Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study

Abstract

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 immunohistochemical 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 FFS 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. (Blood. 2006; 107:4207-4213)

The Hans algorithm failed to predict outcome in patients with diffuse large B-cell lymphoma treated with rituximab

“…In other words, GC lymphoma according to one algorithm can be classified as non-GC lymphoma according to another algorithm. Another possible reason may be the issue of determining Bcl-6 positivity, whereby discrepancies in technical performance in different laboratories and the interpretation of samples between individual pathologists have been described in literature [8,24]. Nevertheless, if the algorithms using Bcl-6 (according to Hans or Choi) were modified by its exclusion, they gave similar results as unmodified ones [11].…”

Evaluation of BCL-6, CD10, CD138 and MUM-1 Expression in Diffuse Large B-Cell Lymphoma patients: CD138 is a Marker of Poor Prognosis

“…Colomo et al, 2003;Kojima et al, 2006;Lin et al, 2006;Muris et al, 2006). A study by Winter et al (2006), reported a significantly increased OS in DLBCL patients with positive BCL-6 expression that were treated with the CHOP regimen, but no difference in OS related to BCL-6 expression in patients treated with R-CHOP.…”

Rituximab therapy in malignant lymphoma

“…One interesting observation was the fact that prognostic parameters such as those described in the International Prognostic index seem to loose some importance in patients treated with R-CHOP (Sehn et al, 2007). Even the new prognostic parameters described with microarray gene analyses are less important than bcl-2 or bcl-6 protein expression (Farinha et al, 2006;Mounier et al, 2006;Winter et al, 2006). However, which parameters are associated with the risk of recurrence and dying in patients treated with R-CHOP is not yet described.…”