Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma. A clinicobiological study of the GELA
Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma. A clinicobiological study of the GELA
复制标题
DOI：
10.3324/haematol.2011.061507
复制
发表时间：
2012-10-01
期刊：
影响因子：
--
通讯作者：
Haioun, Corinne
中科院分区：
文献类型：
--
作者：
Delfau-Larue, Marie-Helene;de Leval, Laurence;Haioun, Corinne
背景在血管免疫母细胞性T细胞淋巴瘤中，与B淋巴细胞活化相关的症状是常见的，并且在肿瘤组织中发现不同数量的CD 20（+）大B母细胞，通常被EB病毒感染。我们推测，破坏假定的B-T相互作用和/或消耗的EB病毒水库的抗CD 20单克隆抗体（利妥昔单抗）可以提高常规chemotherapy.Design and MethodsTwenty五个新诊断的患者进行治疗，在第二阶段的研究，8个周期的利妥昔单抗+化疗（R-CHOP 21）。肿瘤浸润，B-母细胞和EB病毒状态在肿瘤组织和外周血中的诊断充分的特点，并与临床outcome.Results完全缓解率为44%（95%CI，24%至65%）观察。中位随访时间为24个月，2年无进展生存率为42%（95% CI，22%-61%），总生存率为62%（95% CI，40%-78%）。外周血单个核细胞中EB病毒DNA的检测（14/21例患者）与淋巴结中的EB病毒评分相关（P100拷贝/μ g DNA）与较短的无进展生存期相关结论我们报告了首次同时针对肿瘤性T细胞和微环境相关的CD 20（+）的临床试验结果。血管免疫母细胞性T细胞淋巴瘤患者的B淋巴细胞，显示在常规化疗基础上加用利妥昔单抗无明显获益。循环EB病毒和循环肿瘤细胞之间的强关系，以前没有描述过，突出显示。(This试验在www.clinicaltrials.gov上注册为NCT 00169156。
BackgroundIn angioimmunoblastic T-cell lymphoma, symptoms linked to B-lymphocyte activation are common, and variable numbers of CD20(+) large B-blasts, often infected by Epstein-Barr virus, are found in tumor tissues. We postulated that the disruption of putative B-T interactions and/or depletion of the Epstein-Barr virus reservoir by an anti-CD20 monoclonal antibody (rituximab) could improve the clinical outcome produced by conventional chemotherapy.Design and MethodsTwenty-five newly diagnosed patients were treated, in a phase II study, with eight cycles of rituximab + chemotherapy (R-CHOP21). Tumor infiltration, B-blasts and Epstein-Barr virus status in tumor tissue and peripheral blood were fully characterized at diagnosis and were correlated with clinical outcome.Results A complete response rate of 44% (95% CI, 24% to 65%) was observed. With a median follow-up of 24 months, the 2-year progression-free survival rate was 42% (95% CI, 22% to 61%) and overall survival rate was 62% (95% CI, 40% to 78%). The presence of Epstein-Barr virus DNA in peripheral blood mononuclear cells (14/21 patients) correlated with Epstein-Barr virus score in lymph nodes (P100 copy/mu g DNA) was associated with shorter progression-free survival (P=0.06).Conclusions We report here the results of the first clinical trial targeting both the neoplastic T cells and the microenvironment-associated CD20(+) B lymphocytes in angioimmunoblastic T-cell lymphoma, showing no clear benefit of adding rituximab to conventional chemotherapy. A strong relationship, not previously described, between circulating Epstein-Barr virus and circulating tumor cells is highlighted. (This trial was registered at www.clinicaltrials.gov as NCT00169156.)