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
N1 - Publisher Copyright:
Copyright © 2016 John Wiley & Sons, Ltd.
PY - 2017/12
Y1 - 2017/12
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.
KW - 3-dioxygenase
KW - immunological tolerance
KW - indoleamine 2
KW - l-tryptophan catabolism
KW - not otherwise specified (PTCL-NOS)
KW - peripheral T-cell lymphoma
KW - prognostic factor
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
SN - 0278-0232
VL - 35
SP - 637
EP - 644
JO - Hematological Oncology
JF - Hematological Oncology
IS - 4
ER -