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Annals of Oncology Advance Access originally published online on March 29, 2007
Annals of Oncology 2007 18(5):931-939; doi:10.1093/annonc/mdm012
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© 2007 European Society for Medical Oncology

hematologic malignancies

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

H Veelken1,*, S Vik Dannheim1, J Schulte Moenting2, UM Martens1, J Finke1 and A Schmitt-Graeff3

1 Departments of Internal Medicine I (Hematology/Oncology)
2 Department of Biometry and Statistics
3 Department of Pathology, Freiburg University Medical Center, Freiburg, Germany

* Correspondence to: Dr H. Veelken, Department of Hematology/Oncology, University Medical Center, Hugstetter Strasse 55, D-79106 Freiburg, Germany. Tel: +49-761-270-7175; Fax: +49-761-270-7177; E-mail: hendrik.veelken{at}uniklinik-freiburg.de

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.

Key words: Bcl-6 protein, diffuse large-cell lymphoma, hematopoietic stem-cell transplantation, HLA-DR antigens, immunohistochemistry

Received for publication August 24, 2006. Revision received December 19, 2006. Accepted for publication January 11, 2007.


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