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 - 01-12-2017
Externally publishedYes

Fingerprint

Peripheral T-Cell Lymphoma
Kynurenine
Serum
Indoleamine-Pyrrole 2,3,-Dioxygenase
Essential Amino Acids
Survival
T-Cell Lymphoma
Vincristine
Prednisolone
L-Lactate Dehydrogenase
ROC Curve
Tryptophan
Doxorubicin
Cyclophosphamide
Multivariate Analysis
Survival Rate
High Pressure Liquid Chromatography

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Shibata, Y., Hara, T., Matsumoto, T., Nakamura, N., Nakamura, H., Ninomiya, S., ... 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
Shibata, Yuhei ; Hara, Takeshi ; Matsumoto, Takuro ; Nakamura, Nobuhiko ; Nakamura, Hiroshi ; Ninomiya, Soranobu ; Kitagawa, Junichi ; Goto, Naoe ; Nannya, Yasuhito ; Ito, Hiroyasu ; Kito, Yusuke ; Miyazaki, Tatsuhiko ; Takeuchi, Tamotsu ; Saito, Kuniaki ; Seishima, Mitsuru ; Takami, Tsuyoshi ; Moriwaki, Hisataka ; Shimizu, Masahito ; Tsurumi, Hisashi. / Serum concentrations of l-kynurenine predict clinical outcomes of patients with peripheral T-cell lymphoma, not otherwise specified. In: Hematological Oncology. 2017 ; Vol. 35, No. 4. pp. 637-644.
@article{7f89b7bc4e3d41d9a32ccb678cdb3c1e,
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.",
author = "Yuhei Shibata and Takeshi Hara and Takuro Matsumoto and Nobuhiko Nakamura and Hiroshi Nakamura and Soranobu Ninomiya and Junichi Kitagawa and Naoe Goto and Yasuhito Nannya and Hiroyasu Ito and Yusuke Kito and Tatsuhiko Miyazaki and Tamotsu Takeuchi and Kuniaki Saito and Mitsuru Seishima and Tsuyoshi Takami and Hisataka Moriwaki and Masahito Shimizu and Hisashi Tsurumi",
year = "2017",
month = "12",
day = "1",
doi = "10.1002/hon.2318",
language = "English",
volume = "35",
pages = "637--644",
journal = "Hematological Oncology",
issn = "0278-0232",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

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, vol. 35, no. 4, pp. 637-644. https://doi.org/10.1002/hon.2318

Serum concentrations of l-kynurenine predict clinical outcomes of patients with peripheral T-cell lymphoma, not otherwise specified. / Shibata, Yuhei; Hara, Takeshi; Matsumoto, Takuro; Nakamura, Nobuhiko; Nakamura, Hiroshi; Ninomiya, Soranobu; Kitagawa, Junichi; Goto, Naoe; Nannya, Yasuhito; Ito, Hiroyasu; Kito, Yusuke; Miyazaki, Tatsuhiko; Takeuchi, Tamotsu; Saito, Kuniaki; Seishima, Mitsuru; Takami, Tsuyoshi; Moriwaki, Hisataka; Shimizu, Masahito; Tsurumi, Hisashi.

In: Hematological Oncology, Vol. 35, No. 4, 01.12.2017, p. 637-644.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Serum concentrations of l-kynurenine predict clinical outcomes of patients with peripheral T-cell lymphoma, not otherwise specified

AU - Shibata, Yuhei

AU - Hara, Takeshi

AU - Matsumoto, Takuro

AU - Nakamura, Nobuhiko

AU - Nakamura, Hiroshi

AU - Ninomiya, Soranobu

AU - Kitagawa, Junichi

AU - Goto, Naoe

AU - Nannya, Yasuhito

AU - Ito, Hiroyasu

AU - Kito, Yusuke

AU - Miyazaki, Tatsuhiko

AU - Takeuchi, Tamotsu

AU - Saito, Kuniaki

AU - Seishima, Mitsuru

AU - Takami, Tsuyoshi

AU - Moriwaki, Hisataka

AU - Shimizu, Masahito

AU - Tsurumi, Hisashi

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85038416096&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85038416096&partnerID=8YFLogxK

U2 - 10.1002/hon.2318

DO - 10.1002/hon.2318

M3 - Article

C2 - 27338762

AN - SCOPUS:85038416096

VL - 35

SP - 637

EP - 644

JO - Hematological Oncology

JF - Hematological Oncology

SN - 0278-0232

IS - 4

ER -