Carobbio Alessandra, Antonioli Elisabetta, Guglielmelli Paola, Vannucchi Alessandro M, Delaini Federica, Guerini Vittoria, Finazzi Guido, Rambaldi Alessandro, Barbui Tiziano
Hematology Department, Ospedali Riuniti di Bergamo, Bergamo, Italy.
J Clin Oncol. 2008 Jun 1;26(16):2732-6. doi: 10.1200/JCO.2007.15.3569. Epub 2008 Apr 28.
Established risk factors for thrombosis in essential thrombocythemia (ET) include age and previous vascular events. We aimed to refine this risk stratification by adding baseline leukocytosis.
We enrolled 657 patients with ET followed for a median of 4.5 years who developed 72 major thrombosis. Cox proportional hazard model was performed to analyze the thrombotic risk and to discriminate ET patients with or without thrombosis, multivariable C statistic index was used. We searched for leukocytes cutoff with the best sensitivity and specificity by a receiver operating characteristic curve.
Results confirmed that age and prior events are independent risk factors for thrombosis and showed a gradient between baseline leukocytosis and thrombosis. On the contrary, no significant association was found either for JAK2(V617F) allele burden and for other laboratory parameters, including platelet number. In the model with conventional risk factors alone, C statistic ratio for total thrombosis was 0.63 and when leukocytosis was added, the change was small (C = 0.67). In contrast, in younger and asymptomatic patients (low-risk category), C statistic value indicated an high risk for thrombosis in patients with leukocytosis, similar to that calculated in conventionally defined high-risk group (C = 0.65). The best leukocyte cutoff values for predicting the events was found to be 9.4 (x 10(9)/L).
We suggest to include baseline leukocytosis in the risk stratification of ET patients enrolled in clinical trials.
真性红细胞增多症(ET)中已确定的血栓形成风险因素包括年龄和既往血管事件。我们旨在通过增加基线白细胞增多症来完善这种风险分层。
我们纳入了657例ET患者,随访时间中位数为4.5年,其中发生了72例主要血栓形成事件。采用Cox比例风险模型分析血栓形成风险,并区分有或无血栓形成的ET患者,使用多变量C统计指数。通过受试者工作特征曲线寻找具有最佳敏感性和特异性的白细胞临界值。
结果证实年龄和既往事件是血栓形成的独立风险因素,并显示基线白细胞增多症与血栓形成之间存在梯度关系。相反,未发现JAK2(V617F)等位基因负荷与包括血小板计数在内的其他实验室参数之间存在显著关联。在仅包含传统风险因素的模型中,总血栓形成的C统计比率为0.63,添加白细胞增多症后变化较小(C = 0.67)。相比之下,在年轻和无症状患者(低风险类别)中,C统计值表明白细胞增多症患者的血栓形成风险较高,与传统定义的高风险组计算值相似(C = 0.65)。发现预测这些事件的最佳白细胞临界值为9.4(×10⁹/L)。
我们建议在参与临床试验的ET患者的风险分层中纳入基线白细胞增多症。