Association Between the Immunohistochemical GCB/non GCB Classification and the Outcome of the Patient With Diffuse Large B - Cell Lymphoma Treated With Rituximab - CHOP Regimen: Single Centre Experience

Abstract

Diffuse large B-cell lymphoma (DLBCL) is sub-classified in to molecular subgroups that correspond to different stages of lymphocyte development- namely germinal center B-cell (GCB) and non- germinal center B-cell DLBCL (non-GCB). In fact, some studies suggest that the distinction between the GCB subgroup and non-GCB had important prognostic implications in the cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) treatment era with better outcome for GCB DLBCL patients. However, recently the results from one large prospective study indicated that in Rituximab (R)-CHOP treatment settings other markers than immunohistochemical features predict the outcome of the DLBCL. In order to investigate the prediction value of the immunohistochemical GCB/non GCB classification of DLBCL of the outcome of our DLBCL patient treated with the R-CHOP regimen we conducted a retrospective study. Our study enrolled 132 DLBCL patients diagnosed and treated with R-CHOP regimen at the University Clinic of Hematology in the period between February 2002 and December 2007. The median follow-up of the patients was 36 months. The biopsy samples were immunostained and analyzed for markers of germinal center (BCL6), post-germinal center (MUM1) and apoptosis (BCL2). The patients were categorized as GCB subgroup (68; 51, 6%) or non-GCB subgroup (64; 48, 4%). The median overall survival time (OS) were 65, 25 months in GCB group and 61, 1 month in non-GCB group, and time to treatment (TT) were 60, 85 and 57,75 months respectively for the both groups. The groups were statistically comparable regarding the both parameters. They were also comparable regarding the age, gender distributions and all others already established prognostic parameters as performance status, advanced International Prognostic Index (IPI), albumin level except for the low IPI 0-2 which was statistically associated with the GCB group (p=.024). In this retrospective study the addition of rituximab to CHOP-based chemotherapy in patients with GCB DLBCL was not associated with statistical survival advantage and better outcome. Also the study indicates that immunohistochemical markers do not really reflect the molecular diversity of the tumor. In that line, results support the studies that suggest that Rituximab eliminates or modulates the significance of some already established prognostic markers for DLBCL. In context of the modern therapy, previously recognized markers should be re-evaluated and new prognostic indicators for DLBL has to be identified.