Polycythemia vera and essential thrombocythemia: 2017 update on diagnosis, risk‐stratification, and management
Authors: Tefferi Ayalew , Barbui Tiziano 
Published: December 2016

Disease overview

Polycythemia Vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms respectively characterized by erythrocytosis and thrombocytosis; other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus, and risk of leukemic or fibrotic transformation.

Diagnosis

PV is defined by aJAK2mutation, whose absence, combined with normal or increased serum erythropoietin level, makes the diagnosis unlikely.JAK2,CALR, andMPLmutations are the mutually exclusive “driver” mutations in ET with respective incidences of 55%, 25%, and 3%; approximately 17% are triple‐negative. However, the same molecular markers might also be present in prefibrotic myelofibrosis, whose morphological distinction from ET is prognostically relevant.

Survival and leukemic/fibrotic transformation

Median survivals are approximately 14 years for PV and 20 years for ET; the corresponding values for younger patients (age <60 years) are 24 and 33 years. Life‐expectancy in ET is inferior to the control population. Driver mutational status has not been shown to affect survival in ET whereas the presence ofJAK2/MPLmutations has been associated with higher risk of arterial thrombosis and that ofMPLwith higher risk of fibrotic progression. Risk factors for overall survival in both ET and PV include advanced age, leukocytosis and thrombosis. Leukemic transformation rates at 20 years are estimated at <10% for PV and 5% for ET; fibrotic transformation rates are slightly higher. Most recently,ASXL1,SRSF2, andIDH2mutations have been associated with inferior overall, leukemia‐free or fibrosis‐free survival in PV; similarly adverse mutations in ET includedSH2B3,SF3B1,U2AF1,TP53,IDH2, andEZH2.

Thrombosis risk stratification

Current risk stratification in PV and ET is designed to estimate the likelihood of recurrent thrombosis. Accordingly, PV includes two risk categories: high‐risk (age >60 years or thrombosis history) and low‐risk (absence of both risk factors). In ET, risk stratification includes four categories: very low risk (age ≤60 years, no thrombosis history,JAK2/MPLun‐mutated), low risk (age ≤60 years, no thrombosis history,JAK2/MPLmutated), intermediate risk (age >60 years, no thrombosis history,JAK2/MPLun‐mutated), and high risk (thrombosis historyorage >60 years withJAK2/MPLmutation). In addition, presence of extreme thrombocytosis (platelets >1000 × 10(9)/L) might be associated with acquired von Willebrand syndrome (AvWS) and, therefore, risk of bleeding.

Risk‐adapted therapy

The main goal of therapy in PV and ET is to prevent thrombohemorrhagic complications. All patients with PV require phlebotomy to keep hematocrit below 45% and once‐daily aspirin (81 mg). In addition, high‐risk patients with PV require cytoreductive therapy. Very low risk ET patients might not require any form of therapy while low‐risk patients require at least once‐daily aspirin therapy. Cytoreductive therapy is also recommended for high‐risk ET patients but it is not mandatory for intermediate‐risk patients. First‐line drug of choice for cytoreductive therapy, in both ET and PV, is hydroxyurea and second‐line drugs of choice are interferon‐α and busulfan. We currently do not recommend treatment with ruxolutinib or otherJAK2inhibitors in PV or ET, unless in the presence of severe and protracted pruritus or marked splenomegaly that is not responding to the aforementioned drugs. Screening for AvWS is recommended before administrating aspirin, in the presence of extreme thrombocytosis. Am. J. Hematol. 92:95–108, 2017. © 2016 Wiley Periodicals, Inc.