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Expert Review of Hematology Nov 2020Essential thrombocythemia (ET) and polycythemia vera (PV) belong to the BCR-ABL1-negative myeloproliferative neoplasms and are characterized by the clonal proliferation... (Review)
Review
INTRODUCTION
Essential thrombocythemia (ET) and polycythemia vera (PV) belong to the BCR-ABL1-negative myeloproliferative neoplasms and are characterized by the clonal proliferation of hematopoietic stem and progenitor cells. The contribution of aberrant immune regulation within the bone marrow microenvironment to ET and PV pathogenesis as well as the underlying molecular landscape is becoming increasingly understood.
AREAS COVERED
Authors searched PubMed and conference abstracts in August 2020 for preclinical and clinical studies to provide an overview of the immune pathobiology in ET and PV and the rationale for several novel agents. A discussion of recent clinical trials on interferon and ruxolitinib in ET and PV patients is provided followed by an outline of the future challenges in the field particularly for novel therapeutics and an increasingly individualized, molecularly driven approach to treatment selection. Several novel agents are currently being actively evaluated and are reviewed herein as well.
EXPERT OPINION
While hydroxyurea remains the first-line treatment for cytoreduction in most high-risk ET and PV patients, the disease-modifying potential of IFN is promising and could make it a preferred option for selected patients. Advances in molecular testing will enable a more individualized approach to prognostication and treatment selection.
Topics: Bone Marrow; Clinical Trials as Topic; Combined Modality Therapy; DNA Methylation; Drugs, Investigational; Forecasting; Histone Code; Humans; Hydroxyurea; Inflammation; Interferon-alpha; Janus Kinase 2; Molecular Diagnostic Techniques; Molecular Targeted Therapy; Mutation, Missense; Nitriles; Polycythemia Vera; Pyrazoles; Pyrimidines; Signal Transduction; Therapies, Investigational; Thrombocythemia, Essential; Thrombophilia; Thrombosis; Tumor Microenvironment
PubMed: 33076714
DOI: 10.1080/17474086.2020.1839887 -
Blood Reviews Jul 2015Thrombotic and cardiovascular events are among the leading causes of death for patients with polycythemia vera (PV), and thrombosis history is a key criterion for... (Review)
Review
Thrombotic and cardiovascular events are among the leading causes of death for patients with polycythemia vera (PV), and thrombosis history is a key criterion for patient risk stratification and treatment strategy. Little is known, however, about mechanisms of thrombogenesis in patients with PV. This report provides an overview of thrombogenesis pathophysiology in patients with PV and elucidates the roles of conventional and nonconventional thrombotic risk factors. In addition to several conventional risk factors for thrombosis, clinical data have implicated increased hematocrit and red blood cell adhesiveness, activated platelets, leukocytosis, and elevated JAK2(V617F) allele burden in patients with PV. Furthermore, PV-related inflammation may exacerbate thrombogenesis through varied mechanisms, including endothelial damage, inhibition of natural anticoagulant pathways, and secretion of procoagulant factors. These findings suggest a direct link between myeloproliferation and thrombogenesis in PV, which is likely to provide new opportunities for targeted antithrombotic interventions aimed at decreasing PV-related morbidity and mortality.
Topics: Humans; Polycythemia Vera; Risk Factors; Thrombosis
PubMed: 25577686
DOI: 10.1016/j.blre.2014.12.002 -
Practical Neurology Mar 2024We report two patients with chorea associated with polycythaemia vera, in whom the haematocrit and haemoglobin were within the reference range. Polycythaemia vera is...
We report two patients with chorea associated with polycythaemia vera, in whom the haematocrit and haemoglobin were within the reference range. Polycythaemia vera is potentially easily treatable and so is important to consider in people developing late-onset chorea.
Topics: Humans; Polycythemia Vera; Chorea
PubMed: 37891000
DOI: 10.1136/pn-2023-003739 -
The American Journal of Nursing Mar 2022Ropeginterferon alfa-2b-njft (Besremi) is the first interferon for treating polycythemia vera and the first approved medication for this condition that can be taken...
Ropeginterferon alfa-2b-njft (Besremi) is the first interferon for treating polycythemia vera and the first approved medication for this condition that can be taken regardless of the patient's treatment history. It is administered subcutaneously every two weeks.Like other interferon alfa products, ropeginterferon alfa-2b-njft has a boxed warning that it can cause or aggravate neuropsychiatric, autoimmune, ischemic, and infectious disorders, which can be life-threatening or fatal. Nurses should closely monitor patients for any persistently severe or worsening signs or symptoms of these adverse effects.
