Bone marrow features and clinical findings in chronic myeloid leukemia - Acomparative, multicenter, immunohistological and morphometric study on 614patients

A multicenter, immunohistochemical and morphometric study was performed on diagnostic pretreatment bone marrow biopsies in 614 adult patients with Ph1 + chronic myeloid leukemia (CML) to compare histological features with clin ical findings. For identification of megakaryopoiesis we used the monoclona l antibody CD61 and additionally the PAS reaction to determine the subfract ion of atypical micromegakaryocytes and precursors. Labelling of erythroid precursors was carried out by a monoclonal antibody directed against glycop horin C. In order to selectively stain macrophages and their activated subs et we applied CD68 and the GSA-1 lectin. Density of argyrophilic fibers (re ticulin plus collagen) was measured following Gomori's silver impregnation method. In accordance with laboratory data morphological variables revealed a comparable amount of congruence in the various groups of CML patients de rived from different sources. In about 26% of patients early (reticulin) to advanced (collagen) fibrosis was detectable, Significant correlations were calculated between the extent of myelofibrosis with splenomegaly, anemia a nd increasing numbers of erythroblasts and myeloblasts in the peripheral bl ood count. These features were assumed to indicate more advanced stages of the disease process with ensuing transition into myeloid metaplasia and con sequently were associated with an unfavorable prognosis. Significant relati onships were revealed between the number of CD61(+) megakaryocytes and more important, also their precursor fraction with the degree of fibrosis. This result extends previous experimental findings regarding the impact of imma ture elements of this cell lineage for the generation of myelofibrosis. The significant association of erythroid precursors with the number of mature (resident) macrophages including their activated GSA-I subset may shed some light on their functional involvement in iron turnover and hemoglobin synt hesis. A modified histological classification of predominant bone marrow fe atures is introduced. This simplified synthesis staging system (Cologne Cla ssification) is not only associated with certain sets of laboratory data, b ut also with different survival patterns.