PROGNOSTIC-SIGNIFICANCE OF BCL-2 EXPRESSION AND BCL-2 MAJOR BREAKPOINT REGION REARRANGEMENT IN DIFFUSE LARGE-CELL NON-HODGKINS-LYMPHOMA - ABRITISH NATIONAL LYMPHOMA INVESTIGATION STUDY

The Bcl-2 protein is capable of preventing apoptosis, and in vitro evi dence suggests a role in drug resistance. It is expressed and the gene is rearranged in a proportion of cases of large-cell non-Hodgkin's ly mphoma (NHL), but the clinical significance of these findings is contr oversial. The purpose of this study was to determine the influence of both Bcl-2 expression and major breakpoint region (MBR) bcl-2 rearrang ement in a large cohort of prospectively accrued patients with interme diate-grade B-cell NHL treated in a standardized manner. All patients with Working Formulation F, G, or H NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in Briti sh National Lymphoma Investigation studies between July 1974 and April 1992 were considered for this study if the appropriate paraffin block s were available. Paraffin sections from the diagnostic specimen were analyzed for evidence of MBR rearrangement using a polymerase chain re action-based method, and for Bcl-2 expression using immunohistochemist ry. Failure to achieve complete remission (CR), relapse, death from NH L, and deaths from all causes were used as end points to measure CR ra te, actuarial relapse rate, actuarial survival from NHL, and actuarial overall survival. One hundred sixty-one suitable patients were identi fied and tested for the bcl-2 MBR translocation, with 27 (17%) found t o be positive; 153 of these patients were tested with immunocytochemis try, and 84 (55%) showed evidence of Bcl-2 expression. For patients wh o achieved CR from the initial treatment, the relapse rate was signifi cantly higher in those with Bcl-2 expression than in those without. In addition, multivariate analysis identified Bcl-2 expression as the on ly factor significantly related to relapse rate in the subjects measur ed. The cause-specific survival for NHL in the series as a whole was s ignificantly lower in patients with Bcl-2 expression than in those wit hout. MBR status had no significant influence on any of the outcome me asures, but the number of MBR-positive patients was relatively small, and larger studies are required. In conclusion, in Working Formulation F, G, and H NHL of B-cell type, expression of Bcl-2 protein predicted independently for relapse. (C) 1996 by The American Society of Hemato logy.