Pharmacokinetics of native Escherichia coli asparaginase (Asparaginase medac) and hypersensitivity reactions in ALL-BFM 95 reinduction treatment

Repeated asparaginase treatment has been associated with hypersensitivity r eactions against the bacterial macromolecule in a considerable number of pa tients. Immunological reactions may range from anaphylaxis without impairme nt of serum asparaginase activity to a very fast decline in enzyme activity without any clinical symptoms. Previous investigations on a limited number of patients have shown high interindividual variability of asparaginase ac tivity time courses and hypersensitivity reactions in about 30% of patients during reinduction treatment. Therefore, monitoring of reinduction. treatm ent was performed prospectively in 76 children with newly diagnosed acute l ymphoblastic leukaemia (ALL). According to the ALL-Berlin-Frankfurt-Munster (BFM) 95 protocol, 10 000 U/m(2) body surface area of native Escherichia c oli asparaginase (Asparaginase medac) was given on d 8, 11, 15 and 18. In 4 5/76 children, trough and peak activities were determined with every dose, and also on d 4 and d 11 after the last administration. Data on asparaginas e activity were not available from the remaining 31 patients, but informati on with regard to hypersensitivity reactions only was given. Eighteen out o f 76 patients (24%) suffered a clinical hypersensitivity reaction; however, no silent inactivation was observed. Activity in the therapeutic range of greater than 100 U/I for at least 14 d was determined in 43 of the 45 patie nts who were analysed for enzyme activity.