Impact of measurable residual disease by decentralized flow cytometry: a PETHEMA real-world study in 1076 patients with acute myeloid leukemia
Impact of measurable residual disease by decentralized flow cytometry: a PETHEMA real-world study in 1076 patients with acute myeloid leukemia
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DOI：
10.1038/s41375-021-01126-3
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发表时间：
2021-02-01
期刊：
影响因子：
11.4
通讯作者：
Montesinos, Pau
中科院分区：
文献类型：
--
作者：
Paiva, Bruno;Vidriales, Maria-Belen;Montesinos, Pau
可测量残留疾病（MRD）的分散评估在急性髓性白血病（AML）风险分层中的作用在很大程度上仍然未知，因此，哪些方法学方面对评估MRD的预后意义至关重要，特别是如果使用多参数流式细胞术（MFC）。我们分析了1076例诱导化疗后首次缓解的AML患者，其中MRD在参与PETHEMA注册的60家医院的当地实验室中由MFC进行评估。我们还对MRD检测的技术方面进行了调查，以确定方法异质性对MFC预后价值的影响。我们的研究结果证实了推荐的0.1%的临界值，以区分具有显著不同的复发累积发生率（-CIR- HR：0.71，P < 0.001）和总生存率（HR：0.73，P = 0.001）的患者，但在包括其他临床、遗传和治疗相关因素的多变量和递归分割模型中，发现基于MFC的MRD的预后价值有限。几乎所有与基于MFC的MRD检测的方法学、解释和报告相关的方面都影响了其区分不同CIR患者的能力。因此，本研究表明，使用MFC对MRD进行“真实世界”评估在首次缓解时对患者具有预后意义，并敦促进一步标准化，以改善AML临床决策的风险分层。
The role of decentralized assessment of measurable residual disease (MRD) for risk stratification in acute myeloid leukemia (AML) remains largely unknown, and so it does which methodological aspects are critical to empower the evaluation of MRD with prognostic significance, particularly if using multiparameter flow cytometry (MFC). We analyzed 1076 AML patients in first remission after induction chemotherapy, in whom MRD was evaluated by MFC in local laboratories of 60 Hospitals participating in the PETHEMA registry. We also conducted a survey on technical aspects of MRD testing to determine the impact of methodological heterogeneity in the prognostic value of MFC. Our results confirmed the recommended cutoff of 0.1% to discriminate patients with significantly different cumulative-incidence of relapse (-CIR- HR:0.71, P < 0.001) and overall survival (HR: 0.73, P = 0.001), but uncovered the limited prognostic value of MFC based MRD in multivariate and recursive partitioning models including other clinical, genetic and treatment related factors. Virtually all aspects related with methodological, interpretation, and reporting of MFC based MRD testing impacted in its ability to discriminate patients with different CIR. Thus, this study demonstrated that "real-world" assessment of MRD using MFC is prognostic in patients at first remission, and urges greater standardization for improved risk-stratification toward clinical decisions in AML.