Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Via Solaroli 17, 28100, Novara, Italy,
Adv Exp Med Biol. 2013;792:173-91. doi: 10.1007/978-1-4614-8051-8_8.
Transformation of chronic lymphocytic leukemia (CLL) to aggressive lymphoma is known as Richter syndrome (RS). In the CLL population considered as a whole, the prevalence of RS development ranges from 2 to 7 %. The most common pathologic phenotype at the time of RS transformation is diffuse large B-cell lymphoma (DLBCL), while, in a small fraction of cases, the transformed phase shows pathologic features mimicking Hodgkin lymphoma. TP53 disruption and MYC activation cooperate as dual hits in driving DLBCL transformation. Two biomarkers (NOTCH1 mutations and usage of the immunoglobulin VH CDR3 subset 8) may help in identifying CLL patients at risk of DLBCL transformation to be considered for close monitoring and a careful biopsy policy. In the presence of clinical features suspicious of RS, diagnosis of transformation and choice of the site of biopsy may take advantage of (18)FDG PET/CT. The prognosis of RS transformation is generally highly unfavorable. However, the pattern of survival is not homogeneous and may be predicted on clinical and biological grounds. RS that are clonally unrelated to the paired CLL phase are biologically and clinically different from clonally related cases, and should be considered, and probably managed, as a de novo DLBCL arising in the context of CLL. Rituximab-containing polychemotherapy represents the backbone for induction treatment in patients with clonally related DLBCL transformation. Younger patients who respond to induction therapy should be offered stem cell transplant to prolong survival.
慢性淋巴细胞白血病（CLL）向侵袭性淋巴瘤的转化称为里希特综合征（RS）。在整个 CLL 人群中，RS 发展的患病率为 2%至 7%。RS 转化时最常见的病理表型为弥漫性大 B 细胞淋巴瘤（DLBCL），而在一小部分病例中，转化阶段表现为模仿霍奇金淋巴瘤的病理特征。TP53 缺失和 MYC 激活协同作用，作为双重打击，推动 DLBCL 转化。两个生物标志物（NOTCH1 突变和免疫球蛋白 VH CDR3 亚群 8 的使用）可能有助于识别有 DLBCL 转化风险的 CLL 患者，以考虑进行密切监测和仔细的活检策略。在存在疑似 RS 的临床特征的情况下，转化的诊断和活检部位的选择可能受益于（18）FDG PET/CT。RS 转化的预后通常非常不利。然而，生存模式并不均匀，并且可以根据临床和生物学基础进行预测。与配对的 CLL 期无关的 RS 在生物学和临床上与克隆相关的病例不同，应被视为在 CLL 背景下发生的新发性 DLBCL，并可能进行管理。含利妥昔单抗的化疗方案是克隆相关 DLBCL 转化患者诱导治疗的基础。对诱导治疗有反应的年轻患者应接受干细胞移植以延长生存。
