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Le Touquet – Paris-Plage, France

Robinson S.,University of Bristol | Dreger P.,University of Heidelberg | Caballero D.,Hospital Clinico Servicio de Hematologica | Corradini P.,University of Milan | And 8 more authors.
Leukemia | Year: 2015

The role of both autologous (autoSCT) and allogeneic stem cell transplantation (alloSCT) in the management of mantle cell lymphoma (MCL) remains to be clarified. We conducted a consensus project using the RAND-modified Delphi consensus procedure to provide guidance on how SCT should be used in MCL. With regard to autoSCT, there was consensus in support of: autoSCT is the standard first-line consolidation therapy; induction therapy should include high-dose cytarabine and Rituximab; complete or partial remission should be achieved before autoSCT; Rituximab maintenance following autoSCT is not indicated; and omission of autoSCT in 'low-risk' patients is not indicated. No consensus could be reached regarding: autoSCT in the treatment of relapsed disease following non-transplant therapy; the value of positron emission tomography scanning and minimal residual disease (MRD) monitoring; in vivo purging with Rituximab; total body irradiation conditioning for autoSCT; and preemptive Rituximab after autoSCT. For alloSCT, consensus was reached in support of: alloSCT should be considered for patients relapsing after autoSCT; reduced intensity conditioning regimens should be used; allogeneic immunotherapy should be used for MRD eradication after alloSCT; and there is a lack of prognostic criteria to guide the use of alloSCT as first-line consolidation. No consensus was reached regarding the role of alloSCT for relapsed disease following non-transplant therapy. © 2015 Macmillan Publishers Limited All rights reserved

Sibiude J.,Hopital Louis Mourier | Sibiude J.,French Institute of Health and Medical Research | Mandelbrot L.,Hopital Louis Mourier | Mandelbrot L.,French Institute of Health and Medical Research | And 16 more authors.
PLoS Medicine | Year: 2014

Background:Antiretroviral therapy (ART) has major benefits during pregnancy, both for maternal health and to prevent mother-to-child transmission of HIV. Safety issues, including teratogenic risk, need to be evaluated. We estimated the prevalence of birth defects in children born to HIV-infected women receiving ART during pregnancy, and assessed the independent association of birth defects with each antiretroviral (ARV) drug used.Methods and Findings:The French Perinatal Cohort prospectively enrolls HIV-infected women delivering in 90 centers throughout France. Children are followed by pediatricians until 2 y of age according to national guidelines.We included 13,124 live births between 1994 and 2010, among which, 42% (n = 5,388) were exposed to ART in the first trimester of pregnancy. Birth defects were studied using both European Surveillance of Congenital Anomalies (EUROCAT) and Metropolitan Atlanta Congenital Defects Program (MACDP) classifications; associations with ART were evaluated using univariate and multivariate logistic regressions. Correction for multiple comparisons was not performed because the analyses were based on hypotheses emanating from previous findings in the literature and the robustness of the findings of the current study. The prevalence of birth defects was 4.4% (95% CI 4.0%-4.7%), according to the EUROCAT classification. In multivariate analysis adjusting for other ARV drugs, maternal age, geographical origin, intravenous drug use, and type of maternity center, a significant association was found between exposure to zidovudine in the first trimester and congenital heart defects: 2.3% (74/3,267), adjusted odds ratio (AOR) = 2.2 (95% CI 1.3-3.7), p = 0.003, absolute risk difference attributed to zidovudine +1.2% (95% CI +0.5; +1.9%). Didanosine and indinavir were associated with head and neck defects, respectively: 0.5%, AOR = 3.4 (95% CI 1.1-10.4), p = 0.04; 0.9%, AOR = 3.8 (95% CI 1.1-13.8), p = 0.04. We found a significant association between efavirenz and neurological defects (n = 4) using the MACDP classification: AOR = 3.0 (95% CI 1.1-8.5), p = 0.04, absolute risk +0.7% (95% CI +0.07%; +1.3%). But the association was not significant using the less inclusive EUROCAT classification: AOR = 2.1 (95% CI 0.7-5.9), p = 0.16. No association was found between birth defects and lopinavir or ritonavir with a power >85% for an odds ratio of 1.5, nor for nevirapine, tenofovir, stavudine, or abacavir with a power >70%. Limitations of the present study were the absence of data on termination of pregnancy, stillbirths, tobacco and alcohol intake, and concomitant medication.Conclusions:We found a specific association between in utero exposure to zidovudine and heart defects; the mechanisms need to be elucidated. The association between efavirenz and neurological defects must be interpreted with caution. For the other drugs not associated with birth defects, the results were reassuring. Finally, whatever the impact that some ARV drugs may have on birth defects, it is surpassed by the major role of ART in the successful prevention of mother-to-child transmission of HIV.Please see later in the article for the Editors' Summary. © 2014 Sibiude et al.

Ouss-Ryngaert L.,Hopital Necker
Medecine Therapeutique Pediatrie | Year: 2012

Autism continues to be diagnosed too late, despite the fact that parents often notice early signs. Although diagnosis cannot normally be made before two years, certain signs may be present within the first year, as early-onset and almost always before two years. Different studies, particularly those involving home video recordings, have attempted to identify early and specific signs, before the age of one, however, it is reasonable to assume that before 18 months, the signs of developmental problems are not specific to age. Above all, diagnosis is clinical. Two screening tools are available (CHAT and M CHAT) and three diagnostic tools are currently used (CARS, ADI R, and ADOS G). Communicating a diagnosis is a delicate task and it is sometimes difficult to establish rapid and intensive treatment. These cumulative difficulties certainly explain why autism is diagnosed at a late stage, but early diagnosis is crucial as it can enable early treatment, which changes the prognosis of autism.

Lemonnier F.,French Institute of Health and Medical Research | Lemonnier F.,University Paris Est Creteil | Couronne L.,French Institute of Health and Medical Research | Couronne L.,University Paris - Sud | And 16 more authors.
Blood | Year: 2012

Inactivating mutations of the Ten-Eleven Translocation 2 (TET2) gene were first identified in myeloid malignancies and more recently in peripheral T-cell lymphomas (PTCLs). In the present study, we investigated the presence of TET2 coding sequence mutations and their clinical relevance in a large cohort of 190 PTCL patients. TET2 mutations were identified in 40 of 86 (47%) cases of angioimmunoblastic T-cell lymphoma (AITL) and in 22 of 58 (38%) cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), but were absent in all other PTCL entities, with the exception of 2 of 10 cases of enteropathy-associated T-cell lymphoma. Among PTCL-NOS, a heterogeneous group of lymphoma-comprising cases likely to derive from Th follicular (T FH) cells similarly to AITL, TET2 mutations were more frequent when PTCL-NOS expressed T FH markers and/or had features reminiscent of AITL (58% vs 24%, P = .01). In the AITL and PTCL-NOS subgroups, TET2 mutations were associated with advanced-stage disease, thrombocytopenia, high International Prognostic Index scores, and a shorter progression-free survival. © 2012 by The American Society of Hematology.

Bader-Meunier B.,Hopital Necker
Medecine Therapeutique Pediatrie | Year: 2011

Henoch-Schönlein purpura (HSP) is an acute small-vessel leucocytoclastic vasculitis, which is the most common vasculitis in children. In most cases, HSP is a self-limited condition, which resolves spontaneously. Nephritis is the one feature of HSP that may have chronic consequences, and the long-term prognosis heavily depends on the severity of nephritis. Renal biopsy has to be promptly discussed in children who present with proteinuria greater than 0,5 g/L, renal insufficiency and/or nephrotic syndrome.

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