Effects of interferon and hydroxyurea on bone marrow fibrosis in chronic myelogenous leukaemia: a comparative retrospective multicentre histological and clinical study

A retrospective multicentre clinicopathological study was performed on sequ ential bone marrow trephine biopsies in 100 patients with Ph1+-chronic myel ogenous leukaemia (CML) to elucidate the effect of interferon (IFN) alpha 2 b and hydroxyurea (HU) treatment on myelofibrosis and megakaryopoiesis. Acc ording to strictly defined therapeutic regimens, 38 patients received IFN a s monotherapy, 23 patients a combination of IFN and HU and 39 patients HU o nly Using standardized intervals of biopsies and histochemical and morphome tric methods, a significant increase in reticulin fibre density and in the number of CD61(+) megakaryocytes was detectable in the majority of IFN-trea ted patients. To a lesser degree, these changes were also expressed in the cohort with a combined IFN and HU regimen. In contrast to these findings. i n the group of patients with HU as single-agent treatment, a stable state o r reversal of myelofibrosis was detectable together with corresponding chan ges in megakaryopoiesis. Further evaluations revealed that these effects ha d occurred within the first year, mostly after 6 months of treatment, and w ere prominently expressed in those patients with a slight to relevant grade of myelofibrosis at presentation. In conclusion, this study provides persu asive evidence that monotherapy by IFN exerts a fibrogenic effect, while HU treatment seems to prevent and even resolves bone marrow fibrosis in CML. Probably, in relation to the complex pathomechanisms responsible for the ge neration of myelofibrosis, the changing content of reticulin fibres was usu ally accompanied by corresponding alterations in the number of CD61(+) mega karyocytes, including atypical microforms and precursor cells.