Background: We have previously reported that serum interleukin-18 (IL-18) concentration predicted the clinical outcome of patients with aggressive non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). When rituximab (R) was added to this regimen, the prognosis of diffuse large B-cell lymphoma (DLBCL) was markedly improved. Patients and Methods: In this study, we re-evaluated the prognostic significance of serum IL-18 in 227 DLBCL patients. Seventy-three patients received CHOP before R-era, and 154 patients received rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) recently. Result: Four-year overall survival (4-yr OS) rates for patients in CHOP group with IL-18≥720pg/mL and <720pg/mL were 8.2% and 67.3% (P<0.0001), respectively, and 4-yr OS rates with IL-18≥590 and <590pg/mL in R-CHOP group were 53.4% and 77.8% (P=0.0008), respectively. Multivariate analysis revealed that serum IL-18 correlated most significantly with OS and progression-free survival (PFS) in both groups (OS: P<0.0001, PFS: P<0.0001, in CHOP group; OS: P=0.0147, PFS: P=0.0084 in R-CHOP group). The high serum IL-18 patients with poor prognostic group in revised IPI or with non-germinal center B-cell phenotype had a very poor prognosis. Conclusion: Serum IL-18 might be a powerful prognostic factor for DLBCL in R-era.
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