{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:34:08Z","timestamp":1790746448274,"version":"4.1.0"},"reference-count":85,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T00:00:00Z","timestamp":1540512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Disease overview<\/jats:title><jats:p>Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell\u2010derived clonal myeloproliferation that is often but not always accompanied by <jats:italic>JAK2<\/jats:italic>, <jats:italic>CALR<\/jats:italic>, or <jats:italic>MPL<\/jats:italic> mutations; additional disease features include bone marrow stromal reaction including reticulin fibrosis, abnormal cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Diagnosis<\/jats:title><jats:p>Diagnosis of PMF is based on bone marrow morphology. Presence of <jats:italic>JAK2<\/jats:italic>, <jats:italic>CALR<\/jats:italic>, or <jats:italic>MPL<\/jats:italic> mutation, expected in \u223c 90% of the patients, is supportive but not essential for diagnosis. The revised 2016 World Health Organization (WHO) classification system distinguishes \u201cprefibrotic\u201d 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:title>Risk stratification<\/jats:title><jats:p>Two new prognostic systems for PMF have recently been introduced: GIPSS (genetically inspired prognostic scoring system) and MIPSS70+ <jats:italic>version 2.0<\/jats:italic> (mutation\u2010 and karyotype\u2010enhanced international prognostic scoring system). GIPSS is based exclusively on mutations and karyotype. MIPSS70+ <jats:italic>version 2.0<\/jats:italic> utilizes both genetic and clinical risk factors. GIPSS features four and MIPSS70+ <jats:italic>version 2.0<\/jats:italic> five risk categories. MIPSS70+ <jats:italic>version 2.0<\/jats:italic> requires an online score calculator (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.mipss70score.it\">http:\/\/www.mipss70score.it<\/jats:ext-link>) while GIPPS offers a lower complexity prognostic tool.<\/jats:p><\/jats:sec><jats:sec><jats:title>Risk\u2010adapted therapy<\/jats:title><jats:p>Observation alone is advised for MIPSS70+ version 2.0 \u201clow\u201d and \u201cvery low\u201d risk disease (estimated 10\u2010year survival 56%\u201092%); allogeneic stem cell transplant is the preferred treatment of choice for \u201cvery high\u201d and \u201chigh\u201d risk disease (estimated 10\u2010year survival 0\u201013%); treatment\u2010requiring patients with intermediate\u2010risk disease (estimated 10\u2010year survival 30%) are best served by participating in clinical trials. All other treatment approaches, including the use of JAK2 inhibitors, are mostly palliative and should not be used in the absence of clear treatment indications. Conventional treatment for anemia includes androgens, prednisone, thalidomide and danazol, for symptomatic splenomegaly hydroxyurea and ruxolitinib and for constitutional symptoms ruxolitinib. Splenectomy is considered for drug\u2010refractory splenomegaly and involved field radiotherapy for nonhepatosplenic EMH and extremity bone pain.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajh.25230","type":"journal-article","created":{"date-parts":[[2018,7,24]],"date-time":"2018-07-24T06:04:35Z","timestamp":1532412275000},"page":"1551-1560","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":133,"title":["Primary myelofibrosis: 2019 update on diagnosis, risk\u2010stratification and management"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4605-3821","authenticated-orcid":false,"given":"Ayalew","family":"Tefferi","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Medicine Mayo Clinic  Rochester 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