F Monpoux

University of Nice-Sophia Antipolis, Nice, Provence-Alpes-Côte d'Azur, France

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Publications (91)338.36 Total impact

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    ABSTRACT: Background: In paƟents with β-thalassemia major, hematopoieƟc stem cell (HSC) gene therapy has the potenƟal to induce
    American Society of Hematology (ASH) 56th Annual Meeting, San Francisco (CA); 12/2014
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    ABSTRACT: Gene therapy, cellular immunotherapy and vaccination ABSSUB-3287 (abstract Number S742) OUTCOMES OF GENE THERAPY FOR BETA-THALASSEMIA MAJOR VIA TRANSPLANTATION OF AUTOLOGOUS HEMATOPOIETIC STEM CELLS TRANSDUCED EX VIVO WITH A LENTIVIRAL BETA GLOBIN VECTOR. Marina Cavazzana* 1, Jean-Antoine Ribeil^1, Emmanuel Payen^2, 3, Felipe Suarez4, Olivier Negre5, Yves Beuzard2, 3, Fabien Touzot1, Resy Cavallesco6, François Lefrere1, Stany Chretien2, 3, Philippe Bourget7, Fabrice Monpoux8, Corinne Pondarre9, Benedicte Neven10, Frederic D. Bushman11, Manfred Schmidt12, Christof von Kalle12, Laura Sandler13, Sandeep Soni13, Byoung Ryu13, Robert Kutner13, Gabor Veres13, Mitchell Finer13, Stéphane Blanche10, Olivier Hermine4, Salima Hacein-Bey-Abina1, Philippe Leboulch2, 3, 6 1Département de Biothérapie, Hôpital Universitaire Necker - Enfants Malades, Paris, 2CEA, Institute of Emerging Diseases and Innovative Therapies (iMETI), 3UMR 962 (Inserm-CEA-University of Paris-Sud), Fontenay-aux-Roses, 4Service d'hématologie Adulte, Hôpital Universitaire Necker - Enfants Malades, Paris, 5bluebird bio France, CEA-iMETI, Fontenay-aux-Roses, France, 6Harvard Medical School and Brigham & Women's Hospital, Boston, United States, 7Clinical Pharmacy Department, Hôpital Universitaire Necker - Enfants Malades, Paris, 8Unité d’Hemato-Oncologie infantile, Centre Hospitalier de Nice Sophia-Antipolis, Nice, 9Service de pédiatrie, Centre de référence de la Drépanocytose, Centre Hospitalier Intercommunal de Créteil (CHIC), Créteil, 10Unité d'Immunologie-Hématologie Pédiatrique, Hôpital Universitaire Necker - Enfants Malades, Paris, France, 11Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States, 12Translational Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany, 13bluebird bio, Cambridge, United States Background: In patients with β-thalassemia major, haematopoietic stem cell (HSC) gene therapy has the potential to induce production of β-globin, γ-globin or modified β-globin in the RBC lineage and reduce or stop the need for transfusions. A prior clinical trial (LG001) demonstrated benefit of autologous CD34+ cells transduced with a replication-defective, self-inactivating lentiviral vector (HPV569) containing an engineered β-globin gene (βA-T87Q). A further modified βA-T87Q vector (LentiGlobin BB305) has achieved greater transduction efficiency and a similar pre-clinical safety profile. LentiGlobin BB305 is now being evaluated in the HGB-205 clinical trial. Aims: To provide (i) long-term follow-up data on two subjects treated in LG001 and (ii) initial results from the HGB-205 study. Methods: After the provision of informed consent, subjects with β-thalassemia major underwent HSC collection via peripheral blood apheresis and CD34+ cells were selected. Estimation of the mean ex vivo vector copy number (VCN) was obtained by qPCR performed on pooled in vitro colony-forming progenitors. Subjects underwent myeloablation with intravenous busulfan, followed by infusion of transduced CD34+ cells. Subjects were monitored for haematological engraftment, βA-T87Q expression (by HPLC) and transfusion requirements. Integration site analysis (by LAM-PCR and high-throughput sequencing on nucleated cells) and replication-competent lentivirus assays were performed. Results: In LG001, two subjects (#1003 and #1004) with βE/β0 thalassemia major successfully engrafted following gene therapy with autologous HSCs transduced with HPV569. Neither subject experienced a cell infusion related adverse event. As reported previously (Nature 2010), #1003 became transfusion-independent one year post–transplant and remains so 5 years later, with the production of 2.5 - 3.5 g/dL βA-T87Q-globin (~30% of total haemoglobin). The most recent VCN in #1003's peripheral neutrophils is 0.23. Subject #1003 also demonstrated partial dominance of a clone with vector integration within the HMGA2 gene that peaked at 4 years post-treatment (22% of the nucleated cells) and has now fallen to 6.8% while maintaining transfusion independence. For #1004, the current VCN (2 years post-treatment) in neutrophils is 0.016 and βA-T87Q–globin accounts for ~5% of total haemoglobin. This subject remains transfusion dependent. Two subjects with βE/β0 thalassemia major (#1201 and #1202) have enrolled in the current HGB-205 trial and one has undergone transplantation. Transduction efficiency of the new BB305 vector compared to HPV569 is shown in Table 1. Data on the transplant outcomes and up to 6 months of follow-up in subjects treated in the HGB-205 trial will be presented at the meeting. Summary/Conclusion: Long-term transfusion independence is achievable with gene therapy for β thalassemia major. Use of the LentiGlobin BB305 vector has resulted in substantially higher VCN in CD34+ cells. It remains to be seen how the clinical outcomes will reflect this improvement. Table1. Comparison of gene transfer efficiencies and transplantation outcomes with HPV569 vs. BB305 βA‑T87Q‑LentiGlobin vectors ^these authors contributed equally Keywords: beta thalassemia, Gene therapy, Lentiviral vector, Transduction
    European Hematology Association - 19th Congress, Milano (Italy); 06/2014
  • Amandine Rubio · Fabrice Monpoux ·

