Conventional and New Treatment Modalities in Myelofibrosis and the Current Role of Transplantation

Abstract

Conventional treatment of myelofibrosis includes a wait-and-see approach for asymptomatic patients, the use of oral cytolytic drugs such as hydroxyurea for the hyperproliferative forms of the disease, androgens or erythropoietin for anemia, and splenectomy in selected patients. Although these treatment modalities can improve quality of life, many patients do not respond, and the impact on survival is scant. This fact has stimulated the search for newer therapies for the disease. Antiangiogenic and immunomodulatory drugs such as thalidomide and lenalidomide have shown efficacy against anemia and thrombocytopenia but have frequent side effects. The combination of low-dose thalidomide with prednisone can also be effective and has a better tolerability. The therapeutic role of imatinib is limited, while tipifarnib, a farnesyltransferase inhibitor, has a modest effect in anemia and splenomegaly. Allogeneic stem cell transplantation (alloSCT) is the only curative therapy of myelofibrosis. AlloSCT with a standard conditioning regimen has an associated mortality rate of 30% and is indicated in younger patients with high-risk disease or resistance to conventional treatment. Because of its low mortality and curative potential, reduced-intensity conditioning alloSCT is being used in patients aged 45-70 years with high- or intermediate-risk myelofibrosis or resistance to treatment. Autologous SCT can be a palliative measure in patients without a suitable donor. The efficacy in myelofibrosis of newer immunomodulatory drugs, including pomalidomide, proteasome inhibitors, hypomethylating agents, and especially, Janus kinase 2 inhibitors, is currently being evaluated.