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Thoennissen N.H.,Cedars Sinai Medical Center | Krug U.O.,University of Munster | Lee D.H.T.,Cedars Sinai Medical Center | Kawamata N.,Cedars Sinai Medical Center | And 24 more authors.
Blood | Year: 2010

Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and primary myelofibrosis show an inherent tendency for transformation into leukemia (MPN-blast phase), which is hypothesized to be accompanied by acquisition of additional genomic lesions.We, therefore, examined chromosomal abnormalities by high-resolution single nucleotide polymorphism (SNP) array in 88 MPN patients, as well as 71 cases with MPN-blast phase, and correlated these findings with their clinical parameters. Frequent genomic alterations were found in MPN after leukemic transformation with up to 3-fold more genomic changes per sample compared with samples in chronic phase (P < .001). We identified commonly altered regions involved in disease progression including not only established targets (ETV6, TP53, and RUNX1) but also new candidate genes on 7q, 16q, 19p, and 21q. Moreover, trisomy 8 or amplification of 8q24 (MYC) was almost exclusively detected in JAK2V617F- cases with MPN-blast phase. Remarkably, copy number-neutral loss of heterozygosity (CNN-LOH) on either 7q or 9p including homozygous JAK2V617F was related to decreased survival after leukemic transformation (P = .01 and P = .016, respectively). Our high-density SNP-array analysis of MPN genomes in the chronic compared with leukemic stage identified novel target genes and provided prognostic insights associated with the evolution to leukemia. © 2010 by The American Society of Hematology.


Johnson-Ansah H.,University of Caen Lower Normandy | Guilhot J.,University of Poitiers | Rousselot P.,University of Versailles | Rea D.,Saint Louis Hospital | And 6 more authors.
Cancer | Year: 2013

BACKGROUND The pegylated form of interferon-α-2a (PegIFNa2a) in combination with imatinib has demonstrated a molecular improvement in patients with chronic-phase chronic myeloid leukemia. However, to the authors' knowledge, the appropriate dose of PegIFNa2a has not been established to date. METHODS In the French SPIRIT trial, the authors compared 2 initial doses of PegIFNa2a, taking into account an amendment that recommended reducing that dose from 90 μg/week to 45 μg/week because of toxicities. Accordingly, 2 subgroups of patients were identified: the PegIFN90 group (171 patients who were treated with the 90-μg/week dose) and the PegIFN45 group (50 patients who were treated with the 45-μg/week dose). Both groups were compared for toxicity and efficacy. RESULTS PegIFNa2a at a dose of 90 μg/week resulted in a rate of 54% of grade 3 to 4 hematologic toxicity compared with 27% with the dose of 45 μg/week (P <.001), leading to discontinuation rates of 40% and 10%, respectively, before 6 months. The dose reduction did not significantly affect the efficacy of the combination. By 12 months, the cumulative molecular response rates (ie, BCR-ABL/abl ≤ 0.01 [IS: molecular responses graded as molecular response 4 (MR4)]) were 14% and 25%, respectively, for the subgroup treated with imatinib at a dose of 400 mg and the PegIFN90 subgroup. After the amendment, the MR4 rates were 10% and 28%, respectively, for the subgroup treated with imatinib at the 400-mg dose and PegIFN45 subgroup (P <.0001). CONCLUSIONS The results of the current study demonstrate that in combination with imatinib, the efficient dose of PegIFNa2a appears to be 45 μg/week.


Mounier N.,Archet Hospital | Brice P.,Saint Louis Hospital | Bologna S.,Nancy Hospital | Briere J.,Saint Louis Hospital | And 14 more authors.
Annals of Oncology | Year: 2014