    Journal of AIDS & Clinical Research 01/2012; 03(03). DOI:10.4172/2155-6113.1000146 · 6.83 Impact Factor
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    ABSTRACT: Primary immunoglobulin deficiencies lead to recurrent bacterial infections of the respiratory tract and bronchiectasis, even with adequate immunoglobulin replacement therapy. It is not known whether patients able to secrete IgM (eg, those with hyper-IgM [HIgM] syndrome) are as susceptible to these infections as patients who lack IgM production (eg, those with panhypogammaglobulinemia [PHG]). This study is aimed at identifying specific microbiological and clinical (infections) characteristics that distinguish immunoglobulin-substituted patients with PHG from patients with HIgM syndrome. A cohort of patients with HIgM syndrome (n = 25) and a cohort of patients with PHG (n = 86) were monitored prospectively for 2 years while receiving similar polyvalent immunoglobulin replacement therapies. Regular bacterial analyses of nasal swabs and sputum were performed, and clinical events were recorded. In parallel, serum and saliva IgM antibody concentrations were measured. When compared with patients with PHG, patients with HIgM syndrome were found to have a significantly lower risk of nontypeable Haemophilus influenzae carriage in particular (relative risk, 0.39; 95% CI, 0.21-0.63). Moreover, patients with HIgM syndrome (including those unable to generate somatic hypermutations of immunoglobulin genes) displayed anti-nontypeable H influenzae IgM antibodies in their serum and saliva. Also, patients with HIgM syndrome had a lower incidence of acute respiratory tract infections. IgM antibodies appear to be microbiologically and clinically protective and might thus attenuate the infectious consequences of a lack of production of other immunoglobulin isotypes in patients with HIgM syndrome. Polyvalent IgG replacement therapy might not fully compensate for IgM deficiency. It might thus be worth adapting long-term antimicrobial prophylactic regimens according to the underlying B-cell immunodeficiency phenotype.
    The Journal of allergy and clinical immunology 12/2011; 129(3):770-7. DOI:10.1016/j.jaci.2011.09.047 · 11.48 Impact Factor
  • J Benadiba · F Monpoux · A Appert-Flory · F Fischer · N Sirvent ·
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    ABSTRACT: The study of hemostasis often arises in paediatrics. Evidence of activated partial thromboplastin time (aPTT) prolongation sometime due to the presence of a circulating anticoagulant (antiphospholipid syndrome [APS]) may be embarrassing for the physician. To evaluate the prevalence of this situation, to identify the leading indicators and assess their impact. All children aged 1 to 18 years old undergoing blood sample whatever was the reason, at the Nice University Hospital with existing isolated aPTT prolongation, were included. The assessment was completed by a mixing test, calculation of Rosner's index as well as the study of an APS and the measurement of factor VIII, IX, XI, XII. Between July 2006 and March 2008, 27 of 1845 children observed (1.5%) were selected for further study. Mean age was 6.17 years old. For 16 of the patients, aPTT prolongation was fortuitously discovered. Symptomatic subjects were older (9.8 vs. 5.2 years of age; P = 0.03). A significantly higher aPTT was indicative of an APS and predicted a positive Rosner Test outcome. A prolongated kaolin clotting time, observed among the younger subjects (3.45 vs. 8.88 years of age; P = 0.0011), was associated with a high aPTT prolongation (57.3 vs. 42.6s; P = 0.0009). In our study, the discovery of a prolongated aPTT is most often incidental and tends to occur during winter. The presence of a highly prolongated aPTT, abnormal kaolin clotting time and positive Rosner Test are strong predictors of the existence of an APS, especially in very young children. These antibodies are nonpathogenic and transitional.
    Pathologie Biologie 12/2011; 59(6):314-8. DOI:10.1016/j.patbio.2010.07.003 · 1.20 Impact Factor

