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occurrence or absence of fever in the patients. While many of the patients 
were febrile before therapy with asparaginase was started, there was a 30 
percent incidence of fever that was attributed to the enzyme, and the low 
purity lots produced a greater incidence of fever. 
Anorexia, nausea, and vomiting were experienced by about half the patients; 
again, there was a rough inverse correlation with specific activity, and 
also a direct correlation with dosage. A 30 percent incidence of immune 
reactions of various kinds was observed during the first course of 
treatment. As might be expected, a somewhat higher 41 percent incidence was 
found when second courses of treatment were instituted at a later time. 
Antibody formation to the enzyme preparations, as determined by immuno- 
diffusion and complement fixation, occurred in about 70 percent of the 
cases. Cross reactivity among the products of the four suppliers was 
evident. The Ouchterlony tests indicated that antibodies were directed 
against several antigenic determinants. Urticaria was the most common 
clinical symptom of hypersensitivity. Conclusions drawn from this study 
that are especially relevant to the bacterial contaminants are summarized 
below. 
1. Treatment with col i asparaginase produces a variety 
of similar toxic side effects in animals and in human 
patients. While certain of the side effects can be 
attributed to bacterial contaminants, the enzymatic 
activity and the immunogen icity of this foreign protein 
are the major factors in the toxic manifestations 
observed. 
[ 459 ] 
