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Petro E Petrides, Christian Schoergenhofer, Rudolf Widmann, Bernd Jilma, Christoph S Klade
Anagrelide is an established therapy for essential thrombocythemia. Common adverse effects have been linked to peak plasma concentrations of anagrelide and its 3OH metabolite. Our study was performed to investigate the pharmacokinetics (PK) of a novel anagrelide extended-release (AER) formulation and its active metabolites. Thirty healthy volunteers were randomized to receive either 2 mg AER (under fasting and fed conditions) or 2 mg commercially available reference product (CARP) in an open-label, 3-way crossover trial with washout periods of 6 days...
March 16, 2017: Clinical Pharmacology in Drug Development
Andrea Piccin, Michael Steurer, Clemens Feistritzer, Ciaran Murphy, Elva Eakins, Muriel Van Schilfgaarde, Daisy Corvetta, Angela Maria Di Pierro, Irene Pusceddu, Luigi Marcheselli, Roberto Gambato, Martin Langes, Dino Veneri, Omar Perbellini, Enrica Pacquola, Michele Gottardi, Filippo Gherlinzoni, Andrea Mega, Martina Tauber, Guido Mazzoleni, Elisa Piva, Mario Plebani, Mauro Krampera, Günther Gastl
Essential thrombocythemia (ET) patients are at risk of developing thrombotic events. Qualitative platelet (PLT) abnormalities and activation of endothelial cells (ECs) and PLTs are thought to be involved. Microparticles (MPs) can originate from PLTs (PMPs), ECs (EMPs), or red cells (RMPs). Previous studies have indicated that MPs contribute to ET pathophysiology. Endothelial modulators (eg, nitric oxide [NO], adrenomedullin [ADM], and endothelin-1 [ET-1]) are also involved in the pathophysiology of this condition...
February 14, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
Péter Dombi, Árpád Illés, Judit Demeter, Lajos Homor, Zsófia Simon, Miklós Udvardy, Éva Karádi, Ádám Kellner, Miklós Egyed
INTRODUCTION: In order to establish and use a national registry, several Hungarian hematology centers collected data of myeloproliferative neoplasia patients. AIM: The recent publication is an analysis of the data of registered essential thrombocythaemic patients. METHOD: an online electronic registry has been established, using 2008 World Health Organization's diagnostic criteria and thrombotic risk was evaluated according to Landolfi stratification...
January 2017: Orvosi Hetilap
Francesco Passamonti, Martin Griesshammer, Francesca Palandri, Miklos Egyed, Giulia Benevolo, Timothy Devos, Jeannie Callum, Alessandro M Vannucchi, Serdar Sivgin, Caroline Bensasson, Mahmudul Khan, Nadjat Mounedji, Guray Saydam
BACKGROUND: In the pivotal RESPONSE study, ruxolitinib, a Janus kinase (JAK)1 and JAK2 inhibitor, was superior to best available therapy at controlling haematocrit and improving splenomegaly and symptoms in patients with polycythaemia vera with splenomegaly who were inadequately controlled with hydroxyurea. In this study, we assessed the efficacy and safety of ruxolitinib in controlling disease in patients with polycythaemia vera without splenomegaly who need second-line therapy. METHODS: RESPONSE-2 is a randomised, open-label, phase 3b study assessing ruxolitinib versus best available therapy in patients with polycythaemia vera done in 48 hospitals or clinics across 12 countries in Asia, Australia, Europe, and North America...
January 2017: Lancet Oncology
Sarah Lawless, Mary Frances McMullin, Robert Cuthbert, Russell Houston
UNLABELLED: (32)P has been available for the treatment of myeloproliferative neoplasms (MPNs) for over seventy years. It was first used in 1938 by John H Lawrence in the treatment of polycythaemia and chronic leukaemias. With the introduction of agents such as hydroxycarbamide, interferon and anagrelide the role of (32)P has been diminished. Today, Polycythaemia Rubra Vera (PRV) and Essential Thrombocythaemia (ET) remain the only myeloproliferative conditions in which (32)P is indicated...
May 2016: Ulster Medical Journal
Péter Dombi, Árpád Illés, Judit Demeter, Lajos Homor, Zsofia Simon, Eva Karadi, Miklos Udvardy, Miklos Egyed
OBJECTIVE: To evaluate the reduction in thrombotic events (TE) in patients with essential thrombocythaemia (ET) treated with anagrelide versus hydroxyurea + aspirin (HU + ASA). METHODS: A questionnaire was developed using 2008 WHO diagnostic criteria, and thrombotic risk factors were stratified according to Landolfi criteria. Through questionnaire completion, clinicians at Hungarian haematological centres entered data into the Hungarian MPN Registry on patients with myeloproliferative neoplasms...
