Molecular Monitoring of Minimal Residual Disease in the Peripheral Blood of Patients with Multiple Myeloma
Molecular Monitoring of Minimal Residual Disease in the Peripheral Blood of Patients with Multiple Myeloma
复制标题
DOI：
10.1016/j.bbmt.2013.04.025
复制
发表时间：
2013-07-01
影响因子：
4.3
通讯作者：
Fenk, Roland
中科院分区：
文献类型：
--
作者：
Korthals, Mark;Sehnke, Nina;Fenk, Roland
最小残留病（MRD）在多发性骨髓瘤患者中的预后相关性仍然是一个悬而未决的问题。在骨髓中，残余骨髓瘤细胞的水平与治疗结果相关，但外周血中克隆型细胞（PB）对患者预后的作用尚未确定。在这项研究中，我们回顾性分析了42例接受高剂量治疗后自体骨髓干细胞移植作为多发性骨髓瘤一线治疗的患者的骨髓MRD，采用定量实时荧光定量pcr （IgH-qPCR）。PB样品的MRD水平中位数比同一天采集的骨髓样品低40倍，个体内和个体间差异很大（范围）。4 ~ 4628倍)。在PB中是否存在可检测的MRD水平与血清学缓解状态无关。尽管如此，在高剂量治疗和PB干细胞移植后3个月PCR结果为阴性的患者，其国际分期系统分期较低（P = 0.01）， β(2)-微球蛋白水平较低（P = 0.02），血红蛋白水平较高（P = 0.01），无事件生存期延长（中位数，15个月vs 4个月；P = 0.004）和总生存期延长（中位数，52个月vs 17个月；P = 0.03）。重要的是，通过连续监测PB中的克隆型细胞，在29例进行性疾病患者中有19例（66%），在中位4个月（范围，1）内可以检测到2IgH/ β -肌动蛋白比值增加至少1 log步。根据欧洲血液和骨髓移植组织的标准诊断为复发前8至13个月。这些在血清学复发前发生分子复发的PB患者的总生存期明显短于其他患者（中位，17个月vs中位未达到，P = 0.02）。综上所述，IgH-qPCR是一种检测PB克隆型细胞的灵敏技术，可用于临床复发前的克隆型细胞检测。需要进一步的研究来评估这些循环肿瘤细胞是否在促进疾病复发中起作用。(C) 2013年美国血液和骨髓移植学会。
The prognostic relevance of minimal residual disease (MRD) in patients with multiple myeloma is still an open question. In bone marrow, the level of residual myeloma cells is associated with treatment outcome, but the role of clonotypic cells in the peripheral blood (PB) for the prognosis of patients is not identified yet. In this study, we retrospectively analyzed MRD by quantitative real-time IgH-PCR (IgH-qPCR) in the PB of 42 patients undergoing high-dose therapy followed by autologous PB stem cell transplantation as first-line therapy for multiple myeloma. The MRD level of PB samples was in median 40-fold lower than in bone marrow samples, collected on the same day, with a wide intra- and interindividual variation (range, .4- to 4628-fold). The presence or absence of detectable MRD levels in PB did not correlate with the serological remission status. Still, patients with negative PCR results in PB 3 months after high-dose therapy and PB stem cell transplantation had lower International Staging System stage (P = .01), lower levels of beta(2)-microglobulin (P = .02), higher hemoglobin levels (P = .01), and a prolonged event-free (median, 15 versus 4 months; P = .004) and overall (median, 52 versus 17 months; P = .03) survival. Importantly, by sequential monitoring of clonotypic cells in PB, in 19 of 29 patients (66%) with progressive disease, an increase of the 2IgH/beta-actin ratio of at least 1 log step could be detected in median 4 months (range, .8 to 13 months) before the relapse was diagnosed on the basis of the European Group for Blood and Marrow Transplantation criteria. These patients with a molecular relapse in PB before a serological relapse had a significantly shorter overall survival than other patients (median, 17 months versus median not reached, P = .02). In conclusion, IgH-qPCR is a sensitive technique for the detection of clonotypic cells in PB, which precede clinical relapse. Future studies are needed to evaluate whether these circulating tumor cells play a role in promoting disease recurrence. (C) 2013 American Society for Blood and Marrow Transplantation.