Friedberg Jonathan W
Samuel Durand Professor of Medicine, University of Rochester, Rochester, NY.
Hematology Am Soc Hematol Educ Program. 2015;2015:618-24. doi: 10.1182/asheducation-2015.1.618.
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non Hodgkin lymphoma in the Western world, and is potentially curable with standard R-CHOP chemoimmunotherapy. Historically, clinical risk assessments provided prognostic information, but did not define treatment approach. We are now in an era where the heterogeneity of DLBCL is defined genetically and molecularly, and rational subset-specific therapeutic targets are guiding clinical trials. Primary mediastinal DLBCL is a unique clinicopathologic entity, and alternatives to R-CHOP may confer superior outcome. Rearrangement of the myc oncogene occurs in ~10% of patients with DLBCL, and confers a very poor prognosis with standard R-CHOP, particularly when there is concomitant rearrangement of bcl-2, a condition referred to as "double-hit" DLBCL. A larger subset of DLBCL demonstrates overexpression of both myc and bcl-2 by immunohistochemistry. Cell of origin, determined by gene expression analysis, immunohistochemistry algorithms, or a novel Lymph2Cx platform, provides prognostic information, and guides therapeutic decisions in both relapsed and de novo disease. This article will define specific subsets of DLBCL and provide subtype-specific treatment options, including novel approaches under investigation. Understanding these key features of the pathology report, and limitations of these assays defining subsets of DLBCL, allows for an evolving precision medicine approach to this disease.
弥漫性大B细胞淋巴瘤（DLBCL）是西方世界非霍奇金淋巴瘤最常见的亚型，采用标准的R-CHOP化疗免疫疗法有可能治愈。从历史上看，临床风险评估可提供预后信息，但无法确定治疗方法。我们现在所处的时代，DLBCL的异质性已从基因和分子层面得到明确，合理的亚型特异性治疗靶点正引领着临床试验。原发性纵隔DLBCL是一种独特的临床病理实体，R-CHOP之外的治疗方案可能带来更好的疗效。约10%的DLBCL患者存在myc癌基因重排，采用标准R-CHOP治疗时预后很差，尤其是当伴有bcl-2重排时，这种情况被称为“双打击”DLBCL。更大比例的DLBCL通过免疫组化显示myc和bcl-2均过表达。通过基因表达分析、免疫组化算法或新型Lymph2Cx平台确定的细胞起源，可提供预后信息，并指导复发和初发疾病的治疗决策。本文将定义DLBCL的特定亚型，并提供亚型特异性治疗方案，包括正在研究的新方法。了解病理报告的这些关键特征以及这些定义DLBCL亚型的检测方法的局限性，有助于采用不断发展的精准医学方法来治疗这种疾病。
