{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T01:35:46Z","timestamp":1789349746352,"version":"build-2803163510"},"reference-count":93,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,1,24]],"date-time":"2013-01-24T00:00:00Z","timestamp":1358985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:sec><jats:title>Disease overview<\/jats:title><jats:p>Primary myelofibrosis (<jats:styled-content style=\"fixed-case\">PMF<\/jats:styled-content>) is a myeloproliferative neoplasm characterized by stem cell\u2010derived clonal myeloproliferation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (<jats:styled-content style=\"fixed-case\">EMH<\/jats:styled-content>), constitutional symptoms, cachexia, leukemic progression, and shortened survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Diagnosis<\/jats:title><jats:p>Diagnosis is based on bone marrow morphology. The presence of fibrosis,<jats:styled-content style=\"fixed-case\"><jats:italic>JAK2<\/jats:italic>\/<jats:italic>MPL<\/jats:italic><\/jats:styled-content>mutation, or +9\/13q\u2212 cytogenetic abnormality is supportive but not essential for diagnosis. Prefibrotic<jats:styled-content style=\"fixed-case\">PMF<\/jats:styled-content>mimics essential thrombocythemia in its presentation and the distinction is prognostically relevant. Differential diagnosis of myelofibrosis should include chronic myeloid leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Risk stratification<\/jats:title><jats:p>The Dynamic International Prognostic Scoring System\u2010plus (DIPSS\u2010plus) prognostic model for<jats:styled-content style=\"fixed-case\">PMF<\/jats:styled-content>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, \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. 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. Most recently, mutations involving<jats:styled-content style=\"fixed-case\"><jats:italic>ASXL1<\/jats:italic><\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"><jats:italic>SRSF2<\/jats:italic><\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"><jats:italic>EZH2<\/jats:italic><\/jats:styled-content>, and<jats:styled-content style=\"fixed-case\"><jats:italic>IDH1\/2<\/jats:italic><\/jats:styled-content>or increased plasma IL\u20102R, IL\u20108, or serum\u2010free light chain levels have been shown to adversely affect survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Risk\u2010adapted therapy<\/jats:title><jats:p>Observation alone is adequate for asymptomatic low\/intermediate\u20101 risk disease. Allogeneic stem cell transplantation (<jats:styled-content style=\"fixed-case\">ASCT<\/jats:styled-content>) is often considered for high risk disease. Conventional or experimental drug therapy is reasonable for symptomatic intermediate\u20101 or intermediate\u20102 risk disease; however,<jats:styled-content style=\"fixed-case\">ASCT<\/jats:styled-content>is an acceptable treatment option for such patients in the presence of<jats:styled-content style=\"fixed-case\"><jats:italic>ASXL1<\/jats:italic><\/jats:styled-content>or other prognostically adverse mutations. Splenectomy and low\u2010dose radiotherapy are used for drug\u2010refractory splenomegaly. Radiotherapy is also used for the treatment of non\u2010hepatosplenic<jats:styled-content style=\"fixed-case\">EMH<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">PMF<\/jats:styled-content>\u2010associated pulmonary hypertension, and extremity bone pain. Am. J. 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