Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk-stratification and management

Disease overview Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPN) respectively characterized by clonal erythrocytosis and thrombocytosis; other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus and risk of leukemic or fibrotic transformation. Diagnosis Bone marrow morphology remains the cornerstone of diagnosis. In addition, the presence ofJAK2mutation is expected in PV while approximately 90% of patients with ET express mutually exclusiveJAK2,CALRorMPLmutations (so called driver mutations). In ET, it is most important to exclude the possibility of prefibrotic myelofibrosis. Survival Median survivals are approximately 15 years for PV and 18 years for ET; the corresponding values for patients age 40 or younger were 37 and 35 years. Certain mutations (mostly spliceosome) and abnormal karyotype might compromise survival in PV and ET. Life-expectancy in ET is inferior to the control population. Driver mutations have not been shown to affect survival in ET but risk of thrombosis is higher inJAK2mutated cases. Leukemic transformation rates at 10 years are estimated at <1% for ET and 3% for PV. Thrombosis risk In PV, two risk categories are considered: high (age > 60 years or thrombosis history present) and low (absence of both risk factors). In ET, four risk categories are considered: very low (age <= 60 years, no thrombosis history,JAK2wild-type), low (same as very low butJAK2mutation present), intermediate (age > 60 years, no thrombosis history,JAK2wild-type) and high (thrombosis history presentorage > 60 years withJAK2mutation). Risk-adapted therapy The main goal of therapy in both PV and ET is to prevent thrombohemorrhagic complications. All patients with PV require phlebotomy to keep hematocrit below 45% and once-daily or twice-daily aspirin (81 mg), in the absence of contraindications. Very low risk ET might not require therapy while aspirin therapy is advised for low risk disease. Cytoreductive therapy is recommended for high-risk ET and PV, but it is not mandatory for intermediate-risk ET. First-line drug of choice for cytoreductive therapy, in both ET and PV, is hydroxyurea and second-line drugs of choice are interferon-alpha and busulfan. We do not recommend treatment with ruxolutinib in PV, unless in the presence of severe and protracted pruritus or marked splenomegaly that is not responding to the aforementioned drugs. New treatment directions Controlled studies are needed to confirm the clinical outcome value of twice-daily vs once-daily aspirin dosing and the therapeutic role of pegylated interferons and direct oral anticoagulants.