多发性骨髓瘤中IGH缺失的临床特征与预后

The clinical characteristics and prognosis of IGH deletion in multiple myeloma.

作者信息

He Haiyan, Fu Weijun, Jiang Hua, Du Juan, Zhou Lili, Zhang Chunyang, Xi Hao, Li Rong, Hou Jian

机构信息

Myeloma and Lymphoma Center, Department of Hematology, Changzheng Hospital, Shanghai, China.

出版信息

Leuk Res. 2015 May;39(5):515-9. doi: 10.1016/j.leukres.2015.02.010. Epub 2015 Mar 18.

DOI:10.1016/j.leukres.2015.02.010

PMID:25817540

Abstract

OBJECTIVE

To analyze the frequency, clinical characteristics, and prognosis of IGH deletion in multiple myeloma (MM).

METHODS

A total of 310 consecutive patients with multiple myeloma were analyzed. Among them 251 patients were newly diagnosed and 59 patients were previously treated, fluorescence in situ hybridization (FISH) with IGH break apart probes were done for each case. Patterns of IGH deletion, response rate, overall survival, and progression free survival were analyzed.

RESULTS

Several patterns of IGH deletion were identified, including monoallelic deletion of whole locus of IGH, monoallelic deletion of 3' IGH, monoallelic deletion of 5' IGH, biallelic deletion of 3' IGH deletion, and complicated deletions with various types. The incidence rate of IGH deletion was 22.7% (57/251) in newly diagnosed patients and 27.2% (16/59) in previously treated patients, no significant difference was found between the two groups (p=0.375). IGH deletion was associated with κ light chain M component (p<0.001), 13q deletion (p=0.006), and absence of t(4; 14)(p=0.033). In the cases with 13q deletion, the frequency of IGH deletion is 3.5% (1/28) in patients with t(4;14) and 40.5% (32/79) in patients without t(4;14), significant difference was found (p=0.006). We further analyzed the response rates of patients with IGH deletion who received a uniform induction regimen of PAD composing of bortezomib, epirubicin, and dexamethasone. Overall response rate (ORR) in patients with IGH deletion was better than that in patients without IGH deletion (87.5 vs. 73.6%, p<0.001), while no significant difference was found in survival analysis, either OS or PFS (p=0.158 and p=0.177, respectively).

CONCLUSION

IGH deletion is frequent in multiple myeloma, the incidence rate was higher in patients with 13q deletion and without t(4;14). Patients with IGH deletion had better ORR to PAD induction therapy, while it has no influence on the prognosis of multiple myeloma.

摘要

目的

分析多发性骨髓瘤（MM）中IGH缺失的频率、临床特征及预后。

方法

共分析310例连续的多发性骨髓瘤患者。其中251例为新诊断患者，59例为既往接受过治疗的患者，对每例患者均采用IGH分离探针进行荧光原位杂交（FISH）检测。分析IGH缺失模式、缓解率、总生存期和无进展生存期。

结果

确定了几种IGH缺失模式，包括IGH整个基因座的单等位基因缺失、IGH 3'端的单等位基因缺失、IGH 5'端的单等位基因缺失、IGH 3'端的双等位基因缺失以及各种类型的复杂缺失。新诊断患者中IGH缺失的发生率为22.7%（57/251），既往接受过治疗的患者中为27.2%（16/59），两组之间无显著差异（p = 0.375）。IGH缺失与κ轻链M成分相关（p < 0.001）、13q缺失相关（p = 0.006）以及不存在t(4;14)相关（p = 0.033）。在有13q缺失的病例中，有t(4;14)的患者中IGH缺失的频率为3.5%（1/28），无t(4;14)的患者中为40.5%（32/79），差异有统计学意义（p = 0.006）。我们进一步分析了接受由硼替佐米、表柔比星和地塞米松组成的PAD统一诱导方案的IGH缺失患者的缓解率。IGH缺失患者的总缓解率（ORR）优于无IGH缺失的患者（87.5%对73.6%，p < 0.001）而在生存分析中，总生存期（OS）或无进展生存期（PFS）均未发现显著差异（分别为p = 0.158和p = 0.177）。