Conventional and new treatment options for myelofibrosis with myeloid metaplasia.

The pathogenetic mechanisms underlying the clonal myeloproliferation and reactive marrow fibrosis that characterize myelofibrosis with myeloid metaplasia (MMM) are poorly understood. Recent advances into the pathophysiology of the disease have not yet translated into effective therapeutic options for patients. There is no standard treatment, and no therapies identified yet, besides allogeneic stem cell transplantation, that will significantly change the natural history of MMM. Treatment is therefore palliative and is geared towards alleviating symptoms of the disease and improving blood counts. Conventional therapies for anemia include androgens and corticosteroids. Cytoreductive agents such as hydroxyurea are indicated for symptomatic organomegaly and the control of leucocytosis or thrombocytosis. Several novel agents have been investigated in the recent past, and include antiangiogenic agents and signal transduction inhibitors that target the angiogenic and fibrogenic cytokines that have been implicated in the pathogenesis of the detrimental bone marrow stromal reaction. Ultimately, an improved understanding of the biological factors that cause the clonal myeloproliferation in MMM will lead to the development of effective therapeutic interventions.