Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Duesseldorf, Germany.
Biol Blood Marrow Transplant. 2012 Mar;18(3):423-431.e3. doi: 10.1016/j.bbmt.2011.07.002. Epub 2011 Jul 13.
The prognostic relevance of minimal residual disease (MRD) in patients with multiple myeloma is still an open question. We measured MRD levels in bone marrow (BM) samples of 53 patients treated with high-dose therapy (HDT) and autologous peripheral blood stem cell transplantation using real-time quantitative (RQ)-IgH-PCR with allel-specific oligonucleotide probes. We identified a prognostically relevant threshold level of 0.2% 2IgH/β-actin ratio in the BM before HDT. Twenty-six patients with MRD levels below this value were termed as the "low-MRD group," whereas 27 patients with levels above this threshold were allocated to the "high-MRD group." Median event-free-survival (EFS) in the low-MRD group was significantly (P = .001) longer than in the high-MRD group with 35 versus 20 months, respectively. Overall survival (OS) within the low-MRD group was also significantly longer with 70 versus 45 months (P = .04). Using multivariate analysis, we found that the pretransplantation MRD level was an independent prognostic factor for EFS (P = .003) and OS (P = .05). Further, EFS of patients in the high-MRD could be improved (P = .005) when they achieved a low MRD level after HDT. In conclusion, measuring MRD is of prognostic relevance in patients with MM, and low MRD levels should be a goal of treatment.
多发性骨髓瘤患者的微小残留病（MRD）的预后相关性仍然是一个悬而未决的问题。我们使用实时定量（RQ）-IgH-PCR 结合等位基因特异性寡核苷酸探针，测量了 53 例接受高剂量治疗（HDT）和自体外周血干细胞移植的患者骨髓（BM）样本中的 MRD 水平。我们在 HDT 前确定了一个具有预后相关性的 0.2% 2IgH/β-actin 比值的阈值水平。MRD 水平低于该值的 26 例患者被称为“低 MRD 组”，而 MRD 水平高于该阈值的 27 例患者被分配到“高 MRD 组”。低 MRD 组的无事件生存（EFS）明显（P =.001）长于高 MRD 组，分别为 35 个月和 20 个月。低 MRD 组的总生存（OS）也明显较长，分别为 70 个月和 45 个月（P =.04）。使用多变量分析，我们发现移植前的 MRD 水平是 EFS（P =.003）和 OS（P =.05）的独立预后因素。此外，高 MRD 患者在 HDT 后达到低 MRD 水平时，EFS 可以得到改善（P =.005）。总之，MRD 测量在 MM 患者中具有预后相关性，低 MRD 水平应该是治疗的目标。
