Department of Medicine, Turku University Central Hospital, Vaasa, Finland.
Eur J Haematol. 2010 Nov;85(5):416-23. doi: 10.1111/j.1600-0609.2010.01510.x.
Achievement of complete response (CR) is a new goal of therapy for multiple myeloma (MM). By sensitive methods, the depth of response can be measured even among the patients in CR. We used a sensitive real-time quantitative polymerase chain reaction by allele-specific primers (qASO-PCR) to assess the level of minimal residual disease (MRD) in bone marrow of 37 patients with myeloma who had achieved CR/near-to-CR after autologous or allogeneic stem cell transplantation (SCT). Allele-specific primers could be successfully designed for 86% of patients. Three to six months after autotransplantation, the PCR target was not detectable in 53% of patients (16/30 patients), and the respective figure after allotransplantation was 71% (5/7 patients); the median sensitivity of PCR assay was <0.002%. The proportion of patients without detectable PCR target was 22% of all autotransplanted patients. A threshold level of 0.01% in the qASO-PCR assay 3-6 months after SCT was found to be a useful cut-off limit to divide the patients into two prognostic groups: MRD low/negative vs. MRD high. Low/negative MRD after SCT was a significant predictive factor for the prolongation of progression free (70 vs. 19 months; P = 0.003) and suggestively also for overall survival. We conclude that not only CR but also its depth is important for the long-term outcome in MM.
完全缓解（CR）是多发性骨髓瘤（MM）治疗的新目标。通过敏感的方法，即使在 CR 患者中，也可以测量反应的深度。我们使用敏感的实时定量聚合酶链反应（qASO-PCR），通过等位基因特异性引物（ASO-PCR）评估 37 例接受自体或异基因干细胞移植（SCT）后达到 CR/接近 CR 的骨髓瘤患者骨髓中微小残留病（MRD）的水平。能够成功地为 86%的患者设计等位基因特异性引物。在自体移植后 3-6 个月，53%的患者（16/30 例）的 PCR 靶标无法检测到，而异基因移植后相应的比例为 71%（5/7 例）；PCR 检测的中位敏感性<0.002%。在所有接受自体移植的患者中，无法检测到 PCR 靶标的患者比例为 22%。在 SCT 后 3-6 个月，qASO-PCR 检测中 0.01%的阈值水平被发现是将患者分为两个预后组的有用截止值：MRD 低/阴性与 MRD 高。SCT 后低/阴性的 MRD 是无进展生存（70 个月与 19 个月；P=0.003）和总生存时间延长的显著预测因素。我们得出结论，在 MM 中，不仅 CR，而且 CR 的深度对长期结果很重要。
