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Keywords:

  • megakaryocytes;
  • platelets

In a prospective study investigating the therapeutic role of anagrelide in myelofibrosis with myeloid metaplasia, 20 patients received anagrelide in daily oral doses of 0.5–3 mg. 17 patients were evaluable and received anagrelide for a median of 2 years (range 0.5–4 years). No patient had a clinically appreciable benefit. Bone marrow (BM) examinations at baseline and after 6 and 12 months of treatment were available for 17, 17 and 12 patients, respectively. In all evaluable cases, BM megakaryocyte number increased after 6 months of anagrelide treatment. Also, Ulex europaeus agglutinin-1 staining of megakaryocytes revealed a left-shifted maturation pattern in most patients with a platelet response to anagrelide. However, megakaryocyte staining intensity for transforming (TGF-β) and platelet-derived (PDGF) growth factors was not affected consistently by treatment. No patient had a geqslant R: gt-or-equal, slanted2 grade change in either BM fibrosis or osteosclerosis. These in-vivo data support our previous in-vitro observations that anagrelide interferes with megakaryocyte maturation rather than proliferation. Lack of a positive treatment effect is consistent with the finding that anagrelide did not significantly alter megakaryocyte expression of TGF-β and PDGF.