Serious neutropenia in ALL patients treated with L-asparaginase may be avoided by therapeutic monitoring of the enzyme activity in the circulation

The antineoplastic enzyme L-asparaginase is commonly used for the induction of remission in acute lymphoblastic leukemia (ALL). L-Asparagine is an essential amino acid for many lymphoid tumor cells and L-asparaginase catalyzes its conversion to L-aspartic acid and ammonia. The dosage of this highly toxic drug is individualized based on the body surface area of the patient, but monitoring of L-asparaginase activity during the L-asparaginase therapy is not commonly used. We measured L-asparaginase activity in the serum of ten children (aged 3-13 y) with ALL (ALL NOPHO-92 standard or intermediate risk groups) during their L-asparaginase therapy. L-asparaginase was given 30,000 IU/m2 IM during days 37-46 of the induction therapy and no other chemotherapeutic drug except for prednisone was given at the same time. We observed that this dosage schedule resulted in almost 6-fold differences in the serum activity of L-asparaginase between the patients. There was also a relationship between the area under the L-asparaginase activity-time curve (AUC) and even peak L-asparaginase activity in serum during the enzyme therapy and neutropenia after the therapy in the patients: the higher the AUC or peak value was, the more severe was the neutropenia in the patients after treatment. Monitoring L-asparaginase in serum could be useful in optimization of the therapy with this toxic drug.