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