Cell-free circulating DNA in Hodgkin's and non-Hodgkin's lymphomas.

BACKGROUND: Levels of cell-free circulating DNA have been correlated to clinical characteristics and prognosis in patients with cancers of epithelial origin, while there are no data on patients with B-lymphoproliferative diseases. PATIENTS AND METHODS: Cell-free DNA levels in the plasma samples of 142 patients with lymphomas [45 with Hodgkin's lymphoma (HL), 63 with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL), 24 with follicular, and 10 with mantle cell non-Hodgkin's lymphoma (NHL)] at diagnosis and of 41 healthy individuals were determined using a quantitative PCR for the beta-globin gene. RESULTS: Levels of circulating DNA in patients with HL, DLBCL, and mantle cell NHL were significantly higher than in controls (P < 0.01 for all). Increased levels of plasma DNA were associated with advanced stage disease, presence of B-symptoms, elevated lactate dehydrogenase levels, and age >60 years (P = 0.009; <0.0001; <0.0001; 0.04, respectively). In HL, histological signs of necrosis and grade 2 type of nodular sclerosis were associated with increased plasma DNA. Elevated plasma DNA levels were associated with an inferior failure-free survival in patients with HL (P = 0.01) and DLBCL (P = 0.03). CONCLUSION: Quantification of circulating DNA by real-time PCR at diagnosis can identify patients with elevated levels that are associated with disease characteristics indicating aggressive disease and poor prognosis.

Polymorphism in cytokine genes as prognostic markers in Hodgkin's lymphoma.

BACKGROUND: In Hodgkin's lymphoma (HL), the production of cytokines by Reed-Sternberg cells and the surrounding tissue is thought to contribute to the biology of the disease. Cytokine expression can be altered by common single nucleotide polymorphisms (SNPs) in the 5'-promoter regions. PATIENTS AND METHODS: We studied polymorphic allele variants of the cytokine genes interleukin (IL)-10 (T-3575A, G-2849A, C-2763A, A-1082G and C-592A), IL-6 (G-174C) and tumor necrosis factor-alpha (C-863A and G-308A) in 184 patients with HL, and analyzed for associations with treatment outcome. RESULTS: Carriers of the IL-10-592AA and the IL-6-174GG genotypes had a significantly lower probability of freedom from treatment failure (FFTF) with adjusted hazard ratios (HRs) for failure of 2.92 [95% CI (confidence interval) 1.58-5.41, P = 0.001] and of 1.75 (95% CI 1.04-2.92, P = 0.03), respectively. Reconstructing haplotypes from the five SNPs in the IL-10 promoter revealed that homozygous carriers of the IL-10.4 haplotype (T-G-C-A-A) had a worse FFTF (HR, 2.35; 95% CI 1.2-4.6, P = 0.01). In the Cox multivariate analysis, the IL-10-592AA, the IL-6-174GG genotypes and stage were independent prognostic factors. CONCLUSIONS: Our study indicates that cytokine genotypes predict clinical outcome in patients with HL and points to the importance of the genetic background of the host for treatment response.

Use of a constraint satisfaction network model for the evaluation of the methadone treatments of drug addicts.

Constraint Satisfaction Networks were used by Semeion, a Research Center of Science of Communication, in order to analyze drug-addict patient data files, provided by the Jerusalem Methadone Treatment Center. The short and partial analysis carried out in this article is presented to show how this high technology can be a support for treatment staff in order to improve the quality and the timeliness of the necessary intervention with patients. One of the problems for which the networks could offer support is, for example, the individuation or "matching" of the most suitable therapy for the patient during the treatment planning phase. In this field the networks need to analyze data files of patients in therapy at different centers, with the results collected after many years of observation. What follows, obviously, only has demonstrative values.