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Hematology (Amsterdam, Netherlands) Mar 2015
Topics: Age Factors; Antineoplastic Agents; Blood Platelets; Calreticulin; Gene Expression; Humans; Hydroxyurea; Immunologic Factors; Interferon-alpha; Janus Kinase 2; Mutation; Platelet Aggregation Inhibitors; Quinazolines; Receptors, Thrombopoietin; Risk Factors; Thrombocythemia, Essential
PubMed: 25715049
DOI: 10.1179/1024533215Z.000000000349 -
Expert Opinion on Pharmacotherapy Jun 2015New treatment options for polycythemia vera (PV) have recently become available. This article reviews current treatment strategies for PV with a focus on anagrelide and... (Review)
Review
INTRODUCTION
New treatment options for polycythemia vera (PV) have recently become available. This article reviews current treatment strategies for PV with a focus on anagrelide and ruxolitinib.
AREAS COVERED
The current treatment of PV is directed towards reducing the risk of additional thrombotic events. In addition to phlebotomy and aspirin, patients who are believed to have high-risk disease also receive cytoreductive therapy. Hydroxyurea (HU) and PEG-IFN are most commonly used first-line treatments. The use of anagrelide in PV is limited to situations where patient develops thrombohemorrhagic episodes in the setting of extreme thrombocytosis. The role of ruxolitinib in treatment of PV has not been fully established but based on a recently completed Phase III trial it will likely serve as a second-line option for patients with systemic symptoms.
EXPERT OPINION
HU and PEG-IFN are frontline therapies for patients with high-risk PV. Anagrelide use should be restricted to patients with clinical consequences of extreme thrombocytosis. Ruxolitinib is a treatment option for patients who fail frontline therapies. However, long-term effects and toxicities are not yet fully known.
Topics: Aspirin; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Hydroxyurea; Interferon-alpha; Nitriles; Platelet Aggregation Inhibitors; Polycythemia Vera; Polyethylene Glycols; Pyrazoles; Pyrimidines; Quinazolines
PubMed: 25873215
DOI: 10.1517/14656566.2015.1036029 -
Clinical Lymphoma, Myeloma & Leukemia Dec 2015Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by an increase in blood platelets and dominated by a predisposition to vascular events.... (Review)
Review
Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by an increase in blood platelets and dominated by a predisposition to vascular events. Cutaneous manifestations can complicate its course. itching has been the most common symptom reported; however, the percentage has ranged from 3% to 46%, depending on the survey. Erythromelalgia is found in 6% of cases, and livedo reticularis, minor bleeding, acrocyanosis, and Raynaud's phenomenon are rare manifestations. It is important to recognize and treat these events, because they can affect patients' quality of life and could worsen the prognosis. In addition to skin involvement as a possible sign of ET, the treatment of ET can be associated with cutaneous complications. Hydroxycarbamide, interferon-alfa, and anagrelide can induce different skin lesions. Hydroxycarbamide has been associated with major complications, including painful leg ulcers and actinic keratoses. Minor events include alopecia and hyperpigmentation. Xerosis, pruritus, and photosensitivity are some of the complications reported by patients treated with interferon-alfa. Anagrelide has proved to be associated with fewer dermatologic effects, only detected in single cases. Knowledge of the ET cutaneous manifestations, together with the clinical examination findings, can result in an earlier diagnosis and the start of effective treatment.
Topics: Antineoplastic Agents; Humans; Hydroxyurea; Interferon-alpha; Quinazolines; Skin Diseases; Thrombocythemia, Essential
PubMed: 26432058
DOI: 10.1016/j.clml.2015.08.086 -
Clinical Case Reports Apr 2021Long-term use of hydroxyurea can cause leg ulcers which usually do not heal unless the drug is discontinued. Patients should be counseled regarding alternative lines of...
Long-term use of hydroxyurea can cause leg ulcers which usually do not heal unless the drug is discontinued. Patients should be counseled regarding alternative lines of treatment like anagrelide and pegylated-interferon.
