Özet:

Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm (MPN) characterized by anemia, teardropshaped red cells in blood, leukoerythroblastosis, bone marrow fibrosis, osteosclerosis and extramedullary hematopoiesis. Approximately 50% of PMF patients harbor JAK2V617F mutation and MPL mutations are present in a further 10%. Bone marrow examination reveals a hypercellular bone marrow with atypical megakaryocytes and slight marrow fibrosis in cellular phase of PMF. Diagnosis requires the exclusion of other MPN. Most patients are diagnosed in the fibrotic phase of PMF, when fibrosis is typically extensive with reticulin fibers and often subsequently accompanied by collagen fibrosis. Overall median survival is approximately 5 years. Death is mainly due to leukemic transformation, accounting for 20% of PMF patients. Others succumb to consequences of cytopenias such as infection or bleeding or to comorbid conditions including cardiovascular events. A number of prognostic scoring systems have been developed for PMF (eg. IPSS, DIPPS, DIPSS Plus). Analysis of a total of 879 patients included in a European and Mayo Clinic cohort showed that ASXL1, SRSF2 and EZH2 mutations independently predicted shortened survival. Leukemia-free survival (LFS) was negatively affected by IDH1/2, SRSF2, and ASXL1 mutations. Profiling for ASXL1, EZH2, SRSF2 and IDH mutations may identify PMF patients at risk for leukemic transformation or death. Currently, these molecular markers are mainly of research interest. Allogeneic hematopoietic stem cell transplantation (AHSCT) is the only curative treatment modality in PMF, yet it is associated with high treatment-related mortality. All other treatment modalities are palliative and show differences in efficacy and toxicity. There are few randomized trials comparing these modalities. Thus, it is not possible to make strong recommendations for selecting one treatment over another. This review aims to highlight the pathogenesis, diagnosis and current management in PMF

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