Chronologic sequence in appearance of clinical and laboratory findings characteristic of chronic myelocytic leukemia.

Clinical and laboratory findings of chronic myelocytic leukemia (CML) were analyzed by means of two different methods; first, retrospective analysis of hematologic data from 16 patients whose laboratory examinations had been performed twice a year for 5-10 yr prior to the development of CML and whose diagnosis was made in a very early stage of the disease, and, second, analysis of hematologic data at the time of diagnosis from 102 Ph’-positive CML patients. The same results were obtained with each method. A possible chronologic sequence in the appearance of abnormalities was the demonstration of the Ph’ chromosome in the bone marrow (leukocyte count of less than 10 x iO / liter), basophilia, thrombocytosis and low neutrophil alkaline phosphatase activity (10 x 109/liter), increase of immature granulocytes(20 x 109/liter), increase of vitamin B,2 in the serum (25 x 109/liter), splenomegaly (52 x 109/liter), and subjective symptoms (higher than 70 x 10 / liter). The curve showing proliferation of Ph’-positive cells was calculated to be log y = 0.053x + 10.023 (x, months from time when the leukocyte count was 10 x 109/liter; y, leukocyte count of x i09/ liter). From the formula, the elapsed time from outbreak of a single cell with a Ph’ chromosome in the body to a leukemic cell mass of 10 x 109/liter was estimated to be 6.3 yr. The hypothesis that malignant transformation of Ph’-positive cells could develop in the early proliferative stage may contribute to elucidating the pathophysiology of blastic crisis of CML.