Quality of Life in Myeloproliferative Neoplasms: Symptoms and Management Implications.

Myeloproliferative neoplasms include essential thrombocythemia, polycythemia vera, and myelofibrosis. They are characterized by abnormal myeloid proliferation. Patients suffer from debilitating constitutional symptoms and splenomegaly. There have been advances in understanding the impact on quality of life in myeloproliferative neoplasms. Owing to the chronicity of these diseases, symptoms are considered in response criteria for clinical trials. This review wills cover how quality of life is measured in patients with myeloproliferative neoplasm. We review the impact of treatment options, including JAK inhibitors, allogeneic stem cell transplantation, and medications in development. We discuss nonpharmacologic methods of improving symptoms and quality of life.

Cytoreductive treatment patterns among US veterans with polycythemia vera.

BACKGROUND: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased thrombotic and cardiovascular risk, which are key contributors to patient morbidity and mortality. The Veterans Health Administration (VHA) is the largest integrative health network in the United States. Available data concerning patients with PV in this population are limited. METHODS: This retrospective observational study evaluated the characteristics, management, and outcomes of patients with PV in the VHA Medical SAS® Dataset (October 1, 2005, to September 30, 2012). Inclusion criteria were ≥ 2 claims for PV (ie, PV diagnostic code was recorded) ≥30 days apart during the identification period, age ≥ 18 years, and continuous health plan enrollment from ≥12 months before the index date until the end of follow-up. All data were analyzed using descriptive statistics. RESULTS: The analysis included 7718 patients (median age, 64 years; male, 98%; white, 64%). The most common comorbidities before the index date were hypertension (72%), dyslipidemia (54%), and diabetes (24%); 33% had a history of smoking. During the follow-up period (median, 4.8 years), most patients did not receive treatment with cytoreductive therapy, including phlebotomy (53%), or antiplatelet agents, such as aspirin (57%). The thrombotic and cardiovascular event rates per 1000 patient-years were 60.5 and 83.8, respectively. Among patients who received cytoreductive treatment, the thrombotic event rate was 48.9 per 1000 patient-years. The overall mortality rate was 51.2 per 1000 patient-years. CONCLUSION: The notable rates of thrombotic and cardiovascular events observed in this analysis, even among patients receiving cytoreductive treatment, highlight the important unmet clinical needs of patients with PV in the VHA.

A Polycythemia Vera JAK2 Mutation Masquerading as a Duodenal Cancer Mutation.

Next-generation sequencing (NGS) is increasingly being used in cancer care to identify both somatic tumor driver mutations that can be targeted for therapy, and heritable mutations in the germline associated with increased cancer risk. This report presents a case of a JAK2 V617F mutation falsely identified as a duodenal cancer mutation via NGS. The patient was found to have a history of polycythemia vera, a disorder with a high incidence of JAK2 somatic mutations. Buccal cell DNA showed heterozygosity for the mutation, suggesting that it was potentially germline. However, subsequent resequencing of tumor, adjacent normal tissue, and fingernail DNA confirmed the mutation was somatic, and its presence in tumor and buccal cells resulted from contaminating blood cells. This report highlights important nuances of NGS that can lead to misinterpretation of results with potential clinical implications.

Polycythemia vera-associated pruritus and its management.

BACKGROUND: Pruritus is a defining feature of polycythemia vera (PV) and is seen in approximately 40% of patients. In most cases, the pruritus is characteristically triggered by contact with water (aquagenic) at any temperature. MATERIALS AND METHODS: A detailed MEDLINE search for all English language articles related to PV, PV-associated pruritus and aquagenic pruritus that were published from 1965 till date was carried out. RESULTS: Many different treatment options have been tried over the past several decades, including antihistamines, antidepressants, interferon alpha, phlebotomy, phototherapy, iron supplements and myelosuppressive medications, all demonstrating mixed results. Recently, agents that target JAK2 and mammalian target of rapamycin (mTOR) have shown impressive clinical benefit. CONCLUSION: PV-associated pruritus is a major cause of morbidity amongst patients with PV. Antidepressant medications interfering with serotonin uptake are somewhat efficacious. Cytoreductive therapy is reserved for refractory cases. Targeted therapy with JAK2 and mTOR inhibitors offers renewed hope.

Polycythemia vera: plethora, from prehistory to present.

The term polycythemia (literally, "many blood cell disease") and its obsolete synonym, erythremia, postdate Robert Hooke's 17th century discovery of cells, but the concept of a clinically problematic excess of blood was formulated in antiquity. Observation of plethoric patients by clinicians of the Hippocratic school informed the classical humoral framework that dominated theoretical constructs of human disease for more than a thousand years. In the golden era of disease description at the end of the 19th century, the idiopathic entity polycythemia rubra vera (PRV) was first described and distinguished from secondary and relative polycythemia (red cell excess not caused by a primary bone marrow disorder, and artifactual red cell excess caused by plasma volume contraction, respectively). This review traces some of the principal events in the history of polycythemia vera (PV) as a discrete clinical entity.

Polycythemia vera: a review.