  • Haemophilia 10/2011; 18(1):e24-5. DOI:10.1111/j.1365-2516.2011.02664.x · 2.60 Impact Factor
  • P. Boutte · C. Dageville · A.-M. Maillotte · F. Monpoux ·

    Archives de Pédiatrie 05/2011; 18(5). DOI:10.1016/S0929-693X(11)70949-6 · 0.41 Impact Factor
  • F. Monpoux · P. Brunet · F. Fischer · A. Appert-Flory ·

    Archives de Pédiatrie 01/2011; 18(1):45-48. DOI:10.1016/j.arcped.2010.10.012 · 0.41 Impact Factor
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    ABSTRACT: Galactosemia and congenital Rogers syndrome or thiamine-responsive megaloblastic anemia are 2 rare inherited metabolic diseases. The combination of the 2 diseases has never been reported in the literature. We describe the case of an infant followed for congenital galactosemia since the age of 8 days, with thiamine-responsive megaloblastic anemia diagnosed at the age of 10 months. Galactosemia's symptoms occur in the first 2 weeks of life with severe liver disease. Total eviction of the galactose allows complete regression and prevention of early symptoms but does not prevent late complications. Rogers syndrome associates megaloblastic anemia, deafness, and diabetes mellitus that begin in childhood. Supplementation with thiamine allows regression of anemia and prevents the onset of diabetes at least until adolescence.
    Archives de Pédiatrie 01/2011; 18(1):54-7. · 0.41 Impact Factor
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    ABSTRACT: Galactosemia and congenital Rogers syndrome or thiamine-responsive megaloblastic anemia are 2 rare inherited metabolic diseases. The combination of the 2 diseases has never been reported in the literature. We describe the case of an infant followed for congenital galactosemia since the age of 8 days, with thiamine-responsive megaloblastic anemia diagnosed at the age of 10 months. Galactosemia's symptoms occur in the first 2 weeks of life with severe liver disease. Total eviction of the galactose allows complete regression and prevention of early symptoms but does not prevent late complications. Rogers syndrome associates megaloblastic anemia, deafness, and diabetes mellitus that begin in childhood. Supplementation with thiamine allows regression of anemia and prevents the onset of diabetes at least until adolescence.
    Archives de Pédiatrie 01/2011; 18(1):54-57. DOI:10.1016/j.arcped.2010.10.013 · 0.41 Impact Factor
  • F Monpoux · P Brunet · F Fischer · A Appert-Flory ·
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    ABSTRACT: Willebrand disease is the most common constitutional abnormality of hemostasis. It reflects a qualitative or quantitative abnormality of von Willebrand factor (vWF) responsible for hemorrhagic syndrome, mainly mucosal, of variable expression. Type 2N (Normandy) is a rare form of von Willebrand disease due to a qualitative abnormality of vWF that disrupts its ability to bind to factor VIII. The disease biologically combines APTT prolongation, a lower level of factor VIII, and a normal or subnormal rate of vWF, which may suggest a mild form of hemophilia A. This confusion can lead not only to a misdiagnosis but also to inappropriate treatment.
    Archives de Pédiatrie 01/2011; 18(1):45-8. · 0.41 Impact Factor
  • S Berthet · F Monpoux · A-M Soummer · E Bérard · J Sarles · C Badens ·
