Is polycythemia cancer

Polycythemia vera is a very rare, malignant blood disease, its hallmark is increased haematopoiesis. The incidence is 5–6 per 100,000 / year, its prevalence is significantly higher, as many patients are unaware of their disease because of the unspecific symptoms, so that the correct diagnosis is often only made by chance. Previous therapy strategies can only improve the patient's situation to a limited extent. Recently, the JAK2 inhibitor ruxolitinib can also be used to improve the blood count in polycythemia vera.

The majority of patients with polycythemia vera (PV) have a point mutation in the gene for Janus kinase 2 (JAK2): 95% have a V617F mutation in exon 14, and 3% have a mutation in exon 12. It leads to constitutive kinase -Activation with increased cell proliferation, especially erythropoiesis, but also granulo- and megakaryopoiesis. In addition, the production of proinflammatory cytokines and growth factors, which are responsible for many disease symptoms, is increased in PV patients. The overproduction of erythrocytes and the resulting increased hematocrit values ​​increase blood viscosity, which in turn favors the occurrence of thromboembolism: 45% of deaths from PV are due to thromboembolic complications.

A variety of symptoms

In addition to plethora, the symptoms of PV include thromboses, heart attacks and strokes. The patients feel sick, weak, complain of severe exhaustion (fatigue) during the day and insomnia at night, burning itching (pruritus), especially in connection with water, possibly visual disturbances, night sweats, occasionally fever and bone pain, which often does not correspond for years be assigned. Usually only pain in the upper abdomen leads to the diagnosis of PV. Because the enlargement of the spleen (splenomegaly) is typical for PV, according to Prof. Thomas Fischer from the Magdeburg University Hospital. The blood count shows erythrocytosis with simultaneous leukocytosis and / or thrombocytosis. The diagnosis is based on the WHO criteria from 2008, mainly based on the Hb level and evidence of the JAK2 mutation. However, the differential diagnosis of PV should be differentiated from secondary erythrocytosis or secondary erythrocytosis with impaired erythropoietin (EPO) counterregulation.

Reduction of the risk of thromboembolism

The therapeutic goal of PV is to reduce the risk of thromboembolic events in order to extend life expectancy and prevent later complications. At the same time, the patients - more than 25% are over 65 years old - attach great importance to alleviating their very stressful symptoms, which often have psychosocial consequences.
To prevent thromboembolism, the first priority is phlebotomy, in order to lower the hematocrit to below 45% and to reduce the hyperviscosity of the blood. But phlebotomies are exhausting and tiring. In addition to phlebotomy, low-dose acetylsalicylic acid (ASA) is also recommended to avoid arterial thrombosis. In the long term, however, this combination is not sufficient for many patients: if the PV progresses or there is a high risk of thrombosis, cytoreductive therapies such as hydroxyurea (HU) are used. However, according to PD Dr. Florian Heidel, Magdeburg, not suitable for all patients, they can also cause severe side effects (HU resistance, intolerance, mucositis, ulcerations). For younger patients in particular, he sees interferon as an alternative, not least in order to possibly achieve a therapy-free interval. In contrast to other medications, with interferon there is a chance of a cure, albeit only a slight one.

Extension of the indication of ruxolitinib

Recently, the JAK inhibitor ruxolitinib (Jakavi®) can be used to treat adult PV patients who are resistant or intolerant to hydroxyurea. To date, ruxolitinib has only been approved for the treatment of disease-related splenomegaly or symptoms in adults with primary myelofibrosis, post-PV myelofibrosis, or myelofibrosis following essential thrombocythemia. The extension of the indication is based on the results of the phase III study
RESPONSE, in which ruxolitinib was compared with the best available therapy (BAT) in patients with therapy resistance or intolerance to HU [1]. The JAK inhibitor proved to be significantly superior to BAT in terms of the combined primary endpoint control of hematocrit and reduction in spleen size after 32 weeks (p <0.001). In addition, almost all disease-associated symptoms such as fatigue, pruritus and night sweats improved.

Take psychological complaints into account

In a US study, PV patients (n = 380) mainly complained about fatigue, disorders of sexual desire, inactivity, difficulty concentrating, etc. Around two thirds of the patients considered their quality of life to be limited overall. The University Hospital Magdeburg is the only one in Germany to offer a quality of life consultation in the field of psycho-oncology with needs-based advice. Twelve patients are currently being cared for there with PV. The psychologist and psychotherapist Dr. Michael Köhler used case studies to explain how different, indeed contradicting, the perceptions or perspectives between doctor and PV patient are: For example, the laboratory blood counts can be in the normal range, but the patient still suffers from fears - the median survival time for PV is 14, 1 year - and for 91% of PV patients, fatigue is almost more burdensome than the blood cancer itself.

Helga Vollmer

1. Vannucchi AM et al. N Engl J Med 2015; 372: 426-35.
Clinic workshop "Polycythemia vera - the underestimated blood cancer" on March 24, 2015 in Magdeburg, supported by Novartis Oncology, Nuremberg.