Observations on the Effect of Various Folic Acid Antagonists on Acute Leukemia

1. Seventy patients with acute leukemia were treated with various folic acid antagonists. Sixty-five survived for a sufficient length of time to evaluate the effect of the therapeutic agents. Types of leukemia observed included 38 cases of acute lymphatic leukemia, 23 patients with acute monocytic leukemia and 4 with the acute myelogenous type of leukemia.

2. The best results, both clinically and hematologically, were obtained in acute lymphatic leukemia. Although the most satisfactory results were observed in the youngest age group, excellent remissions were produced in older individuals. Of 65 cases observed, an excellent clinical and hematologic remission was observed in 11 patients, a partial emission in 19 subjects, and no response in 35 individuals.

3. When a response occurred, a rater definite hematologic pattern was noted. An increased platelet count in most instances was the first evidence of regeneration and occurred in about the third or fourth week. The neutrophilic polymorphonuclear leukocytes began to regenerate at about the same time and an increase in their number was followed by a rise in the erythrocyte count.

4. Observations of the bone marrow indicated that although excellent clinical and hematologic remissions might occur, primitive leukemic cells were still present. In some instances megaloblasts were observed in addition to a peripheral macrocytosis and anisocytosis of erythrocytes.

5. Toxic manifestations were common. These included glossitis, ulceration of the oral cavity, nausea, vomiting, diarrhea and alopecia. In one instance there was ulceration of the entire gastro-intestinal tract, including the esophagus and colon. Hematologic toxic reactions included thrombocytopenia, leukopenia and anemia. Aplasia of marrow tissue was observed in 1 instance. In many instances the margin of safety between a toxic reaction and death was indeed small.

6. It should be emphasized that in no instance has a cure of leukemia resulted from treatment with a folic acid antagonist although prolonged remissions have occurred.