Fms-样酪氨酸激酶 3 内部串联重复突变对非移植成人急性髓系白血病患者预后的意义：系统评价和荟萃分析。
Prognostic Significance of Fms-Like Tyrosine Kinase 3 Internal Tandem Duplication Mutation in Non-Transplant Adult Patients with Acute Myeloblastic Leukemia: A Systematic Review and Meta-Analysis.
机构信息
Department of Internal Medicine Division of Hematology and Medical Oncology, Faculty of Medicine Universitas Indonesia-Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia.
Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Indonesia.
出版信息
Asian Pac J Cancer Prev. 2020 Oct 1;21(10):2827-2836. doi: 10.31557/APJCP.2020.21.10.2827.
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).
CONCLUSION
FLT3-ITD mutation is associated with worse prognosis in adult, non-transplant patients with AML, both for OS and EFS.
背景
Fms 样酪氨酸激酶-3，内部串联重复（FLT3-ITD）突变是急性髓系白血病（AML）患者预后不良的已知预测因子。然而，FLT3-ITD 突变在成人非移植患者中的预后意义尚不清楚，因此我们进行了系统评价和荟萃分析来解释这个问题。主要结局是总生存期（OS），其他结局包括无事件生存期（EFS）。
方法
检索了 7 个数据库（ScienceDirect、Scopus、PubMed、Cochrane、SpringerLink、ProQuest 和 EBSCOhost），截至 2020 年 8 月。选择了研究 AML 中 FLT3-ITD 突变状态对成人患者预后价值的研究。排除了接受移植、诊断为急性早幼粒细胞白血病（APL）或继发性 AML 的患者的研究。根据细胞遗传学特征将选定的研究分为亚组。使用固定效应模型计算汇总风险比（HR）和 95%置信区间（CI）。进行了异质性检验，并以 I2 值表示。森林图用于帮助理解结果。通过漏斗图检验分析发表偏倚。
结果
共有十项研究描述了 1999 年至 2020 年进行的研究，符合本研究的纳入标准。九项研究报告了 HR 中的 OS，四项研究报告了 EFS。OS 的最高 HR 为 6.33（95%CI，2.61-15.33；p<0.001），EFS 的最高 HR 为 3.58（95%CI，1.59-8.05；p=0.002），OS 的最低 HR 为 1.33（95%CI，0.88-2.01；P=0.174），EFS 的最低 HR 为 1.29（95%CI，0.75-2.23；p=0.34）。共有九项研究纳入荟萃分析，OS 的 HR 为 1.91（95%CI，1.59-2.30，p<0.00001），而四项研究纳入 EFS 的荟萃分析，HR 为 1.64（95%CI，1.25-2.14；p=0.0003）。
结论
FLT3-ITD 突变与成人非移植 AML 患者的预后不良相关，无论是 OS 还是 EFS。
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