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文章:

循环多发性骨髓瘤细胞(CMMCs)作为多发性骨髓瘤及冒烟型骨髓瘤患者的预后与预测标志物

Circulating Multiple Myeloma Cells (CMMCs) as Prognostic and Predictive Markers in Multiple Myeloma and Smouldering MM Patients

原文发布日期:23 August 2024

DOI: 10.3390/cancers16172929

类型: Article

开放获取: 是

 

英文摘要:

In recent years, liquid biopsy has emerged as a promising alternative to the bone marrow (BM) examination, since it is a minimally invasive technique allowing serial monitoring. Circulating multiple myeloma cells (CMMCs) enumerated using CELLSEARCH®were correlated with patients’ prognosis and measured under treatment to assess their role in monitoring disease dynamics. Forty-four MM and seven smouldering MM (SMM) patients were studied. The CMMC medians at diagnosis were 349 (1 to 39,940) and 327 (range 22–2463) for MM and SMM, respectively. In the MM patients, the CMMC count was correlated with serum albumin, calcium, β2-microglobulin, and monoclonal components (p< 0.04). Under therapy, the CMMCs were consistently detectable in 15/40 patients (coMMstant = 1) and were undetectable or decreasing in 25/40 patients (coMMstant = 0). High-quality response rates were lower in the coMMstant = 1 group (p= 0.04), with a 7.8-fold higher risk of death (p= 0.039), suggesting that continuous CMMC release is correlated with poor responses. In four MM patients, a single-cell DNA sequencing analysis on residual CMMCs confirmed the genomic pattern of the aberrations observed in the BM samples, also highlighting the presence of emerging clones. The CMMC kinetics during treatment were used to separate the patients into two subgroups based on the coMMstant index, with different responses and survival probabilities, providing evidence that CMMC persistence is associated with a poor disease course.

 

摘要翻译: 

近年来,液体活检因其微创特性且可实现连续监测,已成为骨髓检查的一种有前景的替代方法。通过CELLSEARCH®系统计数的循环多发性骨髓瘤细胞(CMMCs)与患者预后相关,并在治疗过程中进行测量以评估其在监测疾病动态中的作用。本研究共纳入44例多发性骨髓瘤(MM)患者和7例冒烟型多发性骨髓瘤(SMM)患者。诊断时MM和SMM患者的CMMC中位数分别为349(范围1-39,940)和327(范围22-2463)。在MM患者中,CMMC计数与血清白蛋白、钙、β2-微球蛋白及单克隆成分具有相关性(p<0.04)。治疗期间,15/40例患者(coMMstant=1组)持续检测到CMMCs,而25/40例患者(coMMstant=0组)未检测到或呈下降趋势。coMMstant=1组的高质量缓解率较低(p=0.04),死亡风险增加7.8倍(p=0.039),表明持续的CMMC释放与治疗反应不良相关。对4例MM患者残留CMMCs进行的单细胞DNA测序分析,证实了其基因组异常模式与骨髓样本中观察到的一致,同时揭示了新克隆的出现。基于coMMstant指数将治疗期间CMMC动力学不同的患者分为两个亚组,其治疗反应和生存概率存在显著差异,这为CMMC持续存在与不良疾病进程相关的观点提供了证据。

 

原文链接:

Circulating Multiple Myeloma Cells (CMMCs) as Prognostic and Predictive Markers in Multiple Myeloma and Smouldering MM Patients

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