Modified Number of Extranodal Involved Sites as a Prognosticator in R-CHOP-Treated Patients with Disseminated Diffuse Large B-Cell Lymphoma

BACKGROUND/AIMS: Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP) has improved survival in patients with diffuse large B-cell lymphoma (DLBCL) and weakened the prognostic power of the international prognostic index (IPI). We evaluated the efficacy of the IPI and revised IPI (R-IPI) in patients with DLBCL who were treated with R-CHOP, focusing on extranodal site number (ENS) because extranodal involvement occurs frequently in Koreans. METHODS: A total of 126 R-CHOP-treated patients with stage III/IV DLBCL were analyzed. We performed a retrospective analysis of the clinicopathologic factors and verified the predictive power of the standard IPI and R-IPI. Various numbers of extranodal sites were analyzed for further stratification, and we set the extranodal site-modified IPI (E-IPI) as the IPI when the number of extranodal sites was stratified as < 3 vs. ≥ 3. RESULTS: A univariate analysis showed that ENS was associated with complete response (CR, p = 0.04), event-free survival (EFS, p = 0.01), and overall survival (OS, p < 0.001) when the ENS cut-off was set at ≥ 3. A multivariate analysis revealed that an ENS ≥ 3 remained associated with EFS (p < 0.01; hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.29 to 5.26) and OS (p < 0.01; HR, 3.52; 95% CI, 1.68 to 7.35). The IPI was effective for determining prognosis in terms of OS (p = 0.04) but not EFS (p = 0.17). The R-IPI was effective in terms of both variables (p = 0.02 and 0.04, respectively), as was the E-IPI (p = 0.01 and 0.001, respectively). CONCLUSIONS: An ENS < 3 vs. ≥ 3, rather than the original < 2 vs. ≥ 2, was the most significant prognostic factor for EFS and OS. All three indices were predictive, but only the E-IPI identified the high-risk group of R-CHOP-treated Korean patients with disseminated DLBCL.