{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:07:26Z","timestamp":1785420446968,"version":"3.56.0"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Thrombosis is the largest contributor to morbidity and mortality in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Our understanding of the risk factors and pathophysiology of thrombosis in PV and ET patients is developing, including recent insights into the role of aberrant platelet-neutrophil interactions, <jats:italic>JAK2<\/jats:italic> mutated endothelial cells and the pro-thrombotic inflammatory milieu. To date, few available therapies have demonstrated the ability to reduce the thrombotic burden in patients with these diseases. Although numerous therapeutic agents have been investigated in both PV and ET patients, few studies are designed to assess their impact on thrombotic events. In this review, we first describe the burden of thrombosis in patients with these myeloproliferative neoplasms (MPNs) and briefly explore their pathophysiologic mechanisms. We then critically assess and summarize the evidence behind currently available therapies with attention toward thrombotic endpoints. Finally, we describe a path forward for clinical research in MPNs that involves surrogate endpoint validation, biomarker development, and clinical trial design strategies in order to accurately assess reduction of thrombotic events when evaluating novel therapies.<\/jats:p>","DOI":"10.3389\/fonc.2020.636675","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T16:16:32Z","timestamp":1613664992000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Evaluation of Therapeutic Strategies to Reduce the Number of Thrombotic Events in Patients With Polycythemia Vera and Essential Thrombocythemia"],"prefix":"10.3389","volume":"10","author":[{"given":"Douglas","family":"Tremblay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi E.","family":"Kosiorek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amylou C.","family":"Dueck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41408-018-0054-y","article-title":"The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion","volume":"8","author":"Barbui","year":"2018","journal-title":"Blood Cancer J"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.163","article-title":"Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study","volume":"27","author":"Tefferi","year":"2013","journal-title":"Leukemia"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67785-9","article-title":"Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study","volume":"366","author":"Campbell","year":"2005","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13335","article-title":"Outcomes of Splanchnic Vein Thrombosis in Patients with Myeloproliferative Neoplasms in a Single Center Experience","volume":"104","author":"Tremblay","year":"2020","journal-title":"Eur J Haematol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-123-9-199511010-00003","article-title":"Polycythemia vera: the natural history of 1213 patients followed for 20 years","volume":"123","year":"1995","journal-title":"Ann Intern Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-339002","article-title":"Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients","volume":"117","author":"Carobbio","year":"2011","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.7326\/M17-0028","article-title":"Risk for Arterial and Venous Thrombosis in Patients With Myeloproliferative Neoplasms: A Population-Based Cohort Study","volume":"168","author":"Hultcrantz","year":"2018","journal-title":"Ann Intern Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0077-1","article-title":"Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet","volume":"32","author":"Barbui","year":"2018","journal-title":"Leukemia"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.07.062","article-title":"Vascular and neoplastic risk in a large cohort of patients with polycythemia vera","volume":"23","author":"Marchioli","year":"2005","journal-title":"J Clin Oncol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"5128","DOI":"10.1182\/blood-2012-07-444067","article-title":"Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis)","volume":"120","author":"Barbui","year":"2012","journal-title":"Blood"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e369","DOI":"10.1038\/bcj.2015.94","article-title":"Practice-relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia","volume":"5","author":"Barbui","year":"2015","journal-title":"Blood Cancer J"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-04-424911","article-title":"Correlation of blood counts with vascular complications in essential thrombocythemia: analysis of the prospective PT1 cohort","volume":"120","author":"Campbell","year":"2012","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-01-478891","article-title":"Revised response criteria for polycythemia vera and essential thrombocythemia: an ELN and IWG-MRT consensus project","volume":"121","author":"Barosi","year":"2013","journal-title":"Blood"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08430.x","article-title":"Clinical evaluation of the European LeukaemiaNet criteria for clinicohaematological response and resistance\/intolerance to hydroxycarbamide in essential thrombocythaemia","volume":"152","author":"Hernandez-Boluda","year":"2011","journal-title":"Br J