The effect of thiouracil on leukemia.

By LOUIS R. LIMARZI, M.D., RICHARD J. KULASAVAGE, M.D., AND CONRAD L. PIRANI, M.D. O NE of the toxic reactions of therapeutic doses of thiouracilt in the treatment of hyperthyroidism is the development of granulocytopenia. A nonfatal granulocytopenia and a fatal type of agranulocytosis have been reported. The selective action of thiouracil on the granulopoietic tissue is the basis for the present evaluation of the drug in the treatment of leukemia. The 6 cases studied included 4 of chronic myeloid leukemia, i of chronic lymphatic leukemia, and i of acute myeloid leukemia. Hematologic surveys, including sternal marrow examination, were made in each case prior to and at frequent intervals during and after the administration of thiouracil. The method used for obtaining and studying the marrow is described by Limarzi.’ The basal metabolic rate and certain blood chemical constituents including uric acid and cholesterol were determined before, during, and following treatment with thiouracil. Creatine balance studies were carried out in i case of acute myeloid leukemia during the administration of the drug. It will be noted in table i that the total amount of thiouracil given varied from i.6 Gm. administered over a period of 8 days to 2.74 Gm. administered in gradually increasing doses over a period of 3 months. The average daily dose ranged from 0.2. Gm. to 3.0 Gm. Thiouracil was without effect on the basal metabolic rate, and the blood chemical findings were not appreciably changed except in case In the patient (case ) with chronic myeloid leukemia, who developed an extreme neutropenic leukopenia following treatment with thiouracil, the blood uric acid gradually rose to 11.4 mg. per 100 cc. of blood prior to death. The blood picture and bone marrow (table 2.), except in case , failed to show any marked change after the administration of thiouracil. In a 7 year old boy (case i) with acute myeloid leukemia who received approximately 0.3 Gm. of thiouracil daily for a period of i month, there were no changes either in the blood picture or the creatine metabolism. A case of chronic myeloid leukemia with specific cutaneous lesions (case 2.) received a daily dose of 0.2. Gm. of thiouracil for a period of 8 days. The rapid terminal phase with an acute blood pattern (“hiatus leukemicus”) was similar