流式细胞术动态监测微小残留病在非清髓异基因造血干细胞移植治疗急性白血病患者中的意义

Significance of Monitoring Minimal Residual Disease by Flow Cytometry in Acute Leukemia Patients Underwent Nonmyeloablative Allo-HSCT

目的:研究非清髓造血干细胞移植(NST)前后采用流式细胞术(FCM)动态监测微小残留病(MRD),以预测移植后急性白血病(AL)复发的意义,为临床早期干预提供指导。方法:回顾性研究2011年1月至2015年12月在军事医学科学院附属医院血液科行NST的成人AL患者51例,对所有患者移植前骨髓形态学完全缓解(CR)期内,移植前35 d内、移植后1、2、3月内,以后每3月至移植后2年、2年后每6个月内采集骨髓监测MRD。低水平MRD组(A组)共33例(移植后每次检测MRD<0.2%),高水平MRD组(B组)共18例(移植后动态监测MRD,至少1次≥0.2%)。结果:移植后2组2年累计复发率分别为6.1%和50%(P=0.001)。多因素分析表明:移植后M RD≥0.2%是AL移植后复发的独立的高危因素,高水平MRD组复发风险是低水平MRD组的5.84倍(P=0.036)。移植后复发组与未复发组的死亡率分别为81.8%和46.3%(P=0.036)。结论:非清髓异基因造血干细胞移植治疗急性白血病中,采用FCM动态监测MRD是预测移植后早期复发的重要方法,移植后MRD≥0.2%可作为白血病早期复发的预警,以及指导临床早期给予干预措施的重要依据。

Objective： To explore the value of dynamically monitoring minimal residual disease （MRD） by flow cytometry before and after non-myeloablative allo-HSCT （NST） for prediction of acute leukemia （AL） relapse after transplantation. Methods： The clinical data of 51 AL patients underwent NST were analyzed retrospectively in Department of Hematology of Affiliated Hospital of Academy of Military Medical Sciences from January 2011 to December 2015. All AL patients achieved the morphologic complete remission of bone marrow before transplantation. The bone marrow samples were collected for monitoring of MRD within 35 days before transplant, every month till 3 months after transplant, every 3 months till 24 months after transplant, and then every 6 months after 2 years of transplant. According to the MRD cutoff value of 0.2%, the AL patients were divided into high level MRD group （ 18 cases） which was defined as MRD I〉0.2% after transplantantion at least for 1 time, and low level MRD group （33 cases） which was defined as MRD 〈0.2% after transplant all the time. 2 year cumulative relapse rate in 2 groups were compared. Results： Two -year relapse rates were 6.1% and 50% in low-level MRD group and high-level MRD group post NST（P = 0.001 ）respectively. Multivariate analysis indicated that the risk of relapse in high level MRD group was 5.84 times of low level MRD group （ P = 0. 036）. MRD/〉 0.2% post transplant was an independent risk factor for leukemia relapse post NST. The mortality rate was 81.8% and 46.3% （P 〈0.05） in relapse and non-relapse groups respectively. Conclusion： Dynamically monitoring MRD by FCM is a crucial tool for early relapse estimation of acute leukemia in adult patients after allogeneic nonmyeloablative hematopoietic stem cell transplantation. MRD i〉 0. 2 % after transplant can be used as a early valuable evidence for predicting relapse and guiding active medical intervention.