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多参数流式细胞术对急性髓系白血病微小残留病变与疾病复发的监测
引用本文:万岁桂,赵弘,孙雪静,贺景娟,苏力,徐娟.多参数流式细胞术对急性髓系白血病微小残留病变与疾病复发的监测[J].中国实验血液学杂志,2009,17(3):557-562.
作者姓名:万岁桂  赵弘  孙雪静  贺景娟  苏力  徐娟
作者单位:首都医科大学宣武医院血液科,北京,100053
摘    要:本研究探讨微小残留病变(MRD)检测对急性髓系白血病(AML)治疗后疾病复发的预测作用。采用多参数流式细胞术(multiparameter flow cytometry,MPFC)分析AML治疗前白血病相关免疫表型(1eukemiaassociatedimmunphenotypes,LAIP),检测诱导和巩固治疗后MRD(Post—IndMRD,Post—ConsMRD)的水平。结果表明:122例初发AML患者中(AML—M3除外),有115例(94.3%)存在明确的LAIP,其中存在单一LAIP类型的患者15例(13.0%),存在2个或2个以上LAIP类型的患者100例(87.0%)。抗原跨系列表达者占40.9%,抗原跨阶段表达者、抗原过度表达者和抗原表达减弱或缺失者分别占20.9%、27.0%和34.8%。对41例诱导化疗后达完全缓解并进行2个疗程以上巩固治疗的AML患者MRD监测显示,Post—IndMRD+的24例中,巩固治疗后18例复发;Post—IndMRD-者17例中,巩固治疗后5例复发;Post—IndMRD-患者和Post—IndMRD+患者的平均无病生存时间(RFS)分别为43.05±6.25个月和12.48±1.69月(P〈0.0001)。Post—ConsMRD+者18例均复发;Post—ConsMRD一者23例中仅5例复发。Post—ConsMRD-患者和Post—ConsMRD+患者的平均RFS分别为39.32±5.44月,9.72±1.51个月(P〈0.0001)。结论:Post—IndMRD水平和Post—ConsMRD水平均与AML患者的RFS密切相关,可作为AML治疗依赖的预后因素。

关 键 词:急性髓系白血病  白血病相关免疫表型  多参数流式细胞术  微小残留病变  预后

Prognosticating Relapse Risk Based on Multiparameter Flow Cytometric Assessment of Minimal Residual Disease in Patients with Acute Myeloid Leukemia
WAN Sui-Gui,ZHAO Hong,SUN Xue-Jing,HE Jing-Juan,SU Li,XU Juan.Prognosticating Relapse Risk Based on Multiparameter Flow Cytometric Assessment of Minimal Residual Disease in Patients with Acute Myeloid Leukemia[J].Journal of Experimental Hematology,2009,17(3):557-562.
Authors:WAN Sui-Gui  ZHAO Hong  SUN Xue-Jing  HE Jing-Juan  SU Li  XU Juan
Institution:( Department of Hematology, Xuanwu Hospital, Capital University of Medical Sciences, Beijing, 100053, China)
Abstract:The objective of this study was to investigate the prognosticating value of multiparameter flow cytometry in detection of minimal residual disease (MRD) and relapse risk of patients with acute myeloid leukemia (AML). Multiparameter flow cytometry (MPFC) analysis was used to detect the leukemia-associated aberrant immunophenotype (LAIP) of the pretreated patients with AML and to assess the levels of MRD after remission induction (Post-Ind MRD) and consolidation therapy ( Post-Cons MRD). The results showed that the definite LAIP could be detected in 94.3 % of the patients (115/122) with AML (except APL). Among 115 cases only one LAIP was identified in 15 cases ( 13.0% ), but two or more LAIP were identified in other 100 cases ( 87, 0% ). The most frequent LAIP identified was cross-lineage antigen expression(40.9% ). The percentages of asynchronous antigen expression, antigen over-expression and antigen lack expression were 20.9%, 27.0% and 34.8% respectively. MRD frequency was monitored in 41 AML patients with CR after remission induction chemotherapy and 2 or more cycles of consolidation chemotherapy. 24 patients were Post-Ind MRD+ and 17 patients were Post-Ind MRD -. The percentages of relapse in cases of Post-Ind MRD+ and Post-Ind MRD - were 75.0% ( 18/24 ) and 29.4% ( 5/17 ) respectively after consolidation chemotherapy. The relapse free survival (RFS) times of the patients with Post-Ind MRD+ and Post-Ind MRD- were 49.06± 6.53 months and 11.92 ± 1.64 months (p 〈 0. 0001 ) respectively. 18 patients were Post-Cons MRD+ and 23 patients were Post-Cons MRD-. The percentages of relapse in cases of Post-Cons MRD + and Post-Cons MRD- patients were 100% ( 18/18 ) and 21.7% (5/23) respectively after consolidation chemotherapy. The RFS times of the patients with Post-Cons MRD +and Post-Cons MRD - were 41.74 ± 5.52 months and 10.06±1.72 months (p 〈 0. 0001 ) respectively. It is concluded that the levels of post-Ind MRD and post-Cons MRD identified in the patients with AML was highly associated with their RFS. The detection of MRD by MPFC provides prognostic information in AML patients.
Keywords:acute myeloid leukemia  leukemia-associated immunophenotype  multiparameter flow cytometry  minimal residual disease  prognosis
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