INTERFERON THERAPY, BUT NOT BUSULFAN RESTORES NORMAL-SIZED MEGAKARYOPOIESIS IN CML - A COMPARATIVE HISTOMORPHOMETRIC AND IMMUNOMORPHOMETRICSTUDY

To assess possible alterations of megakaryocytes associated with inter feron (IFN) and busulfan (BU) therapy of Ph(1+)-CML, an immunohistoche mical and morphometric study was performed on trephine biopsies of the bone marrow taken before and at varying intervals during treatment, F or the identification of megakaryopoiesis and its endoreduplicative ac tivity the monoclonal antibodies CD61 (anti-platelet glycoprotein IIIa ) and PC10 raised against proliferating cell nuclear antigen (PCNA) we re used, We compared 60 specimens from 20 patients following IFN alpha -2b administration (in combination with IFN gamma in seven patients) w ith 57 specimens from 22 patients after monotherapy with BU, A close c orrelation with clinical follow-up studies revealed that in the IFN-tr eated group the prevalence of atypical micro-megakaryocytes, usually c haracterizing CML, was conspicuously reduced in repeatedly taken bone marrow samples. Initially, even an increase in size which was levelled to normal values during maintenance therapy was observed, These featu res were most prominently expressed in the 13 patients with a complete hematologic and/or partial cytogenetic response, Associated with this phenomenon was a significant enhancement of the PCNA-labelling index which indicated a stimulation of endoreduplicative (endomitotic) activ ity necessary for achieving normal size and ploidy. In the second grou p of patients treated by BU these changes were absent. For this reason , our findings are in keeping with the assumption that during IFN trea tment, there is at least partial recovery and expansion of a putative normal (Ph(1-)) megakaryopoiesis. In conclusion, megakaryocyte morphol ogy, i.e. normalization in size, is thought to be a useful indicator t o evaluate the response to IFN in CML patients.