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


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.
Veelken
H
H
Department of Internal Medicine I (Hematology/Oncology), Freiburg university Medical Center, Freiburg, Germany. hendrik.veelken@uniklinik-freiburg.de
Vik Dannheim
S
S
Schulte Moenting
J
J
Martens
U M
UM
Finke
J
J
Schmitt-Graeff
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018858:Germinal Center; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D016393:Lymphoma, B-Cell / Q000737:chemistry* / Q000235:genetics / Q000628:therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry* / Q000235:genetics / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D015260:Neprilysin / Q000032:analysis; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000032:analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D006684:HLA-DR Antigens; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D015260:Neprilysin