文章：

1306例原发性骨髓纤维化患者中白血病转化的风险因素及预测模型构建

Leukemic transformation among 1306 patients with primary myelofibrosis: risk factors and development of a predictive model

原文发布日期：2019-01-25

DOI: 10.1038/s41408-019-0175-y

类型: Article

开放获取: 是

英文摘要：

Among 1306 patients with primary myelofibrosis (PMF), we sought to identify risk factors that predicted leukemic transformation (LT) in the first 5 years of disease and also over the course of the disease. 149 (11%) LT were documented; patients who subsequently developed LT (n = 149), compared to those who remained in chronic phase disease (n = 1,157), were more likely to be males (p = 0.02) and display higher circulating blasts (p = 0.03), ASXL1 (p = 0.01), SRSF2 (p = 0.001) and IDH1 (p = 0.02) mutations. Logistic regression analysis identified IDH1, ASXL1 and SRSF2 mutations, very high-risk karyotype, age > 70 years, male sex, circulating blasts ≥ 3%, presence of moderate or severe anemia and constitutional symptoms, as predictors of LT in the first 5 years of diagnosis. Time-to-event Cox analysis confirmed LT prediction for IDH1 mutation (HR 4.3), circulating blasts ≥ 3% (HR 3.3), SRSF2 mutation (HR 3.0), age > 70 years (HR 2.1), ASXL1 mutation (HR 2.0) and presence of moderate or severe anemia (HR 1.9). HR-based risk point allocation resulted in a three-tiered LT risk model: high-risk (LT incidence 57%; HR 39.3, 95% CI 10.8–114), intermediate-risk (LT incidence 17%; HR 4.1, 95% CI 2.4–7.3) and low-risk (LT incidence 8%). The current study provides a highly discriminating LT predictive model for PMF.

摘要翻译： 

在1306例原发性骨髓纤维化（PMF）患者中，我们试图识别在疾病前5年及整个病程中预测白血病转化（LT）的风险因素。共记录到149例（11%）LT发生；与维持在慢性期的患者（n=1157）相比，后续发生LT的患者（n=149）更可能为男性（p=0.02），并表现出更高的外周血原始细胞比例（p=0.03）以及ASXL1（p=0.01）、SRSF2（p=0.001）和IDH1（p=0.02）基因突变。逻辑回归分析确定IDH1、ASXL1和SRSF2突变、极高危核型、年龄＞70岁、男性、外周血原始细胞≥3%、中重度贫血及体质性症状是诊断前5年内预测LT的因素。事件时间 Cox分析证实了以下因素对LT的预测作用：IDH1突变（HR 4.3）、外周血原始细胞≥3%（HR 3.3）、SRSF2突变（HR 3.0）、年龄＞70岁（HR 2.1）、ASXL1突变（HR 2.0）以及中重度贫血（HR 1.9）。基于HR的风险评分分配形成了三级LT风险模型：高风险（LT发生率57%；HR 39.3，95%CI 10.8-114）、中风险（LT发生率17%；HR 4.1，95%CI 2.4-7.3）和低风险（LT发生率8%）。本研究为PMF建立了一个具有高度区分度的LT预测模型。

原文链接：

Leukemic transformation among 1306 patients with primary myelofibrosis: risk factors and development of a predictive model