Huang Sai, Chen Peng, Wang Lu, Xu Lingmin, Wang Nan, Li Fei, Dou Liping, Liu Daihong
Department of Hematology, Senior Department of Hematology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China.
National Clinical Research Center of Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China.
Cancer Pathog Ther. 2023 Oct 12;2(2):112-120. doi: 10.1016/j.cpt.2023.10.002. eCollection 2024 Apr.
Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy whose prognosis is associated with several biomarkers. Decitabine, a deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor, combined with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor (DCAG), has been used in patients newly diagnosed with AML. This regimen has been especially used in older and fragile patients who are immunocompromised or have co-morbidities, as well as those with specific gene mutations. However, the integration of molecular risk stratification and treatment guidance for the DCAG regimen has not been well defined. Therefore, this study aimed to investigate the genetic mutations associated with AML and establish appropriate treatment strategies for patients newly diagnosed with AML.
This study analyzed the clinical data and genetic mutations based on next-generation sequencing (NGS) in 124 newly diagnosed patients with AML who received the DCAG regimen at the People's Liberation Army (PLA) General Hospital from January 2008 to August 2020. Factors associated with the cumulative incidence of relapse (CIR) and leukemia-free survival (LFS) in patients newly diagnosed with AML were analyzed.
The most adverse prognosis of DCAG-treated patients was observed in those with or mutations during univariable analysis, whereas mutation was solely significant in multivariable analysis, with an increased likelihood of CIR ( = 0.001) and reduced LFS duration ( = 0.077). Hyperleukocytosis was maintained as an independent risk factor for increased CIR risk ( = 0.044) and decreased LFS duration ( = 0.042) in multivariable analysis. In this study, we validated the risk classification of patients with AML receiving an epigenetic modifier-based induction regimen across a broad age range.
NGS demonstrated a dismal overall outcome in patients with the rare mutations, indicating the need for new therapies that target this high-risk subtype of AML. These results offer a potential molecular stratification and treatment guidance for patients with AML.
急性髓系白血病（AML）是一种异质性造血系统恶性肿瘤，其预后与多种生物标志物相关。地西他滨，一种脱氧核糖核酸（DNA）甲基转移酶（DNMT）抑制剂，联合阿糖胞苷、盐酸阿克拉霉素和粒细胞集落刺激因子（DCAG），已用于新诊断的AML患者。该方案尤其适用于免疫功能低下或有合并症的老年体弱患者，以及有特定基因突变的患者。然而，DCAG方案的分子风险分层与治疗指导的整合尚未明确界定。因此，本研究旨在调查与AML相关的基因突变，并为新诊断的AML患者制定合适的治疗策略。
本研究分析了2008年1月至2020年8月在解放军总医院接受DCAG方案治疗的124例新诊断AML患者的临床数据及基于二代测序（NGS）的基因突变情况。分析了新诊断AML患者复发累积发生率（CIR）和无白血病生存期（LFS）的相关因素。
单因素分析显示，DCAG治疗患者中，具有 或 突变的患者预后最差，而在多因素分析中，只有 突变具有显著性，CIR增加（ = 0.001），LFS持续时间缩短（ = 0.077）。在多因素分析中，高白细胞血症仍然是CIR风险增加（ = 0.044）和LFS持续时间缩短（ = 0.042）的独立危险因素。在本研究中，我们在广泛的年龄范围内验证了接受基于表观遗传修饰剂诱导方案的AML患者的风险分类。
NGS显示，具有罕见 突变的患者总体预后不佳，表明需要针对这种高危AML亚型的新疗法。这些结果为AML患者提供了潜在的分子分层和治疗指导。
