title: 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.
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. j-winter@northwestern.edu
authors.forename: Jane N
authors.initials: JN
authors.lastname: Winter
authors.forename: Edie A
authors.initials: EA
authors.lastname: Weller
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Horning
authors.forename: Maryla
authors.initials: M
authors.lastname: Krajewska
authors.forename: Daina
authors.initials: D
authors.lastname: Variakojis
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Habermann
authors.forename: Richard I
authors.initials: RI
authors.lastname: Fisher
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kurtin
authors.forename: William R
authors.initials: WR
authors.lastname: Macon
authors.forename: Mukesh
authors.initials: M
authors.lastname: Chhanabhai
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Felgar
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: James K
authors.initials: JK
authors.lastname: Weick
authors.forename: John C
authors.initials: JC
authors.lastname: Reed
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000172:deficiency; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D051560:Proto-Oncogene Proteins c-bcl-6; D000069283:Rituximab; D016019:Survival Analysis; D015996:Survival Rate; D017211:Treatment Failure; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone