title: How I treat myelofibrosis.
abstract: It is currently assumed that myelofibrosis (MF) originates from acquired mutations that target the hematopoietic stem cell and induce dysregulation of kinase signaling, clonal myeloproliferation, and abnormal cytokine expression. These pathogenetic processes are interdependent and also individually contributory to disease phenotype-bone marrow stromal changes, extramedullary hematopoiesis, ineffective erythropoiesis, and constitutional symptoms. Molecular pathogenesis of MF is poorly understood despite a growing list of resident somatic mutations that are either functionally linked to Janus kinase (JAK)-signal transducer and activator of transcription hyperactivation (eg JAK2, MPL, and LNK mutations) or possibly involved in epigenetic dysregulation of transcription (TET2, ASXL1, or EZH2 mutations). Current prognostication in primary MF is based on the Dynamic International Prognostic Scoring System-plus model, which uses 8 independent predictors of inferior survival to classify patients into low, intermediate 1, intermediate 2, and high-risk disease groups; corresponding median survivals are estimated at 15.4, 6.5, 2.9, and 1.3 years. Such information is used to plan a risk-adapted treatment strategy for the individual patient, which might include observation alone, conventional or investigational (eg, JAK inhibitors, pomalidomide) drug therapy, allogenic stem cell transplantation with reduced- or conventional-intensity conditioning, splenectomy, or radiotherapy. I discuss these treatment approaches in the context of who should get what and when.
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. tefferi.ayalew@mayo.edu
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000465:Algorithms; D006403:Hematologic Tests / Q000379:methods; D006801:Humans; D008954:Models, Biological; D011087:Polycythemia Vera / Q000145:classification / Q000175:diagnosis / Q000209:etiology / Q000628:therapy; D055728:Primary Myelofibrosis / Q000145:classification / Q000175:diagnosis / Q000209:etiology / Q000628:therapy*; D011379:Prognosis; D018570:Risk Assessment; D013920:Thrombocythemia, Essential / Q000145:classification / Q000175:diagnosis / Q000209:etiology / Q000628:therapy; D014944:World Health Organization