PubMed: 33936725
DOI: 10.1002/ccr3.3991 -
The Lancet. Haematology Sep 2021Recommendations regarding management of essential thrombocythaemia rely on studies done before the discovery of the CALR mutation. On May 20, 2020, the European... (Review)
Review
Recommendations regarding management of essential thrombocythaemia rely on studies done before the discovery of the CALR mutation. On May 20, 2020, the European LeukemiaNet annual meeting was held with the goal to identify unmet clinical needs in myeloproliferative neoplasms. Because patients with a CALR mutation have specific clinical characteristics, treatment of CALR-mutated essential thrombocythaemia was considered an unmet clinical need by the European LeukemiaNet. The elaboration of a consensus document with recommendations according to current evidence was proposed as a solution for resolving uncertainties in the treatment of CALR-mutated essential thrombocythaemia. A steering committee comprising four European LeukemiaNet members was then formed and a panel of ten experts in the field was recruited. The experts proposed 51 potential unmet clinical needs in the management of CALR-mutated essential thrombocythaemia and were asked to score the relevance of each topic. Those topics that obtained the highest scores as relevant unmet clinical needs were identified, including antiplatelet therapy in patients at low risk, definition of extreme thrombocytosis and its management in patients at low risk, indications of cytoreduction and targets of therapy, first-line treatment of choice in young patients (<60 years), and management of pregnancy. After the steering committee revised the available evidence for each topic, a consensus on management and proposal for improving knowledge was achieved by use of an email-based, two round, Delphi approach. Consensus was achieved when 90% of the panellists agreed with a statement and included 14 recommendations and six solution proposals. Key recommendations included careful observation for asymptomatic patients with classical, low-risk, CALR-mutated essential thrombocythaemia without cardiovascular risk factors; caution in the use of antiplatelet therapy for symptomatic patients at low risk with platelet counts of 1000-1500 × 10 platelets per L, in such cases cytoreduction is an adequate option, especially if adquired Von Willebrand disease is present; cytoreduction is recommended for extreme thrombocytosis (platelet count >1500 × 10 platelets per L) with pegylated interferon alfa being the preferred option for younger patients; both hydroxycarbamide and anagrelide might be given to patients ineligible for pegylated interferon alfa; and treatment algorithms for patients with high-risk pregnancies should not be changed according to genotype. The European LeukemiaNet proposes to use these recommendations in the routine management of patients with CALR-mutated essential thrombocythaemia, and designing new clinical studies in this field might be useful.
Topics: Age Factors; Calreticulin; Female; Heparin, Low-Molecular-Weight; Humans; Platelet Aggregation Inhibitors; Platelet Count; Pregnancy; Severity of Illness Index; Thrombocythemia, Essential
PubMed: 34450103
DOI: 10.1016/S2352-3026(21)00204-0 -
Expert Review of Hematology May 2019Essential thrombocythemia (ET) is a disease which is extremely rare in children. Only recently, data on pediatric ET have become available. Areas covered: In children... (Review)
Review
Essential thrombocythemia (ET) is a disease which is extremely rare in children. Only recently, data on pediatric ET have become available. Areas covered: In children with sustained platelet count over 450 x 10/L, secondary thrombocytosis must be ruled out. ET workup comprehends research of JAK2V617F, CALR and MPL mutations and bone marrow biopsy (BM). In asymptomatic children wait and watch is the best option. Aspirin controls headache and other microvascular disturbances. Patients with venous thrombosis need anticoagulation. Cytoreductive drugs in children with ET should be prescribed as a last choice. Hydroxyurea and IFN-a are first-line therapy at any age including children; Anagrelide is not licensed as first-line therapy for ET in Europe. New JAK2-inhibitors are not clearly useful in ET and hence not approved for ET. Expert opinion: The most challenging problem is to understand if a child with prolonged not secondary thrombocytosis really has ET. Diagnostic workup requires molecular and histological studies. The rare children with clonal ET have features like those of adults. Patients with ET have long expected survival and the treatment in children must be long-term efficacious and well tolerated.
Topics: Anticoagulants; Aspirin; Calreticulin; Child; Disease Management; Humans; Hydroxyurea; Interferon-alpha; Janus Kinase 2; Platelet Aggregation Inhibitors; Platelet Count; Protein Kinase Inhibitors; Receptors, Thrombopoietin; Thrombocythemia, Essential
PubMed: 30925843
DOI: 10.1080/17474086.2019.1602034 -
[Rinsho Ketsueki] the Japanese Journal... 2018The expected survival duration of polycythemia vera (PV) and essential thrombocythemia (ET) patients is not substantially lower than that of the general population. The... (Review)
Review
The expected survival duration of polycythemia vera (PV) and essential thrombocythemia (ET) patients is not substantially lower than that of the general population. The current goal of therapy is to prevent thrombohemorrhagic events associated with PV and ET. The current first line therapy for PV is phlebotomy, hydroxyurea (HU), and aspirin, while that for ET was HU or anagrelide. The follow-up phase 3 randomized trial wherein the hematological response was evaluated in PV patients treated with ropeginterferon alfa-2b, a next-generation monopegylated IFN-α-2b, or HU, demonstrated a superior hematological effect and a lower incidence of adverse events in patients who were treated with ropeginterferon. The prognosis of primary myelofibrosis (PMF) is poorer than that of PV or ET. The only curative therapeutic option for PMF patients is allogeneic hematopoietic stem cell transplantation (HSCT). Other than HSCT options, ruxolitinib ameliorates splenomegaly and MF-associated symptoms and provides an overall survival benefit in PMF patients with intermediate-2 or high risk. Several different JAK inhibitors have been developed; however, many of them were discontinued because of toxicity concerns. Recently, promising results have been demonstrated for the effect of different JAK inhibitors as well as the drugs that directly target anemia and bone marrow fibrosis.
