Myeloproliferative Neoplasms

Abstract

Myeloproliferative neoplasms are characterized by overproduction of fully differentiated myeloid blood cells. The three commonest Philadelphia-negative MPNs are polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF), whilst less common disorders may present with eosinophilia or accumulation of neoplastic mast cells. Patients with PV, ET and PMF may share certain clinical features such as splenomegaly and constitutional symptoms, as well as risks of thrombosis, haemorrhage and transformation to acute myeloid leukaemia. Diagnosis of these disorders requires exclusion of secondary causes of an abnormal blood count, testing for their known associated mutations, most often those in the JAK2, CALR and/or MPL genes and, in many cases, a bone marrow biopsy. Management of PV and ET is centred on reducing the risk of vascular events, for example, with low-dose aspirin, management of other cardiovascular risk factors and, as appropriate, reducing blood counts using venesection and/or cytoreductive drugs. PMF is a more clinically heterogeneous disease with a more marked reduction in life expectancy; management strategies may include red cell transfusion, androgen therapy, JAK2 inhibitors and, in a minority of patients, allogeneic stem cell transplantation. Management of clonal eosinophilias and mast cell disease depends both on the specific clinical features and the associated molecular abnormalities, making accurate diagnosis of these rare disorders essential.