摘要
目的探讨1q21扩增(简称1q)对硼替佐米(Btz)治疗多发性骨髓瘤(MM)疗效和预后的影响。方法以2009年11月至2016年8月180例初治MM患者为研究对象,比较伴与不伴1q的MM患者的临床特征,分析其对Btz疗效及患者预后的影响,并通过R2分析平台,比较伴和不伴1q MM样本间基因表达谱的差异。结果①180例患者中,男98例、女82例,中位年龄60(33-86)岁。1q发生率为51.1%(92/180),174例患者随访资料完整,其中1q组88例,无1q组86例。②1q组和无1q组伴del(1p)的发生率分别为27.8%和9.4%(χ^2=3.71,P=0.040),伴IGH重排的发生率分别为72.2%和57.6%(χ^2=4.09,P=0.017),差异均有统计学意义。③1q组和无1q组患者的中位无进展生存(PFS)时间分别为15.0(95% CI 15.0-22.1)、20.3(95% CI 20.7-31.2)个月,中位总生存(OS)时间分别为29.4(95% CI 28.9-38.7)、44.0(95% CI 36.4-47.6)个月,1q组较无1q组均显著缩短(P值分别为0.029、0.038),且1q为影响患者预后的独立不良因素(PFS:HR=1.910,95%CI 1.105-3.303,P=0.020;OS:HR=2.353,95%CI 1.090-5.078,P=0.029)。④伴1q患者中,Btz治疗组深度缓解率(≥非常好的部分缓解率)明显优于非Btz组(62.1%对40.0%,P=0.032),序贯auto-HSCT组较非移植组PFS期明显延长(19对13个月,P=0.048)。⑤基因表达谱分析结果显示,有1q和无1q样本的基因表达谱不同,1q上调1q21区〉50%基因表达,并导致1号染色体及全基因组基因表达的异常,差异显著的基因与DNA修复和细胞周期等相关(P值均〈0.001)。结论1q是影响患者生存的独立预后不良因素,其常伴del(1p)和IgH重排等,Btz诱导治疗可明显提高1q患者的深度缓解率,但不改善患者的总生存,而序贯auto-HSCT巩固治疗则可能延长PFS,基因表达谱分析可能有助于解析1q高危的分子基础。
ObjectiveTo investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients.MethodsA total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform.Results① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of 〉50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle.Conclusions1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.
作者
刘雪莲
杨珮钰
于小源
陈敬成
刘晓亮
白晶
刘英敏
何华
孙京男
樊红琼
张晨
张烨
苏克举
刘春水
谭业辉
高素君
李薇
靳凤艳
Liu Xuelian, Yang Peiyu, Yu Xiaoyuan, Chen Jingcheng, Liu Xiaoliang, Bai Jing, Liu Hngmin, He Hua, Sun Jingnan, Fan Hongqiong, Zhang Chen, Zhang Ye, Su Keju, Liu Chunshui, Tan Yehui, Gao Sujun, Li Wei, Jin Fengyan(Department of Hematology, Cancer Center, the First Hospital of Jilin University, Changchun 130012, Chin)
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2018年第5期408-413,共6页
Chinese Journal of Hematology
基金
国家自然科学基金(81471165、81670190)
吉林省卫生和计划生育研究计划(20142041)
关键词
多发性骨髓瘤
1q21扩增
硼替佐米
造血干细胞移植
预后
Multiple myeloma
1q21 amplification
Bortezomib
Hematopoietic stem cell transplantation
Prognosis