Haematol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2017.0157","article-title":"NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018","volume":"15","author":"Mesa","year":"2017","journal-title":"J Natl Compr Canc Netw"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-139229","article-title":"Direct Oral Anticoagulants for Myeloproliferative Neoplasms (MPN-DOACs): Results from an International Study on 442 Patients","volume":"136","author":"Barbui","year":"2020","journal-title":"Blood"},{"key":"B17","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41408-018-0151-y","article-title":"Hydroxyurea prevents arterial and late venous thrombotic recurrences in patients with myeloproliferative neoplasms but fails in the splanchnic venous district. Pooled analysis of 1500 cases","volume":"8","author":"De Stefano","year":"2018","journal-title":"Blood Cancer J"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035572","article-title":"Efficacy and safety of low-dose aspirin in polycythemia vera","volume":"350","author":"Landolfi","year":"2004","journal-title":"N Engl J Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1997.362682.x","article-title":"Low-dose aspirin in polycythaemia vera: a pilot study","volume":"97","year":"1997","journal-title":"Br J Haematol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1056\/NEJMoa1208500","article-title":"Cardiovascular events and intensity of treatment in polycythemia vera","volume":"368","author":"Marchioli","year":"2013","journal-title":"N Engl J Med"},{"key":"B21","first-page":"17","article-title":"From efficacy to safety: a Polycythemia Vera Study group report on hydroxyurea in patients with polycythemia vera","volume":"34","author":"Fruchtman","year":"1997","journal-title":"Semin Hematol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24851","article-title":"A reappraisal of the benefit-risk profile of hydroxyurea in polycythemia vera: A propensity-matched study","volume":"92","author":"Barbui","year":"2017","journal-title":"Am J Hematol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019001158","article-title":"Ruxolitinib for the prevention of thrombosis in polycythemia vera: a systematic review and meta-analysis","volume":"4","author":"Masciulli","year":"2020","journal-title":"Blood Adv"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1182\/blood-2010-01-263319","article-title":"Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia","volume":"116","author":"Alvarez-Larran","year":"2010","journal-title":"Blood"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199504273321704","article-title":"Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis","volume":"332","author":"Cortelazzo","year":"1995","journal-title":"N Engl J Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.78.8414","article-title":"Hydroxycarbamide Plus Aspirin Versus Aspirin Alone in Patients With Essential Thrombocythemia Age 40 to 59 Years Without High-Risk Features","volume":"36","author":"Godfrey","year":"2018","journal-title":"J Clin Oncol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3233\/CH-2011-1455","article-title":"Viscosity, platelet activation, and hematocrit: progress in understanding their relationship with clinical and subclinical vascular disease","volume":"49","author":"Gori","year":"2011","journal-title":"Clin Hemorheol Microcirc"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(78)92098-6","article-title":"Vascular occlusive episodes and venous haematocrit in primary proliferative polycythaemia","volume":"2","author":"Pearson","year":"1978","journal-title":"Lancet"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1172\/JCI92077","article-title":"Platelet-RBC interaction mediated by FasL\/FasR induces procoagulant activity important for thrombosis","volume":"128","author":"Klatt","year":"2018","journal-title":"J Clin Invest"},{"key":"B30","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.thromres.2013.05.003","article-title":"ADP-induced platelet aggregation and thrombin generation are increased in Essential Thrombocythemia and Polycythemia Vera","volume":"132","author":"Panova-Noeva","year":"2013","journal-title":"Thromb Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1182\/blood.2019002756","article-title":"Prevalence and phenotypes of JAK2 V617F and calreticulin mutations in a Danish general population","volume":"134","author":"Cordua S","year":"2019","journal-title":"Blood"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-11-191544","article-title":"The presence of JAK2V617F mutation in the liver endothelial cells of patients with Budd-Chiari syndrome","volume":"113","author":"Sozer","year":"2009","journal-title":"Blood"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2009.08.005","article-title":"Human CD34+ cells are capable of generating normal and JAK2V617F positive endothelial like cells in vivo","volume":"43","author":"Sozer","year":"2009","journal-title":"Blood Cells Mol Dis"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-404889","article-title":"Spleen endothelial cells from patients with myelofibrosis harbor the JAK2V617F mutation","volume":"121","author":"Rosti","year":"2013","journal-title":"Blood"},{"key":"B35","doi-asserted-by":"publisher","first-page":"70","DOI":"10.3324\/haematol.2018.195321","article-title":"Vascular endothelial cell expression of JAK2(V617F) is sufficient to promote a pro-thrombotic state due to increased