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Daunomycin is a new antibiotic in the anthracycline group obtained from Streptomyces peucetius. It consists of a pigmented aglycone (daunomycinone) in glycoside linkage with an amino sugar (daunosamine). Differences in the biological effects of daunomycin, which reacts with DNA, and actinomycin D which complexes with DNA in a different manner to inhibit RNA production, are discussed. The toxic effects of daunomycin are a severe local reaction if the drug extravasates, bone marrow depression resulting in leucopenia, anemia, thrombocytopenia and bleeding, fever, oral ulcers and alopecia. In patients receiving maintenance doses of daunomycin the development of tachypnea, tachycardia pulmonary insufficiency, heart failure and hypotension possibly is associated with daunomycin but the evidence is unclear. Sixty per cent of children with leukemia obtained brief complete or partial hematological remissions from a single course of daunomycin. The remission could be prolonged by maintenance therapy. Daunomycin is temporarily effective in some cases of neuroblastoma, reticulum cell sarcoma and rhabdomyosarcoma.

During therapeutic trials with E. coli L‐asparaginase in 131 children and 143 adults with neoplastic disease the following signs of toxicity have been observed: fever, nausea and vomiting, weight loss, somnolence, lethargy, confusion, hypolipidemia, hyperlipidemia, hypoproteinemia, abnormal liver function tests, fatty metamorphosis of the liver, pancreatitis (in rare instances), azotemia, granulocytopenia, lymphopenia, thrombocytopenia, and hypersensitivity reactions. While these effects have been moderately severe and reversible in most instances, some patients have shown dangerous degrees of toxicity. This has been the case most frequently in adult patients receiving a dose of 5000 IU/kg/day.

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One hundred thirty‐one children between 1 and 15 years of age have been treated. Ninety‐five children had acute lymphoblastic leukemia (ALL); 13 had other types of leukemia; 8 had lymphoma; and 15 had other solid tumors. The dosage ranged from 10 to 5,000 IU/kg daily. Treatment schedules included maintenance after remission and no maintenance. Nine patients in bone marrow remission with other chemotherapy prior to treatment with A‐ase received a 28‐day course. Six patients received the enzyme intrathecally for meningeal leukemia. Of the 73 adequately treated (over 14 days) ALL patients, the overall remission rate was 62%; the median duration of remission was 60 days with a range of 15 to 248 days. The duration of remission appeared to be independent of dose. Six nonlymphoblastic leukemias demonstrated transient fall in WBC and decreased organ size but no bone marrow remission. One of 4 with Hodgkin's disease demonstrated decrease in size of nodes, liver, and spleen. None of the solid tumors responded. The usual side effects of conventional chemotherapeutic agents, mucous membrane ulcerations, alopecia, and diarrhea were not seen. Side effects included reversible abnormal biochemical liver function tests, fever, and anaphylaxis.

1. A new antimetabolite, 6-mercaptopurine, has been shown to produce good clinical and hematologic remissions in fifteen out of forty-five children with acute leukemia. Another ten showed partial remissions and clinical improvement. 2. Remissions in adults with acute leukemia have occasionally been brought about by 6-mercaptopurine, and in a few cases it has produced temporary remissions in both the early and the late stages of chronic myelocytic leukemia. 3. The compound has been effective in some children whose disease was resistant to the folic acid antagonists, as shown by the fact that out of twenty-four children with acute leukemia whose disease had been proved to be resistant to amethopterin, five had good clinical and hematologic remissions and five had partial remissions with some marrow and clinical improvement. Some benefit was seen in eight out of eighteen patients whose disease was resistant to ACTH and cortisone. 4. In children the daily oral administration of 2.5 mg./Kg. rarely caused toxic manifestations, but continued therapy at this dose in adults or at higher levels in children occasionally produced bone marrow depression or gastrointestinal symptoms. 5. There is evidence that the therapeutic resistance of the acute leukemias to 6MP develops somewhat more rapidly than it does to the folic acid antagonists but there is, as yet, no laboratory or clinical evidence of cross resistance between these two types of antimetabolites. 6. In a total of thirty-five patients with lymphomas and miscellaneous carcinomas and sarcomas, 6MP did not produce any definite clinical improvement at doses which produced hematologic toxicity. 7. Although 6-mercaptopurine acts as a purine antagonist in certain forms of bacteria, the exact mechanism of its action in leukemia is at present unknown. Since its mode of action appears to differ from that of other agents previously employed clinically in the treatment of leukemia, this compound would appear to be of fundamental as well as practical interest.