TP53 mutation in patients with high-risk acute myeloid leukaemia treated with allogeneic haematopoietic stem cell transplantation
TP53 mutation in patients with high-risk acute myeloid leukaemia treated with allogeneic haematopoietic stem cell transplantation
复制标题
DOI：
10.1111/bjh.13912
复制
发表时间：
2016-03-01
影响因子：
6.5
通讯作者：
Schetelig, Johannes
中科院分区：
文献类型：
--
作者：
Middeke, Jan M.;Herold, Sylvia;Schetelig, Johannes
急性髓系白血病(AML)患者的治疗成功是不同的。细胞遗传学和分子改变是影响预后的重要因素，已被用于个体化治疗。在这里，我们研究了TP53突变对接受异基因造血干细胞移植(HSCT)治疗的具有不利细胞遗传学风险的AML患者预后的影响。分析了在三个随机试验中接受过HSCT的97名AML患者和有不良风险的细胞遗传学患者的样本。使用下一代测序对TP53编码区进行完整测序。中位年龄为51岁。总体而言，在40名患者(41%)中发现了TP53突变。中位随访期67个月，野生型TP53患者的3年总生存率和无事件生存率分别为33%[95%可信区间(CI)，21%~45%]和24%(95%CI，13%~35%)，而突变型患者分别为10%(95%CI，0%~19%)和8%(95%CI，0%~16%)(P=0002和P=0007)。在多因素分析中，TP53突变状态对OS有负面影响(危险比=17；P=0066)。TP53基因突变分析可能是预测HSCT后不良核型AML患者预后的重要辅助工具。
Treatment success in patients with acute myeloid leukaemia (AML) is heterogeneous. Cytogenetic and molecular alterations are strong prognostic factors, which have been used to individualize treatment. Here, we studied the impact of TP53 mutations on the outcome of AML patients with adverse cytogenetic risk treated with allogeneic haematopoietic stem cell transplantation (HSCT). Samples of 97 patients with AML and adverse-risk cytogenetics who had received a HSCT within three randomized trials were analysed. Complete sequencing of the TP53 coding region was performed using next generation sequencing. The median age was 51years. Overall, TP53 mutations were found in 40 patients (41%). With a median follow up of 67months, the three-year probabilities of overall survival (OS) and event-free survival for patients with TP53 wild type were 33% [95% confidence interval (CI), 21% to 45%] and 24% (95% CI, 13% to 35%) compared to 10% (95% CI, 0% to 19%) and 8% (95% CI, 0% to 16%) (P=0002 and P=0007) for those with mutated TP53, respectively. In multivariate analysis, the TP53-mutation status had a negative impact on OS (Hazard Ratio=17; P=0066). Mutational analysis of TP53 might be an important additional tool to predict outcome after HSCT in patients with adverse karyotype AML.