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


METHODS
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 microm (range 0.537-9.588). The complete response (CR) rates of patients with L-kynurenine <1.5 and > or =1.5 microm were 83% and 61%, respectively (P < 0.05). The three-yr overall survival (OS) rates for patients with L-kynurenine <1.5 and > or =1.5 microm 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.
Yoshikawa
Takeshi
T
First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
Hara
Takeshi
T
Tsurumi
Hisashi
H
Goto
Naoe
N
Hoshi
Masato
M
Kitagawa
Junichi
J
Kanemura
Nobuhiro
N
Kasahara
Senji
S
Ito
Hiroyasu
H
Takemura
Masao
M
Saito
Kuniaki
K
Seishima
Mitsuru
M
Takami
Tsuyoshi
T
Moriwaki
Hisataka
H
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007737:Kynurenine / Q000097:blood*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage; D012074:Remission Induction; D000069283:Rituximab; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007737:Kynurenine; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone