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The presence of<jats:italic>JAK2<\/jats:italic>,<jats:italic>CALR<\/jats:italic>, or<jats:italic>MPL<\/jats:italic>mutation is supportive but not essential for diagnosis; approximately 90% of patients carry one of these mutations and 10% are \u201ctriple\u2010negative.\u201d None of these mutations are specific to PMF and are also seen in essential thrombocythemia (ET). Prefibrotic PMF mimics ET in its presentation and the distinction, enabled by careful bone marrow morphological examination, is prognostically relevant. Differential diagnosis also includes chronic myeloid leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.<jats:bold><jats:italic>Risk Stratification<\/jats:italic><\/jats:bold>: The Dynamic International Prognostic Scoring System\u2010plus (DIPSS\u2010plus) uses eight predictors of inferior survival: age &gt;65 years, hemoglobin &lt;10 g\/dL, leukocytes &gt;25 \u00d7 10<jats:sup>9<\/jats:sup>\/L, circulating blasts \u22651%, constitutional symptoms, red cell transfusion dependency, platelet count &lt;100 \u00d7 10<jats:sup>9<\/jats:sup>\/L, and unfavorable karyotype (i.e., complex karyotype or sole or two abnormalities that include +8, \u22127\/7q\u2212, i(17q), inv(3), \u22125\/5q\u2212, 12p\u2212, or 11q23 rearrangement). The presence of 0, 1, \u201c2 or 3,\u201d and \u22654 adverse factors defines low, intermediate\u20101, intermediate\u20102, and high\u2010risk disease with median survivals of approximately 15.4, 6.5, 2.9, and 1.3 years, respectively. High risk disease is also defined by<jats:italic>CALR<\/jats:italic><jats:sup>\u2212<\/jats:sup>\/<jats:italic>ASXL1<\/jats:italic><jats:sup>+<\/jats:sup>mutational status.<jats:bold><jats:italic>Risk\u2010Adapted Therapy<\/jats:italic><\/jats:bold>: Observation alone is adequate for asymptomatic low\/intermediate\u20101 risk disease, especially with<jats:italic>CALR<\/jats:italic><jats:sup>+<\/jats:sup>\/<jats:italic>ASXL1<\/jats:italic><jats:sup>\u2212<\/jats:sup>mutational status. Stem cell transplant is considered for DIPSS\u2010plus high risk disease or any risk disease with<jats:italic>CALR<\/jats:italic><jats:sup>\u2212<\/jats:sup>\/<jats:italic>ASXL1<\/jats:italic><jats:sup>+<\/jats:sup>mutational status. Investigational drug therapy is reasonable for symptomatic intermediate\u20101 or intermediate\u20102 risk disease. Splenectomy is considered for drug\u2010refractory splenomegaly. Involved field radiotherapy is most useful for post\u2010splenectomy hepatomegaly, non\u2010hepatosplenic EMH, PMF\u2010associated pulmonary hypertension, and extremity bone pain. Am. J. Hematol. 89:916\u2013925, 2014. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.23703","type":"journal-article","created":{"date-parts":[[2014,8,14]],"date-time":"2014-08-14T13:57:47Z","timestamp":1408024667000},"page":"915-925","source":"Crossref","is-referenced-by-count":85,"title":["Primary myelofibrosis: 2014 update on diagnosis, risk\u2010stratification, and management"],"prefix":"10.1002","volume":"89","author":[{"given":"Ayalew","family":"Tefferi","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Medicine Mayo Clinic Rochester 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