Pharmacokinetics and drug monitoring of L-asparaginase treatment.

The enzyme L-asparaginase is an important component of the treatment protocols for Acute Lymphoblastic Leukemia (ALL). This enzyme is derived from different biological sources (E. coli and Erwinia chrysanthemi). An increasing number of hemorrhagic and thrombotic events prompted us to initiate a monitoring program for asparaginase treatment. Different asparaginase preparations were monitored in children on the ALL-BFM induction and reinduction treatment (10,000 U/m2 every 3-4 days). The different preparations resulted in significantly different trough levels of parameters of asparaginase activity, asparagine depletion, and coagulation. Not even the two preparations from E. coli were interchangeable: In a subsequent study, a mere 2500 U/m2 of the E. coli preparation Asparaginase medac resulted in trough levels comparable to 10,000 U/m2 of Crasnitin. The Erwinia preparation Erwinase, however, did not maintain measurable trough levels at the protocol schedule. We conclude that different L-asparaginase preparations are not readily interchangeable and that changes in the preparation, dosage or schedule require careful observation and possibly pharmacokinetic monitoring.