Primary myelofibrosis: 2013 update on diagnosis, risk‐stratification, and management
Open Access
- 24 January 2013
- journal article
- review article
- Published by Wiley in American Journal of Hematology
- Vol. 88 (2), 141-150
- https://doi.org/10.1002/ajh.23384
Abstract
Disease overview Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by stem cell‐derived clonal myeloproliferation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival. Diagnosis Diagnosis is based on bone marrow morphology. The presence of fibrosis, JAK2/MPL mutation, or +9/13q− cytogenetic abnormality is supportive but not essential for diagnosis. Prefibrotic PMF 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. Risk stratification The Dynamic International Prognostic Scoring System‐plus (DIPSS‐plus) prognostic model for PMF can be applied at any point during the disease course and uses eight independent predictors of inferior survival: age >65 years, hemoglobin 25 × 109/L, circulating blasts ≥1%, constitutional symptoms, red cell transfusion dependency, platelet count 80% two‐year mortality is predicted by monosomal karyotype, inv(3)/i(17q) abnormalities, or any two of circulating blasts >9%, leukocytes ≥40 × 109/L or other unfavorable karyotype. Most recently, mutations involving ASXL1, SRSF2, EZH2, and IDH1/2 or increased plasma IL‐2R, IL‐8, or serum‐free light chain levels have been shown to adversely affect survival. Risk‐adapted therapy Observation alone is adequate for asymptomatic low/intermediate‐1 risk disease. Allogeneic stem cell transplantation (ASCT) is often considered for high risk disease. Conventional or experimental drug therapy is reasonable for symptomatic intermediate‐1 or intermediate‐2 risk disease; however, ASCT is an acceptable treatment option for such patients in the presence of ASXL1 or other prognostically adverse mutations. Splenectomy and low‐dose radiotherapy are used for drug‐refractory splenomegaly. Radiotherapy is also used for the treatment of non‐hepatosplenic EMH, PMF‐associated pulmonary hypertension, and extremity bone pain. Am. J. Hematol. 88:141–150, 2013.Keywords
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