53 research outputs found
Deep sequencing reveals clonal evolution patterns and mutation events associated with relapse in B-cell lymphomas
CONTRIBUTION A L'ETUDE DES HELMINTHOSES DIGESTIVES DES LEMURIENS APPARTENANT AUX GENRES LEMUR ET EULEMUR, AU PARC ZOOLOGIQUE DE TSIMBAZAZA, MADAGASCAR
MAISONS-ALFORT-Ecole Vétérin (940462302) / SudocSudocFranceF
Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial
Background The outcome of diff use large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in patients aged 18–59 years, the potential survival benefi t provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab.
Methods We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclo phosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) with subsequent consolidation versus standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Random assignment was done with a computer-assisted randomisation-allocation sequence with a block size of four. Patients were aged 18–59 years with untreated diff use large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of effi cacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595.
Findings One patient withdrew consent before treatment and 54 did not complete treatment. After a median follow-up of 44 months, our 3-year estimate of event-free survival was 81% (95% CI 75–86) in the R-ACVBP group and 67% (59–73) in the R-CHOP group (hazard ratio [HR] 0·56, 95% CI 0·38–0·83; p=0·0035). 3-year estimates of progression-free survival (87% [95% CI, 81–91] vs 73% [66–79]; HR 0·48 [0·30–0·76]; p=0·0015) and overall survival (92% [87–95] vs 84% [77–89]; HR 0·44 [0·28–0·81]; p=0·0071) were also increased in the R-ACVBP group. 82 (42%) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 (15%) of 183 in the R-CHOP group. Grade 3–4 haematological toxic eff ects were more common in the R-ACVBP group, with a higher proportion of patients experiencing
a febrile neutropenic episode (38% [75 of 196] vs 9% [16 of 183]).
Interpretation Compared with standard R-CHOP, inten sifi ed immunochemotherapy with R-ACVBP signifi cantly improves survival of patients aged 18–59 years with diff use large B-cell lymphoma with low-intermediate risk according to the International Prognostic Index. Haematological toxic eff ects of the intensive regimen were raised but manageable.
Funding Groupe d’Etudes des Lymphomes de l’Adulte and Amgen
Hyperferritinemia increases the risk of hyperuricemia in HFE-hereditary hemochromatosis
International audienceObjectives: Hyperuricemia is becoming increasingly frequent in the population, and is known to besometimes the cause of gout. The impact of uric acid is still not clearly understood, however. The ironmetabolism may interact with the uric acid metabolism. The aim of this study was to examine the relationship between the serum uric acid and serum ferritin levels in a cohort of hemochromatosis patientswho were homozygous for the HFE p. Cys282Tyr mutation. Methods: 738 patients with the HFE gene mutation Cys282Tyr in the homozygous state were includedin the study. The variables measured during the initial evaluation were compared in univariate analysisby Student's t test. In multivariate analysis, linear stepwise regression was used. Results: In the group of hyperuricemic patients, ferritinemia was significantly higher than in the group ofnonhyperuricemic patients (1576.7 +/- 1387.4 mu g/l vs. 1095.63 +/- 1319.24 mu g/l, P < 0.005). With multivariate analysis, only ferritin and BMI independently explained the uricemia (R-2= 0.258) after adjustmentfor age, glycemia and CRP. The correlation between uricemia and log(ferritin) with partial regressioncorrelation coefficients was 0.307 (P < 0.01). Conclusions: The increase in uricemia is associated with the increase in ferritin in a population of patientswho were homozygous for the HFE gene mutation p. Cys282Tyr and this independently of factors commonly associated with hyperuricemia. The increase in uric acid associated with hyperferritinemia, couldbe a response to the visceral toxicity of excess non-transferrin bound iron linked to oxidative stress viathe antioxidant properties of uric acid. (C) 2016 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved
Relevance of using both aerobic and anaerobic enrichment vials for optimizing rapid diagnosis of osteoarticular infections
International audienceThe performance of a pair of blood culture vials (BACTEC® Plus Aerobic/F, and Anaerobic Lytic/F) were analyzed in 496 osteoarticular specimens (246 synovial fluids and 250 crushed bone samples), obtained in patients during routine diagnostic procedure at the Teaching Hospital of Rennes (France). The positive detection times were recorded for a 14 day-incubation period, and compared between both vials and with agar cultures. For samples from infected patients, the positive detection time was significantly shortened when vials were used compared to agar plates (p < 0.001). Median positive detection time was later with the Anaerobic Lytic/F vials (15.0 h) compared to the Plus Aerobic/F (13.0 h). Positivity rate was similar for Anaerobic Lytic/F vials (80.4%) and Plus Aerobic/F vials (83.2%) (p = 0.25). Some microorganisms were only identified from aerobic vials (15.5%) or from anaerobic vials (12.7%). The use of both atmosphere conditions for optimal positive detection time is therefore critical
Phase I Study of Escalating Doses of Lenalidomide Combined with R-CHOP (R2-CHOP) for Front-Line Treatment of B-Cell Lymphomas
