Deng S H, Xu Y, Sui W W, Wang H J, Li Z J, Wang T Y, Liu W, Huang W Y, Lyu R, Li J, Fu M W, Zou D H, An G, Qiu L G
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China.
Zhonghua Xue Ye Xue Za Zhi. 2018 May 14;39(5):376-381. doi: 10.3760/cma.j.issn.0253-2727.2018.05.006.
To assess the feasibility and prognostic value of the minimal residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) in the newly diagnosed multiple myeloma (MM) patients of China. Clinical data of 106 consecutively newly diagnosed MM patients with MRD data were retrospectively analyzed in a single center in China from June 2013 to June 2015. ① Of 106 patients, 48 (45.3%) achieved MRD negativity. The median time to MRD-negative was 3 months. More patients undergoing autologous stem cell transplantation (ASCT) achieved MRD negativity compared with non-ASCT patients (62.2% 36.2%, (2)=6.536, =0.011). ② Of 48 patients in complete remission (CR), 7 (14.6%) was MRD positive, 5 of them showed disease progression (PD) during the follow-up, and 3 died. The median progression free survival (PFS) was 19 months, and the median overall survival (OS) was 28 months, both were significantly shorter than the CR patients with MRD-negative (<0.05). ③At a median follow-up of 38 months, MRD-negative patients showed significantly superior outcomes compared with MRD positive ones, the PFS was not reach versus 17 months and the OS was not reach for both (<0.001). Patients were grouped into 4 categories according to their MRD levels: 1% or higher, 0.1% to less than 1%, 0.01% to less than 0.1%, or negative. It showed that the outcomes (PFS and OS) tended to be improved along with the tumor depletion. ④ Multivariate prognostic analysis showed that MRD was a powerful independent prognostic factor for PFS[=0.133 (95% 0.062-0.288) , <0.001] and OS[=0.156 (95% 0.050-0.484) , =0.001]. According to MRD and cytogenetics, the patients were classified into 4 groups. High risk patients with MRD negative presented a significantly better outcome than high risk patients with MRD-positive, and a similar one to the standard risk patients with MRD-negative. MRD negativity by MFC was more popular in MM patients undergoing ASCT. MRD was an independent prognostic factor in MM. And the prognosis of MM patients can be stratified according to the level of MRD. MRD-negative patients with high risk cytogenetics presented a similar outcome to the standard risk ones. MRD by MFC should therefore be considered more widely applied in the clinic.
评估多参数流式细胞术（MFC）检测的微小残留病（MRD）在中国新诊断多发性骨髓瘤（MM）患者中的可行性及预后价值。对2013年6月至2015年6月在中国某单中心连续收治的106例有MRD数据的新诊断MM患者的临床资料进行回顾性分析。①106例患者中，48例（45.3%）达到MRD阴性。达到MRD阴性的中位时间为3个月。与未接受自体干细胞移植（ASCT）的患者相比，接受ASCT的患者更多达到MRD阴性（62.2%对36.2%，χ² = 6.536，P = 0.011）。②48例完全缓解（CR）患者中，7例（14.6%）MRD阳性，其中5例在随访期间疾病进展（PD），3例死亡。无进展生存期（PFS）的中位时间为19个月，总生存期（OS）的中位时间为28个月，均显著短于MRD阴性的CR患者（P<0.05）。③中位随访38个月时，MRD阴性患者的结局显著优于MRD阳性患者，PFS未达到对17个月，OS两者均未达到（P<0.001）。根据MRD水平将患者分为4类：1%及以上、0.1%至<1%、0.01%至<0.1%或阴性。结果显示，随着肿瘤负荷降低，结局（PFS和OS）趋于改善。④多因素预后分析显示，MRD是PFS[HR = 0.133（95%CI 0.062 - 0.288），P<0.001]和OS[HR = 0.156（95%CI 0.050 - 0.484），P = 0.001]的有力独立预后因素。根据MRD和细胞遗传学将患者分为4组。MRD阴性的高危患者结局显著优于MRD阳性的高危患者，与MRD阴性的标危患者相似。MFC检测的MRD阴性在接受ASCT的MM患者中更常见。MRD是MM的独立预后因素。MM患者的预后可根据MRD水平分层。MRD阴性且细胞遗传学高危的患者结局与标危患者相似。因此，MFC检测的MRD应更广泛地应用于临床。
