Poor outcome in patients with diffuse large B-cell lymphoma is associated with high percentage of bcl-2 and Ki 67-positive tumor cells

Abstract

Newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) tretaed with immunochemotherapy have durable remission and improved overall survival. It is important to identify high risk patients who may benefit from even more effective therapies. In a group of 50 newly diagnosed patients with DLBCL, treated with CHOP/R-CHOP (cyclophosphemide doxorubicine, vincristine, prednisone with or without rituximab) regimen, we analyzed the prognostic value of the expression of Ki67 and bcl-2 at diagnosis as well as other standard clinical parameters: International Prognostic Index (IPI), bulky disease, extranodal distribution and lactat dehydrogenase (LDH). Significance was tested according to response rate and overall survival. Univariate survival analysis showed that high IPI had a statistically significant negative influence on overall and event free survival time (log rank, p < 0.01). The log rank test analysis signified that patients with a high proliferative fraction (Ki-67 > 60%) had a worse overall survival rate (OS5y) of 40% compared to those with low proliferation (Ki-67 < 60%) with OS5y of 80% (p < 0.01). There was a clear difference between bcl-2 positivity (treshold 50%) and the achievement of complete remission (66% vs 86% in patients with bcl-2 high and low levels respectively, p < 0.05). In survival analysis, patients with low bcl-2 expression had significantly higher OS5y - 68% compared to those with high bcl-2+ with OS5y 37% (p < 0.05). Multivariate analysis performed by Cox model revealed that IPI > 3, high Ki-67+, bcl-2 positivity had a significant independent prognostic value concerning overall survival (p < 0.05). An initial high IPI score associated with high Ki-67+ and bcl2+ could represent possible predictive factors of poor prognosis, which would help to identify a high risk subgroup of newly diagnosed DLBCL.