title: Serum concentrations of l-kynurenine predict clinical outcomes of patients with peripheral T-cell lymphoma, not otherwise specified.
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.
authors.affiliation: First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hara
authors.affiliation: First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Soranobu
authors.initials: S
authors.lastname: Ninomiya
authors.affiliation: First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kitagawa
authors.affiliation: First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Naoe
authors.initials: N
authors.lastname: Goto
authors.affiliation: First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Nannya
authors.affiliation: Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ito
authors.affiliation: Department of Pathology and Translational Research, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kito
authors.affiliation: Pathology Division, Gifu University Hospital, Gifu, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Department of Pathology and Translational Research, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: Human Health Sciences, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Seishima
authors.affiliation: Department of Pathology and Translational Research, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takami
authors.affiliation: First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
authors.affiliation: First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tsurumi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D006801:Humans; D007737:Kynurenine / Q000097:blood*; D016411:Lymphoma, T-Cell, Peripheral / Q000097:blood* / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012016:Reference Values; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D007737:Kynurenine
keywords: 3-dioxygenase; immunological tolerance; indoleamine 2; l-tryptophan catabolism; not otherwise specified (PTCL-NOS); peripheral T-cell lymphoma; prognostic factor