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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). According to the revised 2016 World Health Organization (WHO) classification and diagnostic criteria, \u201cprefibrotic\u201d PMF (pre\u2010PMF) is distinguished from \u201covertly fibrotic\u201d PMF; the former might mimic ET in its presentation and it is prognostically relevant to distinguish the two.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:bold>Risk stratification:<\/jats:bold><jats:italic>The Dynamic International Prognostic Scoring System\u2010plus (DIPSS\u2010plus)<\/jats:italic>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\u2010, i(17q), inv(3), 5\/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 approximately 15.4, 6.5, 2.9 and 1.3 years, respectively. Most recently, DIPSS\u2010plus\u2010independent adverse prognostic relevance has been demonstrated for certain mutations including<jats:italic>ASXL1<\/jats:italic>and<jats:italic>SRSF2<\/jats:italic>whereas patients with type 1\/like<jats:italic>CALR<\/jats:italic>mutations, compared to their counterparts with other driver mutations, displayed significantly better survival.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:bold>Risk\u2010adapted therapy:<\/jats:bold>Observation alone is a reasonable treatment strategy for asymptomatic<jats:italic>low<\/jats:italic>or<jats:italic>intermediate\u20101<\/jats:italic>DIPSS\u2010plus risk disease, especially in the absence of high\u2010risk mutations. All other patients with<jats:italic>high<\/jats:italic>or<jats:italic>intermediate\u20102 risk<\/jats:italic>disease, or those harboring high\u2010risk mutations such as<jats:italic>ASXL1<\/jats:italic>or<jats:italic>SRSF2<\/jats:italic>, should be considered for stem cell transplant, which is currently the only treatment modality with the potential to favorably modify the natural history of the disease. Non\u2010transplant candidates should be encouraged to participate in clinical trials, since the value of conventional drug therapy, including the use of JAK2 inhibitors, is limited to symptoms palliation and reduction in spleen size. Specifically, JAK2 inhibitors have not been shown to induce complete clinical or cytogenetic remissions or significantly affect<jats:italic>JAK2\/CALR\/MPL<\/jats:italic>mutant allele burden. 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. 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