Most patients with essential thrombocythemia or primary myelofibrosis that was not associated with a JAK2 or MPL alteration carried a somatic mutation in CALR. The clinical course in these patients was more indolent than that in patients with the JAK2 V617F mutation. (Funded by the MPN Research Foundation and Associazione Italiana per la Ricerca sul Cancro.).

WPSS is a dynamic prognostic scoring system that provides an accurate prediction of survival and risk of leukemic evolution in MDS patients at any time during the course of their disease. This time-dependent system seems particularly useful in lower risk patients and may be used for implementing risk-adapted treatment strategies.

Age older than 65 years, hemoglobin level lower than 100 g/L (10 g/dL), white blood cell count greater than 25 ؋ 10 9 /L, peripheral blood blasts 1% or higher, and constitutional symptoms have been shown to predict poor survival in primary myelofibrosis (PMF) at diagnosis. To investigate whether the acquisition of these factors during follow-up predicts survival, we studied 525 PMF patients regularly followed. All 5 variables had a significant impact on survival when analyzed as time- IntroductionPrimary myelofibrosis (PMF) is a Philadelphia-negative myeloproliferative neoplasm (MPN) whose diagnostic criteria have been recently updated. 1 Among MPNs, PMF has the most heterogeneous clinical presentation, which may encompass anemia, splenomegaly, leukocytosis or leukopenia, thrombocytosis or thrombocytopenia, and constitutional symptoms. The discovery of the activating mutation JAK2 (V617F) in more than 70% of patients with MPNs 2 led to the development of new biochemically selective JAK2 inhibitors. 3 These agents are currently being tested in clinical trials that usually include patients with long disease history.Advanced age, 4-7 anemia, 4-11 red blood cell transfusion need, 12 leukopenia, 8 leukocytosis, 8 thrombocytopenia, 9 peripheral blast count, 4,6 systemic symptoms, 6,10 degree of microvessel density, 13 and cytogenetic abnormalities 5,7,9,[14][15][16] were shown to be associated with poor outcome in patients with PMF. The presence of the JAK2 (V617F) mutation per se does not seem to imply worse survival, 17 although a low JAK2 (V617F) allele burden seems associated with poorer outcome. 18,19 Recently, Cervantes et al 17 on behalf of the International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) developed a prognostic scoring system to estimate survival of PMF patients. This model uses 5 factors (age older than 65 years, hemoglobin level Ͻ 100 g/L [10 g/dL], white blood cell count Ͼ 25 ϫ 10 9 /L, peripheral blood blasts Ն 1%, and presence of constitutional symptoms) to identify 4 risk categories with different survival.Prognostic models for PMF developed so far are based on the evaluation of risk factors present at diagnosis. However, the acquisition of additional risk factors during the disease course may substantially modify the patients' outcome. A dynamic prognostic model that accounts for modifications of the risk profile after diagnosis may prove useful in clinical practice. On behalf of IWG-MRT, first we investigated whether the acquisition anytime during follow-up of one or more of the prognostic factors identified by Cervantes et al 17 predicts survival. Then, a new prognostic score based on a time-dependent risk evaluation was developed: the Dynamic International Prognostic Scoring System (DIPSS) for PMF. MethodsThe study was carried out through an international cooperation on behalf of the IWG-MRT. An ad hoc database was developed for data collection. For personal use only. on May 12, 2018. by guest www.bloodjournal.org From Study designThe Institutional Rev...

Key Points JAK2 (V617F)-mutated essential thrombocythemia and polycythemia vera are different phenotypes in the evolution of a single neoplasm. CALR-mutated essential thrombocythemia is a distinct disease entity not only at the molecular level, but also with respect to clinical outcomes.