HISTOLOGICAL FEATURES OF PROGNOSTIC-SIGNIFICANCE IN CML - AN IMMUNOHISTOCHEMICAL AND MORPHOMETRIC STUDY (MULTIVARIATE REGRESSION-ANALYSIS) ON TREPHINE BIOPSIES OF THE BONE-MARROW

To evaluate the prognostic significance of clinical as well as histological disease features at the time of diagnosis, an immunohistochemical and morphometric study was performed on bone marrow trephine biopsies in 130 patients with Ph1+-CML. For identification of all cell elements of the megakaryocytopoiesis we used the monoclonal antibody CD61 (Y2/51) and for the macrophages, the recently characterized antibody PG-M1. Density of argyrophilic fibers was determined per fat cell-free marrow area. Based on a multivariate analysis-derived risk model, the reproducibility of the prognostic score described by Sokal and co-workers was tested, particularly with regard to histological variables. Additionally, we calculated the disease-specific loss in life expectancy. Our prognostic model (Cox model) consisted of the variables: age, spleen size, peripheral erythro-normoblasts, pseudo-Gaucher cells, and fiber density. To assess the validity of this new CML score, a receiver-operating curve (ROC) of sensitivity and specificity was constructed. The improved prognostic efficiency of this newly developed risk model in predicting death within 3 years after diagnosis of CML was demonstrated in comparison with generally accepted staging systems. Immunohistochemistry revealed that not the total number of macrophages, but only the subfraction of pseudo-Gaucher cells exerted a significant impact on survival. Furthermore, it was feasible to calculate the number of atypical micromegakaryocytes and pro- and megakaryoblasts. This abnormal and immature cell population showed a significant correlation with fiber density and prognosis. Finally, the practical value of the Hannover classification was tested. This histological classification enabled a discrimination between two groups with different survival patterns, i.e., granulocyte and/or megakaryocyte-rich subtypes versus subtypes with increase in reticulin and collagen fibers.