Topics: Antiviral Agents; Humans; Polycythemia Vera
PubMed: 35200182
DOI: 10.1097/01.NAJ.0000822968.37066.5c -
Expert Opinion on Investigational Drugs Jun 2020Polycythemia vera (PV), a Philadelphia chromosome-negative myeloproliferative neoplasm, is characterized by panmyelosis, pancytosis, and a mutation. Patients are at... (Comparative Study)
Comparative Study Review
INTRODUCTION
Polycythemia vera (PV), a Philadelphia chromosome-negative myeloproliferative neoplasm, is characterized by panmyelosis, pancytosis, and a mutation. Patients are at increased risk of thrombohemorrhagic events, and progression to myelofibrosis or acute leukemia. Current treatments include aspirin, phlebotomy, and cytoreductive drugs (most commonly hydroxyurea). Givinostat is a potent, class I/II histone deacetylase (HDAC) inhibitor that is in phase I/II clinical trials in PV. Givinostat was well tolerated and yielded promising clinico-hematological responses. A phase III study of givinostat versus hydroxyurea in high-risk PV patients is planned.
AREAS COVERED
We present an overview of PV, current treatment guidelines, and the putative mechanism(s) of action of givinostat. We discuss the preclinical and clinical studies of givinostat in PV and briefly review approved and investigational competitor compounds.
EXPERT OPINION
HDAC inhibitors have long been known to be active in PV, but chronic toxicities can be challenging. Givinostat, however, is active and well tolerated, and is entering a pivotal Phase III randomized trial. Givinostat offers the possibility of replacing hydroxyurea as the standard first-line cytoreductive choice for PV patients. This would completely change the current therapeutic paradigm and guidelines for PV management. Although surrogate clinical study endpoints may suffice for regulatory purposes, thrombosis reduction and prevention of disease progression remain most important to patients and clinicians.
Topics: Animals; Carbamates; Disease Progression; Histone Deacetylase Inhibitors; Humans; Hydroxyurea; Janus Kinase 2; Mutation; Polycythemia Vera
PubMed: 32693648
DOI: 10.1080/13543784.2020.1761323 -
Oncology 2017Patients with polycythemia vera (PV) experience shortened survival, increased risk of thromboembolic and hemorrhagic events, and burdensome symptoms. For all patients... (Review)
Review
Patients with polycythemia vera (PV) experience shortened survival, increased risk of thromboembolic and hemorrhagic events, and burdensome symptoms. For all patients with PV, treatment with aspirin and hematocrit control with phlebotomy are recommended. In addition, patients with high-risk status or poor hematocrit control benefit from cytoreductive therapy with hydroxyurea, although approximately 1 in 4 patients develops resistance or intolerance. For patients who are resistant to or intolerant of hydroxyurea, studies have shown that ruxolitinib, a Janus kinase 1/2 inhibitor, provides hematocrit control, reduces spleen size, normalizes blood counts, and improves PV-related symptoms. For many patients, PV is managed in a community health setting, and it is important that community hematologists, oncologists, and internists are familiar with the contemporary management of PV to improve patient outcomes, including management for patients who present with unique health-care needs. This review provides an overview of current treatment options for patients with PV and discusses challenging circumstances encountered by community providers in the management of PV, including symptom assessment, identification of hydroxyurea resistance/intolerance, pregnancy, elective surgeries, concomitant immunosuppressants, and managing patients in areas with limited access to specialized hematologic care.
Topics: Community Health Centers; Drug Resistance, Neoplasm; Elective Surgical Procedures; Female; Hematocrit; Humans; Hydroxyurea; Immunosuppressive Agents; Interferon-alpha; Nitriles; Polycythemia Vera; Polyethylene Glycols; Pregnancy; Pyrazoles; Pyrimidines; Recombinant Proteins
PubMed: 28095380
DOI: 10.1159/000454953 -
Current Hematologic Malignancy Reports Oct 2016Polycythemia vera (PV) is a chronic myeloproliferative neoplasm (MPN) characterized by an overactive Janus kinase/signal transducer and activator of transcription... (Review)
Review
Polycythemia vera (PV) is a chronic myeloproliferative neoplasm (MPN) characterized by an overactive Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway through mutations in JAK2 exons 12 or 14 (JAK2 V617F). The dominant clinical characteristics include erythrocytosis (with or without leukocytosis/thrombocytosis), thrombotic events, and symptoms. Increased risk of mortality is mainly caused by thrombotic events and progression to post-polycythemia vera myelofibrosis (PPV-MF) or secondary acute myeloid leukemia (sAML). The most important prognostic factors include age and a history of thrombotic events, although recent evidence has indicated that leukocytosis and additional cytogenetic aberrations may also be of significant prognostic value. First-line therapies include aspirin and phlebotomies, which significantly reduce the incidence of thrombotic events and prolong survival. Cytoreductive treatment with hydroxyurea (approved) and conventional or pegylated interferon-α (effective, but not approved in many countries) is initiated for high-risk or inadequately controlled disease, e.g., uncontrolled hematocrit, leukocytosis, thrombocytosis, thrombotic events, splenomegaly, or symptoms. However, some patients may not receive initial benefit from first-line therapy or may become resistant or intolerant in due course. Although second-line treatment options are limited, clinical trials have shown the efficacy of ruxolitinib toward improving blood counts, enlarged spleen, and symptoms and potentially reducing thrombotic events. Identification of patients with uncontrolled PV is important for clinical care, as such patients have a high risk of complications, and future studies with JAK inhibitors or other agents alone or in combination are needed to test their potential to reduce rates of thrombotic events and transformation to PPV-MF or sAML.
