Myeloproliferative neoplasms

The Philadelphia-negative myeloproliferative neoplasms, polycythaemia vera, essential thrombocythaemia and myelofibrosis, are uncommon clonal haematological malignancies generally diagnosed from late middle age onwards, although they can occur in children and young adults. Each of these disorders has unique features, but their clinical courses have similarities, including thrombosis, haemorrhage, a tendency to progressive myelofibrosis and the development of acute myeloid leukaemia. Myelofibrosis is associated with a much poorer prognosis and significant disease burden affecting quality of life, usually from progressive bone marrow failure, extramedullary haemopoiesis or transformation to aggressive leukaemia. Recent advances in diagnostics have helped stratify patients into more accurate risk categories. Furthermore, the development of treatment modalities aimed at targeting specific molecular pathways, such as Janus kinase (JAK) inhibitors, has resulted in a paradigm shift; several ground-breaking studies have proved their efficacy and they are now being licensed for first-line therapy in myelofibrosis. Ongoing studies aim to determine if these JAK inhibitors are effective in patients with polycythaemia vera. Additional targets are under evaluation in clinical trials, but the mainstay of treatment for patients with polycythaemia vera and essential thrombocythaemia remains aggressive management of thrombotic risk factors, antiplatelet therapy for most patients unless contraindicated, and cytoreductive agents such as hydroxycarbamide and interferon for patients at high risk of thrombosis. This is, however, a rapidly evolving landscape.