February 2017: European Journal of Haematology
Gunnar Birgegård
Anagrelide (ANA) is a drug with specific platelet-lowering activity, used primarily in ET, registered as a second-line drug in essential thrombocythemia (ET) in Europe and in some countries as first-line therapy, in USA licensed by FDA for thrombocythemia in myeloproliferative neoplasms (MPN). The platelet-lowering efficacy is similar to that of hydroxycarbamide (HC), around 70 % complete response and 90 % partial response. Side effects are common, especially headache and tachycardia, but usually subside or disappear within a few weeks...
October 2016: Current Hematologic Malignancy Reports
Akira Kitanaka, Kazuya Shimoda
No abstract text is available yet for this article.
May 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Cecilia Bozzetti, Seval Türkmen, Ulrich Richter, Lars Fransecky, Gürkan Bal, Carsten-Oliver Schulz, Philipp Hemmati, Renate Arnold, Hanno Riess, Philipp le Coutre
We hereby report a case of acute myeloid leukemia with translocation t(2;3) and involvement of the ectopic virus integration site-1 (EVI1) gene. Like most other 3q26-related disorders reported thus far, we describe a phenotype with elevated platelet counts and dysmegakaryopoesis. The clinical course of our patient was complicated by symptomatic thrombophilia and chemoresistance. In addition, our case exhibited FLT3 (Fms-related tyrosine kinase 3) internal tandem duplication. Although anagrelide was successful in controlling elevated platelet counts, allogeneic stem cell transplantation failed to overcome chemoresistance due to simultaneous graft-versus-host-disease and relapse of acute myeloid leukemia...
2016: Journal of Clinical and Experimental Hematopathology: JCEH
Roberto Collado-Borrell, Vicente Escudero-Vilaplana, Rosa Romero-Jiménez, Irene Iglesias-Peinado, Ana Herranz-Alonso, María Sanjurjo-Sáez
OBJECTIVE: To review interactions between oral antineoplastic agents (OAAs) for the treatment of solid and hematological tumors and common food and medicinal plants. MATERIALS AND METHODS: All potential interactions between OAAs, medicinal plants and food were reviewed. OAAs were considered to be drugs for oral administration that have direct antitumor activity and were approved by the European Medicines Agency in April 2015. We performed the literature search in Pubmed(®) considering only medicinal plants and food...
November 2016: Journal of Cancer Research and Clinical Oncology
Vanja Zeremski, Aleksandar Savić, Tatjana Ilić, Ivana Milosević, Marina Maksimović, Biljana Vucković
INTRODUCTION: A high platelet count, or thrombocytosis, is either a reactive process or a result of a myeloproliferative disorder. Ankylosing spondylitis is a chronic inflammatory rheumatic disease affecting the spine and sometimes peripheral joints in which reactive mild to moderate thrombocytosis is a common finding. There have been no previously reported cases of essential thrombocythemia associated with ankylosing spondylitis. CASE OUTLINE: We report a case of a 32-year-old man with human leukocyte antigen B27-positive ankylosing spondylitis and Janus kinase 2-positive essential thrombocythemia who was treated first with a combination of anagrelide and disease-modifying antirheumatic drugs and, after liver toxicity, with a combination of anagrelide and etanercept (TNF-α antagonist)...
January 2016: Srpski Arhiv za Celokupno Lekarstvo
Kazuki Sakurai, Tohru Fujiwara, Shin Hasegawa, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Minami Yamada-Fujiwara, Ryo Ichinohasama, Hideo Harigae
Anagrelide is a treatment option for patients with essential thrombocythemia. Although the clinical efficacy of anagrelide has been established, there is limited knowledge of the molecular mechanism underlying its effect. Here, we evaluated the effect of anagrelide on primary megakaryocytic progenitors from cord blood-derived CD34-positive cells. Anagrelide treatment reduced the expression of megakaryocytic markers (CD41 and CD61). Microarray analysis was performed to characterize gene profiles altered by exposure to anagrelide...
August 2016: International Journal of Hematology
Alessandra Iurlo, Daniele Cattaneo, Nicola Orofino, Cristina Bucelli, Sonia Fabris, Agostino Cortelezzi
BACKGROUND: Anagrelide is an orally active, quinazolone-derived, platelet-lowering agent that acts by blocking megakaryocyte maturation and polyploidization as well as proplatelet formation, and is currently indicated for second-line treatment of high-risk patients with essential thrombocythemia (ET) in Europe. In recent years various clinical trials have confirmed the safety and efficacy of this drug in ET, with some also considering Janus kinase 2 (JAK2) mutational status, but have not confirmed the impact that the other driver mutations, i...
