Effect of Interferon Therapy on Bone Marrow Morphology in Chronic Myeloid Leukemia: A Cytochemical and Immunohistochemical Study of Trephine Biopsies

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Abstract
The effect of interferon (IFN) therapy on bone marrow features in chronic myeloid leukemia (CML) has been studied on successive trephine biopsies (mean interval 13 ± 8 months) by cytochemical and immunohistochemical methods in combination with morphometry and in comparison with a control group of patients who received monotherapy by busulfan (BU). Following IFN administration (IFN-α frequently in combination with IFN-γ), there was a decrease in neutrophil granulopoiesis accompanied by a significant expansion of erythroid precursors and increased numbers of hemosiderin-laden macrophages. These changes corresponded with the hematologie response in 21 of the 25 patients investigated. Numbers of megakaryocytes and reticulin/collagen fiber density increased during treatment. Most conspicuously, in responding patients atypical micromegakaryocytes, usually characterizing CML, were partially replaced by normal-sized cells of this lineage. These features are in keeping with the assumption of a reappearance of the normal hematopoietic cell clone as the result of IFN therapy, which was not found in the BU-treated control group. On the other hand, a relevant subpopulation of micromegakaryocytes (about 30%) was still maintained. This result probably relates to the failure to improve myelofibrosis more effectively. Analysis of cell proliferation (proliferating cell nuclear antigen-PCNA) and apoptosis (in situ end labeling) revealed a reduction in PCNA labeling and increased numbers of cells undergoing programmed death. Identification of the activated subset of macrophages (α-D-galactosyl residues expression) by appropriate lectin histochemistry disclosed an increase in the number of GSA-I binding cells. These findings were exclusively limited to IFN administration and reflect an inhibitory effect of IFN on cell proliferation and stimulation of programmed cell death. The latter phenomenon probably results in increased phagocytosis of clonally transformed myeloid cells by GSA-I-positive (activated) macrophages.