Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, the Netherlands.
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
J Clin Oncol. 2024 Dec;42(34):4084-4094. doi: 10.1200/JCO.23.02631. Epub 2024 Sep 4.
AML is a genetically heterogeneous disease, particularly in older patients. In patients older than 60 years, survival rates are variable after the most important curative approach, intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (allo-HCT). Thus, there is an urgent need in clinical practice for a prognostic model to identify older patients with AML who benefit from curative treatment.
We studied 1,910 intensively treated patients older than 60 years with AML and high-risk myelodysplastic syndrome (HR-MDS) from two cohorts (NCRI-AML18 and HOVON-SAKK). The median patient age was 67 years. Using a random survival forest, clinical, molecular, and cytogenetic variables were evaluated in an AML development cohort (n = 1,204) for association with overall survival (OS). Relative weights of selected variables determined the prognostic model, which was validated in AML (n = 491) and HR-MDS cohorts (n = 215).
The complete cohort had a high frequency of poor-risk features, including 2022 European LeukemiaNet adverse-risk (57.3%), mutated (14.4%), and myelodysplasia-related genetic features (65.1%). Nine variables were used to construct four groups with highly distinct 4-year OS in the (1) AML development, (2) AML validation, and (3) HR-MDS test cohorts ([1] favorable: 54% ± 4%, intermediate: 38% ± 2%, poor: 21% ± 2%, very poor: 4% ± 1%; [2] 54% ± 9%, 43% ± 4%, 27% ± 4%, 4% ± 3%; and [3] 54% ± 10%, 33% ± 6%, 14% ± 5%, 0% ± 3%, respectively). This new AML60+ classification improves current prognostic classifications. Importantly, patients within the AML60+ intermediate- and very poor-risk group significantly benefited from allo-HCT, whereas the poor-risk patients showed an indication, albeit nonsignificant, for improved outcome after allo-HCT.
The new AML60+ classification provides prognostic information for intensively treated patients 60 years and older with AML and HR-MDS and identifies patients who benefit from intensive chemotherapy and allo-HCT.
AML 是一种遗传异质性疾病，尤其是在老年患者中。在 60 岁以上的患者中，接受最重要的治愈方法（强化化疗后行异基因造血细胞移植[allo-HCT]）后，生存率各不相同。因此，临床实践中迫切需要一种预后模型来识别那些从治愈性治疗中获益的老年 AML 患者。
我们研究了来自两个队列（NCRI-AML18 和 HOVON-SAKK）的 1910 名接受强化治疗的 60 岁以上 AML 和高危骨髓增生异常综合征（HR-MDS）患者。中位患者年龄为 67 岁。我们使用随机生存森林在 AML 发展队列（n = 1204）中评估临床、分子和细胞遗传学变量与总生存（OS）的相关性。选定变量的相对权重确定了预后模型，并在 AML（n = 491）和 HR-MDS 队列（n = 215）中进行了验证。
全队列具有高比例的不良预后特征，包括 2022 年欧洲白血病网不良风险（57.3%）、突变（14.4%）和与骨髓增生异常相关的遗传特征（65.1%）。九个变量用于构建四个具有高度不同的 4 年 OS 的组，分别为（1）AML 发展、（2）AML 验证和（3）HR-MDS 测试队列[1]（有利：54%±4%，中等：38%±2%，差：21%±2%，极差：4%±1%；[2]54%±9%，43%±4%，27%±4%，4%±3%；和[3]54%±10%，33%±6%，14%±5%，0%±3%）。这种新的 AML60+分类提高了当前的预后分类。重要的是，AML60+中危和极差风险组的患者从 allo-HCT 中显著获益，而高危风险患者接受 allo-HCT 后有改善生存的趋势（尽管无统计学意义）。
新的 AML60+分类为 60 岁及以上接受强化治疗的 AML 和 HR-MDS 患者提供了预后信息，并确定了从强化化疗和 allo-HCT 中获益的患者。