Background: Treatment with escalated BEACOPP achieved a superior time to treatment failure over ABVD in patients with disseminated Hodgkin lymphoma. However, recent clinical trials have failed to confirm BEACOPP overall survival (OS) superiority over ABVD. In addition, the gain in low-risk patients is still a matter of debate. Patients and methods: We randomly compared ABVD (8 cycles) with BEACOPP (escalated 4 cycles ≥baseline 4 cycles) in low-risk patients with an International Prognostic Score (IPS) of 0-2. The primary end point was event-free survival (EFS). This parallel group, open-label phase 3 trial was registered under #RECF0219 at French National Cancer Institute. Results: One hundred and fifty patients were randomized in this trial (ABVD 80, BEACOPP 70): 28 years was the median age, 50% were male and IPS was 0-1 for 64%. Complete remission rate was 85% for ABVD and 90% for BEACOPP. Progression or relapses were more frequent in the ABVD patients than in the BEACOPP patients (17 versus 5 patients). With a median follow-up period of 5.5 years, seven patients died: six in the ABVD arm and one in the BEACOPP arm (HL 3 and 0, 2nd cancer 2 and 1, accident 1 and 0). The EFS at 5 years was estimated at 62% for ABVD versus 77%, for BEACOPP [hazards ratio (HR) = 0.6, P = 0.07]. The progression-free survival (PFS) at 5 years was 75% versus 93% (HR = 0.3, P=0.007). The OS at 5 years was 92% versus 99% (HR = 0.18, P = 0.06). Conclusion: Fewer progressions/relapses were observed with BEACOPP, demonstrating the high efficacy of the more intensive regimen, even in low-risk patients. However, additional considerations, balancing treatment-related toxicity and late morbidity due to salvage may help with decision-making with regard to treatment with ABVD or BEACOPP. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


PubMed | Hopitaux Universitaires, Bordeaux University Hospital Center, ANRS, French Institute of Health and Medical Research and 6 more.
Type: Journal Article | Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America | Year: 2015

Human immunodeficiency virus (HIV) infection is associated with a high risk of classical Hodgkins lymphoma (cHL) in the combined antiretroviral therapy (cART) era.We analyzed the characteristics and outcome of HIV-associated cHL diagnosed in the modern cART era. The French ANRS-CO16 Lymphovir cohort enrolled 159 HIV-positive patients with lymphoma, including 68 (43%) with cHL. HIV-HL patients were compared with a series of non-HV-infected patients consecutively diagnosed with HL.Most patients (76%) had Ann-Arbor stages III-IV and 96% of patients were treated with ABVD. At diagnosis, median CD4 T-cell count was 387/L and 94% of patients were treated with cART. All patients received cART after diagnosis. Five patients died from early progression (n = 2), sepsis (1) or after relapse (2). Two additional patients relapsed during follow-up. Two-year overall and progression free survivals (PFS) were 94% [95% CI, 89%, 100%] and 89% [82%, 97%], respectively. The only factor associated with progression or death was age with a relative risk of 8.1 [1.0; 67.0] above 45 years. The PFS of Lymphovir patients appeared similar to PFS of HIV-negative patients, 86% [82%, 90%], but patients with HIV infection displayed higher risk features than HIV-negative patients.Although high-risk features still predominate in HIV-HL, the prognosis of these patients, treated with cART and mainly ABVD, has markedly improved in the modern cART era and is now similar to non-HIV-infected patients.


Vassallo M.,University of Nice Sophia Antipolis | Vassallo M.,Cannes General Hospital | Durant J.,University of Nice Sophia Antipolis | Biscay V.,University of Nice Sophia Antipolis | And 9 more authors.
AIDS | Year: 2014

OBJECTIVE:: To assess changes over time in neuropsychological test results (NPr) and risk factors among a regularly followed HIV-infected patient population. METHODS:: Prospective cohort of HIV-infected patients randomly selected to undergo neuropsychological follow-up. Test score was adjusted for age, sex and education. Patients were divided into five groups: normal tests, neuropsychological deficit (one impaired cognitive domain), asymptomatic neurocognitive disorders (ANIs), mild neurocognitive disorders (MNDs) and HIV-associated dementia (HAD). Demographic and background parameters including CSF drug concentration penetration effectiveness (CPE) score 2010 were recorded. Changes in NPr and associated risk factors were analyzed. RESULTS:: Two hundred and fifty-six patients underwent neuropsychological tests and 96 accepted follow-up approximately 2 years later. The groups were comparable. Upon neuropsychological retesting, six patients improved, 31 worsened and 59 were stable. The proportion of patients with HIV-associated neurocognitive disorders (HANDs) rose from 26 to 45%, with ANIs and MNDs still mostly represented. Most patients initially diagnosed with HANDs remained stable, five of 25 showed clinical improvement and three of 25 deteriorated. Of 33 patients with normal tests, four deteriorated, whereas 24 of 38 with initial neuropsychological deficit had poorer NPr, and contributed most of the new HAND cases. Patients with clinical deterioration had a lower CPE score both at inclusion (6.9 vs. 8.1; PS=S0.005) and at the end of follow-up (7.2 vs. 7.8; PS=S0.08) than those with improved or stable performance. This was confirmed by multivariate analysis. CONCLUSION:: Patients with higher CPE scores upon inclusion and at the end of follow-up were at lower risk of clinical worsening, suggesting that combination antiretroviral therapy with better CSF penetration could protect against cognitive deterioration. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


