Survival in patients with intermediate or high grade non-Hodgkin's lymphoma: meta-analysis of randomized studies comparing third generation regimens with CHOP

In patients with intermediate or high grade non-Hodgkin lymphoma (NHL), third generation chemotherapy regimens have been introduced to improve survival in comparison with the standard CHOP regimen. However, most studies have found no difference between these two treatments. We conducted a meta-analysis to assess the effectiveness of third generation regimens as compared with CHOP. Our study included the randomized controlled trials published in English from 1970 to 1999. After a Medline search, 5 trials were found to meet our inclusion criteria. A total of 1982 patients, that were enrolled in these trials, were included in the survival meta-analysis. Our methodology retrieved patient-level information from all of these subjects; survival up to 9 years after randomization was compared between the two treatment options. The results of our meta-analysis showed that, in comparison with CHOP, third generation chemotherapy did not prolong survival at levels of statistical significance (chi-square by log-rank test = 1.44, P = 0.23). The relative death risk for third generation regimens vs. CHOP was 0.92 (95%CI: 0.80 to 1.06;P  = 0.26). We conclude that, on the basis of our meta-analysis, third generation regimens do not confer any survival benefit to patients with intermediate or high grade NHL as compared with CHOP. © 2001 Cancer Research Campaign http://www.bjcancer.co

Exploratory Genome-Wide Association Analysis to Identify Pharmacogenetic Determinants of Response to R-CHOP in Diffuse Large B-Cell Lymphoma

R-CHOP standard chemotherapy is successful in about 60% of diffuse large B-cell lymphoma (DLBCL) patients. Unresponsive patients have a poor prognosis, and predictive biomarkers of response to R-CHOP are lacking. We conducted the first prospective GWAS study aimed at exploring constitutional biomarkers predictive of R-CHOP efficacy and toxicity. Overall, 216 any-stage chemonaive DLBCL patients candidate to R-CHOP were enrolled. The median age of the 185 eligible patients was 59.2 years, 49.7% were women and 45.4% were stage I-II patients. According to the Revised International Prognostic Index (R-IPI), 14.1%, 56.8% and 29.2% were in the very good, good and poor prognosis groups, respectively. Of the patients, 85.9% produced a complete response. Highly significant associations (i.e., p < 5 x 10(-8)) were found between progression-free survival (PFS) and six SNPs (i.e., rs116665727, rs1607795, rs75614943, rs77241831, rs117500207, rs78466241). Additionally, five SNPs (i.e., rs74832512, rs117500207, rs35789195, rs11721010, rs12356569) were highly associated with overall survival (OS). Wild-type patients showed a prolonged PFS or OS compared with patients carrying deleterious alleles (p < 0.001). No association with the adequate significant threshold was observed between SNPs and the objective response or toxicity. In the future, these SNPs, alone or in combination, after a proper validation in an independent cohort, could contribute to improving the prediction of R-CHOP response

Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study

To assess the prognosis of peripheral T-cell lymphoma unspecified, we retrospectively analyzed 385 cases fulfilling the criteria defined by the World Health Organization classification. Factors associated with a worse overall survival (OS) in a univariate analysis were age older than 60 years (P=.0002), equal to or more than 2 extranodal sites (P=.0002), lactic dehydrogenase (LDH) value at normal levels or above (P<.0001), performance status (PS) equal to or more than 2 (Pless than or equal to.0001), stage III or higher (P=.0001), and bone marrow involvement (P=.0001). Multivariate analysis showed that age (relative risk, 1.732; 95% CI, 1.300-2.309; P<.0001), PS (relative risk, 1.719; 95% CI, 1.269-2.327, P<.0001), LDH level (relative risk, 1.905; 95% CI, 1.415-2.564; P<.0001), and bone marrow involvement (relative risk, 1.454; 95% CI, 1.045-2.023; P=.026) were factors independently predictive for survival. Using these 4 variables we constructed a new prognostic model that singled out 4 groups at different risk: group 1, no adverse factors, with 5-year and 10-year OS of 62.3% and 54.9%, respectively; group 2, one factor, with a 5-year and 10-year OS of 52.9% and 38.8%, respectively; group 3, 2 factors, with 5-year and 10-year OS of 32.9% and 18.0%, respectively; group 4,3 or 4 factors, with a 5-year and 10-year OS of 18.3 and 12.6%, respectively (Pless than or equal to.0001; log-rank, 66.79)

Efecto de la invasión de acacia negra (<i>Gleditsia triacanthos</i> L.) sobre arroyos pampeanos

