Immunophenotype as prognostic factor for diffuse large B-cell lymphoma in patients undergoing clinical risk-adapted therapy

Ann Oncol. 2007 May;18(5):931-9. doi: 10.1093/annonc/mdm012. Epub 2007 Mar 29.

Abstract

Background: For patients with diffuse large B-cell lymphoma (DLBCL), the International Prognostic Index (IPI) predicts the likelihood for cure with chemotherapy. Biological parameters, including expression of Bcl-6, Bcl-2, CD10, major histocompatibility complex class II, and categorization as germinal center (GC) type have been described as IPI-independent prognostic factors.

Patients and methods: Biological parameters were evaluated retrospectively by immunohistochemistry in 60 consecutive DLBCL patients of the prerituximab era. Forty-one of 60 patients underwent a risk-adapted treatment strategy including autologous stem-cell transplantation for high-risk patients (age-adjusted IPI = 2-3; slow response to chemotherapy).

Results: Bcl-6 expression was associated with superior overall survival (OS) independently of the IPI. Inferior progression-free survival (PFS) was independently correlated with high expression of Bcl-2 and low positivity for HLA-DR and CD10. Distinction into GC and non-GC DLBCL on the basis of Bcl-6, CD10, and IRF-4 expression had no independent prognostic value. Within the risk-adapted treatment strategy, only HLA-DR retained a prognostic impact on OS (P = 0.0058) and PFS (P = 0.0002).

Conclusions: In 60 patients with DLBCL treated with risk-adapted therapy, immunohistochemical subcategorization of DLBCL into GC and non-GC type has little clinical value. The IPI-associated risk appears to be mitigated by intensified upfront therapy. Low HLA-DR expression is associated with poor outcome after intensified upfront therapy. Therefore, additional treatment modalities appear to be required.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Biomarkers, Tumor / analysis*
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Germinal Center
  • HLA-DR Antigens / analysis
  • Humans
  • Immunohistochemistry
  • Immunophenotyping*
  • Lymphoma, B-Cell / chemistry*
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / therapy
  • Lymphoma, Large B-Cell, Diffuse / chemistry*
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / therapy
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Neprilysin / analysis
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-6 / analysis
  • Retrospective Studies
  • Survival Analysis
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • HLA-DR Antigens
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-6
  • Neprilysin