PubMed | University of Nice Sophia Antipolis, Pasteur Hospital, Archet Hospital, Antoine Lacassagne Center and Paris-Sorbonne University
Type: Comparative Study | Journal: Journal of the European Academy of Dermatology and Venereology : JEADV | Year: 2016

Knowledge of the BRAFV600E status is mandatory in metastatic melanoma patients (MMP). Molecular biology is currently the gold standard method for status assessment.We assessed and compared the specificity, sensibility, cost-effectiveness and turnaround time (TAT) of immunohistochemistry (IHC) and molecular biology for detection of the BRAFV600E mutation in 188 MMP.IHC, with the VE1 antibody, and pyrosequencing analysis were performed with formalin fixed paraffin embedded tumour samples.The BRAFV600E mutation was detected by pyrosequencing in 91/188 (48%) patients. IHC was strongly positive (3+) in all of these 91 cases. IHC was strongly positive in 9/188 (5%) cases in which the molecular testing failed due to non-amplifiable DNA. Weak or moderate staining was noted in 10/188 (5%) cases in which the molecular biology identified BRAF wild-type tumours. The ratio of the global cost for IHC/molecular biology testing was 1 : 2.2. The average TAT was 48 h vs. 96 h, for IHC vs. molecular biology testing, respectively.This study showed that VE1 IHC should be a substitute for molecular biology in the initial assessment of the BRAFV600E status in MPP. This methodology needs to be set up in pathology laboratories in accordance with quality control/quality assurance accreditation procedures. Under these strict conditions the question is to know if BRAFV600E-IHC can serve not only as a prescreening tool, but also as a stand-alone test (at least in cases displaying an unequivocally staining pattern) as well as an alternative predictive test for samples for which the molecular biology failed.


Stalder J.-F.,University of Nantes | Bernier C.,University of Nantes | Ball A.,University of Nantes | De Raeve L.,Vrije Universiteit Brussel | And 11 more authors.
Pediatric Dermatology | Year: 2013

Therapeutic patient education (TPE) has proven effective in increasing treatment adherence and improving quality of life (QoL) for patients with numerous chronic diseases, especially atopic dermatitis (AD). This study was undertaken to identify worldwide TPE experiences in AD treatment. Experts from 23 hospitals, located in 11 countries, responded to a questionnaire on 10 major items. Patients in TPE programs were mainly children and adolescents with moderate to severe AD or markedly affected QoL. Individual and collective approaches were used. Depending on the center, the number of sessions varied from one to six (corresponding to 2 to 12 hours of education), and 20 to 200 patients were followed each year. Each center's education team comprised multidisciplinary professionals (e.g., doctors, nurses, psychologists). Evaluations were based on clinical assessment, QoL, a satisfaction index, or some combination of the three. When funding was obtained, it came from regional health authorities (France), insurance companies (Germany), donations (United States), or pharmaceutical firms (Japan, Italy). The role of patient associations was always highlighted, but their involvement in the TPE process varied from one country to another. Despite the nonexhaustive approach, our findings demonstrate the increasing interest in TPE for managing individuals with AD. In spite of the cultural and financial differences between countries, there is a consensus among experts to integrate education into the treatment of eczema. © 2013 Wiley Periodicals, Inc.


