The current retrospective study involving a total of 1607 patients was designed to identify clinical and molecular variables that were predictive of inferior myelofibrosis-free survival (MFS) in WHO-defined essential thrombocythemia (ET), utilizing three independent patient cohorts: University of Florence, Italy (n = 718); Mayo Clinic, USA (n = 479) and Policlinico Gemelli, Catholic University, Rome, Italy (n = 410). The Florence patient cohort was first examined to identify independent risk factors for MFS, which included age > 60 years (HR 2.5, 95% CI 1.3–4.9), male sex (2.1, 1.2–3.9), palpable splenomegaly (2.1, 1.2–3.9), CALR 1/1-like or MPL mutation (3.4, 1.9–6.1) and JAK2V617F variant allele frequency > 35% (4.2, 1.6–10.8). Subsequently, an operational molecular risk category was developed and validated in the other two cohorts from Mayo Clinic and Rome: “high molecular risk” category included patients with JAK2V617F VAF >35%, CALR type 1/1-like or MPL mutations; all other driver mutation profiles were assigned to “low molecular risk” category. The former, compared to the latter molecular risk category, displayed significantly higher risk of fibrotic transformation: Florence cohort with respective fibrotic transformation risk rates of 8% vs. 1.2% at 10 years and 33% vs. 8% at 20 years (p < 0.001; HR 6.1; 95% CI 3.2–11.7); Mayo Cohort, 16% vs. 7% at 10 years and 44% vs. 25% at 20 years (p < 0.001; HR 2.5; 95% CI 1.6–4.1); and Rome cohort 7.8% vs. 4.6% at 10 years and 31.2% vs. 7.1% at 20 years (p = 0.007, HR 2.7; 95% CI 1.3–5.8). The present study provides practically useful risk signals for fibrotic transformation in ET and facilitates identification of patients who require close monitoring and appropriate counseling.

中文翻译：

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原发性血小板增多症纤维化进展的临床和分子预测因子：一项涉及 1607 名患者的多中心研究

目前的回顾性研究共涉及 1607 名患者，旨在确定可预测 WHO 定义的原发性血小板增多症 (ET) 中较差的无骨髓纤维化生存期 (MFS) 的临床和分子变量，利用三个独立的患者队列：佛罗伦萨大学，意大利（n  = 718）；美国梅奥诊所 ( n  = 479) 和意大利罗马天主教大学 Policlinico Gemelli ( n  = 410)。首先检查佛罗伦萨患者队列以确定 MFS 的独立危险因素，其中包括年龄 > 60 岁（HR 2.5, 95% CI 1.3–4.9）、男性（2.1, 1.2–3.9）、可触及的脾肿大（2.1, 1.2– 3.9)、CALR 1/1 样或MPL突变 (3.4, 1.9–6.1) 和JAK2V617F 变异等位基因频率 > 35% (4.2, 1.6–10.8)。随后，在 Mayo Clinic 和罗马的另外两个队列中开发并验证了操作分子风险类别：“高分子风险”类别包括JAK2 V617F VAF >35%、CALR 1/1型样或MPL突变的患者；所有其他驱动突变谱都被分配到“低分子风险”类别。与后一种分子风险类别相比，前者显示出明显更高的纤维化风险：Florence 队列在 10 年和 20 年的纤维化风险分别为 8% vs. 1.2% 和 33% vs. 8% ( p  < 0.001；HR 6.1；95% CI 3.2–11.7)；Mayo Cohort，10 年时分别为 16% 和 7%，20 年时分别为 44% 和 25%（p < 0.001; 人力资源 2.5; 95% CI 1.6–4.1)；和罗马队列 10 年分别为 7.8% 和 4.6%，20 年分别为 31.2% 和 7.1%（p  = 0.007，HR 2.7；95% CI 1.3–5.8）。本研究为 ET 中的纤维化转化提供了实际有用的风险信号，并有助于识别需要密切监测和适当咨询的患者。