One hundred and fourteen patients with acute leukemia, 57 children (10 AML and 47 ALL) and 57 adults (37 AML and 20 ALL) were treated with L-asparaginase (Asnase) 200 or 1000 IU/kg daily for 30 days unless withdrawn on account of side effects. Combinations with other cytotoxic drugs were used in all but eight patients. Hypersensitive reactions, decrease in Asnase activity in plasma, and bivalent antibodies to Asnase appeared more frequently in adults (28%, 46%, and 79%, respectively) than i n children (16%, 1796, and 25%, respectively). There was a clear association between these three parameters. T h u s hypersensitive reactions generally developed at the time of or after the decrease in plasma Asnase activity. Antibodies were detected only where Asnase activity had disappeared from the plasma. This time sequence, and in vitro experiments, suggest the formation of antigen-antibody complexes which might be responsible for inactivation of Asnase and for the development of hypersensitive reactions. However i n many cases antibodies were found without concomitant enzyme inactivation or hypersensitive reactions. Antibodies t o Asnase of IgE type (reagins) were found i n only 10 children a n d 6 adults. There was no correlation between hypersensitive reactions, decrease in Asnase activity, and IgE antibodies. The frequency of remission among patients developing bivalent antibodies to Asnase was 68% (13119) in contrast t o 27% (3Jll) among patients whose sera contained no detectable antibodies to Asnase, but the difference was not statistically significant.
Cancer 1976.
H E ENZYME L-ASPARAGINASE (ASNASE) IS for the patients. In practice, hypersensitive T effective in inducing remission in many reactions have been observed frequently and patients with acute leukemia, particularly the they are, in fact, the most undesirable side lymphoblastic type in children. T h e most corn-effects in Asnase therapy. To study this probmonly used type of Asnase is derived from lem further, we have analyzed formation of Escherichia coli and is thus a foreign protein antibodies to Asnase in 114 enzyme-treated pa-