[Treatment options and limitations in the management of myelofibrosis]

Primary myelofibrosis has the worst outcome among classical chronic myeloproliferative neoplasms. The past decade has brought numerous discoveries elucidating the role of proliferative mutations in disease pathogenesis. Mutations of the genes JAK2, MPL and CALR are present in about 90 percent of all primary myelofibrosis cases. The prognosis of myelofibrosis is considered heterogeneous, the expected survival of patients may range from one year to more than a decade based on several prognostic factors. Estimated survival can be assessed based on clinical prognostic scores. The aim of treatment is to reduce mortality and to alleviate the main aspects of disease-associated morbidity, e.g. anemia, splenomegalia and systemic symptoms. The effect of conventionally used cytoreductive agent hydroxyurea is usually transient. Use of allogeneic hematopoietic stem cell transplantation is limited by significant procedure-associated mortality. JAK2 tyrosine kinase inhibitors are the first treatment modality with evidence of improved overall survival, however, even these molecularly targeted therapies have failed to bring complete and permanent remission for the majority of myelofibrosis patients. Further improvement in overall survival for myelofibrosis can be expected from better understanding of the underlying molecular pathology and novel molecular therapeutic targets.