Primary Myelofibrosis Diagnosis, Clinical Presentation and Treatment Options

Background Myelofibrosis can occur both primarily as a distinct subtype of myeloproliferative neoplasms (primary myelofibrosis, PMF) and as a late stage of polycythemia vera or essential thrombocythemia. Objectives In this review, the authors focus on PMF and summarize diagnostic criteria, clinical presentation and therapeutic options. Results The early phase of PMF is associated with an increase in megakaryocytic and granulocytic proliferation. Later, bone marrow fibrosis accompanied by progressive splenomegaly and pancytopenia may be the predominant phenotype. According to the current World Health Organization (WHO) classification, the prefibrotic phase is distinguished from fibrotic "overt" myelofibrosis. Diagnostic criteria include histopathologic characteristics of the bone marrow, molecular evidence of driver mutations, and exclusion of other myeloid neoplasms. Therapeutic strategies in the treatment of PMF are based on risk of progression and symptom burden. In addition to dynamic risk scores with emphasis on clinical and hematologic parameters, molecular and cytogenetically driven predictors are currently gaining relevance to allow reliable risk stratification especially for younger patients. Especially for younger patients with PMF and those without relevant comorbidities, the curative option of allogeneic stem cell transplantation is recommended for intermediate-2 or high-risk constellations. Here, pretreatment with JAK inhibitors is beneficial, especially for patients with splenomegaly and symptom burden. Symptom-oriented treatment with JAK inhibitors or experimental therapies in clinical trials are available if allogeneic stem cell transplantation is not indicated or possible.