WT1表达对急性白血病异基因造血干细胞移植预后的影响

The effect of WT1expression on the prognosis of allogeneic hematopoietic stem cell transplantation in acute leukemia

目的研究WT1表达水平对急性白血病异基因造血干细胞移植预后的影响及其作为分子学标志来动态监测微小残留病(MRD)的意义。方法回顾性分析2016年1月至2017年12月在浙江大学医学院附属第一医院骨髓移植中心行异基因造血干细胞移植的314例急性白血病患者,男163例,女151例,中位年龄30(9~64)岁,比较初诊时、移植前、移植后WT1表达,通过ROC曲线确定移植前、移植后3个月内及移植后6个月WT1表达量预测复发的临界值分别为1.010%、0.079%、0.375%,根据上述临界值将WT1阳性患者分为低表达组和高表达组,分析移植后总生存(OS)、元病生存(DFS)以及累积复发率(CIR)与WT1表达量之间的关系。结果移植前WT1高表达组的OS、DFS率均低于低表达组[69.2%(9/13)对89.1%(57/64),χ2=4.086,P=0.043;53.8%(7/13)对87.5%(56/64),χ2=9.766,P=0.002],CIR高于低表达组[30.8%(4/13)对7.8%(5/64),P=0.017]。移植后3个月WT1高表达组、低表达组OS、DFS率差异均无统计学意义(P=0.558,P=0.269)。移植后6个月WT1高表达组OS、DFS率均低于低表达组(P=0.049,P=0.035)。多因素分析显示,移植后6个月WT1表达>0.375%是影响DFS的独立危险因素(P=0.022),移植后3个月内及移植后6个月WT1高表达组的复发率与低表达组比较差异元统计学意义(P=0.114,P=0.306)。结论移植前及移植后WT1高表达是影响预后的不利因素,将WT1作为急性白血病患者造血干细胞移植的推荐指标和移植后MRD的监测手段存在临床实用价值。

Objective To study the effect of WTI expression on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT)in acute leukemia (AL)and its significance as molecular marker to dynamically monitor minimal residual disease (MRD).Methods Retrospectively analyzed those AL patients who underwent allo-HSCT in the First Hospital Affiliated to Zhejiang University School of Medicine during Jan 2016 to Dec 2017,a total number of 314 cases,163 males and 151 females,median age was 30(9-64)years old.Comparing the difference of WT1 expression at diagnosed,pre-HSCT and after HSCT.Using the receiver operating characteristic (ROC)curve to determine the WT1threshold at different time so as to predict relapse.The threshold of WT1 expression before transplantation was 1.010%,within 3 months after HSCT was 0.079%and 6 months after HSCT was 0.375%.According to these thresholds,WT1 positive patients were divided into low expression groups and high expression groups.Analyzed the relationship between overall survival (OS),disease-free survival (DFS),cumulative incidence of relapse (CIR)and WT1 expression.Results The OS and DFS of high expression group pre-HSCT were lower than low expression group E69.2%(9/13)vs 89.1%(57/64),χ2= 4.086,P=0.043;53.8%(7/13)vs 87.5%(56/64),χ2=9.766,P=0.002],CIR was higher than low expression group [30.8%(4/13)vs 7.8%(5/64),P =0.017].There was no significant difference of OS and DFS between high expression and low expression group of 3 months after HSCT (P =0.558,P =0.269). The OS and DFS of high expression group of 6months after transplantation were both lower than low expression group (P =0.049,P =0.035).Multivariate analysis showed that WT1>0.375%when 6 months after transplantation was the only independent prognostic factor for shorter DFS (P =0.022).There was no statistically significant difference in CIR between the high-expression group and the low-expression group 3 months after transplantation and 6months after transplantation (P=0.114,P=0.306).Conclusion High expression of WT1before and after HSCT was an adverse prognosis factor.It is of clinical practical value to use WT1 as a transplant recommendation index for patients with acute leukemia and as a marker to monitor MRD dynamically.