4th Palermo Conference on INNOVATIVE THERAPIES FOR LYMPHOID MALIGNANCIES
Published online 1 October 2009
Haematologica, Vol 95, Issue 1, 96-101 doi:10.3324/haematol.2009.007203
Copyright © 2010 by Ferrata Storti Foundation
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Malignant Lymphomas

Correlations between BCL6 rearrangement and outcome in patients with diffuse large B-cell lymphoma treated with CHOP or R-CHOP

Jesse Shustik1, Guangming Han2, Pedro Farinha2, Nathalie A. Johnson2, Susana Ben Neriah2, Joseph M. Connors1, Laurie H. Sehn1, Douglas E. Horsman2, Randy D. Gascoyne2, Christian Steidl2

1 Division of Medical Oncology
2 Department of Pathology and Laboratory Medicine, BC Cancer Agency, University of British Columbia, Vancouver, Canada

Correspondence: Christian Steidl, Department of Pathology, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada. E-mail: csteidl{at}bccancer.bc.ca

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).

Design and 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.

Key words: diffuse large B-cell lymphoma, biomarkers, BCL6, FISH, rituximab.