Use of a Folic Acid Antagonist in Chronic Leukemia

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Abstract
Nine patients with chronic leukemia were treated with the folic acid antagonist, 4-amino pteroylglutamic acid. The drug was taken orally, in daily doses ranging from 1.25 to 7.5 mg. over periods from 6 to 25 days. Stem cells in both myelogenous and lymphatic leukemia, and immature granulocytes in myelogenous leukemia decreased in number. Small numbers of megaloblasts appeared in the sternal marrow of the patients after approx. 50-100 mg. of the drug had been ingested. Toxic effects, in the order of appearance, included pharyngitis, stomatitis, sore tongue, crampy abdominal pain, dermatitis, and alopecia. The hematologic effects of therapy were temporary and never completely adequate because treatment had to be stopped when toxic signs appeared. Although the drug had a definite hematologic effect, there was no subjective improvement in any of the patients. The use of the drug in chronic leukemia is limited by the early development of toxic phenomena.