Noninvasive Molecular Monitoring in Multiple Myeloma Patients Using Cell-Free Tumor DNA A Pilot Study
Noninvasive Molecular Monitoring in Multiple Myeloma Patients Using Cell-Free Tumor DNA A Pilot Study
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DOI：
10.1016/j.jmoldx.2018.07.006
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发表时间：
2018-11-01
影响因子：
4.1
通讯作者：
Corradini, Paolo
中科院分区：
文献类型：
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作者：
Biancon, Giulia;Gimondi, Silvia;Corradini, Paolo
多发性骨髓瘤 (MM) 的新疗法提高了完全缓解率，引起了人们对更准确的残留疾病评估方法的兴趣。无细胞肿瘤 DNA (cfDNA) 分析可能代表一种微创方法，与多参数流式细胞术 (MFC) 和骨髓抽吸物分子方法互补。应用使用 Ion Torrent 个人基因组机的测序方法来鉴定肿瘤浆细胞 (PC) 和接受二线治疗的 25 名 MM 患者的系列血浆样本中的克隆 IGH 基因重排。同一个克隆。在配对血浆样本中检测到肿瘤 PC 中发现的 IGH 重排，并且 IGH cfDNA 水平与结果相关，并使用传统实验室参数评估镜像肿瘤动态。此外，即使在完全反应的情况下，IGH cfDNA 水平也反映了 MFC 免疫表型所计数的 PC 数量。 MFC 确定无微小残留病的患者的特点是 cfDNA 中肿瘤克隆型频率较低且生存期较长。该试点研究支持通过 IGH 测序对 MM 患者血浆样本中肿瘤水平进行无创监测的临床适用性。
Novel treatments for multiple myeloma (MM) have increased rates of complete response, raising interest in more accurate methods to evaluate residual disease. Cell-free tumor DNA (cfDNA) analysis may represent a minimally invasive approach complementary to multiparameter flow cytometry (MFC) and molecular methods on bone marrow aspirates. A sequencing approach using the Ion Torrent Personal Genome Machine was applied to identify clonal IGH gene rearrangements in tumor plasma cells (PCs) and in serial plasma samples of 25 patients with MM receiving second-line therapy. The same clonal. IGH rearrangement identified in tumor PCs was detected in paired plasma samples, and levels of IGH cfDNA correlated with outcome and mirrored tumor dynamics evaluated using conventional laboratory parameters. In addition, IGH cfDNA levels reflected the number of PCs enumerated by MFC immuno-phenotyping even in the complete response context. Patients determined by MFC to be free of minimal residual disease were characterized by low frequencies of tumor clonotypes in cfDNA and longer survival. This pilot study supports the clinical applicability of the noninvasive monitoring of tumor levels in plasma samples of patients with MM by IGH sequencing.