Abstract
On the basis that circulating L-asparagine can be reduced to negligible level within minutes of administration of therapeutic doses of L-asparaginase, a two dosage theraputic regimen of enzyme was investigated to determine the effectiveness and toxicity of even lower doses of the enzyme in pediatric patients with advanced leukemia.
Schedule A consisted of vincristine, 2mg/M2/week×4, I. V., prednisone, 60mg/M2/day×21, P. O., and L-asparaginase 300IU/M2/day×15, I. V. Schedule B consisted of vincristine and prednisone, same as schedule A and L-asparaginase 600IU/M2/day×15, I. V.
Among 26 patients, 13 were randomized to schedule A, and 13, schedule B.
Marrow remissions were induced in 10 (83.3%) of 12 patients with schedule A, in 8 (66.7%) of 12 with schedule B. The over-all response rate for the study was 18(75%) of 24.
No death contributed to both regimens was observed. Among the serious side effects of this enzyme, such as hypersensitivity reactions, hyperglycemia, pancreatitis, and seizure, only one patient in schedule A, developed reaction comprising urticaria.
The other signs of toxicity of low plasma fibrinogen levels, abnormal liver function tests, hypoproteinemia, hypolipidemia and leukopenia were observed in most instances to even lower doses of the enzyme. But these were mild and reversible.
These data indicated much lower doses of the enzyme are effective in the therapy of acute leukemia, and seemed to lessen the serious toxicity.
