Serum concentration of L-kynurenine predicts the clinical outcome of patients with diffuse large B-cell lymphoma treated with R-CHOP

Purpose: Introduction of rituximab has largely improved the prognosis of patients with diffuse large B-cell lymphoma(DLBCL). Such change in therapeutic outcome necessitates the identification of additional prognostic factors to conventional indexes that have been validated for CHOP without rituximab. Indoleamine 2,3-dioxygenase (IDO) exerts intense immunomodulatory effects because of enzymatic activities that catalyze the breakdown of the essential amino acid L-tryptophan. The activity of IDO can be estimated by measuring the serum concentration of L-kynurenine. Here, we investigated the role of L-kynurenine as a prognostic marker in R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) therapy. Experimental design: Data from 73 consecutive patients treated with eight cycles of R-CHOP or R-THP (tetrahydropyranyl adriamycin)-COP between December 2002 and March 2007 were analyzed. L-kynurenine concentrations in serum samples obtained at admission were measured by high-performance liquid chromatography. Results: The median serum L-kynurenine level was 1.575 μm (range 0.537-9.588). The complete response (CR) rates of patients with L-kynurenine <1.5 and ≥1.5 μm were 83% and 61%, respectively (P < 0.05). The three-yr overall survival (OS) rates for patients with L-kynurenine <1.5 and ≥1.5 μm were 89% and 58%, respectively (P < 0.005). In addition, higher age, poor performance status, elevated serum lactate dehydrogenase, and unfavorable as well as revised International Prognosis Index were significantly worse factors for CR rate and OS. Multivariate analyses revealed only L-kynurenine as an independent prognostic factor for OS. Conclusions: Serum L-kynurenine might be a novel prognostic factor to determine the treatment outcome of DLBCL with the R-CHOP regimen.