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Conventional therapy of myelofibrosis is essentially palliative. It includes a wait-and-see approach for asymptomatic patients, oral cytolytic drugs such as hydroxyurea for the hyperproliferative forms of the disease, androgens or erythropoietin for the anemia, and splenectomy in selected patients. The lack of impact of these treatment modalities on the patients’ survival has stimulated the search of newer, more effective therapies. Antiangiogenic and immunomodulatory drugs such as thalidomide and lenalidomide have shown efficacy in the anemia and the thrombocytopenia, while the therapeutic role of imatinib and other tyrosine kinase inhibitors is limited. Allogeneic stem cell transplantation (allo-SCT) remains the only curative therapy of myelofibrosis. Its standard modality has an associated mortality of 30% and is indicated in younger patients with high-risk disease or resistant to conventional treatment. Due to its low mortality and curative potential, reduced-intensity conditioning allo-SCT can be used in patients 45 to 70 years old with high- or intermediate-risk myelofibrosis or resistant to treatment. Autologous SCT can be a palliative measure in resistant patients lacking a suitable donor. The next candidates for the treatment of myelofibrosis are newer immunomodulatory drugs, the proteasome inhibitors, vascular endothelial growth factor neutralising antibodies, and the JAK2 inhibitors.