Prognostic impact of tumor microenvironment in diffuse large B-cell lymphoma uniformly treated with R-CHOP chemotherapy

Abstract

Objectives: We evaluated the prognostic impact of cell-oforigin classification as well as intratumoral regulatory T cells (Tregs), macrophages, and microvessel density (MVD) on 115 patients (74 in the training set and 41 in the validation set) diagnosed with de novo diffuse large B-cell lymphoma (DLBCL) and uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. Methods: The prognostic impact of Tregs, macrophages, and MVD was evaluated using FOXP3, CD68, and CD34 immunohistochemical stains, respectively. In addition, we designed a scoring system where 1 point was awarded per each adverse prognostic factor, including non-germinal center B-cell-like subtype, FOXP3 17% or more, CD68 less than 2%, and MVDless than 800 vessels/mm2. Results: Although only MVD was statistically significant on multivariate analysis, the scoring system significantly segregated patients into low- and high-risk groups. Patients having two or more adverse prognostic factors (high-risk group) demonstrated significantly worse event-free and progression- free survivals in the training set and event-free survival in the validation set. Conclusions: The concomitant evaluation of cell of origin along with tumor microenvironment components identifies patients with DLBCL treated with R-CHOP chemotherapy portraying a worse prognosis.