The median survival from time of diagnosis is approximately 5 years. Therapies with biologic agents and the application of reduced-intensity allogeneic stem cell transplantation appear to offer the possibility of improving the outcome for many patients. End-stage myelofibrosis is characterized by generalized asthenia, liver failure, and bleeding from thrombocytopenia, with some cases terminating in AML. The DIPSS-plus incorporates clinical and genetic risk variables and is associated with overall survival. These variables are (1) age older than 65 years, (2) hemoglobin less than 10 g/dL, (3) leukocytes greater than 25 × 109 /L, (4) circulating blasts greater than or equal to 1%, (5) constitutional symptoms, (6) red cell transfusion dependency, (7) platelet count less than 100 × 109 /L, and (8) unfavorable karyotype (ie, complex karyotype or sole or two abnormalities that include +8, –7/7q–, i(17q), inv(3), 5/5q–, 12p–, or 11q23 rearrangement). The presence of 0, 1, 2 or 3 and 4 or more adverse factors defines low, intermediate-1, intermediate-2 and high-risk disease with median survivals of 15.4, 6.5, 2.9 and 1.3 years, respectively. Most recently, DIPSS-plus-independent adverse prognostic relevance has been demonstrated for certain mutations including ASXL1 and SRSF2, whereas patients with type 1/like CALR mutations, compared to their counterparts with other driver mutations, displayed significantly better survival.