Department of Experimental and Clinical Medicine, CRIMM, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy.
Section of Hematology, Department of Radiological and Hematological Sciences, Catholic University, Rome, Italy.
Blood Cancer J. 2021 Dec 11;11(12):199. doi: 10.1038/s41408-021-00581-6.
Arterial (AT) and venous (VT) thrombotic events are the most common complications in patients with polycythemia vera (PV) and are the leading causes of morbidity and mortality. In this regard, the impact of JAK2V617F variant allele frequency (VAF) is still debated. The purpose of the current study was to analyze the impact of JAK2V617F VAF in the context of other established risk factors for thrombosis in a total of 865 2016 WHO-defined PV patients utilizing two independent cohorts: University of Florence (n = 576) as a training cohort and Policlinico Gemelli, Catholic University, Rome (n = 289) as a validation cohort. In the training cohort VT free-survival was significantly shorter in the presence of a JAK2V617F VAF > 50% (HR 4; p < 0.0001), whereas no difference was found for AT (HR 0.9; p = 0.8). Multivariable analysis identified JAK2V617F VAF > 50% (HR 3.8, p = 0.001) and previous VT (HR 2.2; p = 0.04) as independent risk factors for future VT whereas diabetes (HR 2.4; p = 0.02), hyperlipidemia (HR 2.3; p = 0.01) and previous AT (HR 2; p = 0.04) were independent risk factors for future AT. Similarly, JAK2V617F VAF > 50% (HR 2.4; p = 0.01) and previous VT (HR 2.8; p = 0.005) were confirmed as independent predictors of future VT in the validation cohort. Impact of JAK2V617F VAF > 50% on VT was particularly significant in conventional low-risk patients, both in Florence (HR 10.6, p = 0.005) and Rome cohort (HR 4; p = 0.02). In conclusion, we identified JAK2V617F VAF > 50% as an independent strong predictor of VT, supporting that AT and VT are different entities which might require distinct management.
动脉（AT）和静脉（VT）血栓事件是真性红细胞增多症（PV）患者最常见的并发症，也是发病率和死亡率的主要原因。在这方面，JAK2V617F 变异等位基因频率（VAF）的影响仍存在争议。本研究的目的是利用两个独立的队列（佛罗伦萨大学[576 例]作为训练队列和罗马杰梅利大学天主教大学[289 例]作为验证队列），在总共 865 例 2016 年世卫组织定义的 PV 患者中，分析 JAK2V617F VAF 在其他已建立的血栓形成危险因素背景下的影响。在训练队列中，JAK2V617F VAF>50%时 VT 无复发生存率明显缩短（HR 4；p<0.0001），而 AT 则无差异（HR 0.9；p=0.8）。多变量分析确定 JAK2V617F VAF>50%（HR 3.8，p=0.001）和既往 VT（HR 2.2；p=0.04）是未来 VT 的独立危险因素，而糖尿病（HR 2.4；p=0.02）、高脂血症（HR 2.3；p=0.01）和既往 AT（HR 2；p=0.04）是未来 AT 的独立危险因素。同样，JAK2V617F VAF>50%（HR 2.4；p=0.01）和既往 VT（HR 2.8；p=0.005）在验证队列中被确认为未来 VT 的独立预测因子。在佛罗伦萨（HR 10.6，p=0.005）和罗马队列（HR 4；p=0.02）中，JAK2V617F VAF>50%对 VT 的影响在传统低危患者中尤为显著。总之，我们发现 JAK2V617F VAF>50%是 VT 的一个独立的强预测因子，支持 AT 和 VT 是不同的实体，可能需要不同的治疗。
