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L‐asparaginase – Clinical Experience in Leukaemia, Lymphoma and Carcinoma
Author(s) -
Biggs J. C.,
Chestermant C. N.,
Holliday J.
Publication year - 1971
Publication title -
australian and new zealand journal of medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.596
H-Index - 70
eISSN - 1445-5994
pISSN - 0004-8291
DOI - 10.1111/j.1445-5994.1971.tb02253.x
Subject(s) - medicine , asparaginase , lymphoma , asparagine , enzyme , chemotherapy , leukemia , immunology , gastroenterology , pharmacology , biochemistry , lymphoblastic leukemia , biology
Summary: L‐asparaginase was found to be ineffective in the treatment of a small number of patients with solid tumours and advanced Hodgkin's disease. However, four complete and four partial remissions were obtained in a total of 11 cases of adult acute leukaemia. Improvement was also observed in lymphosarcoma. Treatment was limited by a number of toxic side‐effects, the most common of which was a depression of coagulation factors. Although Kidd demonstrated the striking inhibitory effect of guinea pig serum on transplanted lymphoma in rats and mice as early as 1953 1 , the significance of this finding was not truly appreciated until Broome demonstrated the active principle as L‐asparaginase in 1961 2 . L‐asparaginase catalyses the hydrolysis of L‐asparagine to aspartic acid and ammonia 3 . Asparagine has been found to be a necessary nutrient for the culture of some animal tumour cells in vitro 4 , 5 , but is not an essential growth requirement of normal cells 6 , and furthermore, is not a requirement in the diet of man 7 . Before widespread trials of this substance could be undertaken in man, a more readily available source of the enzyme was required. Mashburn and Wriston 8 were able to extract the enzyme from cultures of E. coli and this has subsequently become the major source of the enzyme preparation used in man. We obtained a supply of coliform L‐asparaginase** in 1969 and the following report describes the results of an initial clinical trial in 21 patients who received a standard dose regime in the absence of other cytotoxic drugs.