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This study summarizes the Sloan-Kettering experience over the early and 
mid-phases of clinical evaluation of the enzyme during the years 1967 to 
1969. The enzyme was obtained from four suppliers during that period and 
there was a 10-fold range of specific activities of the batches. The enzyne 
was administered by the usual daily intravenous route, and three dose levels 
were used: 200, 1000 and 5000 I. U. /kg body weight. Depending on the 
specific activity of the preparations, this dose range was equivalent to 
about 5 to 18 milligrams of protein per kilogram. The duration of treatment 
was four weeks and a total of 274 patients was studied. 
While many of the early lots were pyrogenic, it was considered that the 
probable contamination by endotoxin was not sufficient to cause serious 
clinical problems. In animal toxicity studies no clear-cut evidence of 
endotoxemia was observed even with crude preparations of asparaginase. 
Batches were accepted for use if the pyrogen assay in rabbits showed a mean 
temperature rise of not more than 1.5* centigrade in three rabbits. 
Temperatures of this magnitude are induced by endotoxin doses two to three 
orders of magnitude below lethal doses. The investigators attempted to 
correlate low, that is, less than 70 I.U./mg versus high, greater than 150 
I.U./mg specific activity lots. 
Clinical observations of side effects in which bacterial contaminants may 
have played a major role are listed in Table 3. There was good correlation, 
as a rule, between specific activity and pyrogenicity of the lots; the lower 
purity lots were generally more pyrogenic. There was also a good 
correlation between the results of the pyrogen test in rabbits and the 
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