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Le Touquet – Paris-Plage, France

Leverger G.,Service dhematologie oncologie pediatrique | Le Guyader N.,Service pharmacie
Archives de Pediatrie | Year: 2011

Echinocandins are a new class of antifungal agents with a specific mechanism of action. These drugs inhibit the enzyme 1,3β - D-glucan synthetase which is responsible for the formation of 1,3β - D-glucan, an essential fungal cell wall component. They have a good activity against Candida species and Aspergillus. Three agents are available at the present time or under development: caspofungin, micafungin and anidulafungin. These drugs require intravenous administration. Efficacy, safety, rare drugs interactions and specificity of action are advantages for therapy of invasive fungal infections. In France, micafungin and caspofungin are approved for a pediatric use. © 2011 Elsevier Masson SAS.


Chambost H.,Service dhematologie oncologie pediatrique | Chambost H.,Aix - Marseille University
Transfusion Clinique et Biologique | Year: 2014

Rhesus (Rh) antigens are not expressed on platelets but residual red cells carry the risk of anti-D iso-immunization in transfusion recipients of platelet concentrates (PC). The main theoretical risk associated with this reaction relates to female subjects due to potential obstetrical situations of maternal-foetal Rh incompatibility. Isogroup PC transfusion in this system is therefore advised. However, logistical constraints impose frequent Rh-incompatible transfusions that require the recommendation of anti-Rh immunoglobulin in a girl of childbearing age in this situation. This recommendation, already restricted to a group of patients deserves to be questioned over a decade after being issued. Data from published reports are difficult to interpret because of the heterogeneity of the few series (CP type, immune status, timing of biological tests) but the current techniques for preparing products and most common use of CP apheresis limited the risk of immunization. Moreover, platelet transfusions are particularly relevant to immunocompromised populations which, to what extent (heavy chemotherapy and/or hematopoietic stem cells recipients) seems to be protected from this risk. It is noteworthy that the clinical consequences that may be expected from such immunization are not reported. Although some authors emphasize significant isoimmunization rates (maximum 19%), the heterogeneous conditions and the lack of evidence of clinical consequence suggest evaluating the recommendations or revising them towards more targeted indications of seroprophylaxis. © 2014.


Ducassou S.,Institute dHematologie Oncologie Pediatrique | Ferlay C.,Center Leon Berard | Bergeron C.,Institute dHematologie Oncologie Pediatrique | Girard S.,Service dhematologie biologie | And 8 more authors.
British Journal of Haematology | Year: 2011

In children, lymphoblastic lymphomas represent 30% of Non-Hodgkin lymphomas (NHL), and approximately 15% are precursor B-cell lymphomas (PBLL). Our study evaluated their main clinical characteristics, evolution, and prognosis in three trials. From 1989 to 2008, 53 children with PBLL (median age 7·75years) were included in three protocols: Malignant Lymphoma Therapy (LMT) 96, European Organization for Research and Treatment of Cancer (EORTC) 58881, and EORTC 58951 using Berlin-Frankfürt-Münster-derived acute lymphoblastic leukaemia (ALL) therapy. There were 10 stage I disease, 9 stage II, 9 stage III and 25 stage IV. Clinical presentation was heterogeneous with a majority of bone lesions and cutaneous or subcutaneous manifestations. At diagnosis 23 patients had bone marrow involvement, and only three had central nervous system involvement. The median follow-up was 74months. At last follow-up, 45 patients were in continuous complete remission, whereas eight had progressed or had relapsed (7 Stages IV and 1 Stage III) and died. Two patients had a secondary neoplasia, and are still alive. Disease stage was a major prognostic factor, with better overall survival (OS) and event-free survival (EFS) (P<0·05) rates observed in patients with Stage I to III as compared to those with Stage IV. Treatment with protocols derived from ALL therapy are efficient with an 82% EFS and an 85% OS at 5years. © 2011 Blackwell Publishing Ltd.


Levy P.,University of Paris Dauphine | Debre M.,Unite dImmunologie et dHematologie Pediatrique | Tajahmady A.,Mission Nationale dExpertise et dAudit Hospitaliers | Thomas C.,Service dhematologie oncologie pediatrique | And 5 more authors.
Clinical and Experimental Immunology | Year: 2010

Summary Lifelong immunoglobulin replacement is the standard, expensive therapy for severe primary antibody deficiencies. This treatment can be administrated either by intravenous immunoglobulin (IVIG) or subcutaneous infusions (SCIG) and delivered at home or in an out-patient setting. This study aims to determine whether SCIG is cost-effective compared with IVIG from a French social insurance perspective. Because both methods of administration provide similar efficacies, a cost-minimization analysis was performed. First, costs were calculated through a simulation testing different hypothesis on costs drivers. Secondly, costs were estimated on the basis of field data collected by a questionnaire completed by a population of patients suffering from agammaglobulinaemia and hyper-immunoglobulin (Ig)M syndrome. Patients' satisfaction was also documented. Results of the simulation showed that direct medical costs ranged from €19 484 for home-based IVIG to €25 583 for hospital-based IVIG, with home-based SCIG in between at €24 952 per year. Estimations made from field data were found to be different, with significantly higher costs for IVIG. This result was explained mainly by a higher immunoglobulin mean dose prescribed for IVIG. While the theoretical model showed very little difference between SCIG and hospital-based IVIG costs, SCIG appears to be 25% less expensive with field data because of lower doses used in SCIG patients. The reality of the dose difference between both routes of administration needs to be confirmed by further and more specific studies. © 2009 British Society for Immunology.


Calvez T.,University Pierre and Marie Curie | Calvez T.,French Institute of Health and Medical Research | Chambost H.,Service dhematologie oncologie pediatrique | Chambost H.,Aix - Marseille University | And 10 more authors.
Blood | Year: 2014

Six recombinant factor VIII (rFVIII) products have been marketed worldwide. In 2013, the Research of Determinants of Inhibitor Development (RODIN) study group reported an unexpectedly high risk of inhibitor development with a second-generation full-length rFVIII (Product D) in previously untreated patients (PUPs) with severe hemophilia A (HA). In 1994, French public health authorities established a prospective cohort to monitor hemophilia treatment safety. A PUP subgroup was designed to investigate inhibitor risk factors. We analyzed this subcohort in view of the RODIN findings. After excluding 50 patients who participated in the RODIN study, the primary analysis focused on 303 boys with severe HA first treated with a rFVIII product. A clinically significant inhibitor was detected in 114 boys (37.6%). The inhibitor incidence was higher with Product D vs the most widely used rFVIII product (adjusted hazard ratio [aHR], 1.55; 95% confidence interval [CI], 0.97-2.49). Similar results were found for high-titer inhibitors and in 10 sensitivity analyses. No heterogeneity was observed between RODIN and our results. Combined aHRs were 1.58 (95% CI, 1.17-2.14) for all inhibitors and 1.70 (95% CI, 1.15-2.52) for high-titer inhibitors. Our results confirm the higher immunogenicity of Product D vs other rFVIII products in PUPs with severe HA. © 2014 by The American Society of Hematology.

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