Therapeutic decision-making in primary myelofibrosis (PMF) is becoming more challenging because of the increasing use of allogeneic stem cell transplantation and new investigational drugs. To enhance this process by developing a highly discriminative prognostic system, 1054 patients consecutively diagnosed with PMF at 7 centers were studied. Overall median survival was 69 months (95% confidence interval [CI]: 61-76). Multivariate analysis of parameters obtained at disease diagnosis identified age greater than 65 years, presence of constitutional symptoms, hemoglobin level less than 10 g/dL, leukocyte count greater than 25 ؋ 10 9 /L, and circulating blast cells 1% or greater as predictors of shortened survival. Based on the presence of 0 (low risk), 1 (intermediate risk-1), 2 (intermediate risk-2) or greater than or equal to 3 (high risk) of these variables, 4 risk groups with no overlapping in their survival curves were delineated; respective median survivals were 135, 95, 48, and 27 months (P < .001). Compared with prior prognostic models, the new risk stratification system displayed higher predictive accuracy, replicability, and discriminating power. In 409 patients with assessable metaphases, cytogenetic abnormalities were associated with shorter survival, but their independent contribution to prognosis was restricted to patients in the intermediate-risk groups. JAK2V617F did not cluster with a specific risk group or affect survival.
IntroductionPrimary myelofibrosis (PMF) 1 is classified as a chronic myeloproliferative disorder and characterized by variable degrees of cytopenia(s) and/or cytosis, a leukoerythroblastic blood picture, bone marrow fibrosis, and extramedullary hematopoiesis often resulting in hepatosplenomegaly. 2 From a pathogenesis standpoint, the disease features clonal proliferation involving pluripotent hematopoietic stem cells, 3,4 and clonal cell-derived cytokines are implicated for some of the disease aspects such as bone marrow fibrosis and extramedullary hematopoiesis. 2 Most recently, JAK2 5-7 and MPL 8-10 mutations were described in approximately 50% and 10% of patients with PMF, respectively. However, the precise pathogenetic contribution of these mutations is currently not well defined.PMF usually affects subjects with advanced age, 11 but young people are not necessarily spared. 12 Reported median survivals are variable and in the range of 4-7 years. 13,14 Previous studies have identified several adverse prognostic factors for survival, including advanced age, [15][16][17][18][19] marked anemia, 13-22 leukocytosis or leukopenia, 14,16,18,22 abnormal karyotype, 18,23-25 constitutional symptoms, 13,14,17,22 and presence of circulating blasts. 13,14,22 Based on some of these variables, several prognostic scoring systems have been proposed. 12,13,18,19,22,26 More recently, the prognostic value of blood CD34 ϩ cell count 27,28 and JAK2 mutational status [29][30][31] has also been evaluated.Current drug therapy for PMF has not been shown to influence survival and is often used for pal...