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Stromal Gene Signatures Affect Lymphoma Outcomes

Three gene-expression signatures predict survival for B-cell lymphoma after treatment with CHOP or R-CHOP

WEDNESDAY, Nov. 26 (HealthDay News) -- In patients with diffuse large-B-cell lymphoma, differences in immune cells, fibrosis and angiogenesis in the tumor microenvironment affect survival after treatment, according to study findings published in the Nov. 27 issue of the New England Journal of Medicine.

Georg Lenz, M.D., of the National Cancer Institute in Bethesda, Md., and colleagues profiled gene expression in pretreatment biopsy specimens from 181 patients who received cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) and 233 patients who received rituximab in addition to CHOP (R-CHOP).

The researchers found that three gene-expression signatures -- germinal-center B-cell, stromal-1, and stromal-2 -- predicted survival in both groups of patients. They found that the prognostically advantageous stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration while the prognostically disadvantageous stromal-2 signature reflected tumor blood-vessel density.

"The biologic insights gained from our analysis provide a new perspective on current and future clinical trials in diffuse large-B-cell lymphoma," the authors write. "The monoclonal antibody to vascular endothelial growth factor, bevacizumab, is currently being investigated in several phase 2 and phase 3 clinical trials involving patients with diffuse large-B-cell lymphoma. On the basis of our results, it is possible that only a subgroup of such patients -- those with diffuse large-B-cell lymphoma characterized by high relative expression of the stromal-2 signature and increased tumor blood-vessel density -- may benefit from this angiogenesis inhibitor."

Several of the study authors disclose receiving grants and consulting fees from pharmaceutical companies.

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