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老年急性髓系白血病患者通过基因突变分析进行预后分层的重要性。

Importance of prognostic stratification via gene mutation analysis in elderly patients with acute myelogenous leukemia.

机构信息

Department of Hematology, Nippon Medical School, Tokyo, Japan.

Department of Hematology, Yokohama Minami Kyousai Hospital, Kanagawa, Japan.

出版信息

Int J Lab Hematol. 2019 Aug;41(4):461-471. doi: 10.1111/ijlh.13025. Epub 2019 Apr 10.

Abstract

INTRODUCTION

Acute myelogenous leukemia (AML) in elderly patients is associated with an increased incidence of complications and treatment-related toxicity because of the frequency of comorbid disease and age-related deterioration in organ function. Despite advances in AML treatment in recent years, elderly patients have experienced limited benefit, and their outcomes remain poor. This study aimed to perform a comprehensive gene mutation analysis in elderly AML patients and identify gene mutations that could serve as prognostic factors.

METHODS

An analysis of gene mutations was performed for 281 AML patients, including 98 elderly patients aged 65 years or above.

RESULTS

Compared to younger AML patients, elderly patients showed a higher frequency of the following gene mutations: TP53 (P = 0.026), PTPN11 (P = 0.006), RUNX1 (P = 0.024), TET2 (P = 0.002), and ASXL1 (P = 0.023). The complete remission rate was significantly lower in DNMT3A mutation-positive cases (4.26%, P = 0.011) and TP53 mutation-positive cases (2.13%, P = 0.031) than in negative cases. The overall survival rate was significantly poorer in cases with FLT3-ITD (P = 0.003), DNMT3A (P = 0.033), or TP53 mutation (P < 0.001). Conversely, cases with PTPN11 mutation (P = 0.014) had a significantly more favorable prognosis. In multivariate analysis, FLT3-ITD (P = 0.011) and TP53 mutation positivity (P = 0.002) were independent poor prognostic factors, as were a performance status of 3 or above (P < 0.001) and poor cytogenetic prognosis (P = 0.001). In contrast, PTPN11 mutation positivity (P = 0.023) was an independent favorable prognosis factor.

CONCLUSION

Analysis of gene mutations in elderly AML patients is very important, not only for establishing prognosis, but also for introducing appropriate molecular-targeted treatments.

摘要

简介

老年急性髓系白血病(AML)由于合并症的发病率高和与年龄相关的器官功能恶化,与并发症和治疗相关的毒性增加有关。尽管近年来 AML 治疗取得了进展,但老年患者受益有限,其预后仍然较差。本研究旨在对老年 AML 患者进行全面的基因突变分析,并确定可作为预后因素的基因突变。

方法

对 281 例 AML 患者进行基因突变分析,其中 98 例为年龄 65 岁及以上的老年患者。

结果

与年轻 AML 患者相比,老年患者出现以下基因突变的频率更高:TP53(P=0.026)、PTPN11(P=0.006)、RUNX1(P=0.024)、TET2(P=0.002)和 ASXL1(P=0.023)。DNMT3A 突变阳性病例(4.26%,P=0.011)和 TP53 突变阳性病例(2.13%,P=0.031)完全缓解率显著低于阴性病例。FLT3-ITD(P=0.003)、DNMT3A(P=0.033)或 TP53 突变(P<0.001)的患者总生存率明显较差。相反,PTPN11 突变的病例(P=0.014)具有明显更有利的预后。多变量分析显示,FLT3-ITD(P=0.011)和 TP53 突变阳性(P=0.002)是独立的不良预后因素,此外,状态评分为 3 或以上(P<0.001)和不良细胞遗传学预后(P=0.001)也是独立的不良预后因素。相比之下,PTPN11 突变阳性(P=0.023)是独立的有利预后因素。

结论

分析老年 AML 患者的基因突变非常重要,不仅可以确定预后,还可以引入适当的分子靶向治疗。

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