背景:Fms样酪氨酸激酶-3,内部串联重复(FLT3-ITD)突变,是急性粒细胞白血病(AML)患者预后较差的已知预测因子。然而,FLT3-ITD突变在成人中的预后意义,非移植患者尚不清楚,因此我们进行了系统评价和荟萃分析来解释这一问题.主要结果是总生存期(OS),而其他结局包括无事件生存(EFS)。
方法:七个数据库(ScienceDirect,Scopus,PubMed,科克伦,SpringerLink,ProQuest,和EBSCOhost)被搜索到2020年8月。选择调查AML在具有FLT3-ITD突变状态的成人中的预后价值的研究。接受移植的患者的研究,排除诊断为急性早幼粒细胞白血病(APL)或继发性AML.选定的研究根据其细胞遗传学谱分为亚组。使用固定效应模型计算汇总风险比(HR)和95%置信区间(CI)。进行了异质性测试,并以I2值表示。提出了森林地块,以促进对结果的理解。通过漏斗图检验分析发表偏倚。
结果:共有10项研究描述了从1999年到2020年进行的研究,符合本研究的纳入标准。9项研究报告了OS,4项研究报告了HR中的EFS。OS的最高HR为6.33(95%CI,2.61-15.33;p<0.001),EFS为3.58(95%CI,1.59-8.05);p=0.002)。,而最低OS为1.33(95%CI,0.88-2.01;P=0.174),EFS为1.29(95%CI,0.75-2.23;P=0.34)。9项研究纳入荟萃分析,HR为OS1.91(95%CI,1.59-2.30,p<0.00001),而4项研究纳入EFS的荟萃分析,HR为1.64(95%CI,1.25-2.14;p=0.0003).
结论:FLT3-ITD突变与成人预后较差相关,非移植AML患者,适用于OS和EFS。
BACKGROUND: Fms-like tyrosine kinase-3, internal tandem duplication (FLT3-ITD) mutation, is a known predictor for worse outcome in patients with acute myeloblastic leukemia (AML). However, the prognostic significance of FLT3-ITD mutation in adult, non-transplant patients is still unclear therefore we conducted a systematic
review and meta-analysis to explain this issue. The main outcome was overall survival (OS), while additional outcomes included event-free survival (EFS).
METHODS: Seven Databases (ScienceDirect, Scopus, PubMed, Cochrane, SpringerLink, ProQuest, and EBSCOhost) were searched up to August 2020. Studies investigating the prognostic value of AML in adults with FLT3-ITD mutational status were selected. Studies which patients had received transplantation, diagnosed with acute promyelocytic leukemia (APL) or secondary AML were excluded. The selected studies were divided into subgroups based on their cytogenetic profile. Summary hazard ratios (HR) and 95% confidence intervals (CI) were calculated using fixed-effects models. Heterogeneity tests were conducted and presented in I2 value. Forest plot was presented to facilitate understanding of the results. Publication bias was analyzed by Funnel Plot test.
RESULTS: A total of ten studies describing research conducted from 1999 to 2020, met the inclusion criteria for this study. Nine studies reported OS and four studies reported EFS in HR. The highest HR for OS is 6.33 (95% CI, 2.61-15.33; p < 0.001), for EFS is 3.58 (95% CI, 1.59 - 8.05); p = 0.002)., while the lowest for OS is 1.33 (95% CI, 0.88-2.01; P = 0.174) and for EFS is 1.29 (95% CI, 0.75-2.23; p = 0.34). Nine studies were included in meta-analysis with HR for OS 1.91 (95% CI, 1.59-2.30, p < 0.00001), whereas 4 studies were included in meta-analysis for EFS with HR 1.64 (95% CI, 1.25-2.14; p = 0.0003).
CONCLUSIONS: FLT3-ITD mutation is associated with worse prognosis in adult, non-transplant patients with AML, both for OS and EFS.