Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm that develops in a small population of human T-cell lymphotropic virus type 1 (HTLV-1)-infected individuals and is characterized by mostly CD4 þ and CD25 þ mature T-cell phenotypes, and onset at middle age or later [1][2][3][4]. The exact mechanism of immune modulation in ATLL remains unknown. The essential amino acid Ltryptophan (L-TRP) is required for the biosynthesis of proteins and is precursor for several biologically important compounds: (a) 5-hydroxy-tryptamine (serotonin) which is formed by tryptophan 5-hydroxylase following decarboxylation; (b) kynurenine which is produced by L-tryptophan 2,3-dioxygenase (TDO); and indoleamine 2,3-dioxygenase (IDO). The latter two enzymes catabolize tryptophan via the so-called kynurenine-pathway synthesizing nicotinic acid, the vitamin niacin and nicotinamide adenine dinucleotides as end products. Although TDO is localized in the liver and is up-regulated by corticosteroids, IDO is expressed by a variety of cells and is inducible by various cytokines, especially interferon-g [5]. Recently, IDO has been identified as an enzyme endowed with powerful immunomodulatory effects, resulting from its enzymatic activity that leads to catabolism of the essential amino acid L-TRP. For example, certain IDO-generated L-TRP-derived metabolites, in particular L-kynurenine (L-KYN), have been reported to block Ag-driven specific T-cell proliferation and even to induce T-cell death [6]. On the other hand, IDO has been found in various tumors of different histotypes and increments of IDO activity correlate with tumor progression [7]. In addition, we have been reported that IDO is highly expressed in ATLL cells [8]. Therefore, the provided L-TRP catabolism as a result of IDO activity may play an important role in the immune regulation exerted by the antigen-presenting cells. In this study, we investigated whether the level of L-TRP metabolites in blood could be a useful parameter of chemotherapy efficacy for ATLL patients.The patients analysed are a 74-year-old woman in acute type ATLL without chemotherapy and a 67-year-old woman in acute type ATLL with chemotherapy. The diagnosis of ATLL was based on clinical features, hematological characteristics, presence of serum antibodies to ATLL-associated antigens, and presence of HTLV-1 proviral genome in DNA from leukemic cells. Informed consent was provided according to the Declaration of Helsinki. Combination chemotherapy was used according to a multi-agent chemotherapy protocol LSG15. Chemotherapy consisted of two cycles of VCAP (vincristine 1 mg/m 2 , cyclophosphamide 350 mg/m 2 , doxorubicin 40 mg/m 2 and prednisone 40 mg/m 2 ), AMP (doxorubicin 30 mg/m 2 , ranimustine 60 mg/m 2 and prednisone 40 mg/m 2 ), and VECP (vindesine 2.4 mg/m 2 , etoposide 100 mg/m 2 , carboplatin 250 mg/m 2 and prednisone 40 mg/m 2 ).
