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G 带检测到的染色体异常变异与基于 R-CHOP 治疗的弥漫性大 B 细胞淋巴瘤的预后相关。

Chromosomal abnormality variation detected by G-banding is associated with prognosis of diffuse large B-cell lymphoma treated by R-CHOP-based therapy.

机构信息

Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.

出版信息

Cancer Med. 2018 Mar;7(3):655-664. doi: 10.1002/cam4.1342. Epub 2018 Feb 23.

Abstract

Diffuse large B-cell lymphoma (DLBCL), which is the most prevalent disease subtype of non-Hodgkin lymphoma, is highly heterogeneous in terms of cytogenetic and molecular features. This study retrospectively investigated the clinical impact of G-banding-defined chromosomal abnormality on treatment outcomes of DLBCL in the era of rituximab-containing immunochemotherapy. Of 181 patients who were diagnosed with DLBCL and treated with R-CHOP or an R-CHOP-like regimen between January 2006 and April 2014, metaphase spreads were evaluable for G-banding in 120. In these 120 patients, 40 were found to harbor a single chromosomal aberration type; 63 showed chromosomal abnormality variations (CAVs), which are defined by the presence of different types of chromosomal abnormalities in G-banding, including 19 with two CAVs and 44 with ≥3 CAVs; and 17 had normal karyotypes. No specific chromosomal break point or numerical abnormality was associated with overall survival (OS) or progression-free survival (PFS), but the presence of ≥3 CAVs was significantly associated with inferior OS rates (hazard ratio (HR): 2.222, 95% confidence interval (CI): 1.056-4.677, P = 0.031) and tended to be associated with shorter PFS (HR: 1.796, 95% CI: 0.965-3.344, P = 0.061). In addition, ≥3 CAVs more frequently accumulated in high-risk patients, as defined by several conventional prognostic indices, such as the revised International Prognostic Index. In conclusion, our results suggest that the emergence of more CAVs, especially ≥3, based on chromosomal instability underlies the development of high-risk disease features and a poor prognosis in DLBCL.

摘要

弥漫性大 B 细胞淋巴瘤(DLBCL)是最常见的非霍奇金淋巴瘤疾病亚型,在细胞遗传学和分子特征方面具有高度异质性。本研究回顾性分析了在利妥昔单抗为基础的免疫化疗时代,G 显带定义的染色体异常对 DLBCL 治疗结果的临床影响。在 2006 年 1 月至 2014 年 4 月期间,接受 R-CHOP 或类似 R-CHOP 方案治疗的 181 例 DLBCL 患者中,有 120 例患者的中期分裂象可进行 G 显带评估。在这 120 例患者中,有 40 例患者存在单一染色体异常类型;63 例患者存在染色体异常变异(CAVs),即 G 显带中存在不同类型的染色体异常,包括 19 例存在两种 CAVs 和 44 例存在≥3 种 CAVs;17 例患者核型正常。没有特定的染色体断裂点或数量异常与总生存(OS)或无进展生存(PFS)相关,但存在≥3 种 CAVs 与较差的 OS 率显著相关(风险比(HR):2.222,95%置信区间(CI):1.056-4.677,P=0.031),且与较短的 PFS 相关(HR:1.796,95%CI:0.965-3.344,P=0.061)。此外,≥3 种 CAVs 在多个传统预后指标(如修订后的国际预后指数)定义的高危患者中更频繁地累积。总之,我们的结果表明,基于染色体不稳定性的更多 CAVs 的出现,尤其是≥3 种 CAVs 的出现,是 DLBCL 中高危疾病特征和不良预后的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc08/5852349/319fa91782cb/CAM4-7-655-g001.jpg

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