Histopathological and hematological findings in CML - a comparative immunohistochemical-morphometric and clinical study on bone marrow biopsies from 604 patients derived from two institutes of pathology (Cologne/Freiburg)

An immunohistochemical and morphometric study was performed on bone marrow biopsies in 604 patients with chronic myelogenous leukemia (CML) to compare morphological and clinical features and to evaluate effects of interferon (IFN) and chemotherapy. Following morphometry significant correlations were calculated between number of CD61(+) megakaryocytes, including their precu rsors with fiber density. This finding is in line with the close functional relationship between megakaryopoiesis and fibroblasts regarding the comple x pathomechanism of myelofibrosis. The latter was observed in about 28% of patients already at diagnosis. In a similar way, the frequency of CD68(+) m acrophages was correlated with the amount of Ret40f(+) nucleated erythroid precursors, implicating an involvement of this cell lineage in iron turnove r, hemoglobin synthesis,and degradation of the expelled nuclei from normobl asts. The (alpha-D-galactosyl residue-expressing) Pseudo-Gaucher cells were detectable in 30% of pretreatment specimens. Moreover, significant associa tions were calculable between reduction in erythropoiesis or increase in fi bers with clinical features such as hemoglobin level, percentages of myelo- and erythroblasts in the peripheral blood,and spleen size. These Variables are in keeping with more advanced stages of CML. Based on our morphometric evaluations, a classification into three different histological subgroups: granulocytic, megakaryocytic, and myelofibrotic was carried out. This simp lified staging system was correlated with corresponding sets of hematologic al data. Sequential biopsies in 173 patients with monotherapy by IFN, hydro xyurea (HU), or busulfan (BU) revealed a fibrogenic effect of IFN in contra st to a fiber-reducing property of HU. The dynamics of myelofibrosis and ch anges of major cell lineages during treatment were readily demonstrable by calculating corresponding indices. These included the ratios between quanti tative differences of corresponding variables at repeated examinations and time. Thus, in patients with complete hematological remission following IFN administration, regeneration of erythropoiesis was found to be accompanied by an increase in the total number of CD68(+) macrophages, including activ ated subpopulations. Histological subgroups showed a transition from a (non fibrotic) granulocytic and megakaryocyte pattern to the myelofibrotic subty pe in about 40% of patients. This change was opposed to a numerical reducti on in the myelofibrotic subtype which occurred in 17 patients (36%), but pr edominantly in those under HU therapy, in conclusion, the striking heteroge neity of bone marrow features in CML warrants a careful morphological evalu ation of trephine biopsies and appropriate means of processing to achieve r elevant correlations with clinical data and, thus, allows a more elaborate insight into the dynamics of the disease process.