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流式细胞术监测微小残留病(MRD)对急性髓系白血病预后意义

发布时间:2018-10-13 10:23
【摘要】:目的:白血病患者完全缓解后复发最主要的根源是骨髓中微小残留病的持续存在。国内外学者大多数选择化疗后某个时间点检测MRD,较少对MRD在化疗过程中的变化趋势进行研究。本研究目的在于动态监测CR后和巩固化疗后多个时间点微小残留病与复发的关系。进一步探讨微小残留病在监测病程的发展、临床疗效评估、判断预后中的价值。方法:回顾性分析青岛大学附属医院2012年9月至2016年12月收治的急性髓细胞白血病(AML)患者(51例),其中男30例(58.8%),女21例(41.2%),中位年龄40岁(14~66岁),其中M1 1例(2%),M2 9例(18%),M3 11例(21%),M4 18例(35%),M5 12例(24%)。对51例急性髓系白血病完全缓解患者平均每3个月(1-6个月)用FCM检测其骨髓MRD,同时检测骨髓细胞形态学的变化。随访至形态学复发或随访终止,平均跟踪随访12个月,得出完全缓解病人的MRD平均值,分析其变化趋势。同时监测CR后和巩固化疗1个疗程和2个疗程后3个不同时间点微小残留与复发的关系。根据AML患者经诱导治疗达CR时的MRD值分为:MRD≤10-4、10-4MRD10-3、10-3≤MRD≤10-2、MRD10-2 4组,评估不同时间点MRD水平在AML患者预后中的价值。MRD10-4为微小残留病阳性标准。结果:51例AML患者经化疗达到CR后测得MRD最大值4.97%,最小值0.0062%,平均值0.57%;巩固治疗1疗程后测得MRD最大值4.72%,最小值0.0053%,平均值0.38%,其中47例AML患者CR后MRD检测呈阳性(10-4)结果,4例AML患者CR后MRD检测出阴性(10-4)的结果。巩固治疗2疗程后测得MRD最大值3.11%,最小值0.0037%,平均值0.21%;巩固化疗第2个疗程后MRD阳性患者中有5例患者MRD由阳性转为阴性,1例由阴性转为阳性。选择不同时间点平均随访12个月(0-24个月)后获得骨髓形态学复发例数:MRD"f10-4组复发1例,复发率1.96%;10-4MRD10-3组复发4例,复发率7.84%;10-3"fMRD"f10-2组复发8例,复发率15.69%;MRD10-2组复发14例,复发率27.45%。用Kaplan-Meier法分析四组的无复发生存期,差异具有统计学意义(P㩳0.05)。MRD"f10-4组,10-4MRD10-3组,10-3"fMRD"f10-2组,MRD10-2组,平均中位无复发生存时间(RFS)分别为23.1个月、14.3个月、9.1个月、3.5个月。结论:1.MRD是治疗过程中监测急性髓系白血病缓解与复发的重要指标之一,以FCM动态监测AML CR后的MRD变化情况,可为个体化治疗及预后提供临床依据。2.FCM动态监测急性髓系白血病CR后MRD的差异较大,不能作为评价临床预后的单一指标。3.通过上述临床研究结果分析,MRD可以作为预后评价的敏感指标。MRD小于10-4复发可能性小,大于10-4提示疾病复发可能性大,且MRD值越小无复发生存期越长。随着巩固化疗次数的增加、治疗时间的延长,骨毮MRD水平总体上呈下降趋势。
[Abstract]:Objective: the primary cause of relapse after complete remission in leukemia patients is the persistence of minimal residual disease in bone marrow. Most scholars at home and abroad choose to detect MRD, at some time point after chemotherapy, and seldom study the change trend of MRD in the course of chemotherapy. The aim of this study was to dynamically monitor the relationship between minimal residual disease and recurrence at multiple time points after CR and consolidation chemotherapy. To further explore the value of minimal residual disease in monitoring the development of disease course, evaluation of clinical efficacy and judgment of prognosis. Methods: a retrospective analysis of 51 patients with acute myeloid leukemia (AML) admitted from September 2012 to December 2016 in the affiliated Hospital of Qingdao University, including 30 males (58.8%) and 21 females (41.2%), with a median age of 40 (1466 years), including 1 case (2%) of M1, 9 cases (18%) of M 2, M3 11 cases (21%), M 4 18 cases (35%), M 5 12 cases (24%). The bone marrow MRD, of 51 patients with complete remission of acute myeloid leukemia was detected by FCM every three months (1-6 months) and the morphologic changes of bone marrow cells were also detected. The mean value of MRD in patients with complete remission was obtained and the trend of change was analyzed. At the same time, the relationship between minimal residual and recurrence at 3 different time points after CR, one course of consolidation chemotherapy and two courses of treatment were monitored. According to the MRD value of AML patients after induction treatment to CR, they were divided into four groups: MRD 鈮,

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