Serum concentrations of l-kynurenine predict clinical outcomes of patients with peripheral T-cell lymphoma, not otherwise specified

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)637-644
Number of pages8
JournalHematological Oncology
Volume35
Issue number4
DOIs
Publication statusPublished - 12-2017

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

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    Shibata, Y., Hara, T., Matsumoto, T., Nakamura, N., Nakamura, H., Ninomiya, S., Kitagawa, J., Goto, N., Nannya, Y., Ito, H., Kito, Y., Miyazaki, T., Takeuchi, T., Saito, K., Seishima, M., Takami, T., Moriwaki, H., Shimizu, M., & Tsurumi, H. (2017). Serum concentrations of l-kynurenine predict clinical outcomes of patients with peripheral T-cell lymphoma, not otherwise specified. Hematological Oncology, 35(4), 637-644. https://doi.org/10.1002/hon.2318