FOLIC ACID ANTAGONISTS IN THE TREATMENT OF ACUTE AND SUBACUTE LEUKEMIA

Abstract

Forty cases of acute and subacute leukemia were treated with one or more of various folic acid antagonists, usually aminopterin. Thirty-two cases were treated for at least one week, remissions occurring in 10. The remissions were of a temporary nature and variable in duration. As of June 1, 1949, two patients were still alive and in good condition, seven and one-half and thirteen months, respectively, after onset of therapy. Clinical, hematologic, and to lesser extent, marrow remissions were obtained most commonly in the lymphocytic type, none in the 4 monocytic cases. The subacute cases responded far better than did those of the acute, fulminating variety. The exact mechanism of action of the folic acid antagonists is not known, although one may speculate that anti-PGA, an anti-growth factor which resembles PGA so closely, is readily accepted by the primitive white cell with resultant cell death. The margin between a therapeutic or effective dose and one causing a toxic reaction is a narrow one. A "toxic" reaction may in fact be an indication of a therapeutic response. The pattern of therapy was (1) administration of the drug, usually by parenteral injection until a toxic or a pronounced hematologic reaction occurred, at which point (2) the drug was discontinued. With subsidence of the toxic reaction, (3) a maintenance dosage was then given, usually in the form of oral medications, 0.5 mg. daily for adults and 0.25 mg. for children. Transfusions and antibiotics were administered as indicated. Frequent transfusions were usually very helpful at the time of the initial reaction when anemia was ordinarily severe. Penicillin and other antibiotics were used for supportive therapy. Thrombocytopenia and hemorrhage were exceedingly difficult to control. The observed remissions appeared to be directly attributable to the action of the drug. Although temporary, they indicate that acute leukemia is not necessarily completely irreversible. Thus, there is hope that more potent anti-growth factors may someday be discovered which will be of value in ultimate control of the disease.