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

Vojnosanit Pregl. 2009 Sep;66(9):738-43. doi: 10.2298/vsp0909738p.

Abstract

Background/aim: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / analysis
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Female
  • Humans
  • Ki-67 Antigen / analysis*
  • Lymphoma, Large B-Cell, Diffuse / chemistry*
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Male
  • Middle Aged
  • Prednisone / therapeutic use
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / analysis*
  • Survival Rate
  • Vincristine / therapeutic use
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CHOP protocol