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L-Asparaginase in the Treatment of Neoplastic Diseases in Children¹

Children's Cancer Research Foundation, Children's Hospital Medical Center Tumor Therapy Service, and Harvard Medical School, Boston, Massachusetts 02115

Escherichia coli L-asparaginase was administered to 29 children with leukemia in dosage schedules of 200 i.u./kg/day for a minimum of 7 days or 5000 i.u./kg twice weekly for a minimum of 2 weeks. A complete remission was achieved in 7 patients (20%) by L-asparaginase alone and in 2 further patients by a combination of L-asparaginase and prednisone. Remission was maintained with p. o. methotrexate (30 mg/sq m twice weekly) with a median duration of 90 days. Reinduction, generally with the original form of therapy, was possible in 2 out of 6 patients. Hypocellularity of the bone marrow was encountered in 2 patients. Twelve patients with a variety of solid tumors failed to show any response to different dosage schedules.

The most serious side effect was hypersensitivity affecting 13 patients; in 2, the blood pressure was unobtainable for several minutes. A serum sickness-like reaction occurred in 1 patient, pulmonary edema occurred in 2 patients, and diabetic ketoacidosis occurred in 1 patient. Other side effects were generally mild and included hepatic dysfunction, elevation in serum amylase and blood ammonia (27 out of 28 patients), and mild depression and lethargy (in 4 patients with elevated blood ammonia levels). Pancreatitis and renal failure were not observed. There were no fatalities.

¹ This investigation was supported in part by Research Grant C-6516 from the National Cancer Institute, NIH, USPHS.

Received 10/26/70. Accepted 3/ 5/71.

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