Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy characterized by wide heterogeneity of clinical presentation and course. CMML shares myelodysplastic characteristics with features of myeloproliferative disorders. No treatment has proven effective in modifying the natural course of the disease. To improve the prognostic assessment of clinical outcome, the associations of patient and disease characteristics with survival times of 213 patients with CMML was investigated retrospectively. Median survival was 12 months. Univariate analysis identified low hemoglobin level; low platelet count; high white blood cell, monocyte, and lymphocyte counts; presence of circulating immature myeloid cells, high percentage of marrow blasts, low percentage of marrow erythroid cells, abnormal cytogenetics, and high levels of serum lactate dehydrogenase and beta(2)-microglobulin as characteristics associated with shorter survival. Hemoglobin level below 120 g/L (12 g/dL), presence of circulating immature myeloid cells, absolute lymphocyte count above 2.5 x 10(9)/L, and marrow blasts 10% or more were independently associated with shorter survival by multivariate analysis and were used to generate a prognostic score. The model identified 4 subgroups of patients with median survival of 24, 15, 8, and 5 months for low, intermediate-1, intermediate-2, and high risk, respectively. Researchers could not confer objective evidence suggesting that arbitrary divisions of CMML by white blood cell counts into "dysplastic" and "proliferative" categories reflect clinical entities differing in the risk of acute leukemia development, although a trend of shorter survival in patients with leukocytosis was observed. The prognostic model was compared with 6 previously published scoring systems for myelodysplastic syndrome/CMML. The reported results should provide an improved assessment of prognosis in CMML.