P-selectin expression","volume":"104","author":"Guy","year":"2019","journal-title":"Haematologica"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-10-463646","article-title":"Thrombosis: tangled up in NETs","volume":"123","author":"Martinod","year":"2014","journal-title":"Blood"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan8292","article-title":"Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms","volume":"10","author":"Wolach","year":"2018","journal-title":"Sci Transl Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23295","article-title":"Plasma cytokines in polycythemia vera: phenotypic correlates, prognostic relevance, and comparison with myelofibrosis","volume":"87","author":"Vaidya","year":"2012","journal-title":"Am J Hematol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2005.05674.x","article-title":"Serum interleukin (IL)-1, IL-2, sIL-2Ra, IL-6 and thrombopoietin levels in patients with chronic myeloproliferative diseases","volume":"130","author":"Panteli","year":"2005","journal-title":"Br J Haematol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-394775","article-title":"Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer","volume":"119","author":"Hasselbalch","year":"2012","journal-title":"Blood"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2010.031070","article-title":"Inflammation and thrombosis in essential thrombocythemia and polycythemia vera: different role of C-reactive protein and pentraxin 3","volume":"96","author":"Barbui","year":"2011","journal-title":"Haematologica"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V80.8.1965.bloodjournal8081965","article-title":"Increased thromboxane biosynthesis in patients with polycythemia vera: evidence for aspirin-suppressible platelet activation in vivo","volume":"80","author":"Landolfi","year":"1992","journal-title":"Blood"},{"key":"B44","article-title":"Adverse effects of antiaggregating platelet therapy in the treatment of polycythemia vera","volume":"23","author":"Tartaglia","year":"1986","journal-title":"Semin Hematol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.4.1144","article-title":"The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: a survey of American Society of Hematology members\u2019 practice patterns","volume":"99","author":"Streiff","year":"2002","journal-title":"Blood"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199405053301808","article-title":"Aspirin as an antiplatelet drug","volume":"330","author":"Patrono","year":"1994","journal-title":"N Engl J Med"},{"key":"B47","doi-asserted-by":"publisher","first-page":"CD006503","DOI":"10.1002\/14651858.CD006503.pub3","article-title":"Antiplatelet drugs for polycythaemia vera and essential thrombocythaemia","author":"Squizzato","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2006.06430.x","article-title":"The haematocrit and platelet target in polycythemia vera","volume":"136","author":"Di Nisio","year":"2007","journal-title":"Br J Haematol"},{"key":"B49","article-title":"Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols","volume":"23","author":"Berk","year":"1986","journal-title":"Semin Hematol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2001-12-0349","article-title":"Polycythemia vera: myths, mechanisms, and management","volume":"100","author":"Spivak","year":"2002","journal-title":"Blood"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.36.0792","article-title":"Treatment of polycythemia vera with hydroxyurea and pipobroman: final results of a randomized trial initiated in 1980","volume":"29","author":"Kiladjian","year":"2011","journal-title":"J Clin Oncol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404473","article-title":"A unified definition of clinical resistance\/intolerance to hydroxyurea in essential thrombocythemia: results of a consensus process by an international working group","volume":"21","author":"Barosi","year":"2007","journal-title":"Leukemia"},{"key":"B53","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/S0140-6736(88)92881-4","article-title":"Recombinant interferon-alpha for treatment of polycythaemia vera","volume":"2","author":"Silver","year":"1988","journal-title":"Lancet"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-03-143537","article-title":"Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera","volume":"112","author":"Kiladjian","year":"2008","journal-title":"Blood"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000428","article-title":"Pegylated Interferon Alfa-2a for Polycythemia Vera or Essential Thrombocythemia Resistant or Intolerant to Hydroxyurea","volume":"134","author":"Yacoub","year":"2019","journal-title":"Blood"},{"key":"B56","first-page":"Abstract 577","author":"Mascarenhas","year":"2018"},{"key":"B57","article-title":"THREE-YEAR ANALYSIS OF THE DALIAH TRIAL - A RANDOMIZED CONTROLLED PHASE III CLINICAL TRIAL COMPARING RECOMBINANT INTERFERON ALPHA-2 VS","volume-title":"HYDROXYUREA IN PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS","author":"Knudsen","year":""},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.3426089","article-title":"Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study","volume":"7","author":"Gisslinger","year":"2020","journal-title":"Lancet Haematol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(17)30030-3","article-title":"Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial","volume":"4","author":"Masarova","year":"2017","journal-title":"Lancet