Polycythemia vera (PV) is a clonal stem cell disorder characterized by increased erythrocyte production. Its etiology is not fully understood, and hemorrhage, thrombosis, and hyperviscosity may occur at any time during the course of this disorder. Treatment depends on the most affected cell type, duration and severity of the condition, and patient age. PV treatment can involve phlebotomy, administration of myelosuppressive agents, and biologic therapy. The inconsonant nature of the disease and complications related to its various treatments present nursing care challenges. Nurses must work with patients with PV to ensure compliance with treatment, teach awareness of disease- and treatment-related complications, and provide needed support.

Leeching as initial treatment in a cat with polycythaemia vera.

Polycythaemia vera was diagnosed in a three-year-old domestic shorthaired cat referred because of seizures and a high packed cell volume (PCV). Laboratory examination revealed severe erythrocytosis (PCV 79 per cent). Diagnosis was reached by excluding causes for relative and secondary absolute polycythaemia. As phlebotomy proved impossible for initial treatment due to hyperviscosity, four leeches were used to suck blood and the PCV was consequently reduced to 64 per cent. A further 24 hours later, when bleeding at the sites of sucking had stopped, the PCV was 56 per cent. Long-term management of the condition was achieved with hydroxyurea (100 mg/cat once daily) and intermittent phlebotomy. Initial treatment using leeches in cases of polycythaemia vera is a simple, non-invasive, well tolerated and effective method where phlebotomy is not possible.

Water-induced pruritus in haematologically controlled polycythaemia vera: response to phototherapy.

BACKGROUND: Water-induced pruritus is characterized by the development of intense and widespread itching after contact with water at any temperature and without observable skin lesions. Around 40-52% of patients with polycythaemia vera (PV) have water-induced pruritus, and more than 20% of the patients continue with symptoms despite an adequate control of the underlying disease. The aetiology is unknown and treatment is often unsuccessful. We report a patient with a haematologically controlled polycythaemia vera and water-induced pruritus that responded to phototherapy. METHODS: An 83-year-old woman with haematologically controlled PV referred with intense water-induced pruritus without cutaneous lesions. Topical emollients and oral antihistamines were unsatisfactory and so phototherapy treatment (90% UVA/10% UVB) three times a week was commenced. RESULTS: Improvement was visible after 1 month and at the end of 3 months the pruritus had disappeared and treatment was stopped. CONCLUSION: It is considered that the successful treatment in this patient is due to the UVB radiation.

Plasma erythropoietin concentrations in polycythaemia vera with special reference to myelosuppressive therapy.

In 80 patients with polycythaemia vera (PV) a total of 108 venous blood samples were obtained and analysed for EDTA-plasma erythropoietin (EPO) concentration. At the time of study 21 of the PV patients were newly diagnosed and had prior to blood sampling neither received phlebotomy treatment nor therapy with myelosuppressive agents; these subjects had a mean plasma EPO concentration of 0.5+/-0.9 IU/L. Thirty-seven patients treated with phlebotomy only had a mean plasma EPO concentration of 2.5+/-2.9 IU/L. The mean plasma EPO concentrations for 26 patients treated with hydroxyurea, 13 patients treated with radiophosphorous and 11 patients given a combination of myelosuppressive agents were 8.9+/-8.0, 10.9+/-12.6 and 7.2+/-7.4 IU/L, respectively. Untreated patients and patients on phlebotomy only had significantly lower values for plasma EPO than patients on therapy with myelosuppressive drugs. This finding persisted also after a correction for differences in haemoglobin levels had been introduced. Thereby, the present results would suggest a difference in the EPO feedback system in untreated and phlebotomised PV patients compared to PV patients treated with myelosuppressive agents.

A comparison between concentrations of free erythrocyte protoporphyrin and serum ferritin during development of iron deficiency by phlebotomy in polycythaemia vera patients.

Therapeutic venesection for polycythaemia vera (PV) produces iron deficiency. If iron supplementation is avoided, the frequency of venesections can be kept lower than if iron is given. This is the standard treatment for PV in our department, and this model for iron deficiency was used to compare serum ferritin, free erythrocyte protoporphyrin (FEP), serum iron and transferrin as indicators of iron deficiency. Eleven patients with PV were studied on a total of 90 occasions. Five patients were followed from normal iron status to iron deficiency, the other six were iron deficient at the start of the study. Serum ferritin and FEP became abnormal approximately simultaneously during the development of iron deficiency, serum ferritin in all patients, FEP in 8 out of 11 patients. There was a correlation between the two in all specimens (r = 0.75, p less than 0.001), but serum ferritin showed fewer false negative results. Serum transferrin alone was elevated only in 25% of the patients, and serum iron, although mostly subnormal, was rather inconsistent. It is concluded that serum ferritin and FEP can both be used to diagnose iron deficiency during venesection treatment of PV, whereas serum iron and transferrin are of little value.

Does iron deficiency in treated polycythemia vera affect whole blood viscosity?

The relation between whole blood viscosity and iron status was studied in 11 patients with polycythemia vera (PV) who were treated with venesection without iron supplementation. Six were already iron deficient at the start of the study, five were followed from normal iron status to deficiency. Iron status was investigated with serum ferritin, erythrocyte protoporphyrin, mean cell volume and mean cell hemoglobin. There was no correlation between whole blood viscosity at a fixed erythrocyte volume fraction of 44% and any of these variables. The mean whole blood viscosity during iron deficiency and during normal iron state did not differ. Even after several months of iron deficiency there was no increase in whole blood viscosity. It is concluded that iron deficiency in treated PV does not give increased whole blood viscosity.