Topics: Humans; Hydroxyurea; Interferon alpha-2; Interferon-alpha; Janus Kinase Inhibitors; Myeloproliferative Disorders; Nitriles; Polycythemia Vera; Polyethylene Glycols; Primary Myelofibrosis; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; Recombinant Proteins; Thrombocythemia, Essential
PubMed: 29973454
DOI: 10.11406/rinketsu.59.741 -
Clinical Lymphoma, Myeloma & Leukemia Aug 2016Polycythemia vera and essential thrombocythemia (ET) are chronic myeloproliferative neoplasms associated with thrombotic or hemorrhagic complications, and increased risk... (Review)
Review
Polycythemia vera and essential thrombocythemia (ET) are chronic myeloproliferative neoplasms associated with thrombotic or hemorrhagic complications, and increased risk of transformation to myelofibrosis and acute myeloid leukemia. The main goal of therapy is aimed at preventing vascular events that are the leading cause of morbidity and mortality in these patients. Accordingly, risk stratification is the basis for deciding when to treat a patient with cytoreductive therapy. The European LeukemiaNet has developed a series of management recommendations for front-line and second-line therapy to provide the optimal treatment for the individual patient. There is still controversy about the efficacy and safety of several modalities of cytoreductive treatment in the long-term for both diseases and in the use of antiplatelet therapy in ET. The presence of JAK2V617F and CALR mutations in patients with ET has been related to different thrombotic risks, and this will probably lead to different therapeutic approaches in the near future. On the other hand, the near normal life expectancy of these patients makes a careful analysis of the benefits and risks associated with treatment essential. This review provides our current management strategy of patients with polycythemia vera and ET.
Topics: Antineoplastic Agents; Cell Transformation, Neoplastic; Clinical Decision-Making; Combined Modality Therapy; Disease Management; Disease Progression; Drug Resistance; Humans; Platelet Aggregation Inhibitors; Polycythemia Vera; Protein Kinase Inhibitors; Risk Assessment; Risk Factors; Thrombocythemia, Essential; Thrombosis
PubMed: 27521307
DOI: 10.1016/j.clml.2016.02.029 -
Cureus Jun 2022Anagrelide is an inhibitor of the phosphodiesterase-3 (PDE-3) enzyme that suppresses megakaryocytes; hence it is used in the treatment of essential thrombocythemia....
Anagrelide is an inhibitor of the phosphodiesterase-3 (PDE-3) enzyme that suppresses megakaryocytes; hence it is used in the treatment of essential thrombocythemia. Anagrelide can cause positive inotropic and chronotropic effects on the cardiovascular system. Its cardiovascular side effects are rare and include palpitations, tachyarrhythmias, cardiomyopathy, angina, and heart failure. We report the case of a 71-year-old female who presented with sudden onset chest pain. Her only outpatient medications included anagrelide and aspirin. She was found to have supraventricular tachycardia (SVT) with aberrancy that responded to beta-blockers. The chest X-ray, computed tomography angiogram (CTA), and echocardiogram were unremarkable. Her arrhythmia may be attributed to the anagrelide in the absence of any cardiovascular findings.
PubMed: 35747119
DOI: 10.7759/cureus.26119 -
British Journal of Haematology May 2024Essential thrombocythaemia (ET) is a myeloproliferative neoplasm characterized by an increased risk of vascular complications and a tendency to progress to myelofibrosis... (Review)
Review
Essential thrombocythaemia (ET) is a myeloproliferative neoplasm characterized by an increased risk of vascular complications and a tendency to progress to myelofibrosis and acute leukaemia. ET patients have traditionally been stratified into two thrombosis risk categories based on age older than 60 years and a history of thrombosis. More recently, the revised IPSET-thrombosis scoring system, which accounts for the increased risk linked to the JAK2 mutation, has been incorporated into most expert recommendations. However, there is increasing evidence that the term ET encompasses different genomic entities, each with a distinct clinical course and prognosis. Moreover, the effectiveness and toxicity of cytoreductive and anti-platelet treatments differ depending on the molecular genotype. While anti-platelets and conventional cytoreductive agents, mainly hydroxycarbamide (hydroxyurea), anagrelide and pegylated interferon, remain the cornerstone of treatment, recent research has shed light on the effectiveness of novel therapies that may help improve outcomes. This comprehensive review focuses on the evolving landscape of treatment strategies in ET, with an emphasis on the role of molecular profiling in guiding therapeutic decisions. Besides evidence-based management according to revised IPSET-thrombosis stratification, we also provide specific observations for those patients with CALR-, MPL-mutated and triple-negative ET, as well as cases with high-risk mutations.
Topics: Humans; Thrombocythemia, Essential; Janus Kinase 2; Platelet Aggregation Inhibitors; Mutation; Receptors, Thrombopoietin; Calreticulin
PubMed: 38586911
DOI: 10.1111/bjh.19403