染色体异常对硼替佐米治疗初治多发性骨髓瘤疗效及预后的影响

Influence of Chromosome Abnormality on Therapeutic Efficacy and Prognosis of Newly Diagnosed Multiple Myeloma Treated with Bortezomib

目的:探讨染色体异常对硼替佐米治疗初治多发性骨髓瘤(MM)疗效及预后的影响。方法:收集本院2008年1月至2011年12月收治的152例初治MM患者资料,对患者均采用以硼替佐米为主的多药联合化疗方案治疗并于4个用期后分析疗效;同时制备染色体标本,分别采用R显带技术和DNA序列探针进行核型和基因(RB1缺失、D13S319缺失、P53缺失、IgH重排和1q21扩增)分析,分析总体疗效及染色体异常患者的疗效和远期生存情况,采用Kaplan-Meier法进行生存分析,COX风险比例模型进行多因素分析。结果:152例MM患者中检出核型异常者47例(30.92%),RB1异常者43例(28.29%),D13S319异常者49例(32.24%),P53异常者30例(19.74%),IgH异常者58例(38.16%),1q21异常者33例(21.71%)。全组152例患者的疗效均可以评价,其中获CR、nCR、PR、MR和PD者分别为24、54、21、14和39例,总有效率为74.34%,显效率为50.66%;核型、D13S319、P53及IgH异常者的总有效率和显效率均低于相应正常者(P<0.05),RB1、1q21异常者的显效率均低于相应正常者(P<0.05);全组随访22-72个月,中位随访52.0个月,截至随访日期,中位生存期(OS)尚未达。不同染色体异常者的中位OS均低于正常者(P<0.05);经COX多因素模型分析发现,染色体异常均为影响MM预后的独立因素,如核型、RB1、D13S319、P53、IgH和1q21异常相对于正常者的风险分别提高了3.124、1.177、2.639、6.552、2.045和7.264倍,差异均有统计学意义。结论:染色体异常可影响硼替佐米治疗初治MM的疗效及预后,检测染色体异常对初治MM的治疗有一定参考价值。

Objective：To explore the influence of chromosome abnormality on therapeutic efficacy and prognosis of patients with newly diagnosed multiple myeloma（MM） treated with bortezomib.Methods：The clinical data of 152 patients with newly diagnosed MM were collected from January 2008 to December 2011.All patients received bortezomib-based chemotherapy and the therapeutic efficacy were investigated for 4 cycles later.The R banding and DNA probe were used to analyze the chromosome and gene（RBI deletion,D13S319 deletion,P53 deletion,IgHrearrangement and1q21 amplification） of chromosome specimens.Moreover,the therapeutic efficacy and long-term survival data were analyzed among the patients with different types of chromosomal abnormality.The Kaplan-Meier was applied to analyze survival,and COX risk proportional model was used for multivariate analysis.Results：Among 152 patients with MM,there were 47 cases（30.92%） of abnormal karyotype,43 cases（28.29%） of abnormal RBI,49 cases（32.24%） of abnormal D13S319,30 cases（19.74%） of abnormal P53,58 cases（38.16%） of abnormal IgH and 33 cases（21.71%） of abnormal chromosome 1q11.All the patients were evaluable for the therapeutic efficacy,including 24 CR,54 nCR,21 PR,14 MR and 39 PD with response rate of 74.34%and remission rate of 50.66%.Compared with normal controls,the response and remission rate were lower than that in the patients with abnormal karyotype of D13S319,P53 or IgH,and remission rate was lower in the patients with RBI or Iqll（P〈0.05）.All the patients were followd-up（median：52.0 months,range;22-72 months）,but median overall survival（OS） was not yet reached at the end of the follow-up.The median OS was in the patients with different chromosome versus the normal subjects（P〈 0.05）.The chromosome abnormaUty was found to affect the prognosis of MM by COX multivariate analysis.In regard to the normal subjects,the risk for poor prognosis increased by 1.177,2.639,6.552,3.124,2.045 and 7.264 fold in the patients with abnormal Karyotype of RBI,D13S319,P53,IgH and lq21,respectively.Conclusion：The abnormality of chromosome can influence the efficacy and prognosis of newly diagnosed MM patients treated with bortezomib.The detection of chromosomal abnormalities has a certain reference value for the treatment of primary MM.