Initial (prefibrotic) stages of idiopathic (primary) myelofibrosis (IMF) -a clinicopathological study

A clinicopathological follow-up study including sequential bone marrow biop sies was performed on 79 patients with idiopathic (primary) myelofibrosis ( IMF) to characterize initial (prefibrotic) stages and to elucidate whether development of fibrosis was accompanied by corresponding clinical findings. Far this purpose our cohort of patients was divided into two groups of whi ch the first presented with the generally accepted signs and symptoms of IM F (group I; n = 60). Most patients of the second group (group II; n = 19)sh owed mild to moderate therapy-refractory anemia, minimal to slight splenome galy and frequently thrombocytosis, but no bone marrow fibrosis at onset. H ematopoiesis was consistent with a striking hypercellularity In comparison to the age-related involution by adipose tissue, a conspicuous clustering a nd histotopographic dislocation of megakaryocytes, a neutrophil granulocyti c proliferation and a reduction of erythropoietic islets with arrest of mat uration. Most remarkable was the dysplastic cytology of megakaryocytes with a definitive deviation of differentiation resulting in bizarre forms. Foll ow-up examinations revealed that at later stages group II patients were not distinguishable from the first group with more advanced IMF, For this reas on, these patients were regarded as presenting initial, prefibrotic IMF cha racterized by distinctive bone marrow features at the beginning. The promin ent abnormalities of megakaryopoiesis together with the granulocytic prolif eration were extremely helpful to differentiate prefibrotic IMF with accomp anying thrombocythemia from essential thrombocythemia (ET). Dynamics of fib er progression were calculated by regarding increase in density per time. S peed of progression during the first year of observation proved to be signi ficantly higher in group II patients with prefibrotic IMF in comparison to full-blown cases (group I). In conclusion, with respect to prospective clin ical trials, diagnostic criteria for IMF should be re-evaluated by also tak ing initial, prefibrotic stages into account.