Mekinian A.,Claude Huriez Hospital | Durand-Joly I.,Lille University and Hospital | Hatron P.-Y.,Claude Huriez Hospital | Moranne O.,Archet Hospital | And 8 more authors.
Rheumatology | Year: 2011

Objectives: To determine the rate and identify risk factors of Pneumocystis jirovecii (P. jirovecii) colonization among patients with systemic autoimmune diseases. Methods: We conducted an observational study in patients with systemic autoimmune diseases in an internal medicine department. Each week, five patients with systemic diseases were randomly selected for colonization screening. Patients complaining of recent respiratory symptoms were excluded. P. jirovecii PCR was performed on induced sputum samples. Univariate and multivariate logistic regression analyses of clinical and biological data were performed to determine predictors of Pneumocystis colonization. Pneumocystis pneumonia occurrence in P. jirovecii-positive PCR patients was recorded during a 1-year follow-up. Results: P. jirovecii was detected in 11/67 (16%) subjects. Comparing the features in P. jirovecii-positive and P. jirovecii-negative PCR patients, only male gender was significantly associated with Pneumocystis colonization. In multivariate analysis with regard to gender, the higher prevalence of P. jirovecii colonization in men was largely explained by higher daily CSs [odds ratio (OR) = 1.6; 95% CI 1.1, 2.3] and lower total lymphocyte level (OR = 0.9; 95% CI 0.8, 0.99). No P. jirovecii-positive PCR patient developed Pneumocystis pneumonia during the 1-year follow-up, but corticosteroid amounts were significantly lower at the end of follow-up than on inclusion. Conclusion: This is the first study on P. jirovecii colonization in patients with systemic autoimmune diseases. We found a high prevalence of colonization and identified CS therapy and lymphocyte counts as risk factors for colonization. We recommend screening for P. jirovecii colonization in patients with systemic autoimmune diseases receiving immunosuppressant treatment. Further studies are needed to determine the role of subclinical colonization in disease transmission and the persistence of Pneumocystis colonization. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.


Montel S.,University of Lorraine | Albertini L.,Archet Hospital | Spitz E.,University of Lorraine
Muscle and Nerve | Year: 2012

Introduction: The aim of this study was to examine the coping strategies of 49 patients with amyotrophic lateral sclerosis (ALS) and the relationships of these strategies to their perceived health-related quality of life (HRQoL). Methods: Forty-nine subjects were assessed for collection of demographic and medical data. Each one was then asked to complete a questionnaire of coping strategies (Brief COPE) as well as a questionnaire of health-related duality of life (36-item Short Form). Results: Correlation analysis showed strong relationships between some coping and HRQoL dimensions, including: emotional support and physical functioning (P = 0.01) and emotional role functioning (P = 0.02); venting and mental health (P = 0.04); positive reframing and mental health (P = 0.03); and disengagement and emotional role functioning (P = 0.03). Conclusions: The relationships between some coping strategies and certain dimensions of HRQoL are shown. We now understand the usefulness of focusing on coping strategies to improve HRQoL in ALS. © 2011 Wiley Periodicals, Inc.


Montel S.,University of Lorraine | Albertini L.,Archet Hospital | Spitz E.,University of Lorraine
Acta Neurologica Scandinavica | Year: 2012

Introduction- The aim of this study was to examine the coping strategies of 49 patients with amyotrophic lateral sclerosis (ALS) and their relationships with medical and demographic data. Methods- A total of 49 subjects were asked to fill out a document that would provide their demographic and medical data. Then, each one was asked to complete a questionnaire of coping strategies called the Brief COPE. Results- Regarding age groups, we noticed several significant differences concerning emotional support, venting, positive reframing, planning and humour. All these strategies were used significantly more often by younger patients. As for medical variables, the clinical form (bulbar vs spinal ALS), and participation or non-participation in a clinical trial proved to affect the coping style. The correlation analysis showed that disease duration was positively and significantly related to acceptance, positive reframing and humour. Only one significant correlation was observed between coping strategies and ALS Functional Rating Scale (ALSFRS) scores. It concerned blame, which was negatively correlated with ALSFRS scores. Discussion- Our study clearly demonstrated the relationships between coping strategies and medical as well as demographic variables. These results encourage us to develop further investigations to better understand these relationships and to offer better adapted psychological interventions for patients with ALS. © 2011 John Wiley & Sons A/S.

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