Double-hit淋巴瘤诊治新进展

荧光原位杂交技术（FISH）是诊断“二次打击”淋巴瘤（double-hit lymphoma ,DHL ）的金标准,并能够指导治疗。C-myc/Bcl-2 和C-myc/Bcl- 6 双表达淋巴瘤（double-expression lymphoma ,DEL ）的发病率高于DHL ,约2/ 3 的DEL 为non-GCB 亚型,而DHL 大部分是GCB 亚型。对于免疫组织化学检验结果,C-myc/Bcl- 2 或Bcl- 6 高表达的患者需作FISH检查确诊DHL ,但是目前对于界定C-myc/Bcl- 2 或Bcl- 6 高表达的临界值仍存在争议。DHL 具有相对独特的临床特征和不良预后,关于Myc/Bcl- 6 DHL 和Myc/Bcl-2 DHL 之间的预后差异目前还未达成共识。尽管高强度的化疗如R-EPOCH/HyperCVAD 可以延长DHL 患者的无进展生存期（progression-free survival ,PFS）和总生存期（over all survival,OS）,但总体来说现有治疗方案对DHL 疗效不佳。特异性的靶向药物有望取代传统化疗的主导地位,改善其不良预后,并为其制定个体化治疗提供依据和方向。根据以上特征,2016年新版WHO淋巴瘤分类将其定义为高级别B 细胞淋巴瘤伴Bcl- 2 或/ 和Bcl- 6 与Myc 基因重排的独立亚型。本文就DHL 的定义、发病机理、争论的焦点及最新的诊治进展作一综述。 

Research progress on the diagnosis and treatment of double-hit lymphoma

Double-hit lymphoma (DHL) refers to a group of mature B-cell lymphoma with Myc and Bcl- 2 or Bcl- 6 genomic rearrange -ments. DHL mainly occurs in patients with diffused large B-cell lymphoma (DLBCL) and B-cell lymphoma unclassifiable (BCLU). Fluores-cence in situ hybridization (FISH) is the gold standard for diagnosis and is used as the basis for changing regimen. Double-expression lymphoma (DEL) is more common than cytogenetically defined double-hit cases. Unlike true DHL, which are mostly of GCB type, ~ 2/3 DEL cases are non-GCB type. The cut-off value for immunohistochemistry of C-myc and Bcl-2 should be defined to detect the presence of concurrent gene rearrangements by FISH. DHL is characterized by relatively special clinical characteristics and unfavorable progno-sis. A number of studies have shown that Bcl- 6 DHL are more aggressive than Bcl- 2 DHL. Other studies indicated that Bcl-6 DHL is simi-lar to Bcl- 2 DHL in terms of poor prognosis. Compared with CHOP-like regiment, R-EPOCH/HyperCVAD regimen has good performance on progression free survival (PFS) and even on overall survival (OS). Despite this development, current chemotherapy regimens often have poor efficacy. Novel and specific molecular targeted agents, rather than chemotherapy drugs, may overcome poor prognosis and provide insights into future treatment strategies. On the basis of the above characteristics, DHL is defined as high grade B-cell lympho-ma with Bcl-2/Myc or Bcl-6/Myc double-hit in the 2016WHO classification. In this review, we will issue the definition, pathogenesis, and key points of their argument to examine the diagnosis/treatment of the progress of DHL.