Topics: Antineoplastic Agents; Aspirin; Humans; Hydroxyurea; Interferon-alpha; Janus Kinase 2; Nitriles; Polycythemia Vera; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Survival Rate
PubMed: 26894383
DOI: 10.1007/s11899-016-0311-8 -
Leukemia & Lymphoma Mar 2023The Philadelphia-negative myeloproliferative neoplasms (MPNs)-essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF), are characterized by a...
The Philadelphia-negative myeloproliferative neoplasms (MPNs)-essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF), are characterized by a propensity for thrombotic events and variable risks for transformation to MF (for ET and PV) and acute leukemia. Leukocytosis, which serves a minor criterion for the diagnosis of MF, is present in a significant portion of patients with MPNs. The relation and impact of leukocytosis on disease course and outcomes of patients with MPNs has been studied in multiple, large retrospective and prospective studies. Despite this, the association of leukocytosis and thrombosis, fibrosis and leukemic transformation remains unclear. This article details the published investigations regarding the impact of leukocytosis in MPNs and explores the changing role of leukocytosis in disease prognostication as increasing emphasis is placed on molecular and genetic studies.
Topics: Humans; Leukocytosis; Retrospective Studies; Prospective Studies; Myeloproliferative Disorders; Polycythemia Vera; Thrombocythemia, Essential; Primary Myelofibrosis; Thrombosis; Leukemia, Myeloid, Acute
PubMed: 36519233
DOI: 10.1080/10428194.2022.2156794 -
Praxis Sep 2019CME: Polycythemia vera Polycythemia vera is a myeloprolifere disease which is characterized by proliferation of all three (erythroid, megakaryocytic and granulocytic)...
CME: Polycythemia vera Polycythemia vera is a myeloprolifere disease which is characterized by proliferation of all three (erythroid, megakaryocytic and granulocytic) cell lines. The causative mutation is in the JAK2-tyrosine kinase gene. The symptoms are related to the increased red blood cells. Common signs are itching (pruritus) and pain in the hands or feet. The most common complications are thrombotic events. Risk factors are age over 60 years and a thrombotic event in the patient's history. The treatment consists of phlebotomy combined with acetylsalicylic acid 100 mg a day. The goal of the therapy is the prevention of the common thrombotic events. During the course of the disease, cytoreductive treatment is indicated in most of the patients.
Topics: Humans; Janus Kinase 2; Phlebotomy; Polycythemia Vera; Thrombosis
PubMed: 31571535
DOI: 10.1024/1661-8157/a003317 -
Clinical Advances in Hematology &... 2024Polycythemia vera is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by the clonal proliferation of hematopoietic cells, leading to the... (Review)
Review
Polycythemia vera is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by the clonal proliferation of hematopoietic cells, leading to the overproduction of erythrocytes and the elaboration of inflammatory cytokines. Management is aimed at reducing the risk of thromboembolic events, alleviating the symptom burden, decreasing splenomegaly, and potentially mitigating the risk of disease progression. Existing treatment options include therapeutic phlebotomy and cytoreductive agents including hydroxyurea, pegylated recombinant interferon alpha 2a, ropegylated recombinant interferon alpha 2b, and ruxolitinib. We review risk factors for both thrombotic events and disease progression in patients with polycythemia vera. We discuss existing and novel therapeutic approaches to mitigate the risk of disease-related complications and progression.
Topics: Humans; Polycythemia Vera; Goals; Erythrocytes; Risk Factors; Interferon alpha-2; Disease Progression
PubMed: 38294739
DOI: No ID Found