Bone marrow effects of anagrelide therapy in patients with myelofibrosis with myeloid metaplasia

In a prospective study investigating the therapeutic role of anagrelide in myelofibrosis with myeloid metaplasia, 20 patients received anagrelide in d aily oral doses of 0.5-3 mg. 17 patients were evaluable and received anagre lide for a median of 2 years (range 0.5-4 years). No patient had a clinical ly appreciable benefit. Bone marrow (BM) examinations at baseline and after 6 and 12 months of treatment were available for 17, 17 and 12 patients, re spectively In all evaluable cases, BM megakaryocyte number increased after 6 months of anagrelide treatment, Also, Ulex europaeus agglutinin-1 stainin g of megakaryocytes revealed a left-shifted maturation pattern in most pati ents with a platelet response to anagrelide. However, megakaryocyte stainin g intensity for transforming (TGF-beta) and platelet-derived (PDGF) growth factors was not affected consistently by treatment. No patient had a greate r than or equal to 2 grade change in either BM fibrosis or osteosclerosis. These in-vivo data support our previous in-vitro observations that anagreli de interferes with megakaryocyte maturation rather tan proliferation. Lack of a positive treatment effect is consistent with the finding that anagreli de did not significantly alter megakaryocyte expression of TGF-beta and PDG E.