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The presence of fibrosis,<jats:italic>JAK2<\/jats:italic>\/<jats:italic>MPL<\/jats:italic>mutation or +9\/13q\u2010 cytogenetic abnormality is supportive but not essential for diagnosis. Prefibrotic PMF mimics essential thrombocythemia in its presentation and the distinction is prognostically relevant. Differential diagnosis of myelofibrosis should include chronic myelogenous leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.<\/jats:p><jats:p><jats:italic>Risk stratification:<\/jats:italic>The Dynamic International Prognostic Scoring System\u2010plus (DIPSS\u2010plus) prognostic model for PMF can be applied at any point during the disease course and uses eight independent 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, \u20107\/7q\u2010, i(17q), inv(3), \u20105\/5q\u2010, 12p\u2010 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 \u223c 15.4, 6.5, 2.9, and 1.3 years, respectively. A &gt;80% two\u2010year mortality is predicted by monosomal karyotype, inv(3)\/i(17q) abnormalities, or any two of circulating blasts &gt;9%, leukocytes \u226540 \u00d7 10<jats:sup>9<\/jats:sup>\/L or other unfavorable karyotype.<\/jats:p><jats:p><jats:italic>Risk\u2010adapted therapy:<\/jats:italic>Observation alone is adequate for asymptomatic low\/intermediate\u20101 risk disease. Allogeneic stem cell transplantation or experimental drug therapy is considered for intermediate\u20102\/ high risk disease. Conventional or experimental drug therapy is reasonable for symptomatic intermediate\u20101 risk disease. Splenectomy and low\u2010dose radiotherapy are used for drug\u2010refractory splenomegaly. Radiotherapy is also used for the treatment of non\u2010hepatosplenic EMH, PMF\u2010associated pulmonary hypertension, and extremity bone pain.<\/jats:p>","DOI":"10.1002\/ajh.22210","type":"journal-article","created":{"date-parts":[[2011,11,17]],"date-time":"2011-11-17T00:56:25Z","timestamp":1321491385000},"page":"1017-1026","source":"Crossref","is-referenced-by-count":45,"title":["Primary myelofibrosis: 2012 update on diagnosis, risk stratification, and 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