Agar Culture Studies in 127 Cases of Untreated Acute Leukemia: The Prognostic Value of Reclassification of Leukemia According to In Vitro Growth Characteristics
Agar culture of marrow and blood from 127 cases of acute leukemia (including 108 cases of myeloid leukemia and variants) has revealed a spectrum of abnormalities. The observations of deranged proliferation and maturation of granulocyte—macrophage progenitor cells (in vitro CFC), together with abnormalities in CFC buoyant density, was of considerable diagnostic value. The morphologic, hematologic, and cytogenetic heterogeneity of acute myeloid leukemia did not correlate with heterogeneity of in vitro growth parameters, and grouping of patients by conventional hematologic parameters was of no value in predicting response to therapy. Indeed, the age of the patient was the only significant conventional parameter which influenced remission rate. By in vitro criteria, increase in the number of CFC of abnormally light buoyant density and high in vitro "plating efficiency" of the leukemic blast cells adversely affected remission probability. Reclassification of acute myeloid leukemia by in vitro growth pattern was of greatest prognostic value, and four main growth patterns were recognized: (1) colony forming, (2) large cluster forming (maximum cluster size, 40 cells), (3) small cluster forming (maximum cluster size, 20 cells), and (4) nongrowing. Highly significant differences in remission rate were observed in the different growth types. All cases of AML could be divided on the basis of growth pattern into a good prognosis group of 66 patients with a remission rate of 52% and a poor prognosis group of 42 cases with a 10% remission. The influence of age was evident in both groups, and of 30 patients less than 40 yr of age, remission in the favorable prognosis group was 91% and in the poor prognosis group only 14%. The ability to detect, at first diagnosis, a substantial number of patients whose disease is resistant to present therapeutic protocols could lead to application of alternative forms of therapy that may improve prognosis in this category.