EFFECT OF INTERFERON THERAPY ON BONE-MARROW MORPHOLOGY IN CHRONIC MYELOID-LEUKEMIA - A CYTOCHEMICAL AND IMMUNOHISTOCHEMICAL STUDY OF TREPHINE BIOPSIES

The effect of interferon (IFN) therapy on bone marrow features in chro nic myeloid leukemia (CML) has been studied on successive trephine bio psies (mean interval 13 +/- 8 months) by cytochemical and immunohistoc hemical methods in combination with morphometry and in comparison with a control group of patients who received monotherapy by busulfan (BU) . Following IFN administration (IFN-alpha frequently in combination wi th IFN-gamma), there was a decrease in neutrophil granulopoiesis accom panied by a significant expansion of erythroid precursors and increase d numbers of hemosiderin-laden macrophages. These changes corresponded with the hematologic response in 21 of the 25 patients investigated. Numbers of megakaryocytes and reticulin/collagen fiber density increas ed during treatment. Most conspicuously, in responding patients atypic al micromegakaryocytes, usually characterizing CML, were partially rep laced by normal-sized cells of this lineage. These features are in kee ping with the assumption of a reappearance of the normal hematopoietic cell clone as the result of IFN therapy, which was not found in the B U-treated control group. On the other hand, a relevant subpopulation o f micromegakaryocytes (about 30%) was still maintained. This result pr obably relates to the failure to improve myelofibrosis more effectivel y. Analysis of cell proliferation (proliferating cell nuclear antigen- PCNA) and apoptosis (in situ end labeling) revealed a reduction in PCN A labeling and increased numbers of cells undergoing programmed death, Identification of the activated subset of macrophages (alpha-D-galact osyl residues expression) by appropriate lectin histochemistry disclos ed an increase in the number of GSA-I binding cells. These findings we re exclusively limited to IFN administration and reflect an inhibitory effect of IFN on cell proliferation and stimulation of programmed cel l death. The latter phenomenon probably results in increased phagocyto sis of clonally transformed myeloid cells by GSA-I-positive (activated ) macrophages.