Serum concentration of L-kynurenine predicts the clinical outcome of patients with diffuse large B-cell lymphoma treated with R-CHOP

Takeshi Yoshikawa, Takeshi Hara, Hisashi Tsurumi, Naoe Goto, Masato Hoshi, Junichi Kitagawa, Nobuhiro Kanemura, Senji Kasahara, Hiroyasu Ito, Masao Takemura, Kuniaki Saito, Mitsuru Seishima, Tsuyoshi Takami, Hisataka Moriwaki

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Purpose: Introduction of rituximab has largely improved the prognosis of patients with diffuse large B-cell lymphoma(DLBCL). Such change in therapeutic outcome necessitates the identification of additional prognostic factors to conventional indexes that have been validated for CHOP without rituximab. Indoleamine 2,3-dioxygenase (IDO) exerts intense immunomodulatory effects because of enzymatic activities that catalyze the breakdown of the essential amino acid L-tryptophan. The activity of IDO can be estimated by measuring the serum concentration of L-kynurenine. Here, we investigated the role of L-kynurenine as a prognostic marker in R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) therapy. Experimental design: Data from 73 consecutive patients treated with eight cycles of R-CHOP or R-THP (tetrahydropyranyl adriamycin)-COP between December 2002 and March 2007 were analyzed. L-kynurenine concentrations in serum samples obtained at admission were measured by high-performance liquid chromatography. Results: The median serum L-kynurenine level was 1.575 μm (range 0.537-9.588). The complete response (CR) rates of patients with L-kynurenine <1.5 and ≥1.5 μm were 83% and 61%, respectively (P < 0.05). The three-yr overall survival (OS) rates for patients with L-kynurenine <1.5 and ≥1.5 μm were 89% and 58%, respectively (P < 0.005). In addition, higher age, poor performance status, elevated serum lactate dehydrogenase, and unfavorable as well as revised International Prognosis Index were significantly worse factors for CR rate and OS. Multivariate analyses revealed only L-kynurenine as an independent prognostic factor for OS. Conclusions: Serum L-kynurenine might be a novel prognostic factor to determine the treatment outcome of DLBCL with the R-CHOP regimen.

Original languageEnglish
Pages (from-to)304-309
Number of pages6
JournalEuropean Journal of Haematology
Volume84
Issue number4
DOIs
Publication statusPublished - 01-04-2010

Fingerprint

Kynurenine
Lymphoma, Large B-Cell, Diffuse
Vincristine
Prednisolone
Doxorubicin
Cyclophosphamide
Serum
Indoleamine-Pyrrole 2,3,-Dioxygenase
Survival Rate
Essential Amino Acids
Rituximab
L-Lactate Dehydrogenase
Tryptophan
Research Design
Multivariate Analysis
High Pressure Liquid Chromatography
Survival

