Achieving minimal residual disease-negative by multiparameter flow cytometry may ameliorate a poor prognosis in MM patients with high-risk cytogenetics: a retrospective single-center analysis
Achieving minimal residual disease-negative by multiparameter flow cytometry may ameliorate a poor prognosis in MM patients with high-risk cytogenetics: a retrospective single-center analysis
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通过多参数流式细胞术实现微小残留病阴性可能会改善具有高风险细胞遗传学的 MM 患者的不良预后：一项回顾性单中心分析
DOI：
10.1007/s00277-019-03609-x
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发表时间：
2019-05-01
影响因子：
3.5
通讯作者：
Zhai, Yongping
中科院分区：
文献类型：
--
作者：
Li, Hanqing;Li, Feng;Zhai, Yongping
我们研究的目的是评估微小残留病（MRD）和高风险细胞遗传学（HRC）对多发性骨髓瘤（MM）患者预后的影响。我们应用多参数流式细胞术 (MFC) 对 123 名连续首次诊断为 MM 的患者进行 MRD 检测，这些患者在硼替佐米或沙利度胺为基础的诱导治疗后获得了非常好的部分缓解 (VGPR) 或更好。此外，我们在诊断时使用磁激活细胞分选和间期荧光原位杂交 (MACS-iFISH) 检查了 MM 患者的细胞遗传学特征。在所有 123 名 MM 患者中，MRD− 组 (n= 31) 的无进展生存期 (PFS) 和总生存期 (OS) 优于 MRD+ 组 (n= 92)（中位 PFS：未达到 (NR) 与 26 个月 (m)，P =0.0002；4 年 OS，91.7% 对比66.3%,P= 0.008)。每个 MRD 水平每增加一个对数，PFS 和 OS 显着缩短（P< 0.0001 和 P= 0.001）。根据异常浆细胞比例（小于0.01%、0.01-0.1%、0.1-1%和大于1%），四组的中位PFS分别为NR、37 m、26 m和15 m，4年OS率分别为91.7%、69.3%、76.1%和54.0%。分别。此外，我们的结果表明，标准风险细胞遗传学 (SRC) 患者的 PFS 和 OS 优于 HRC 患者（中位 PFS：NR vs. 26 m，P= 0.004；3 年 OS：95.8% vs. 76.0%，P= 0.006）。 PFS 的独立预测因子是 HRC 和 MRD+，其风险比分别为 1.901 (95% CI 1.094–3.303) 和 3.486 (95% CI 1.449–8.386)； OS 为 LDH 水平≥250 U/L、HRC 和 MRD+，其风险比分别为 2.789 (95% CI 1.080–7.199)、2.697 (95% CI 1.053–6.907) 和 7.714 (95% CI 1.040–57.227)。此外，对于 SRC 患者或 HRC 患者，MRD− 患者的 PFS 和 OS 均长于 MRD+ 患者。引人注目的是，MRD-HRC 组和 MRD+SRC 组之间的 PFS 或 OS 没有显着差异（中位 PFS 45 vs. 34 m，P= 0.300；4 年 OS 100% vs. 83.6%，P= 0.196）。 MRD-SRC 中的 PFS 优于 MRD-HRC（NR 与 45 m，P= 0.035）；然而，MRD-SRC 和 MRD-HRC 的 4 年 OS 没有显着差异（87.5% vs 100%，P= 0.480）。 MRD+和HRC都是MM患者的独立预后因素。此外，实现 MRD− 可能会改善患有 HRC 的 MM 患者的不良预后。
The aim of our study was to evaluate the prognostic impact of minimal residual disease (MRD) and high-risk cytogenetics (HRCs) on outcomes in multiple myeloma (MM) patients. We applied multiparameter flow cytometry (MFC) to detect MRD in 123 consecutive patients diagnosed with MM for the first time who achieved very good partial remission (VGPR) or better after bortezomib or thalidomide-based induction therapy. Moreover, we examined the cytogenetic features of MM patients using magnetic-activated cell sorting and interphase fluorescence in situ hybridization (MACS-iFISH) at diagnosis. In all 123 MM patients, progression-free survival (PFS) and overall survival (OS) were better in the MRD− group (n= 31) than in the MRD+ group (n= 92) (median PFS: not reached (NR) vs. 26 months (m),P =0.0002; 4-year OS, 91.7% vs. 66.3%,P= 0.008). PFS and OS were significantly shorter for each increase of one log per MRD level (P< 0.0001 andP= 0.001). The median PFS of the four groups according to the ratio of aberrant plasma cells (less than 0.01%, 0.01–0.1%, 0.1–1%, and more than 1%) were NR, 37 m, 26 m, and 15 m, respectively, and the 4-year OS rates were 91.7%, 69.3%, 76.1%, and 54.0%, respectively. In addition, our results show that PFS and OS were better for the standard-risk cytogenetic (SRC) patients than the HRC patients (median PFS: NR vs. 26 m,P= 0.004; 3-year OS: 95.8% vs. 76.0%,P= 0.006). The independent predictors of PFS were HRC and MRD+, which had hazard ratios of 1.901 (95% CI 1.094–3.303) and 3.486 (95% CI 1.449–8.386), respectively; while those for OS were an LDH level ≥ 250 U/L, HRC, and MRD+, which had hazard ratios of 2.789 (95% CI 1.080–7.199), 2.697 (95% CI 1.053–6.907), and 7.714 (95% CI 1.040–57.227), respectively. Furthermore, for SRC patients or HRC patients, PFS and OS were all longer in MRD− than in MRD+ patients. Strikingly, there was no significant difference in PFS or OS between the MRD-HRC and MRD+SRC groups (median PFS 45 vs. 34 m,P= 0.300; 4-year OS 100% vs. 83.6%,P= 0.196). PFS was superior in MRD-SRC than in MRD-HRC (NR vs. 45 m,P= 0.035); however, there was no significant difference in the 4-year OS between MRD-SRC and MRD-HRC (87.5% vs 100%,P= 0.480). MRD+ and HRCs were both independent prognostic factors in MM patients. Moreover, achieving MRD− may ameliorate a poor prognosis in MM patients with HRCs.