Characteristics and outcome of patients with Philadelphia chromosome negative,bcr/abl negative chronic myelogenous leukemia

BACKGROUND: Up to 5% of patients with chronic myelogenous leukemia (CML) do not have the Philadelphia (Ph) translocation t(9;22)(q34;q11) or a bcr/abl molecular rearrangement. Although the diagnostic criteria of this entity are still under debate, there is general agreement that patients with Ph negative, bcr/abl negative CML have a severe clinical course that is not affected significantly by current treatment options. METHODS: A population of 76 patients with bcr/abl negative CML who had received minimal or no previous therapy was characterized carefully with the intent of investigating clinical and hematologic variables and their association with survival by univariate, correlation, and multivariate analyses. A group of 73 patients with Ph negative CML who were not tested for the bcr/abl rearrangement (bcr/abl unknown) was analyzed separately and used for extension of the analysis. RESULTS: In the bcr/abl negative patient population, the median overall survival was 24 months. At the time of the analysis, 38 patients (50%) had died, and blastic transformation preceded death in 31%. Chromosomal abnormalities were found in 30% of the 76 patients, with trisomy 8 the most common abnormality. Complex chromosomal abnormalities were rare, and monosomy 7 was not observed. Survival was not affected significantly by treatment. Multivariate analysis identified older age (> 65 years), anemia (hemoglobin < 10 g/dL), and severe leukocytosis (white blood cells > 50 x 10(9)/L) as variables with independent prognostic significance for poor survival. A prognostic scoring system stratified patients into a low-risk group (53%) and a high-risk group (47%), with median survivals of 38 months and 9 months, respectively. CONCLUSIONS: Bcr/abl negative CML is a distinct clinical entity associated with very poor prognosis. Two risk categories are identifiable using a simple scoring system based on age, hemoglobin level, and leukocyte number.