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Yoshikawa, Takeshi ; Hara, Takeshi ; Tsurumi, Hisashi ; Goto, Naoe ; Hoshi, Masato ; Kitagawa, Junichi ; Kanemura, Nobuhiro ; Kasahara, Senji ; Ito, Hiroyasu ; Takemura, Masao ; Saito, Kuniaki ; Seishima, Mitsuru ; Takami, Tsuyoshi ; Moriwaki, Hisataka. / Serum concentration of L-kynurenine predicts the clinical outcome of patients with diffuse large B-cell lymphoma treated with R-CHOP. In: European Journal of Haematology. 2010 ; Vol. 84, No. 4. pp. 304-309.
@article{5e11fef35210492fb80f6d76ccdfc739,
title = "Serum concentration of L-kynurenine predicts the clinical outcome of patients with diffuse large B-cell lymphoma treated with R-CHOP",
abstract = "Purpose: Introduction of rituximab has largely improved the prognosis of patients with diffuse large B-cell lymphoma(DLBCL). Such change in therapeutic outcome necessitates the identification of additional prognostic factors to conventional indexes that have been validated for CHOP without rituximab. Indoleamine 2,3-dioxygenase (IDO) exerts intense immunomodulatory effects because of enzymatic activities that catalyze the breakdown of the essential amino acid L-tryptophan. The activity of IDO can be estimated by measuring the serum concentration of L-kynurenine. Here, we investigated the role of L-kynurenine as a prognostic marker in R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) therapy. Experimental design: Data from 73 consecutive patients treated with eight cycles of R-CHOP or R-THP (tetrahydropyranyl adriamycin)-COP between December 2002 and March 2007 were analyzed. L-kynurenine concentrations in serum samples obtained at admission were measured by high-performance liquid chromatography. Results: The median serum L-kynurenine level was 1.575 μm (range 0.537-9.588). The complete response (CR) rates of patients with L-kynurenine <1.5 and ≥1.5 μm were 83{\%} and 61{\%}, respectively (P < 0.05). The three-yr overall survival (OS) rates for patients with L-kynurenine <1.5 and ≥1.5 μm were 89{\%} and 58{\%}, respectively (P < 0.005). In addition, higher age, poor performance status, elevated serum lactate dehydrogenase, and unfavorable as well as revised International Prognosis Index were significantly worse factors for CR rate and OS. Multivariate analyses revealed only L-kynurenine as an independent prognostic factor for OS. Conclusions: Serum L-kynurenine might be a novel prognostic factor to determine the treatment outcome of DLBCL with the R-CHOP regimen.",
author = "Takeshi Yoshikawa and Takeshi Hara and Hisashi Tsurumi and Naoe Goto and Masato Hoshi and Junichi Kitagawa and Nobuhiro Kanemura and Senji Kasahara and Hiroyasu Ito and Masao Takemura and Kuniaki Saito and Mitsuru Seishima and Tsuyoshi Takami and Hisataka Moriwaki",
year = "2010",
month = "4",
day = "1",
doi = "10.1111/j.1600-0609.2009.01393.x",
language = "English",
volume = "84",
pages = "304--309",
journal = "European Journal of Haematology",
issn = "0902-4441",
publisher = "Wiley-Blackwell",
number = "4",

}

Yoshikawa, T, Hara, T, Tsurumi, H, Goto, N, Hoshi, M, Kitagawa, J, Kanemura, N, Kasahara, S, Ito, H, Takemura, M, Saito, K, Seishima, M, Takami, T & Moriwaki, H 2010, 'Serum concentration of L-kynurenine predicts the clinical outcome of patients with diffuse large B-cell lymphoma treated with R-CHOP', European Journal of Haematology, vol. 84, no. 4, pp. 304-309. https://doi.org/10.1111/j.1600-0609.2009.01393.x

Serum concentration of L-kynurenine predicts the clinical outcome of patients with diffuse large B-cell lymphoma treated with R-CHOP. / Yoshikawa, Takeshi; Hara, Takeshi; Tsurumi, Hisashi; Goto, Naoe; Hoshi, Masato; Kitagawa, Junichi; Kanemura, Nobuhiro; Kasahara, Senji; Ito, Hiroyasu; Takemura, Masao; Saito, Kuniaki; Seishima, Mitsuru; Takami, Tsuyoshi; Moriwaki, Hisataka.

In: European Journal of Haematology, Vol. 84, No. 4, 01.04.2010, p. 304-309.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Serum concentration of L-kynurenine predicts the clinical outcome of patients with diffuse large B-cell lymphoma treated with R-CHOP