Ruling out septic arthritis risk in a few minutes using mid-infrared spectroscopy in synovial fluids
International audienceObjectives: The aim of this study was to show the usefulness of a mid-infrared fibre evanescent wave spectroscopy point of care device in the identification of septic arthritis patients in a multicentre cohort, and to apply this technology to clinical practice among physicians.Methods: SF samples from 402 patients enrolled in a multicentre cohort were frozen for analysis by mid-infrared fibre evanescent wave spectroscopy. The calibration cohort was divided into two groups of patients (septic arthritis and non-septic arthritis) and relevant spectral variables were used for logistic regression model. Model performances were tested on an independent set of 86 freshly obtained SF samples from patients enrolled in a single-centre acute arthritis cohort and spectroscopic analyses performed at the patient’s bedside.Results:The model set-up, using frozen–thawed SFs, provided good performances, with area under the curve 0.95, sensitivity 0.90, specificity 0.90, positive predictive value 0.41 and negative predictive value 0.99. Performances obtained in the validation cohort were area under the curve 0.90, sensitivity 0.92, specificity 0.81, positive predictive value 0.46 and negative predictive value 0.98. The septic arthritis probability has been translated into a risk score from 0 to 4 according to septic risk. For a risk score of 0, the probability of identifying a septic patient is very low (negative predictive value of 1), whereas a risk score of 4 indicates very high risk of septic arthritis (positive predictive value of 1).Conclusion:Mid-infrared fibre evanescent wave spectroscopy could distinguish septic from non-septic synovial arthritis fluids with good performances, and showed particular usefulness in ruling out septic arthritis. Our data supports the possibility of technology transfe
A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: the EXPECT trial
BACKGROUND: This multicentre, single-arm, open-label phase 2 trial investigated the efficacy and safety of lenalidomide monotherapy in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL). METHODS: Patients received oral lenalidomide 25mg once daily on days 1-21 of each 28-day cycle for a maximum of 24 months, until disease progression or development of unacceptable adverse events (AEs). The primary end-point was efficacy; safety was evaluated as a secondary end-point. This study was registered with ClinicalTrials.gov, number NCT00655668. FINDINGS: A total of 54 patients with PTCL were treated. The overall response rate was 22% (12 of 54), including complete response (CR) or unconfirmed CR (CRu) in 11% of patients; 31% of patients with angioimmunoblastic T-cell lymphoma (AITL) responded (CR/CRu in 15% of patients). The median progression-free survival and median response duration were 2.5 and 3.6 months, respectively, in the intent-to-treat population, and 4.6 and 3.5 months, respectively, in patients with AITL. Thrombocytopenia and neutropenia were the most common grade 3 or 4 haematological AEs, in 11 (20%) and 8 (15%) patients, respectively. Overall, 19 patients (35%) experienced at least 1AE leading to study dose interruption or reduction (commonly neutropenia or thrombocytopenia). Serious AEs were observed in 54% of patients and 12 patients died during the study; lymphoma progression (n=6); and acute respiratory distress syndrome, dyspnea, lung infiltration, neutropenic sepsis, pneumonia and cerebral ischaemia (n=1 each). INTERPRETATION: Lenalidomide exhibited single-agent activity in heavily pretreated patients with PTCL, particularly in patients with AITL. Future development is warranted in specific histologies, such as AITL, and in combination with chemotherapy or other agents considered active in PTCL. FUNDING: Celgene Corporation
Factors predictive of early death in patients receiving high-dose CHOP (ACVB regimen) for aggressive non-Hodgkin's lymphoma: a GELA study
Death during the induction phase of chemotherapy remains a common event in patients with aggressive non-Hodgkin's lymphoma (NHL). In a series of patients with aggressive NHL homogeneously treated with intensive induction chemotherapy [ACVB (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) regimen], we determined the clinical and biological parameters that were predictive of early death. Early death was defined as death, for whatever reason, occurring within 100 d of randomization. Predictive factors were identified by logistic regression and an index predictive for individual risk of early death was designed. Among the 2210 patients treated with ACVB, there were 162 (7.3%) early deaths. There was no significant reduction in the rate of early death between 1987 and 1998. In a multivariate analysis, age > 60 years, Eastern Cooperative Oncology Group performance status > 1, serum lactate dehydrogenase > normal, serum albumin 10 x 10(9) /l and haemoglobin levels < 8.5 g/dl were found to be independent predictive factors for early death. An early death index was designed, enabling the evaluation of the individual risk of early death in young (range 2-31% risk of early death) and elderly patients (range 5-53%). Clinical and biological parameters available at diagnosis can help physicians identify patients with aggressive lymphoma at low or high risk of early death
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