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Serum concentrations of l‐kynurenine predict clinical outcomes of patients with peripheral T‐cell lymphoma,not otherwise specified
Authors:Yuhei Shibata  Takeshi Hara  Takuro Matsumoto  Nobuhiko Nakamura  Hiroshi Nakamura  Soranobu Ninomiya  Junichi Kitagawa  Naoe Goto  Yasuhito Nannya  Hiroyasu Ito  Yusuke Kito  Tatsuhiko Miyazaki  Tamotsu Takeuchi  Kuniaki Saito  Mitsuru Seishima  Tsuyoshi Takami  Hisataka Moriwaki  Masahito Shimizu  Hisashi Tsurumi
Affiliation:1. First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan;2. Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan;3. Department of Pathology and Translational Research, Gifu University Graduate School of Medicine, Gifu, Japan;4. Pathology Division, Gifu University Hospital, Gifu, Japan;5. Human Health Sciences, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto, Japan
Abstract:Indoleamine 2,3‐dioxygenase exerts intense immunomodulatory effects due to enzymatic activities that catalyze the breakdown of the essential amino acid l ‐tryptophan. The activity of indoleamine 2,3‐dioxygenase can be estimated by measuring serum l ‐kynurenine concentrations. Here, we aimed to determine the role of l ‐kynurenine as a prognostic factor for peripheral T‐cell lymphoma, not otherwise specified (PTCL‐NOS) in a retrospective analysis of data derived from 31 consecutive patients between June 2000 and March 2013 who were histologically diagnosed with PTCL‐NOS according to the World Health Organization classification and treated with 6?8 cycles of cyclophosphamide, doxorubicin or pirarubicin, vincristine, and prednisolone. l ‐kynurenine concentrations in serum samples collected at admission were measured using high‐performance liquid chromatography. The median serum concentration of l ‐kynurenine was 3.28 (range 0.92–8.16) μM. The l ‐kynurenine cutoff was set at 3.07 μM using receiver operating characteristics curves. The complete remission rates of patients with l ‐kynurenine <3.07 and ≥3.07 μM were 69% and 51%, respectively. The 5‐year overall survival (OS) rates for patients with l ‐kynurenine <3.07 and ≥3.07 μM were 80.2% and 23.4%, respectively (p < 0.001). More advanced age, poor performance status, elevated lactate dehydrogenase, an unfavorable International Prognostic Index, and a poor prognostic index for T‐cell lymphoma were significantly worse factors for OS. Multivariate analyses revealed only l ‐kynurenine as an independent prognostic factor for OS. In conclusion, serum concentrations of l ‐kynurenine might comprise a novel prognostic factor with which to determine the outcomes of treatment for PTCL‐NOS. Copyright © 2016 John Wiley & Sons, Ltd.
Keywords:immunological tolerance  indoleamine 2  3‐dioxygenase  prognostic factor  l‐tryptophan catabolism  peripheral T‐cell lymphoma  not otherwise specified (PTCL‐NOS)
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