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and 57 adults (37 AML and 20 ALL) were treated with L-asparaginase (Asnase) 200 or 1000 IU/kg daily for 30 days unless withdrawn on account of side effects.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.
This study presents data on cancer incidence among 37,795 blood donors in an attempt to test the hypothesis that blood donation might be associated with cancer development. At a median follow-up time of nine years (range 5-13 years) a total of 1152 cancer cases have been diagnosed. The expected number of cancer cases derived from an age-matched population was 1459 giving a relative risk ratio (RR) of 0.79 (p less than 0.001). Calculations were made with and without latency periods between first blood donation and the diagnosis of cancer (0, 5, 10, 15 years). Overall, significantly decreased cancer incidence was observed (p less than 0.001) though the number of observed cases of haematological malignancies was not significantly different from that expected. For polycythaemia vera, however, the O/E ratio was 1.81 possibly indicating an association with blood donation. A more likely explanation is that this reflects increased diagnosis of polycythaemia vera in the blood donor population.
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