Treatment considerations for primary myelofibrosis.

j u l y/ a u g u s t 2 0 1 0 , v o l . 6 8 , n o 7 / 8 Primary myelofibrosis (PMF) belongs to the group of Philadelphia chromosome negative (Ph) chronic myeloproliferative neoplasms caused by a clonal stem cell disorder presenting with myeloproliferation and fibrosis. The clinical presentation is characterised by anaemia, marked hepatosplenomegaly, leuko-erythroblastosis, constitutional symptoms and finally leukaemic transformation. Myelofibrosis may also develop as a secondary complication of two other myeloproliferative neoplasms, essential thrombocytosis (ET) and polycythemia vera (PV). The median survival of patients with MF is less than five years; this is, however, strongly dependent on risk factors that have been included in several prognostic scoring systems. The International Prognostic Scoring System (IPSS) for PMF uses five risk factors consisting of age (>65 years), anaemia (Hb <10 g/l), leucocyte count (>25 x 10/l), circulating blasts (>1%) and the presence of constitutional symptoms to categorise patients in either a high (≥3 risk factors), intermediate-high (2 risk factors), intermediatelow (1 risk factor) or low (no risk factors) risk group with a median survival of 27, 48, 95, or 135 months, respectively. Besides these risk factors the prognosis of patients with MF is also strongly dependent on the presence of cytogenetic abnormalities, transfusion dependency and the presence of comorbidity. The pathophysiology of MF is not fully elucidated but is characterised by a disturbed bone marrow physiology with expression of multiple growth factors, the release of cytokines, enhanced neoangiogenesis and profound fibrosis in which megakaryocytes, monocytes and clonal stem cells play an important role. Traditionally, patients with MF are treated with supportive care to reduce anaemia, generally by transfusion and the administration of prednisone, danazol or erythropoietin. Splenectomy, splenic radiation or administration of hydroxyurea has been used to treat the often massive splenomegaly in patients with MF. Although sometimes helpful, these palliative treatments usually only have a limited effect on the clinical presentation with a relatively short duration. The only curative option in patients with ed i t or i a l