What is Polycythemia Vera (PV), a myeloproliferative neoplasm?

From the Guidelines

Polycythemia vera patients should be managed with phlebotomy to maintain the hematocrit at less than 45% and low-dose aspirin, with cytoreduction indicated in high-risk patients. The treatment of polycythemia vera (PV) typically involves a combination of phlebotomy and pharmacotherapy to reduce the risk of thrombotic complications and disease progression. According to the European LeukemiaNet (ELN) recommendations 1, all patients with PV should undergo phlebotomy to maintain a hematocrit level below 45%, and low-dose aspirin should be administered to reduce the risk of thrombosis.

For high-risk patients, cytoreductive therapy is indicated, with hydroxyurea (HU) and interferon-alpha (IFN-α) being recommended as first-line treatments 2. HU is a well-known cytoreductive agent with good efficacy and tolerance in most patients, although its potential leukaemogenic risk should be considered, particularly in young subjects or those previously treated with other myelosuppressive agents. IFN-α has been shown to induce a high rate of haematological response and significantly reduce the malignant clone, as demonstrated by the percentage of mutated allele JAK2V617F in phase II studies 2.

Key considerations in the management of PV include:

• Regular monitoring for disease progression, complications, and transformation to myelofibrosis or acute leukemia
• Lifestyle modifications, such as adequate hydration, avoiding extreme temperatures, and regular exercise, to support overall health and well-being
• Management of symptoms, including headaches, dizziness, itching, fatigue, and visual disturbances
• Prevention and treatment of complications, such as blood clots, bleeding, and enlarged spleen.

It is essential to note that the optimal treatment approach may vary depending on individual patient characteristics, such as age, disease severity, and comorbidities, and should be guided by the most recent and highest-quality evidence, including the ELN recommendations 1 and the ESMO clinical practice guidelines 3, 2.

From the Research

Definition and Characteristics of Polycythemia Vera

• Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by exuberant red cell production leading to a broad range of symptoms that compromise quality of life and productivity of patients 4.
• PV is typically characterized by erythrocytosis and often leukocytosis and thrombocytosis 5.
• The JAK2V617F mutation in exon 14 of JAK2 is known to be present in more than 95% of patients with PV, and testing for this mutation is used in the diagnosis of PV 5.

Clinical Features and Diagnosis

• Clinical features of PV include reduced life expectancy due to hazards of thrombosis, haemorrhage, and transformation to myelofibrosis and less frequently to a form of acute myeloid leukaemia called blast phase 5.
• Erythrocytosis (hemoglobin >16.5 mg/dL in men or >16.0 mg/dL in women) is a required diagnostic criterion, although thrombocytosis and leukocytosis are common 6.
• Patients may have pruritus, erythromelalgia, transient visual changes, and splenomegaly with abdominal discomfort 6.

Treatment and Management

• Current therapeutic first-line recommendations based on risk-adapted classification divided patients into two groups, according to age (< or >60 years) and presence of prior thrombotic events 4.
• Low-risk patients should be treated with aspirin and phlebotomy, to maintain hematocrit <45% 4.
• High-risk patients should receive cytoreductive therapy in addition to aspirin and phlebotomies, with hydroxyurea being the cytoreductive agent of first choice 4.
• Ruxolitinib is a Janus kinase inhibitor that can alleviate pruritus and decrease splenomegaly in patients who are intolerant of or resistant to hydroxyurea 5, 6.
• Interferon is also used as a second-line treatment for hydroxyurea resistant or intolerant polycythemia vera 7.

Prognosis and Complications

• PV reduces survival expectation, primarily due to thrombotic events, transformation to blast phase, and post-PV myelofibrosis or to development of second cancers, which are associated with poor prognosis 4.
• The median survival from diagnosis was 14.1 to 27.6 years, and prior to or at the time of PV diagnosis, arterial thrombosis occurred in 16% of patients and 7% had venous thrombotic events 6.
• PV is also associated with an increased bleeding risk, especially in patients with acquired von Willebrand disease, which can occur with extreme thrombocytosis 6.