FLT3-ITD突变对接受异基因造血干细胞移植的急性髓系白血病患者预后影响的Meta分析

发布时间：2018-02-12 09:21

本文关键词： FLT3-ITD基因突变急性髓系白血病异基因造血干细胞移植预后 Meta分析　出处：《山西医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:FLT3-ITD突变作为AML患者预后不良因素已成为共识,然而目前对于FLT3-ITD突变对接受异基因造血干细胞移植的AML患者预后影响仍有争议,本课题采用Meta分析的方法评价FLT3-ITD突变对接受异基因造血干细胞移植的AML患者预后的影响。方法:以“FLT3”和“hematopoietic transplantation”或“FLT3”和“allogeneic transplantation”为检索词,检索Pubmed、Cochrane、Highwire数据库,以“FLT3”和“造血干细胞移植”或“FLT3”和“异基因移植”为检索主题词,检索相关期刊论文、万方数据库,检索所有收录的关于FLT3-ITD突变与接受异基因造血干细胞移植的AML患者预后关系的文献,检索年限均为从建库至2016年10月31日。以预后相关指标无病生存率、总生存率、复发率、非复发死亡率为评价指标。采用RevMan5.3软件进行Meta分析。结果:共纳入10篇研究,合计1589例患者,其中FLT3-ITD基因突变(FLT3-ITD+)患者465例,FLT3-ITD无突变组(FLT3-ITD-)AML患者1124例。其中5篇研究包含正常染色体核型AML(NK-AML)患者,共计834例患者,其中FLT3-ITD+患者291例,FLT3-ITD-患者543例。Meta分析结果显示:在所有入组AML患者中,FLT3-ITD+与FLT3-ITD-接受异基因造血干细胞移植的AML患者无病生存率(DFS)的风险比(HR)为1.36(95%CI:1.25~1.48,P0.00001);总生存率(OS)的风险比(HR)为1.34(95%CI:1.22~1.46,P0.00001);复发率(RR)的风险比(HR)为1.64(95%CI:1.48~1.83,P0.00001),差异均有统计学意义,提示FLT3-ITD突变为接受异基因造血干细胞移植的AML预后的危险因素;非复发死亡率(NRM)的风险比(HR)为0.80(95%CI:0.37~1.7,P=0.59),差异无统计学意义。在NK-AML患者中,FLT3-ITD+与FLT3-ITD-的接受异基因造血干细胞移植的AML患者无病生存期率(DFS)的风险比(HR)为1.36(95%CI:1.21~1.52,P0.00001);总生存率(OS)的风险比(HR)为1.34(95%CI:1.19~1.52,P0.00001);复发率(RR)的风险比(HR)为1.61(95%CI:1.40~1.85,P0.00001),差异均有统计学意义,提示FLT3-ITD突变为接受异基因造血干细胞移植的NK-AML患者预后的危险因素。结论:根据Meta分析结果,对于所有入组AML和NK-AML亚组患者,FLT3-ITD突变为接受异基因造血干细胞移植的AML患者无病生存率、总生存率和复发率的危险因素;对于所有入组AML患者,FLT3-ITD对接受异基因造血干细胞移植的AML患者非复发死亡率无明显影响。该研究结果提示FLT3-ITD突变为接受异基因造血干细胞移植的AML患者的一个预后不良因素。由于纳入文献数量、质量等差异,还需进一步研究。
[Abstract]:Objective it has been agreed that the FLT3-ITD mutation is a poor prognostic factor in patients with AML. However, there is still controversy about the effect of FLT3-ITD mutation on the prognosis of AML patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In this study, Meta analysis was used to evaluate the effect of FLT3-ITD mutation on the prognosis of AML patients undergoing allogeneic hematopoietic stem cell transplantation. Methods: using "FLT3" and "hematopoietic transplantation" or "FLT3" and "allogeneic transplantation" as the key words, the Pubmedan Cochrane High wire database was searched. "FLT3" and "Hematopoietic stem cell transplantation" or "FLT3" and "allogeneic transplantation" were used to search the full text database of Chinese periodicals and Wanfang database. All the literatures about the relationship between FLT3-ITD mutation and the prognosis of AML patients undergoing allogeneic hematopoietic stem cell transplantation were searched. The searching period was from the establishment of the library to October 31st 2016. The disease-free survival rate, overall survival rate and recurrence rate were determined by the prognostic markers, such as disease-free survival rate, overall survival rate and recurrence rate. RevMan5.3 software was used for Meta analysis. Results: a total of 10 studies were conducted, and 1 589 patients were included in the study. There were 465 patients with FLT3-ITD gene mutation FLT3-ITD and 1124 patients with FLT3-ITD-AML without FLT3-ITD mutation. Among 291 FLT3-ITD patients with FLT3-ITD- 543 patients with FLT3-ITD-, the results of Meta-analysis showed that the risk ratio of FLT3-ITD and FLT3-ITD- AML patients receiving allogeneic hematopoietic stem cell transplantation (AML) was 1.36 卤95% CI 1.251.48P0.00001; the overall survival rate was higher than that of OS). The risk ratio of the recurrence rate (RR) is 1.64% 95% CI: 1.48% 1.88% 1.83% P 0.00001%, the difference is statistically significant. The results suggest that FLT3-ITD mutation is a risk factor for the prognosis of AML after allogeneic hematopoietic stem cell transplantation (HSCT). There was no significant difference in the risk of NK-AML patients with FLT3-ITD and FLT3-ITD- in AML patients receiving allogeneic hematopoietic stem cell transplantation. The risk ratio of FLT3-ITD and FLT3-ITD- was 1.3695 CI: 1.21% 1.21% 1.21% (P 0.00001); the risk of overall survival in patients with NK-AML was 1.3695% CI: 1.21% 1.21% 1.21% (P 0.00001); the risk of overall survival in patients with AML receiving allogeneic hematopoietic stem cell transplantation was 1.3695 CI: 1.21% 1.21%, P 0.00001; overall survival rate of AML patients receiving allogeneic hematopoietic stem cell transplantation (FLT3-ITD-). Compared with HR1.34 / 95 CI: 1.19 / 1.52 / P 0.00001; the risk of recurrence rate / RR is 1.61/ 95 / 1.401.85 / P 0.00001, respectively. The difference is statistically significant. The results suggest that FLT3-ITD mutation is a risk factor for the prognosis of NK-AML patients receiving allogeneic hematopoietic stem cell transplantation. Conclusion: according to the results of Meta analysis, The risk factors of disease-free survival, overall survival rate and recurrence rate of AML patients undergoing allogeneic hematopoietic stem cell transplantation with FLT3-ITD mutation in all subgroups of AML and NK-AML. FLT3-ITD had no significant effect on the non-recurrence mortality of AML patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) for all AML patients. The results of this study suggest that FLT3-ITD mutation is a preconditioning of AML patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Due to the number of documents included, The difference in quality needs further study.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.71

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