Myeloproliferative Neoplasms

Abstract

The myeloproliferative neoplasms previously known as myeloproliferative disorders include, polycythemia vera, essential thrombocythemia and myelofibrosis and also other rarer entities such as chronic eosinophilic and neutrophilic leukemia and overlap or otherwise unclassifiable disorders. They are uncommon clonal hematological malignancies that are generally diagnosed from late middle age onwards although they may occur in children and young adults. They are increasingly common with advanced age. In this chapter we focus almost exclusively on the three commonest entities. Whilst each of these disorders usually have unique features but their clinical courses have similarities, including thrombosis, hemorrhage, a tendency for progressive myelofibrosis and the development of acute myeloid leukemia. Myelofibrosis is associated with a much poorer prognosis than the other conditions and death, usually due to progressive bone marrow failure or leukemia. Recently, mutations at position 617 in exon 14 of the JAK2 gene and exon 9 of the Calreticulin (CALR) [30] gene have has been identified in the majority of patients with polycythemia vera and half of those with essential thrombocythemia or myelofibrosis. This has improved diagnostic pathways, but challenges their current classification as separate entities. Current treatment for these patients involves aggressive management of thrombotic risk factors, aspirin for most patients unless contraindicated and cytoreductive agents such as hydroxycarbamide (hydroxyurea) for patients at highest risk of thrombosis. A new class of drugs, JAK inhibitors, have proven to be effective for symptomatic myelofibrosis and the first of these agents, ruxolitinib, has recently been licensed.