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and 57 adults (37 AML and 20 ALL) were treated with L-asparaginase (Asnase) 200 or 1000 IU/kg daily for 30 days unless withdrawn on account of side effects.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 in children (16%, 17%, and 25% respectively). There was a clear association between these three parameters. Thus 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 in many cases antibodies were found without concomitant enzyme inactivation or hypersensitive reactions. Antibodies to Asnase of IgE type (reagins) were found in only 10 children and 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% (13/19) in contrast to 27% (3/11) among patients whose sera contained no detectable antibodies to Asnase, but the difference was not statistically significant.

In order to study the effect of oxymetholone therapy in advanced myelofibrosis, 11 patients (4 females, 7 males) were given, 3--5 mg per kg body weight, long-term oxymetholone treatment in a prospective multicenter study. Five cases had previously had a diagnosis of polycythemia vera. All patients had anemia initially, 4 leukocytopenia and 10 thrombocytopenia in addition. Hepato-splenomegaly was present in all cases but in varying degree. Five patients required regular blood transfusions before treatment. In 9 of the 15 courses given, there was normalization of the peripheral blood or substantial improvement (better than 3 g hemoglobin/dl or 50 X 10(9) platelets/1) after androgens. Significant effects were noted both on hemoglobin values and platelet counts. The need for blood transfusions ceased completely in all 5 cases. When oxymetholone treatment was reduced or interrupted 4 patients relapsed; 2 of them responded to a renewed course. The red cell counts returned to previous polycythemic values in one patient and another died from acute leukemia. The results of this study suggest that androgens might be of value in advanced cases of myelofibrosis with transfusion-requiring anemia or severe thrombocytopenia.