多参数流式细胞术检测白血病微小残留在急性髓细胞性白血病诱导治疗阶段的临床意义  

Clinical significance of minimal residual disease detection by multi-parameter flow cytometry during induction therapy in acute myeloid leukemia

作　　者：田孝鹏[1] 孙爱宁[1] 李渭阳[1] 朱明清[1] 沈文红[1] 尹佳[1] 彭浩[1] 吴德沛[1] 

机构地区：[1]苏州大学附属第一医院血液科,江苏省血液研究所,卫生部血栓与止血重点实验室,江苏苏州215006

出　　处：《苏州大学学报（医学版）》2012年第3期376-380,399,共6页Suzhou University Journal of Medical Science

基　　金：江苏高校优势学科建设工程资助项目(苏政办发[2011]6号)

摘　　要：目的研究急性髓细胞性白血病(AML)患者第1次诱导治疗后和第1次完全缓解时多参数流式细胞术(MFC)监测白血病微小残留(MRD)对预测疾病复发和判断预后的作用,探讨MRD监测的临床价值。方法回顾性研究246例成人AML患者治疗及MRD的监测数据,分析MRD水平与疾病复发和预后的相关性。结果 (1)第1次标准方案诱导化疗后,ROC分析确定MRD阈值为1.5×10-2,Cox比例风险模型显示相对于MRD阴性组,MRD阳性组的相对危险度(RR)为2.41。在缓解后采用联合方案化疗的患者中,MRD阳性组和MRD阴性组的中位无复发生存时间(RFS)分别为(19.45±3.74)个月和(56.46±4.28)个月,中位总生存时间(OS)分别为(29.37±4.47)个月和(77.97±4.30)个月,差异均有高度统计学意义(均P<0.01)。(2)第1次达完全缓解时,ROC分析所确定的MRD阈值为3.0×10-3,Cox比例风险模型显示相对于MRD阴性组,MRD阳性组的RR值为1.75。缓解后采取联合化疗,MRD阳性组和MRD阴性组患者的中位RFS分别为(28.36±3.40)个月和(55.70±4.32)个月,中位OS分别为(39.30±3.73)个月和(70.19±4.34)个月,差异均有高度统计学意义(均P<0.01)。结论 MFC检测MRD在AML诱导治疗过程中具有预测复发、判断预后的价值。Objective To determine whether the minimal residual disease （MRD） in acute myeloid leu- kemia （AML） monitored by flow eytometry after the initial induction chemotherapy and the first CR could help in predicting the relapse free survival （RFS） and overall survival （OS）, thus to have clinical significance to predict prognosis of these patients. Methods A total of 246 adult AML patients were recruited in this retro- spective research to assess the correlation of between MRD and RFS or OS. Results The cut-off value （ 1.5×10 -2 ） was worked out from ROC curve after the first standard induction chemotherapy, with which the AML patients were separated into two groups. Cox proportional hazards model analysis showed that the relative risk （RR） in the positivity group was 2.41 times compared with that in the negativity group （1.45-4.03, 95% CI）. The clinical outcome of positivity and negativity groups with continuing chemotherapy was significantly different in terms of median RFS [ （56. 46±4.28） months vs （ 19.45±3.74） months, P 〈 0. 01 ] and OS[ （77.97±4.30） months vs （29.37±4.47） months,P 〈 0.01]. Similarly, the cut-off value was 3.0×10-3 after the first CR. Cox proportional hazard model analysis showed that the RR in the positivity group was 1.75 times compared with MRD in the negativity group （1.11-2.77, 95% CI）. The clinical outcome of positivity and negativity groups with continuing chemotherapies was significantly different in terms of RFS [ （28.36±3.40） months vs （55.70±4.32） months, P 〈 0.01 ] and OS [ （39.30±3.73） months vs （70. 19±4.34） mouths, P 〈 0.01 ] as well. Conclusion MRD monitoring of acute myeloid leukemia with MFC during induc- tion chemotherapy might help to predict relapse and prognosis.

关 键 词：急性髓细胞性白血病 多参数流式细胞术 微小残留 复发 预后 

分 类 号：R733.71[医药卫生—肿瘤]