比较下一代测序(NGS)与下一代流式细胞术(NGF)在多发性骨髓瘤微小残留病(MRD)评估中的应用
Comparison of next-generation sequencing (NGS) and next-generation flow (NGF) for minimal residual disease (MRD) assessment in multiple myeloma
原文发布日期:2020-10-30
DOI: 10.1038/s41408-020-00377-0
类型: Article
开放获取: 是
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Detecting persistent minimal residual disease (MRD) allows the identification of patients with an increased risk of relapse and death. In this study, we have evaluated MRD 3 months after transplantation in 106 myeloma patients using a commercial next-generation sequencing (NGS) strategy (LymphoTrack®), and compared the results with next-generation flow (NGF, EuroFlow). The use of different marrow pulls and the need of concentrating samples for NGS biased the applicability for MRD evaluation and favored NGF. Despite that, correlation between NGS and NGF was high (R2 = 0.905). The 3-year progression-free survival (PFS) rates by NGS and NGF were longer for undetectable vs. positive patients (NGS: 88.7% vs. 56.6%; NGF: 91.4% vs. 50%; p < 0.001 for both comparisons), which resulted in a 3-year overall survival (OS) advantage (NGS: 96.2% vs. 77.3%; NGF: 96.6% vs. 74.9%, p < 0.01 for both comparisons). In the Cox regression model, NGS and NGF negativity had similar results but favoring the latter in PFS (HR: 0.20, 95% CI: 0.09–0.45, p < 0.001) and OS (HR: 0.21, 95% CI: 0.06–0.75, p = 0.02). All these results reinforce the role of MRD detection by different strategies in patient prognosis and highlight the use of MRD as an endpoint for multiple myeloma treatment.
检测持续性微小残留病(MRD)可识别复发和死亡风险升高的患者。本研究采用商业化二代测序(NGS)技术(LymphoTrack®)对106例骨髓瘤患者移植后3个月的MRD进行评估,并与二代流式细胞术(NGF, EuroFlow)进行对比。由于需使用不同骨髓穿刺样本及NGS要求样本浓缩,限制了该方法在MRD评估中的应用性,使NGF更具优势。尽管如此,NGS与NGF仍呈现高度相关性(R²=0.905)。通过两种方法均发现,MRD未检出者相比阳性患者3年无进展生存率更高(NGS:88.7% vs. 56.6%;NGF:91.4% vs. 50%;两组比较p均<0.001),并带来3年总生存期优势(NGS:96.2% vs. 77.3%;NGF:96.6% vs. 74.9%,两组比较p均<0.01)。在Cox回归模型中,NGS与NGF阴性结果相似,但NGF在无进展生存期(HR: 0.20, 95%CI:0.09–0.45, p<0.001)和总生存期(HR: 0.21, 95%CI:0.06–0.75, p=0.02)方面更具优势。所有这些结果强化了不同MRD检测策略对患者预后的指导作用,并凸显MRD作为多发性骨髓瘤治疗终点的价值。
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