微小残留病变检测在急性高危白血病异基因造血干细胞移植中的意义

目的 分析急性白血病(AL)高危患者异基因造血干细胞移植(allo-HSCT)前后微小残留病变(MRD)水平与移植后预后的关系.方法 采用以CD45/SS设门的4色或5色荧光标记多参数流式细胞术(MFC)动态检测90例高危AL患者allo-HSCT前第30天、移植后第30、60、100天和6、9、12个月的MRD水平,以0.1％为界,将患者分为MRD高水平组(≥0.1％)和低水平组(＜0.1％),其中高水平组根据移植后是否干预治疗分为两组,回顾性分析MRD水平与预后的关系.结果 移植前MRD水平与移植后预后无明显关系,移植后第60、100天MRD高水平组患者移植后复发率明显高于低水平组.移植后第100天,MRD高水平干预组、MRD高水平未干预组、MRD低水平组1年无复发生存率(RFS)分别为100％、60.87％和91.30％,3年RFS分别为85.71％、44.72％和68.48％,组间差异均有统计学意义(均P＜0.05).复发患者首次检出MRD高水平的时间比临床诊断复发提前了2.5(1.0 ～26.0)个月.移植后第100天,30例MRD高水平组患者中,7例患者及时接受干预治疗后均未复发,而另外23例未接受干预治疗的患者中11例出现复发(P＜0.05).结论 多参数流式细胞术动态监测高危AL患者移植后MRD可以有效评估其临床预后,并可根据移植后第100天MRD进行危险分层,MRD≥0.1％的患者预后较差,及时进行有效的干预可以明显降低其复发率,增加长期生存率.

Detecting minimal residual disease status in allogeneic hematopoietic stem cell transplantation of patients with high-risk acute leukemia

Objective To explore the relationship between minimal residual disease (MRD) and the outcome of patients with high-risk acute leukemia (AL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT).Methods By 4/5-color multi-parameter flow cytometry (MFC,CD45/SSC gating) for detecting MRD at pre- (day-30) and post-transplant( day + 30,+ 60,+ 100,6 months,9 months and 12 months),the investigators retrospectively analyzed the MRD levels and the prognosis of 90high-risk patients.According to the MRD cutoff value of 0.1％,the low-level and high-level groups were defined.In the high-level group,the patients were divided into two sub groups according to the subsequent treatment ( intervention therapy group and non-intervention therapy group).Results MRD pre-transplant had no predictive value for the clinical outcome.The patients with high levels of MRD post-transplant ( + 60 d and + 100 d) showed higher relapse rates than those of the low-level group.In addition,regarding MRD +100 d post-transplant,differences were significant among 3 groups (high-level MRD and intervention theray group,high-level MRD and non-intervention therapy group and low-level MRD group)including 1-year relapse-free survival (RFS) ( 100％ vs 60.87％ vs 91.30％,P ＜ 0.05 ) and 3-year RFS (85.71％ vs 44.72％ vs 68.48％,P ＜0.05).The median time from first high level MRD detected to clinical relapse was 2.5 (1 -26) months.In the high level MRD group ( + 100 d post-transplant),7 of 30 patients received intervention therapy without relapse.However another 23 patients had no intervention treatment and 11 of them relapsed latter (P ＜ 0.05 ).Conclusion The MFC-based quantification of MRD post-transplant reveals important prognostic information in patients with high-risk AL.MRD check point at day + 100 (cutoff:0.1％ ) may discriminate different risk populations.Those patients with MRD levels ≥0.1％ should receive early intervention at an early stage and a low tumor burden so as to reduce the relapse rate and boost survival.