{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T14:49:49Z","timestamp":1792853389536,"version":"4.5.0"},"reference-count":154,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T00:00:00Z","timestamp":1675641600000},"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":[[2023,5]]},"abstract":"Abstract<\/jats:title>\n \n Disease Overview<\/jats:title>\n \n Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell\u2010derived clonal myeloproliferation that is often but not always accompanied by\n JAK2<\/jats:italic>\n ,\n CALR<\/jats:italic>\n , or\n MPL<\/jats:italic>\n mutations; additional features include bone marrow reticulin\/collagen fibrosis, aberrant inflammatory cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, risk of leukemic progression, and shortened survival.\n <\/jats:p>\n <\/jats:sec>\n \n Diagnosis<\/jats:title>\n \n Bone marrow examination with cytogenetic and mutation studies provides integrated diagnostic information; presence of\n JAK2<\/jats:italic>\n ,\n CALR<\/jats:italic>\n or\n MPL<\/jats:italic>\n mutation is expected but not required.\n <\/jats:p>\n <\/jats:sec>\n \n New Classification System<\/jats:title>\n The International Consensus Classification distinguishes \u201cprefibrotic\u201d from \u201covertly fibrotic\u201d PMF; the former might mimic essential thrombocythemia (ET) in its presentation. Approximately 15% of patients with ET or polycythemia vera (PV) might progress into post\u2010ET\/PV MF.<\/jats:p>\n <\/jats:sec>\n \n Mutations<\/jats:title>\n \n SRSF2<\/jats:italic>\n ,\n ASXL1<\/jats:italic>\n , and\n U2AF1<\/jats:italic>\n \u2010Q157 mutations predict inferior survival in PMF;\n RAS\/CBL<\/jats:italic>\n mutations predict resistance to ruxolitinib therapy. Type 1\/like\n CALR<\/jats:italic>\n mutation is associated with superior survival.\n <\/jats:p>\n <\/jats:sec>\n \n Karyotype<\/jats:title>\n Very high\u2010risk abnormalities include \u22127, inv (3), i(17q), +21, +19, 12p\u2010 and 11q\u2010. Favorable risk abnormalities include normal karyotype or isolated +9, 13q\u2010, 20q\u2010, 1q abnormalities and loss of Y chromosome.<\/jats:p>\n <\/jats:sec>\n \n Risk Stratification<\/jats:title>\n \n Contemporary prognostic systems include GIPSS (genetically\u2010inspired prognostic scoring system) and MIPSS70+\n version 2.0<\/jats:italic>\n (MIPSS\n v2<\/jats:italic>\n ; mutation\u2010and karyotype\u2010enhanced international prognostic scoring system). GIPSS is based exclusively on mutations and karyotype; MIPSS\n v2<\/jats:italic>\n includes, in addition, clinical risk factors.\n <\/jats:p>\n <\/jats:sec>\n \n Risk\u2010Adapted Therapy<\/jats:title>\n \n Observation alone is advised for MIPSS\n v2<\/jats:italic>\n \u201clow\u201d and \u201cvery low\u201d risk disease (estimated\n 10\u2010year survival 56%\u201392%<\/jats:italic>\n ); allogeneic hematopoietic stem cell transplant (AHSCT) is the preferred treatment of choice for \u201cvery high\u201d and \u201chigh\u201d risk disease (\n estimated 10\u2010year survival 0\u201313%<\/jats:italic>\n ), as well as in carefully selected patients with intermediate\u2010risk disease (\n estimated 10\u2010year survival 30%<\/jats:italic>\n ). Drug therapy in MF is currently palliative and targets anemia, splenomegaly, and constitutional symptoms.\n <\/jats:p>\n <\/jats:sec>\n \n \n JAK2<\/jats:styled-content>\n Inhibitors\n <\/jats:title>\n Ruxolitinib, fedratinib, and pacritinib are FDA approved and respectfully utilized in patients failing treatment with hydroxyurea, ruxolitinib, or with platelet count <50\u2009\u00d7\u200910 (9)\/L. Momelotinib is another JAK2 inhibitor that is poised for approval sometime in 2023 and has shown erythropoietic benefits, in addition to affecting spleen and symptom responses.<\/jats:p>\n <\/jats:sec>\n \n Other Treatment Modalities<\/jats:title>\n Splenectomy is considered for drug\u2010refractory splenomegaly and involved field radiotherapy for non\u2010hepatosplenic EMH and extremity bone pain.<\/jats:p>\n <\/jats:sec>\n \n New Directions<\/jats:title>\n \n New agents, alone or in combination with ruxolitinib, are currently under clinical trial investigation (\n ClinicalTrials.gov<\/jats:italic>\n ) and preliminary results were presented at the 2022 ASH annual meeting and highlighted in the current review.\n <\/jats:p>\n 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