Pampean fluvial ecosystems of low order usually lack of riparian vegetation. In recent years the invasion of honey locust (Gleditsia triacanthos L.) has caused changes in landscape composition. The aim of this study was to evaluate the effect of honey locust invasion on pampean streams. Three reaches with different degree of invasion were selected and compared with three control reaches with no canopy. In order to evaluate the effect of invasion, nutrients (soluble reactive phosphorus, ammonium and nitrates), biomass of producers (seston, macrophytes, periphyton and phytobenthos) and net production in each reach were determined. Significant differences were observed for all of variables estimated between reaches with and without canopy, but not in all cases. The amount of variables with significant differences between both reaches rises following a gradient of increasing invasion levels. Furthermore, differences are more pronounced with increasing percentage of honey locust coverage on the stream. We conclude that sustained invasion of honey locust modifies the concentration of nutrients in water, the biomass of some communities and the production of these communities. This effect could be avoided with early management of the invasion of honey locust.Facultad de Ciencias Naturales y Muse

Efecto de la invasión de acacia negra (<i>Gleditsia triacanthos</i> L.) sobre arroyos pampeanos

Pampean fluvial ecosystems of low order usually lack of riparian vegetation. In recent years the invasion of honey locust (Gleditsia triacanthos L.) has caused changes in landscape composition. The aim of this study was to evaluate the effect of honey locust invasion on pampean streams. Three reaches with different degree of invasion were selected and compared with three control reaches with no canopy. In order to evaluate the effect of invasion, nutrients (soluble reactive phosphorus, ammonium and nitrates), biomass of producers (seston, macrophytes, periphyton and phytobenthos) and net production in each reach were determined. Significant differences were observed for all of variables estimated between reaches with and without canopy, but not in all cases. The amount of variables with significant differences between both reaches rises following a gradient of increasing invasion levels. Furthermore, differences are more pronounced with increasing percentage of honey locust coverage on the stream. We conclude that sustained invasion of honey locust modifies the concentration of nutrients in water, the biomass of some communities and the production of these communities. This effect could be avoided with early management of the invasion of honey locust.Facultad de Ciencias Naturales y Muse

Efecto de la invasión de acacia negra (<i>Gleditsia triacanthos</i> L.) sobre arroyos pampeanos

Pampean fluvial ecosystems of low order usually lack of riparian vegetation. In recent years the invasion of honey locust (Gleditsia triacanthos L.) has caused changes in landscape composition. The aim of this study was to evaluate the effect of honey locust invasion on pampean streams. Three reaches with different degree of invasion were selected and compared with three control reaches with no canopy. In order to evaluate the effect of invasion, nutrients (soluble reactive phosphorus, ammonium and nitrates), biomass of producers (seston, macrophytes, periphyton and phytobenthos) and net production in each reach were determined. Significant differences were observed for all of variables estimated between reaches with and without canopy, but not in all cases. The amount of variables with significant differences between both reaches rises following a gradient of increasing invasion levels. Furthermore, differences are more pronounced with increasing percentage of honey locust coverage on the stream. We conclude that sustained invasion of honey locust modifies the concentration of nutrients in water, the biomass of some communities and the production of these communities. This effect could be avoided with early management of the invasion of honey locust.Facultad de Ciencias Naturales y Muse

Cytotoxicity of apigenin on leukemia cell lines: implications for prevention and therapy

Natural-food-based compounds show substantial promise for prevention and biotherapy of cancers including leukemia. In general, their mechanism of action remains unclear, hampering rational use of these compounds. Herein we show that the common dietary flavonoid apigenin has anticancer activity, but also may decrease chemotherapy sensitivity, depending on the cell type. We analyzed the molecular consequences of apigenin treatment in two types of leukemia, the myeloid and erythroid subtypes. Apigenin blocked proliferation in both lineages through cell-cycle arrest in G2/M phase for myeloid HL60 and G0/G1 phase for erythroid TF1 cells. In both cell lines the JAK/STAT pathway was one of major targets of apigenin. Apigenin inhibited PI3K/PKB pathway in HL60 and induced caspase-dependent apoptosis. In contrast, no apoptosis was detected in TF1 cells, but initiation of autophagy was observed. The block in cell cycle and induction of autophagy observed in this erythroleukemia cell line resulted in a reduced susceptibility toward the commonly used therapeutic agent vincristine. Thus, this study shows that although apigenin is a potential chemopreventive agent due to the induction of leukemia cell-cycle arrest, caution in dietary intake of apigenin should be taken during disease as it potentially interferes with cancer treatment