June 2016: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
Veronika Buxhofer-Ausch, Michael Steurer, Siegfried Sormann, Ernst Schloegl, Wolfgang Schimetta, Bettina Gisslinger, Reinhard Ruckser, Günther Gastl, Heinz Gisslinger
OBJECTIVES: Although guidelines recommend normalization of platelet counts as an appropriate endpoint for treatment in high-risk essential thrombocythemia (ET), retrospective studies could not prove a correlation of diagnostic platelet counts with an increased thrombotic rate. There is, however, an increasing evidence that leukocytosis is an important risk factor for arterial thrombosis in myeloproliferative neoplasms. METHODS: This study considers the Austrian cohort of a European registry regarding the platelet-lowering therapeutic anagrelide...
December 2016: European Journal of Haematology
Daniel Aruch, John Mascarenhas
PURPOSE OF REVIEW: Management of polycythemia vera and essential thrombocythemia requires understanding of the key concepts regarding diagnosis, risk stratification, and management. RECENT FINDINGS: Essential thrombocythemia and polycythemia vera are among the Philadelphia chromosome negative myeloproliferative neoplasms. They are characterized by overproduction of blood cells and their complications include thrombosis, hemorrhage, and progression to myelofibrosis or acute myeloid leukemia (AML)...
March 2016: Current Opinion in Hematology
Julie C Wigton, Jean M Tersak
A 12-year-old female with Budd-Chiari syndrome underwent liver transplant and subsequent splenectomy. Her platelet count began to rise postoperatively after previous normal values. JAK2V617F-positive essential thrombocythemia (ET) was diagnosed. This case demonstrates that the diagnosis of ET should be considered in the face of normal platelet counts and included on the differential diagnosis for pediatric patients. With this population in mind, we review the current literature on long-term use of platelet-lowering agents...
January 2016: Journal of Pediatric Hematology/oncology
Emanuele Cozzani, Alessandra Iurlo, Giulia Merlo, Daniele Cattaneo, Martina Burlando, Ivana Pierri, Luigi Gugliotta, Aurora Parodi
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...
December 2015: Clinical Lymphoma, Myeloma & Leukemia
María Luisa Antelo, Natalia de Las Heras, Jose Ramón Gonzalez Porras, Ana Kerguelen, Jose María Raya
Although hydroxyurea is considered the first-line cytoreductive therapy in high-risk patients with polycythemia vera or essential thrombocythemia, approximately 20-25% of patients develop resistance or intolerance and they need an alternative therapy. Anagrelide is the treatment of choice in patients with essential thrombocythemia intolerant or with resistance to hydroxyurea. Anagrelide is usually well tolerated. Although there is concern about the increased risk of cardiac side effects, in most cases these are mild, and easily manageable...
December 2015: Expert Review of Hematology
Xiaoyan Ge, Linhua Yang, Jie Jin, Wenbin Qian, Jianyong Li, Renchi Yang, Xiangshan Cao, Bin Jiang, Zhao Wang, Ming Hou, Weihua Zhang, Zhongping Xiao, Yongqiang Zhao, Da Gao, Xiaohong Zhang, Shuye Wang, Aining Sun, Jinxiang Fu, Li Su, Kang Li
OBJECTIVE: To evaluate the efficacy and safety of anagrelide in essential thrombocythemia (ET). METHODS: Patients who diagnosed as ET according to the World Health Organization classification were enrolled. Each patient was assigned to take anagrelide hydrochloride capsule or hydroxyurea tablet by random 1∶1 ratio. Dose of anagrelide started at 2 mg/d, then increased gradually and the maximum dose was 10 mg/d until the platelet counts dropped to (100-400) × 10⁹/L, one month later gradually reduced to maintain dose...
July 2015: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Umit Yavuz Malkan, Gursel Gunes, Eylem Eliacik, Okan Yayar, Ibrahim Celalettin Haznedaroglu
Hydroxycarbamide is used in the treatment of essential thrombocytosis and other myeloproliferative disorders. We report the case of a 63-year-old woman with essential thrombocytosis who had melanonychia after the long-term use of the hydroxycarbamide with a dose of 1000 mg/day. Two years after the initiation of the hydroxycarbamide, our patient had pain on her toes and melanonychia on her nails. Hydroxycarbamide treatment was discontinued because of pain and she was given anagrelide treatment. The pathogenesis of melanonychia secondary to long-term hydroxycarbamide treatment is not yet well understood...
2015: Case Reports in Hematology
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