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

Jane N. Winter, Edie A. Weller, Sandra J. Horning, Maryla Krajewska, Daina Variakojis, Thomas M. Habermann, Richard I. Fisher, Paul J. Kurtin, William R. Macon, Mukesh Chhanabhai, Raymond E. Felgar, Eric D. Hsi, L. Jeffrey Medeiros, James K. Weick, John C. Reed, Randy D. Gascoyne

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234 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4207-4213
Number of pages7
JournalBlood
Volume107
Issue number11
DOIs
StatePublished - Jun 1 2006

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Winter, J. N., Weller, E. A., Horning, S. J., Krajewska, M., Variakojis, D., Habermann, T. M., Fisher, R. I., Kurtin, P. J., Macon, W. R., Chhanabhai, M., Felgar, R. E., Hsi, E. D., Medeiros, L. J., Weick, J. K., Reed, J. C., & Gascoyne, R. D. (2006). Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: A prospective correlative study. Blood, 107(11), 4207-4213. https://doi.org/10.1182/blood-2005-10-4222