AU - Yoshikawa, Takeshi

AU - Hara, Takeshi

AU - Tsurumi, Hisashi

AU - Goto, Naoe

AU - Hoshi, Masato

AU - Kitagawa, Junichi

AU - Kanemura, Nobuhiro

AU - Kasahara, Senji

AU - Ito, Hiroyasu

AU - Takemura, Masao

AU - Saito, Kuniaki

AU - Seishima, Mitsuru

AU - Takami, Tsuyoshi

AU - Moriwaki, Hisataka

PY - 2010/4/1

Y1 - 2010/4/1

N2 - Purpose: Introduction of rituximab has largely improved the prognosis of patients with diffuse large B-cell lymphoma(DLBCL). Such change in therapeutic outcome necessitates the identification of additional prognostic factors to conventional indexes that have been validated for CHOP without rituximab. Indoleamine 2,3-dioxygenase (IDO) exerts intense immunomodulatory effects because of enzymatic activities that catalyze the breakdown of the essential amino acid L-tryptophan. The activity of IDO can be estimated by measuring the serum concentration of L-kynurenine. Here, we investigated the role of L-kynurenine as a prognostic marker in R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) therapy. Experimental design: Data from 73 consecutive patients treated with eight cycles of R-CHOP or R-THP (tetrahydropyranyl adriamycin)-COP between December 2002 and March 2007 were analyzed. L-kynurenine concentrations in serum samples obtained at admission were measured by high-performance liquid chromatography. Results: The median serum L-kynurenine level was 1.575 μm (range 0.537-9.588). The complete response (CR) rates of patients with L-kynurenine <1.5 and ≥1.5 μm were 83% and 61%, respectively (P < 0.05). The three-yr overall survival (OS) rates for patients with L-kynurenine <1.5 and ≥1.5 μm were 89% and 58%, respectively (P < 0.005). In addition, higher age, poor performance status, elevated serum lactate dehydrogenase, and unfavorable as well as revised International Prognosis Index were significantly worse factors for CR rate and OS. Multivariate analyses revealed only L-kynurenine as an independent prognostic factor for OS. Conclusions: Serum L-kynurenine might be a novel prognostic factor to determine the treatment outcome of DLBCL with the R-CHOP regimen.

AB - Purpose: Introduction of rituximab has largely improved the prognosis of patients with diffuse large B-cell lymphoma(DLBCL). Such change in therapeutic outcome necessitates the identification of additional prognostic factors to conventional indexes that have been validated for CHOP without rituximab. Indoleamine 2,3-dioxygenase (IDO) exerts intense immunomodulatory effects because of enzymatic activities that catalyze the breakdown of the essential amino acid L-tryptophan. The activity of IDO can be estimated by measuring the serum concentration of L-kynurenine. Here, we investigated the role of L-kynurenine as a prognostic marker in R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) therapy. Experimental design: Data from 73 consecutive patients treated with eight cycles of R-CHOP or R-THP (tetrahydropyranyl adriamycin)-COP between December 2002 and March 2007 were analyzed. L-kynurenine concentrations in serum samples obtained at admission were measured by high-performance liquid chromatography. Results: The median serum L-kynurenine level was 1.575 μm (range 0.537-9.588). The complete response (CR) rates of patients with L-kynurenine <1.5 and ≥1.5 μm were 83% and 61%, respectively (P < 0.05). The three-yr overall survival (OS) rates for patients with L-kynurenine <1.5 and ≥1.5 μm were 89% and 58%, respectively (P < 0.005). In addition, higher age, poor performance status, elevated serum lactate dehydrogenase, and unfavorable as well as revised International Prognosis Index were significantly worse factors for CR rate and OS. Multivariate analyses revealed only L-kynurenine as an independent prognostic factor for OS. Conclusions: Serum L-kynurenine might be a novel prognostic factor to determine the treatment outcome of DLBCL with the R-CHOP regimen.

UR - http://www.scopus.com/inward/record.url?scp=77949456437&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77949456437&partnerID=8YFLogxK

U2 - 10.1111/j.1600-0609.2009.01393.x

DO - 10.1111/j.1600-0609.2009.01393.x

M3 - Article

C2 - 19995374

AN - SCOPUS:77949456437

VL - 84

SP - 304

EP - 309

JO - European Journal of Haematology

JF - European Journal of Haematology

SN - 0902-4441

IS - 4

ER -