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.
Division of Medical Oncology, Laboratory Medicine, BC Cancer Agency, University of British Columbia, Vancouver, Canada.
Jesse
J
Shustik
Guangming
G
Han
Pedro
P
Farinha
Nathalie A
NA
Johnson
Susana
S
Ben Neriah
Joseph M
JM
Connors
Laurie H
LH
Sehn
Douglas E
DE
Horsman
Randy D
RD
Gascoyne
Christian
C
Steidl
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