Leukemic cells are unable to synthesize asparagine due to a lack of asparagine synthetase and are dependent on an exogenous source of asparagine for survival. Rapid depletion of asparagine which results from treatment with the enzyme L-asparaginase, kills the leukemic cells. Normal cells, however, are less affected by the rapid depletion due to their ability to synthesize asparagine. This is an approach to therapy based on a specific metabolic defect in some leukemic cells which do not produce asparagine synthetase.¹

In a study in predominately L-asparaginase naive adult patients with leukemia and lymphoma, initial plasma levels of L-asparaginase following intravenous administration were determined. Plasma half-life did not appear to be influenced by dose levels, and it could not be correlated with age, sex, surface area, renal or hepatic function, diagnosis or extent of disease. Apparent volume of distribution was equal to estimated plasma volume. L-asparaginase was measurable for at least 15 days following the initial treatment with ONCASPAR^Ò. The enzyme could not be detected in the urine.²

In a study of newly diagnosed pediatric patients with acute lymphoblastic leukemia (ALL) who received either a single intramuscular injection of ONCASPAR^Ò (2,500 IU/m²), E. coli L-asparaginase (25,000 IU/m²),orErwinia L-asparaginase (25,000 IU/m²), the plasma half-lives for the three forms of L-asparaginase were:³

In this same study of newly diagnosed pediatric ALL patients, the in vivo early leukemic cell kill after a single intramuscular injection of native E. coli L-asparaginase (25,000 IU/m²), Erwinia L-asparaginase (25,000 IU/m²), and ONCASPAR^Ò (2,500 IU/m²) during a five-day ²investigational window² was studied.⁴ Bone marrow aspirates were taken before and five days after a single dose of one of the three different forms of L-asparaginase. Rhodamine-123 (RH-123), a selectively incorporated fluorescent mitochondrial dye, was used in an in vitro assay on the bone marrow aspirates to ascertain cell viability. The percent reduction of viable lymphoblasts at day five for each group is presented in the following table:⁴

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