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

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, I2: 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.

研究目的：肿瘤蛋白p53（tumor protein p53, TP53）基因变异被认为与急性髓系白血病（acute myeloid leukemia, AML）患者的不良预后密切相关。本荟萃分析旨在系统阐明TP53突变在成人急性髓系白血病患者中的预后价值。
研究方法：我们系统性检索了2021年8月之前发表的符合纳入标准的相关研究。本研究的主要终点为总生存期（overall survival, OS）；通过合并计算风险比（hazard ratio, HR）及其95%置信区间（confidence interval, CI）以评估预后参数，并基于强化治疗方案开展亚组分析。
研究结果：本研究共纳入32项相关研究，共计7062例患者。与TP53野生型携带者相比，携带TP53突变的急性髓系白血病患者总生存期显著更短（HR=2.40，95%CI：2.16~2.67，I²=46.6%）。在无病生存期（disease-free survival, DFS）、无事件生存期（event-free survival, EFS）以及无复发生存期（relapse-free survival, RFS）中均得到了一致的结果：无病生存期的合并HR为2.87（95%CI：1.88~4.38），无事件生存期为2.56（95%CI：1.97~3.31），无复发生存期为2.40（95%CI：1.79~3.22）。在强化治疗亚组中，与非强化治疗组（合并HR=1.89，95%CI：1.58~2.26）相比，TP53突变可预测更差的总生存期（合并HR=2.77，95%CI：2.41~3.18）；在接受强化治疗的急性髓系白血病患者中，年龄≥65岁并未对TP53突变的预后价值产生影响。此外，TP53突变还与不良细胞遗传学风险显著相关，该特征同样会导致急性髓系白血病患者预后不良（HR=2.03，95%CI：1.74~2.37）。
研究结论：TP53突变具备良好的临床应用潜力，可有效区分预后较差的急性髓系白血病患者，有望成为急性髓系白血病诊疗过程中预后评估与治疗决策制定的新型工具。