外周血幼淋巴细胞比例在慢性淋巴细胞白血病中的预后价值研究  

Prognostic value of prolymphocyte percentage in chronic lymphocytic leukemia

作　　者：张昭亮 周家豪 邢凌霄 王琰[1,2] 邱彤璐 王蓉 王慧[1,2] 范磊 朱华渊[1,2] 缪祎 李建勇[1,2] Zhang Zhaoliang;Zhou Jiahao;Xing Lingxiao;Wang Yan;Qiu Tonglu;Wang Rong;Wang Hui;Fan Lei;Zhu Huayuan;Miao Yi;Li Jianyong(Department of Hematology,the First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing 210029,China;Lymphoma Center,The First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院,江苏省人民医院血液科,南京210029 [2]南京医科大学第一附属医院,江苏省人民医院淋巴瘤中心,南京210029

出　　处：《中华血液学杂志》2025年第2期140-146,共7页Chinese Journal of Hematology

基　　金：国家自然科学基金(82100207);江苏省科教能力提升工程(ZDXK202209)。

摘　　要：目的探讨幼淋巴细胞比例对慢性淋巴细胞白血病(CLL)患者预后的影响。方法研究纳入了2011年10月至2020年12月在南京医科大学第一附属医院确诊为CLL的300例患者,分析外周血幼淋巴细胞比例与其他基线特征的相关性,然后通过X-tile分析得到外周血幼淋巴细胞比例的最佳临界值,并通过后续的生存分析和预后模型构建验证其预后价值。结果共300例符合条件的CLL患者纳入研究,其中有50例CLL患者接受布鲁顿酪氨酸激酶抑制剂(BTKi)作为一线治疗。外周血幼淋巴细胞比例较高的患者多为晚期(P=0.010)、β2微球蛋白较高(P<0.001)、免疫球蛋白重链可变区(IGHV)未突变(P<0.001)和伴有TP53异常(P=0.004)。外周血幼淋巴细胞比例的最佳临界值为1%。外周血幼淋巴细胞比例高于1%的患者的无治疗生存(TFS)期(P<0.001)和总生存期(P=0.007)短。在多因素分析中,外周血幼淋巴细胞比例>1%对TFS的独立预测价值尚不明确,但表现出一定的趋势[HR=1.405(95%CI 0.971~2.032),P=0.071]。将CLL国际预后指数(CLL-IPI)和外周血幼淋巴细胞比例结合构建的新预后模型比CLL-IPI有更好的区分度[曲线下面积(AUC):0.778对0.637,P=0.006]。此外,外周血幼淋巴细胞比例>1%的患者在接受布鲁顿酪氨酸激酶抑制剂治疗后无进展生存期更短(P=0.038)。结论外周血幼淋巴细胞比例与治疗前CLL患者的基线特征及预后相关。ObjectiveTo investigate the impact of peripheral blood prolymphocyte percentage on the prognosis of patients with chronic lymphocytic leukemia(CLL).MethodsThis study included 300 patients diagnosed with CLL at the Department of Hematology of Jiangsu Provincial People’s Hospital from October 2011 to December 2020.The association between prolymphocyte percentage and other parameters was analyzed,and the optimal cutoff prolymphocyte percentage was determined by X-tile analysis.Further survival analysis and prognostic model construction were used to validate the predictive value of prolymphocyte percentage.ResultsOf the 300 eligible patients with CLL who were enrolled,50 received Bruton tyrosine kinase inhibitors(BTKi)as first-line treatment.The group with higher prolymphocyte percentage comprised more patients in the advanced stages(P=0.010)and had higherβ2-microglobulin(P<0.001),unmutated immunoglobulin heavy-chain variable region gene(P<0.001),and TP53 aberration(P=0.004).The optimal cutoff percentage of prolymphocytes was 1%.Patients with a prolymphocyte percentage>1%had significantly shorter treatment-free survival(TFS)(P<0.001)and overall survival time(P=0.007)than patients with a prolymphocyte percentage≤1%.On multivariate analysis,prolymphocyte percentage>1%tended to have an independent prognostic value for TFS[HR=1.405(95%CI 0.971~2.032),P=0.071].Compared with the nomogram of CLL international prognostic index(CLL-IPI)alone,the nomogram of CLL-IPI combined with prolymphocyte percentage showed better discrimination(area under the curve:0.778 vs.0.637;P=0.006).In addition,patients with a prolymphocyte percentage>1%were more likely to progress after BTKi treatment(P=0.038).ConclusionPeripheral blood prolymphocyte percentage was associated with various clinical and biological parameters and prognosis among patients with treatment-naive CLL.

关 键 词：白血病 淋巴细胞 慢性 B细胞 幼淋巴细胞 布鲁顿酪氨酸激酶抑制剂 

分 类 号：R733.7[医药卫生—肿瘤]