Mutations and thrombosis in essential thrombocythemia: prognostic interaction with age and thrombosis history. (4th December 2014)

• Record Type: Journal Article
• Authors: Gangat, Naseema; Wassie, Emnet A.; Lasho, Terra L.; Finke, Christy; Ketterling, Rhett P.; Hanson, Curtis A.; Pardanani, Animesh; Wolanskyj, Alexandra P.; Maffioli, Margherita; Casalone, Rosario; Passamonti, Francesco; Tefferi, Ayalew
• Is Part Of: European journal of haematology. Volume 94:Number 1(2015:Jan.)
• Page Start: 31
• Page End: 36
• Publication Date: 2014-12-04
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; Blood -- Periodicals; 616.15005
• DOI: 10.1111/ejh.12389
• Languages: English
• ISSNs: 0902-4441

Abstract

<abstract abstract-type="main" id="ejh12389-abs-0001"> <title>Abstract</title> <sec id="ejh12389-sec-0001" sec-type="section"> <title>Background</title> <p>Vascular events in essential thrombocythemia (ET) are associated with advanced age and thrombosis history. Recent information suggests additional effect from the presence of specific mutations.</p> </sec> <sec id="ejh12389-sec-0002" sec-type="section"> <title>Objectives</title> <p>To examine the influence of age and thrombosis history on the reported association between mutational status and thrombosis‐free survival in ET.</p> </sec> <sec id="ejh12389-sec-0003" sec-type="section"> <title>Patients and Methods</title> <p>Analysis was performed using a Mayo Clinic cohort of 300 ET patients, and key findings were reanalyzed by including additional 102 Italian patients.</p> </sec> <sec id="ejh12389-sec-0004" sec-type="section"> <title>Results</title> <p>Among 300 Mayo patients with ET (median age 55 yr, 60% females), mutational frequencies were 53% <italic>JAK2</italic>, 32% <italic>CALR</italic>, 3% <italic>MPL</italic>, and 12% <italic>JAK2</italic>, <italic> CALR</italic> and <italic>MPL</italic> wild type. One hundred and six (35%) patients experienced arterial (<italic>n </italic>=<italic> </italic>75) or venous (<italic>n </italic>=<italic> </italic>43) events, before (<italic>n </italic>=<italic> </italic>55) or after (<italic>n </italic>=<italic> </italic>71) diagnosis. In univariate analysis, compared to <italic>JAK2</italic>‐mutated cases, <italic>JAK2</italic>, <italic> CALR</italic> and <italic>MPL</italic> wild type (HR 0.31, 95% CI 0.11–0.86), and <italic>CALR</italic>‐mutated (0.53, 95% CI 0.30–0.92) patients displayed better thrombosis‐free survival. <italic>JAK2</italic>, <italic> CALR, </italic> and <italic>MPL</italic> wild type remained significant (<italic>P</italic> = 0.03; HR 0.32, 95% CI 0.11–0.9) during multivariable analysis that included age (<italic>P</italic> = 0.01) and thrombosis history (<italic>P</italic> = 0.0006); a favorable impact from <italic>CALR</italic> mutations was of borderline significance (<italic>P</italic> = 0.1; HR 0.62, 95% CI 0.35–1.1), but became significant (<italic>P</italic> = 0.02) when multivariable analysis including thrombosis history (<italic>P</italic> = 0.02) was performed on patients younger than 60 yr of age.</p> </sec> <sec id="ejh12389-sec-0005" sec-type="section"> <title>Conclusions</title> <p>The favorable impact of mutational status on thrombosis‐free survival in ET might be most evident for <italic>JAK2</italic>, <italic> CALR, </italic> and <italic>MPL</italic> wild type patients, whereas the favorable effect from <italic>CALR</italic> mutations might be confined to young patients.</p> </sec> </abstract>