Management of myeloproliferative neoplasms: from academic guidelines to clinical practice

Abstract

Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by excessive production of mature cells. In most of the classic Philadelphia-negative MPNs-polycythemia vera (PV), essential thrombocythemia (ET), and MPN-associated myelofibrosis (MPN-MF)-oncogenic mutations affecting JAK2 or MPL lead to constitutive activation of cytokine-regulated intracellular signalling pathways. The traditional therapy for PV and ET is the prevention of thrombotic events with antiproliferative agents in association with aspirin. New drugs such as pegylated interferon and anti-JAK agents are candidates for slowing the evolution to myelofibrosis or leukemia. Conventional therapy for MPN-MF is driven by clinical needs, primarily anemia and splenomegaly. Lenalidomide and pomalidomide are new candidates for treating anemia. JAK2 ATP-competitive inhibitors or drugs that indirectly inhibit the JAK-STAT pathway, like RAD001, are the new candidates for splenomegaly in MPN-MF, but in spite of their strong rationale, they have shown only a palliative benefit. Allogeneic stem cell transplantation remains the only potentially curative approach.