Hypersensitivity reactions are relevant adverse effects of
asparaginase therapy. Therefore, children treated with native Escherichia coli
asparaginase in induction
therapy of acute lymphoblastic leukaemia (ALL) or
non-Hodgkin's lymphoma (NHL) were switched to the pegylated
enzyme for reinduction under
drug monitoring. Seventy children, including four patients with
allergic reactions during induction, were given one dose of
Oncaspar 1,000 U/m2 intravenously. Activity was determined every third or fourth day until it dropped below the limit of quantification. In current reinduction protocols [ALL/NHL-Berlin-Frankfurt-Münster (BFM) 95 trials], four doses of 10,000 U/m2 E. coli
asparaginase deplete
asparagine for about 2-3 weeks, therefore activities of >/= 100 U/l up to day 14 and >/= 50 U/l up to day 21 were targeted. In 66 patients without an
allergic reaction during induction, the mean activity was 606 +/- 313 U/l, 232 +/- 211 U/l and 44 +/- 50 U/l after 1, 2 and 3 weeks respectively. In 44/66 patients, activity was >/= 100 U/l after 14 d. A rapid decline in activity was seen in the remaining 22 patients, including 8/22 patients who showed no activity after 1 week. Toxicity was low and comparable to the native
enzymes but, in contrast to about 30% of
hypersensitivity reactions with conventional reinduction
therapy, no
allergic reaction was seen. Substituting 4 x 10,000 U/m2
asparaginase medac for one dose of 1,000 U/m2
Oncaspar was safe and well tolerated. Comparable pharmacokinetic treatment intensity was achieved in about two-thirds of patients.