Drug monitoring of low-dose PEG-asparaginase (Oncaspar (TM)) in children with relapsed acute lymphoblastic leukaemia

Use of asparaginase (ASNase) in the treatment of relapsed childhood acute l ymphoblastic leukaemia (ALL) is associated with a high rate of hypersensiti ve reactions. 'Silent' inactivation may additionally reduce treatment inten sity. Therefore, PEG-ASNase (Oncaspar(TM)), a polyethylene glycol conjugate of the native Escherichia coli-ASNase, was introduced into the Berlin-Fran kfurt-Munster (BFM) 96 treatment protocol for relaped ALL under drug monito ring conditions. A single i.v. dose of 500 IU/m(2) PEG-ASNase, substituted for the native ASNases, was administered to supply a plasma activity of 100 IU/I for 1 week. From November 1997 to March 2000, 35 patients from 23 BFM -associated hospitals, with or without a previous allergic reaction to one or both native preparations, underwent monitoring. After 82 applications, a total of 270 samples were submitted to be tested for ASNase activity. The ASNase activity on the day of the administration and the following day rang ed between <20 and 693 IU/I, with a median of 413 IU/I (53 samples). The me dian on d 7 +/- 1 was 199 IU/I (range <20-421 IU/1; 41 samples) and on d 14 +/- 1, 105 IU/I (range <20-188 IU/I; 19 samples). An ASNase activity of > 100 IU/I was seen on d 7 in 36 activity time courses of 52 interpretable ap plications (69%). Intraindividual variability of activity time courses was low. However, a rapid decrease in ASNase activity after repeated applicatio ns was observed in 4 out of 20 children. Previously experienced allergic re actions to native ASNases did not influence PEG-ASNase pharmacokinetics. PE G-ASNase is a useful alternative to the native ASNases in children with rel apsed ALL. Whenever possible, drug monitoring should be performed to identi fy patients with 'silent' inactivation.