Forty-six children with acute lymphocytic leukemia in relapse were divided randomly into two groups and treated with combinations of asparaginase (l-asparagine amidohydrolase, EC 3.5.1.1), cytosine arabinoside, and 6-azauridine. The objectives were to improve the 41% incidence of remission induction obtained earlier at this hospital with asparaginase alone and to compare the efficacy and toxicity of combining cytosine arabinoside versus cytosine arabinoside plus 6-azauridine with asparaginase. The first group, 24 children, received 10,000 i.u. of asparaginase per sq m and 300 mg of cytosine arabinoside per sq m on Days 1 and 8 (Schedule A). The second group, 22 children, received identical doses of these two agents plus 15 g of 6-azauridine per sq m on Days 1 and 8 (Schedule B). Complete remission was induced in 15 of the patients on Schedule A and in 13 of those on Schedule B. The median duration of response for the first group was 48 days (range, 14 to > 365); for the second group it was 52 days (range 9 to 177). When compared retrospectively with asparaginase alone, asparaginase combined with cytosine arabinoside increased the incidence but not the duration of remission induction. As determined by simultaneous comparison, there was no advantage in the present study from adding 6-azauridine to the asparaginase-cytosine arabinoside combination.

Thymidine incorporation into DNA by leukemic lymphoblasts was severely inhibited after asparaginase and cytosine arabinoside administration, and remained on the average more than 90% inhibited for over 24 hr.

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Supported by USPHS Cancer Center Grant CA-08480 and Research Project Grants CA-11148 and CA-12732 from the National Cancer Institure and by ALSAC.

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