急性髓系白血病微小残留病评估临床应用中的风险分层

Risk stratification in the clinical application of minimal residual disease assessment in acute myeloid leukemia.

作者信息

Zhang Congxiao, Gu Runxia, Wang Huijun, Zhou Chunlin, Li Yan, Liu Yuntao, Wei Shuning, Lin Dong, Liu Kaiqi, Fang Qiuyun, Gong Xiaoyuan, Gong Benfa, Qiu Shaowei, Zhang Guangji, Liu Bingcheng, Wang Ying, Mi Yingchang, Wei Hui, Wang Jianxiang

机构信息

National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.

Tianjin Institutes of Health Science, Tianjin, China.

出版信息

Cancer. 2025 Jan 1;131(1):e35641. doi: 10.1002/cncr.35641. Epub 2024 Nov 10.

DOI:10.1002/cncr.35641

PMID:39522053

Abstract

BACKGROUND

In acute myeloid leukemia (AML), further investigation is warranted to integrate measurable residual disease (MRD) with genetic characteristics for formulating a dynamic prognostic system for predicting response and selecting appropriate postremission therapeutic strategies.

METHODS

The authors incorporated MRD with genetic risk classification and assessed its impact on transplantation decision making within different risk cohorts, comprising 769 patients with newly diagnosed AML across three clinical trials. Only patients who achieved complete remission (CR) within two courses of chemotherapy were selected.

RESULTS

In the favorable-risk and intermediate-risk groups, patients who underwent transplantation according to the protocol experienced significant 3-year overall survival (OS) benefits compared with those who did not (favorable-risk group: hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20-0.73l p = .004; intermediate-risk group: HR, 0.53; 95% CI, 0.33-0.85; p = .008). In the intermediate-risk group, early detection of MRD positivity, even after the initial course of chemotherapy, was associated with a significantly elevated cumulative incidence of relapse (47.2% vs. 36.0%; p = .009) and a notable extension of OS with allogeneic hematopoietic stem cell transplantation (HR, 0.47; 95% CI, 0.28-0.79; p = .004). Conversely, patients who achieved MRD negativity at either of the two time points had comparable OS in the favorable-risk and intermediate-risk groups, regardless of whether they underwent transplant or not. In the adverse-risk group, allogeneic hematopoietic stem cell transplantation led to improvements in OS irrespective of MRD status (HR, 0.51; 95% CI, 0.38-0.69; p < .001).

CONCLUSIONS

Early clearance of MRD demonstrated significant prognostic value, particularly for patients in the favorable-risk and intermediate-risk groups. Positive MRD status after two courses of intensive chemotherapy were associated with a higher relapse rate and inferior OS, necessitating allogeneic hematopoietic stem cell transplantation.

摘要

背景

在急性髓系白血病（AML）中，有必要进一步研究将可测量残留病（MRD）与基因特征相结合，以构建一个动态预后系统，用于预测缓解反应并选择合适的缓解后治疗策略。

方法

作者将MRD与基因风险分类相结合，并评估其对不同风险队列中移植决策的影响，该队列包括来自三项临床试验的769例新诊断的AML患者。仅选择在两个化疗疗程内达到完全缓解（CR）的患者。

结果

在低危和中危组中，按照方案接受移植的患者与未接受移植的患者相比，3年总生存期（OS）有显著获益（低危组：风险比[HR]，0.38；95%置信区间[CI]，0.20 - 0.73；p = 0.004；中危组：HR，0.53；95% CI，0.33 - 0.85；p = 0.008）。在中危组中，即使在初始化疗疗程后早期检测到MRD阳性，也与复发累积发生率显著升高相关（47.2%对36.0%；p = 0.009），并且接受异基因造血干细胞移植后OS显著延长（HR，0.47；95% CI，0.28 - 0.79；p = 0.004）。相反，在两个时间点中的任何一个达到MRD阴性的患者，无论是否接受移植，在低危和中危组中的OS相当。在高危组中，无论MRD状态如何，异基因造血干细胞移植均可改善OS（HR，0.51；95% CI，0.38 - 0.69；p < 0.001）。