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• W2912302259 abstract "Abstract Current prognostic scoring systems are not able to easily integrate clinical, histological and molecular data in primary myelofibrosis (PMF) as they required additional information, mainly concerning non-driver mutations, which are available only in a very limited number of research laboratories. The present multicenter study developed a simple method to integrate, at diagnosis, the prognostic information from two well-defined prognostic scoring systems [IPSS and bone marrow fibrosis grade (GBMF)] with the molecular status (MS) concerning the so-called driver mutations to obtain an overall prognostic stratification of PMF patients applicable worldwide. The study included 401 PMF patients who were diagnosed at three Italian Hematological Centers (Milan, Monza, and Bologna) between November 1983 and December 2016 and were followed up for a minimum of 12 months. Follow-up information was updated in December 2017. An integrated score (ISC) was developed based on the sum of the scores attributed to the following variables: IPSS risk categories (low risk = 0 point; intermediate-1 risk = 1 point; intermediate-2 and high risk = 2 points), GBMF (pre-fibrotic stage = 0 point; overt fibrotic stage = 1 point), and MS (CALR type 1 = 0 point; CALR type 2 or other / JAK2V617F / MPL = 1 point; triple-negative = 3 points). An ISC ranging from 0 to 6 was obtained using the following formula: ISC = IPSS + GBMF score + MS score. Based on the ISC results, patients were divided into four prognostic categories: ISC-low risk, score = 0-1 (126 patients); ISC-intermediate-1 risk, score = 2 (142 patients); ISC-intermediate-2 risk, score = 3 (70 patients); and ISC-high risk, score = 4-6 (63 patients). Considering patients with an ISC-low risk as the reference group, the odds of death was 3.5 times higher (95% CI, 1.7-7.0) for ISC-intermediate-1 risk, 5.6 times higher (95% CI, 2.6-12.1) for ISC-intermediate-2 risk, and 10.5 times higher (95% CI, 4.8-22.6) for ISC-high risk patients. Interestingly, the ISC was significantly associated (p<0.004) with constitutional symptoms, splenomegaly, and transfusion need, and a higher frequency of cytoreductive therapy. In addition, median time from diagnosis to the development of an index event (including thrombotic events and leukemic evolution) was shorter in ISC-high risk patients than in ISC-low risk patients: 2.8 vs. 6.8 years for thrombotic events, and 3.5 vs. 4.8 years for leukemic evolution. As reported in Figure 1, the median overall survival (Kaplan-Meier estimate) was 11.9 years in ISC-intermediate-1 risk, 8.8 years in ISC-intermediate-2 risk, and 6.4 years in ISC-high risk patients (log-rank test <0.0001). The results were confirmed using the multivariate Cox model: the Hazard Ratio (HR) for death using the ISC-low risk group as reference was 4.3 (95% CI, 2.2-8.3) for the ISC-intermediate-1 risk group, 7.0 (95% CI, 3.5-14.0) for the ISC-intermediate-2 risk group, and 13.9 (95% CI, 7.1-27.3) for the ISC-high risk group. When patients were instead stratified according to the IPSS, the median overall survival was 10.8 years in IPSS-intermediate-1 risk, 6.9 years in IPSS-intermediate-2 risk, and only 4 years in IPSS-high risk patients. The HR for death was 13.0-times higher for intermediate-2 risk and 35.3-times higher for high risk than for the low IPSS risk categories. Accordingly, these results suggest that the prognostic stratification of risk according to the IPSS can be modulated by applying the ISC score, thereby preventing the overestimation of the real risk of death. The present study had two main limitations related to its retrospective nature and the inability to evaluate the impact of new drugs such as JAK1/2 inhibitors on the natural history of this disease, mainly because of the wide range of the time of diagnosis. Therefore, additional prospective studies involving other Hematological Centers and a larger number of patients are needed to draw definite conclusions. In conclusion, the comprehensive approach proposed in the present study is an improved tool for predicting mortality in PMF patients. The proposed model will allow clinicians to evaluate the mutual interactions between IPSS, GBMF, and MS to identify high-risk patients with a poor prognosis who may benefit from more aggressive treatments. In addition, the present model is applicable worldwide in the real-life clinical practice. Figure 1. Figure 1. Disclosures Palandri: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cortelezzi:roche: Consultancy; novartis: Consultancy; abbvie: Consultancy; janssen: Consultancy." @default.
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• W2912302259 date "2018-11-29" @default.
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• W2912302259 title "Integrating Clinical, Morphological, and Molecular Data to Assess Prognosis in Patients with Primary Myelofibrosis: A Practical Approach" @default.
• W2912302259 doi "https://doi.org/10.1182/blood-2018-99-114933" @default.
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