Haematol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-014-2152-7","article-title":"Busulfan in patients with polycythemia vera or essential thrombocythemia refractory or intolerant to hydroxyurea","volume":"93","author":"Alvarez-Larran","year":"2014","journal-title":"Ann Hematol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-09-3426","article-title":"Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study","volume":"105","author":"Finazzi","year":"2005","journal-title":"Blood"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1409002","article-title":"Ruxolitinib versus standard therapy for the treatment of polycythemia vera","volume":"372","author":"Vannucchi","year":"2015","journal-title":"N Engl J Med"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.143644","article-title":"Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial","volume":"101","author":"Verstovsek","year":"2016","journal-title":"Haematologica"},{"key":"B64","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/S1470-2045(16)30558-7","article-title":"Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study","volume":"18","author":"Passamonti","year":"2017","journal-title":"Lancet Oncol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-018-3365-y","article-title":"Ruxolitinib for the treatment of inadequately controlled polycythemia vera without splenomegaly: 80-week follow-up from the RESPONSE-2 trial","volume":"97","author":"Griesshammer","year":"2018","journal-title":"Ann Hematol"},{"key":"B66","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1111\/bjh.14382","article-title":"The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized, double-blind, double-dummy, symptom study (RELIEF)","volume":"176","author":"Mesa","year":"2017","journal-title":"Br J Haematol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-08-236679","article-title":"The contribution of cyclooxygenase-1 and -2 to persistent thromboxane biosynthesis in aspirin-treated essential thrombocythemia: implications for antiplatelet therapy","volume":"115","author":"Dragani","year":"2010","journal-title":"Blood"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019004596","article-title":"A randomized double-blind trial of 3 aspirin regimens to optimize antiplatelet therapy in essential thrombocythemia","volume":"136","author":"Rocca","year":"2020","journal-title":"Blood"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.7326\/M17-0284","article-title":"Benefits and Risks of Antithrombotic Therapy in Essential Thrombocythemia: A Systematic Review","volume":"167","author":"Chu","year":"2017","journal-title":"Ann Intern Med"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1007\/s11899-020-00588-z","article-title":"Thrombocytosis and Thrombosis: Is There Really a Correlation","volume":"15","author":"Galvez","year":"2020","journal-title":"Curr Hematol Malig Rep"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21086","article-title":"Interferon alpha therapy for patients with essential thrombocythemia: final results of a phase II study initiated in 1986","volume":"103","author":"Saba","year":"2005","journal-title":"Cancer"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V126.23.4064.4064","article-title":"Long-Term Interferon-\u03b1 Treatment in Essential Thrombocythemia","volume":"126","author":"Stegelmann","year":"2015","journal-title":"Blood"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.5.1602","article-title":"Effects of anagrelide on in vivo megakaryocyte proliferation and maturation in essential thrombocythemia","volume":"99","author":"Tomer","year":"2002","journal-title":"Blood"},{"key":"B74","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/0002-9343(92)90017-6","article-title":"Anagrelide, a therapy for thrombocythemic states: experience in 577 patients","volume":"92","year":"1992","journal-title":"Am J Med"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20646","article-title":"Anagrelide for thrombocytosis in myeloproliferative disorders: a prospective study to assess efficacy and adverse event profile","volume":"101","author":"Steurer","year":"2004","journal-title":"Cancer"},{"key":"B76","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1056\/NEJMoa043800","article-title":"Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia","volume":"353","author":"Harrison","year":"2005","journal-title":"N Engl J Med"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-443770","article-title":"Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial","volume":"121","author":"Gisslinger","year":"2013","journal-title":"Blood"},{"key":"B78","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1093\/biostatistics\/1.1.49","article-title":"The validation of surrogate endpoints in meta-analyses of randomized experiments","volume":"1","author":"Buyse","year":"2000","journal-title":"Biostatistics"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2020.636675\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T16:16:38Z","timestamp":1613664998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2020.636675\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,16]]},"references-count":78,"alternative-id":["10.3389\/fonc.2020.636675"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2020.636675","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,16]]},"article-number":"636675"}}