Correlations between BCL6 rearrangement and outcome in patients with diffuse large B-cell lymphoma treated with CHOP or R-CHOP.
BACKGROUND
BCL6 gene rearrangement is the most frequent chromosomal abnormality in diffuse large B-cell lymphoma, a malignancy characterized by genetic heterogeneity and wide variability in clinical outcome. The prognostic significance of BCL6 rearrangement has not been evaluated in the context of rituximab therapy for diffuse large B-cell lymphoma. We analyzed the effect of the BCL6 rearrangement on survival in patients with diffuse large B-cell lymphoma treated with CHOP and CHOP plus rituximab (R-CHOP).


METHODS
BCL6 rearrangement status was analyzed by fluorescence in situ hybridization with break-apart probes in 164 patients with diffuse large B-cell lymphoma treated with CHOP (n=65) or R-CHOP (n=99). Cell-of-origin immunophenotype including BCL6 protein expression were determined by immunohistochemistry on a tissue microarray.


RESULTS
BCL6 rearrangement was detected in 19.5% of cases. The presence of the gene rearrangement was associated with a non-germinal center B-cell immunophenotype (P=0.006), and showed no correlation with BCL6 protein expression. A trend toward inferior overall survival was observed in association with the BCL6 rearrangement among patients treated with R-CHOP (P=0.08), but not among patients treated with CHOP (P=0.64). However, BCL6 rearrangement also correlated with a high International Prognostic Index score (P=0.02), and did not demonstrate independent prognostic value by multivariate analysis.


CONCLUSIONS
The introduction of rituximab may have altered the prognostic impact of BCL6 gene rearrangement in patients with diffuse large B-cell lymphoma. However, prospective analysis within large randomized clinical trials will be needed to clarify the prognostic significance of this biomarker in the rituximab era.
Shustik
Jesse
J
Division of Medical Oncology, Laboratory Medicine, BC Cancer Agency, University of British Columbia, Vancouver, Canada.
Han
Guangming
G
Farinha
Pedro
P
Johnson
Nathalie A
NA
Ben Neriah
Susana
S
Connors
Joseph M
JM
Sehn
Laurie H
LH
Horsman
Douglas E
DE
Gascoyne
Randy D
RD
Steidl
Christian
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000235:genetics; D015331:Cohort Studies; D003520:Cyclophosphamide; D004268:DNA-Binding Proteins / Q000235:genetics*; D004317:Doxorubicin; D005260:Female; D005500:Follow-Up Studies; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011241:Prednisone; D051560:Proto-Oncogene Proteins c-bcl-6; D012189:Retrospective Studies; D000069283:Rituximab; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D014750:Vincristine; D055815:Young Adult
D058846:Antibodies, Monoclonal, Murine-Derived; C084103:BCL6 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone