多参数流式细胞术动态监测急性髓系白血病微小残留病的临床研究  

Clinical Study on Dynamic Detection of Minimal Residual Disease in Acute Myeloid Leukemia by Multiparameter Flow Cytometry

作　　者：金焱 汪安友[1] 王兴兵[1] 杨会志[1] 刘欣[1] JIN Yan;WANG An-You;WANG Xing-Bing;YANG Hui-Zhi;LIU Xin(Department of Hematology,Anhui Provincial Hospital,Hefei 230001,Anhui Province,China)

机构地区：[1]安徽省立医院血液科,安徽合肥230001

出　　处：《中国实验血液学杂志》2022年第3期737-743,共7页Journal of Experimental Hematology

基　　金：安徽省重点研究与开发计划项目(201904a07020102)。

摘　　要：目的:探讨8色流式细胞术动态监测急性髓系白血病(AML)患者微小残留病(MRD)的预后意义。方法:使用8色流式细胞术对282例初治缓解的AML患者进行MRD动态监测,通过受试者工作特征曲线(ROC)确定预测复发的MRD阈值,分析患者从出现MRD;到临床复发的时间,比较不同MRD变化情况的患者总生存时间(OS)和无复发生存时间(RFS)的差异,对影响MRD;患者复发的相关因素进行单因素和Logistic回归分析。结果:ROC曲线确定预测复发的MFC-MRD阈值为0.105%,MRD;患者复发率明显高于MRD;患者[52.45%(75/143例) vs 35.97%(50/139例),P=0.005]。MRD持续阳性组和阴性转阳性组患者比阳性转阴性组和阴性阳性波动组患者在出现MRD;后更早出现复发(P<0.005)。生存分析结果表明,MRD持续阳性组患者的OS、RFS时间较持续阴性组、阳性转阴性组和阴性阳性波动组患者明显缩短(P<0.005)。MRD阴性转阳性组与持续阳性组患者的OS、RFS比较差异无统计学意义(P>0.005),MRD持续阴性组与MRD阳性转阴性组患者的OS、RFS比较差异亦无统计学意义(P>0.005)。139例MRD;患者中50例复发,单因素和Logistic回归分析表明,随着白细胞水平增加,患者的复发风险增加(95%CI:1.000-1.013,P=0.045),未接受造血干细胞移植患者的复发风险是接受造血干细胞移植患者的9.694倍(95%CI:1.720-54.651,P=0.010),危险度分层高危组患者的复发风险是低危组患者的5.848倍(95%CI:1.418-24.121,P=0.015)。结论:不同MRD变化情况的AML患者预后存在明显差异,无论患者初次缓解时MRD阳性或阴性,治疗后监测MRD动态变化情况更有助于精准指导治疗。Objective: To investigate the prognostic significance of dynamic detection of minimal residual disease(MRD) in patients with acute myeloid leukemia(AML) by 8-color flow cytometry. Methods: MRD of 282 AML patients who achieved remission after initial therapy was detected by 8-color flow cytometry. MRD threshold for predicting r ecurrence was determined by receiver operating characteristic(ROC) curve, and time from MRD-positive to clinical recurrence was analyzed. The differences in overall survival(OS) time and relapse-free survival(RFS) time of patients with different MRD-changes were compared, and the related factors of recurrence in patients with MRD-negative were analyzed by univariate and logistic regression analysis. Results: ROC curve determined that the MFC-MRD threshold for predicting the recurrence of AML was 0.105%, and the recurrence rate of MRD-positive patients was significantly h igher than that of MRD-negative patients [52.45%(75/143 cases) vs 35.97%(50/139 cases), P=0.005]. The patients in M RD persistent positive group and negative to positive group recurred earlier than those in positive to negative group and negative-positive fluctuation group(P<0.005). Survival analysis showed that OS and RFS time of patients with MRD p ersistent positive were significantly shorter than those of patients with MRD persistent negative, positive to negative, and negative-positive fluctuation(P<0.005). There was no significant difference in OS and RFS between MRD negative t o positive group and MRD persistent positive group(P>0.005), either between MRD persistent negative group and MRD p ositive to negative group(P>0.005). Among 139 MRD-negative patients, 50 recurred. Univariate and logistic regression analysis showed that the risk of recurrence increased with the increase of white blood cells level(95%CI: 1.000-1.013,P=0.045). The risk of recurrence in patients without hematopoietic stem cell transplantation(HSCT) was 9.694 timesh igher than that in patients who received HSCT(95%CI: 1.720-54.651, P=0.010), and in

关 键 词：急性髓系白血病 微小残留病 总生存时间 无复发生存时间 复发 

分 类 号：R733.71[医药卫生—肿瘤]