Effects of chemotherapy (busulfan-hydroxyurea) and interferon-alfa on bonemarrow morphologic features in chronic myelogenous leukemia - Histochemical and morphometric study on sequential trephine biopsy specimens with special emphasis on dynamic features

We performed a retrospective clinicopathologic study on sequential biopsy s pecimens from 90 patients with Philadelphia chromosome-positive chronic mye logenous leukemia to study therapy-specific effects of busulfan (28 patient s), hydroxyurea (32 patients), and interferon-alfa (IFN-alfa; 30 patients). Bone marrow specimens were evaluated by morphometry after silver impregnat ion and staining with monoclonal antibodies to identify reticulin fibers, n ucleated erythroid precursors, megakaryocytes, and macrophages. To compute dynamics of histopathology implicating corresponding changes in time, relev ant indices were calculated. Quantification of megakaryocytopoiesis and its precursor cell population showed a significant increase in the IFN-alfa an d busulfan groups compared with the hydroxyurea group. These changes were a ssociated with a development of myelofibrosis during therapy. Although a si gnificant increase in fiber density was detectable in the busulfan group, t he progression index proved to be twice as high after IFN-alfa therapy. In contrast a considerable number of patients displayed a regression of myelof ibrosis after hydroxyurea treatment. The general association of the megakar yocyte lineage with myelofibrosis was inline with experimental findings. Th e mature macrophage population and its activated subfraction revealed a mar ked proliferation (IFN-alfa group) during treatment. Growth and activation of macrophages may be compatible with their putative function during erythr ocytopoietic regeneration and with stimulation of their phagocytic properti es.