TY - JOUR
T1 - Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP
T2 - A prospective correlative study
AU - Winter, Jane N.
AU - Weller, Edie A.
AU - Horning, Sandra J.
AU - Krajewska, Maryla
AU - Variakojis, Daina
AU - Habermann, Thomas M.
AU - Fisher, Richard I.
AU - Kurtin, Paul J.
AU - Macon, William R.
AU - Chhanabhai, Mukesh
AU - Felgar, Raymond E.
AU - Hsi, Eric D.
AU - Medeiros, L. Jeffrey
AU - Weick, James K.
AU - Reed, John C.
AU - Gascoyne, Randy D.
PY - 2006/6/1
Y1 - 2006/6/1
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2005-10-4222
DO - 10.1182/blood-2005-10-4222
M3 - Article
C2 - 16449523
AN - SCOPUS:33645791771
SN - 0006-4971
VL - 107
SP - 4207
EP - 4213
JO - Blood
JF - Blood
IS - 11
ER -