Prognostic implications of extranodal involvement in patients with diffuse large B-cell lymphoma treated with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone

The addition of rituximab (R) to standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy has altered the significance of previously recognized prognostic factors. We sought to re-examine the prognostic utility of (1) the number of extranodal sites of disease involvement, and (2) a primary extranodal presentation in patients with DLBCL treated with immunochemotherapy. We retrospectively analyzed all patients with DLBCL diagnosed between January 1979 and May 2006 who were treated with an anthracycline-based therapy with curative intent. In all, 1781 patients were identified, of whom 513 (29%) received R-CHOP. In the R-CHOP group, extranodal involvement as defined by the International Prognostic Index (≥2 sites) was not prognostic on multivariate analysis, but the presence of any extranodal involvement (≥1 site) was associated with decreased progression-free survival (HR 1.6, 95% CI 1.1-2.4, p = 0.024) and overall survival (HR 1.8, 95% CI 1.1-2.7, p = 0.011). A total of 133 (26%) R-CHOP treated patients presented with primary extranodal DLBCL. There was no difference in outcome between patients with primary extranodal and nodal DLBCL, and no primary site of involvement was associated with an inferior outcome. In patients with DLBCL treated with R-CHOP, the presence of extranodal disease remains prognostic, whereas a primary extranodal presentation did not affect outcome.