Clinical significance of tryptophan catabolism in Hodgkin lymphoma

Summary

Indoleamine 2,3-dioxygenase 1 (IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway. The purpose of the present study was to determine the clinical significance of Trp catabolism in newly-diagnosed Hodgkin Lymphoma (HL) patients. We quantified serum Trp and Kyn in 52 HL patients, and analyzed their associations with different clinical parameters including serum soluble CD30 (sCD30) concentration. IDO expression was evaluated in the patients′ affected lymph nodes. The enrolled patients comprised 22 males and 30 females (age range 15-81, median 45 years), with a 5-year overall survival (OS) of 88.6%. The OS was significantly shorter for patients with a high Kyn/Trp ratio (OS at 5 years, 60.0%-vs-92.2%), for those with stage IV disease, and for those with lymphocytopenia (< 600/mm³ and/or < 8% of the white blood cell [WBC] count). The latter two parameters are components of the international prognostic score for advanced HL. In contrast, there were no significant differences in OS according to age, serum albumin, hemoglobin, sex, WBC count, or serum sCD30 (≥ or < 285.6 ng/mL). Multivariate analysis using the three variables stage, lymphocytopenia and serum Kyn/Trp ratio demonstrated that only the latter significantly affected OS. IDO was produced by macrophages/dendritic cells, but not by HL tumor cells, and IDO levels determined by immunohistochemistry had a significant positive correlation with the serum Kyn/Trp ratio. In conclusion, quantification of serum Kyn and Trp is useful for predicting prognosis of individual HL patients.

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