RESUMO
BACKGROUND: Published data indicate that common genetic variants in immune/inflammatory response genes can affect the outcome of diffuse large B-cell lymphomas (DLBCL). This study investigated the association of interleukin (IL)-10 (-3575, -1082), tumor necrosis factor (TNF)-α -308 and transforming growth factor (TGF)-ß Leu10Pro gene polymorphisms with clinical characteristics and outcome of DLBCL patients treated with rituximab-CHOP therapy. METHODS: Between January 2004 and December 2007, a total of 84 patients with newly diagnosed DLBCL entered into this study. Genotypes were determined with PCR-based methodology. RESULTS: Patients presenting with B symptoms had IL-10 -3575 TA/AA genotypes more frequently than TT genotype [odds ratio (OR) 2.89, 95 % confidence interval (CI) 1.11-7.57; p = 0.03]. Carriers of TGF-ß Pro10 allele more frequently had an advanced clinical stage III/IV (OR 4.65, 95 % CI 1.33-16.19; p = 0.016) and intermediate-high/high IPI score (OR 5.37, 95 % CI 1.45-20.0; p = 0.012). In rituximab-CHOP-treated patients (n = 64), the TNF-α -308 AG/AA carriers had shorter overall (p = 0.048) and event-free survival (p = 0.07) compared to GG carriers. In multivariate analysis of prognostic factors for survival, the TNF-α AG/AA genotypes were significantly associated with inferior survival of lymphoma patients (OR 0.23, 95 % CI 0.07-0.78; p = 0.018). CONCLUSION: Our results indicate the association of IL-10 -3575 and TGF-ß Leu10Pro gene variations with clinical characteristics. In patients treated with rituximab-CHOP therapy, the TNF-α -308 AG/AA genotypes showed a significantly less favorable survival than the GG genotype.
Assuntos
Interleucina-10/genética , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Fator de Crescimento Transformador beta/genética , Fator de Necrose Tumoral alfa/genética , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Farmacológicos , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , Prednisona/administração & dosagem , Rituximab , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
The aim of this research was to determine the serum dipeptidyl peptidase IV (DPPIV) activity as well as the percentages of CD26 + lymphocytes and CD26 + overall white blood cells in patients with hematological malignancies: non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), leukemia, plasmacytoma and multiple myeloma, and in healthy individuals. Data from our study showed significantly decreased serum DPPIV activity and a significant decrease in the percentage of: CD26 + lymphocytes, CD26 + overall white blood cells and lymphocytes in patients with NHL in comparison to healthy controls. Patients with leukemia had a statistically significant lower activity of DPPIV in serum and significant decrease in the percentage of CD26 + lymphocytes in relation to healthy controls. Furthermore, significantly decreased DPPIV serum activity associated with a significantly reduced percentage of CD26 + overall white blood cells and percentage of lymphocytes was found in patients with multiple myeloma when compared to the healthy control group. The obtained results indicate that immune disturbances that can occur in hematological malignancies might be related to the decreased expression and activity of CD26/DPPIV that we observed.