Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study
Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study
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DOI：
10.1182/blood-2005-10-4222
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发表时间：
2006-06-01
期刊：
影响因子：
20.3
通讯作者：
Gascoyne, Randy D.
中科院分区：
文献类型：
--
作者：
Winter, Jane N.;Weller, Edie A.;Gascoyne, Randy D.
Bcl-6蛋白表达是生发中心起源的标志物，与弥漫性大B细胞淋巴瘤（DLBCL）的良好预后相关。为了确定利妥昔单抗（R）加入环磷酰胺、多柔比星、长春新碱和泼尼松（CHOP）化疗时该标志物的预后意义，我们通过免疫组织化学染色对199例石蜡包埋标本进行了Bcl-6蛋白表达的前瞻性研究，这些标本来自参加美国Intergroup III期试验的患者，该试验比较了R-CHOP与CHOP联合或不联合维持R。在Bcl-6（-）患者中，与单独使用CHOP相比，单独使用R-CHOP治疗的患者的无失败生存期（FFS）和总生存期（OS）延长（2年FFS 76% vs 9%，P < .001; 2年OS 79% vs 17%，P < .001）。相反，对于Bcl-6（+）病例，在治疗组之间未检测到IFFS和OS差异。在多变量分析中，治疗组（CHOP与R-CHOP）是Bcl-6-亚组的FFS（P < .001）和OS（P < .001）的主要决定因素，而国际预后指数风险组是Bcl-6（+）病例中唯一显著的预后预测因素。Bcl-2蛋白表达在两组中均不能预测预后。在本研究中，我们观察到仅在Bcl-6（-）DLBCL病例中在CHOP中加入R治疗失败和死亡的减少。我们的发现，Bcl-6（+）的情况下，没有受益于R添加到CHOP需要独立的确认。
Bcl-6 protein expression, a marker of germinal center origin, has been associated with a favorable prognosis in diffuse large B-cell lymphoma (DLBCL). To determine the prognostic significance of this marker when rituximab (R) was added to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, we prospectively studied Bcl-6 protein expression by immunolhistochemical staining of 199 paraffin-embedded specimens from patients enrolled in the US Intergroup phase 3 trial comparing R-CHOP to CHOP with or without maintenance R. In Bcl-6(-) patients, failure-free survival (FFS) and overall survival (OS) were prolonged for those treated with R-CHOP alone compared to CHOP alone (2-year FFS 76% versus 9%, P < .001; 2-year OS 79% versus 17%, P < .001). In contrast, no differences in IFFS and OS were detected between treatment arms for Bcl-6(+) cases. In the multivariate analysis, treatment arm (CHOP versus R-CHOP) was the major determinant of both FFS (P < .001) and OS (P < .001) for the Bcl-6- subset, whereas the International Prognostic Index risk group was the only significant predictor of outcome among Bcl-6(+) cases. Bcl-2 protein expression was not predictive of outcome in either group. in this study, we observed a reduction in treatment failures and death with the addition of R to CHOP in Bcl-6(-) DLBCL cases only. Our finding that Bcl-6(+) cases did not benefit from the addition of R to CHOP requires independent confirmation.