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TP53突变在成人急性髓系白血病中的预后价值:一项荟萃分析

The Prognostic Value of TP53 Mutations in Adult Acute Myeloid Leukemia: A Meta-Analysis.

作者信息

Qin Guoxiang, Han Xueling

机构信息

Department of Hematology, Jincheng People's Hospital, Jincheng, China.

Hospital Office, Zezhou People's Hospital, Jincheng, China.

出版信息

Transfus Med Hemother. 2022 Nov 4;50(3):234-244. doi: 10.1159/000526174. eCollection 2023 Jun.

Abstract

OBJECTIVE

Mutations of the tumor protein p53 (TP53) gene were considered to be associated with an unfavorable prognosis in acute myeloid leukemia (AML). This meta-analysis aimed to systematically elucidate the prognostic value of TP53 mutation in adult patients with AML.

METHOD

A comprehensive literature search was conducted for eligible studies published before August 2021. The primary endpoint was overall survival (OS). Pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were calculated for prognostic parameters. Subgroup analyses based on intensive treatment were performed.

RESULTS

Thirty-two studies with 7,062 patients were included. As compared to wild-type carriers, AML patients with TP53 mutations had significantly shorter OS (HR: 2.40, 95% CI: 2.16-2.67, : 46.6%). Similar results were found in DFS (HR: 2.87, 95% CI: 1.88-4.38), EFS (HR: 2.56, 95% CI: 1.97-3.31), and RFS (HR: 2.40, 95% CI: 1.79-3.22). Mutant TP53 predicted inferior OS (HR: 2.77, 95% CI: 2.41-3.18) in the intensively treated AML subgroup, compared with the non-intensively treated group (HR: 1.89, 95% CI: 1.58-2.26). Among intensively-treated AML patients, the age of 65 did not affect the prognostic value of TP53 mutations. Besides, TP53 mutation was also strongly associated with an elevated risk of adverse cytogenetics, which conferred a dismal OS in AML patients (HR: 2.03, 95% CI: 1.74-2.37).

CONCLUSION

TP53 mutation exhibits a promising potential for discriminating AML patients with a worse prognosis, thus being capable of serving as a novel tool for prognostication and therapeutic decision-making in the management of AML.

摘要

目的

肿瘤蛋白p53(TP53)基因的突变被认为与急性髓系白血病(AML)的不良预后相关。本荟萃分析旨在系统阐明TP53突变在成年AML患者中的预后价值。

方法

对2021年8月之前发表的符合条件的研究进行全面的文献检索。主要终点为总生存期(OS)。计算预后参数的合并风险比(HRs)及其95%置信区间(CIs)。基于强化治疗进行亚组分析。

结果

纳入了32项研究,共7062例患者。与野生型携带者相比,TP53突变的AML患者的OS显著缩短(HR:2.40,95%CI:2.16 - 2.67,P<0.001)。在无病生存期(DFS,HR:2.87,95%CI:1.88 - 4.38)、无事件生存期(EFS,HR:2.56,95%CI:1.97 - 3.31)和复发生存期(RFS,HR:2.40,95%CI:1.79 - 3.22)方面也发现了类似结果。与非强化治疗组(HR:1.89,95%CI:1.58 - 2.26)相比,在强化治疗的AML亚组中,突变型TP53预测较差的OS(HR:2.77,95%CI:2.41 - 3.18)。在强化治疗的AML患者中,65岁并不影响TP53突变的预后价值。此外,TP53突变还与不良细胞遗传学风险升高密切相关,这使得AML患者的OS较差(HR:2.03,95%CI:1.74 - 2.37)。

结论

TP53突变在鉴别预后较差的AML患者方面具有潜在价值,因此能够作为AML管理中预后评估和治疗决策的新工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bd4/10331159/a652bfb500ed/tmh-0050-0234-g01.jpg

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