive pegaspargase for newly diagnosed ALL should be tested further in a larger population.

Original languageEnglish (US)
Pages (from-to)1986-1994
Number of pages9
JournalBlood
Volume99
Issue number6
DOIs
StatePublished - Mar 15 2002

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    Avramis, V. I., Sencer, S., Periclou, A. P., Sather, H., Bostrom, B. C., Cohen, L. J., Ettinger, A. G., Ettinger, L. J., Franklin, J., Gaynon, P. S., Hilden, J. M., Lange, B., Majlessipour, F., Mathew, P., Needle, M., Neglia, J. P., Reaman, G., & Holcenberg, J. S. (2002). A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: A Children's Cancer Group study. Blood, 99(6), 1986-1994. https://doi.org/10.1182/blood.V99.6.1986