Pegylated asparaginase (Oncaspar) in children with ALL: drug monitoring in reinduction according to the ALL/NHL-BFM 95 protocols.

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.