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    ABSTRACT: Screening for sickle cell disease, the most common of recessive autosomic hemoglobin disorders, allows detection of sickle cell disease SCD (homozygous sickle cell disease, compound heterozygote SC, and S β-thalassemia) in a target population. Our objective was to evaluate its effectiveness at the Nice University Hospital. This prospective study was conducted between 1 January 2000 and 31 December 2008. The national targeted newborn screening, run together with the Guthrie test on the 3rd day of life, offered at-risk newborns (based on ethnicity and family history), allow the detection of qualitative hemoglobin abnormalities. A confirmatory test is performed when positive. Gender, ethnicity, type of hemoglobin found, zygosity, age at diagnosis, the presence at a 2nd consultation of the families identified, and acceptance of the confirmatory test were collected and analyzed. A total of 19,775 children were born in Nice University Hospital during this period, among whom screening detected 151 hemoglobinopathies: 139 heterozygotes and 12 major sickle cell syndrome (9 SS and 3 S β-thalassemia). The prevalence of SCD on the targeted and the total population was, respectively, 1 out of 659 and 1 out of 1648 and the prevalence of heterozygotes was 1 out of 57 and 1 out of 142. The sex ratio was close to 1. Hemoglobin S predominated (74% of pathogens Hb). The Maghreb and sub-Saharan Africa were the 2 main areas of origin. One hundred and four of 151 families, including 12 cases of SCD, returned to consultation after they received a letter requesting attendance at a 2nd consultation. For 80 children, the confirmatory test was accepted. Feedback was possible for 72 of the 80 families. The number of children screened is increasing, thanks to better awareness among medical staff. The prevalence of SCD and heterozygotes found in Nice University Hospital is similar to what is described in the literature. With screening, early diagnosis allows early treatment at the age of 2 months before the occurrence of complications, reducing morbidity and mortality. Screening for sickle cell disease appears effective in Nice. It seems necessary to continue focusing on the importance of screening among maternity healthcare actors.
    Archives de Pédiatrie 11/2010; 17(12):1652-6. DOI:10.1016/j.arcped.2010.09.011 · 0.41 Impact Factor
  • F Monpoux · H Chambost · S Haouy · J Benadiba · N Sirvent ·
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    ABSTRACT: NovoSeven (eptacog alfa [activated]) is a concentrate of recombinant activated factor VII currently indicated in 3 types of situation: (1) hemorrhagic syndromes in patients with acquired haemophilia or constitutional A or B haemophilia with inhibitor; (2) Glanzmann thrombasthenia in patients with ineffective platelet transfusion due to alloimmunization; (3) constitutional factor VII deficiency. NovoSeven is also used, off label, in a very large number of bleeding conditions or bleeding risk especially in adult's trauma; abdominal, cardiac or chest surgery; gastroenterology; gynaecology and obstetrics or haematology. In these situations and sometimes in the context of randomized trials, against placebo studies, a large number of publications are reported, with variable scientific value according to evidence-based proofs. Studies conducted in children are far fewer and most of them did not achieve a high-level of evidence. However, we wanted to write a synthesis of the paediatric experience reported in the literature. Whereas it is important to build on work done in adults published data, the conclusions drawn from them are not perfectly applicable in paediatric practice. This bibliographical work is not an accurate guide of recommendations but should allow everyone to get an idea of situations where the use of this drug should or might be considered.
    Archives de Pédiatrie 08/2010; 17(8):1210-9. DOI:10.1016/j.arcped.2010.05.018 · 0.41 Impact Factor
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    ABSTRACT: Objectifs Le Centre de référence national des cytopénies auto-immunes de l’enfant (CEREVANCE), regroupant 30 centres de la Société d’Hématologie et d’Immunologie Pédiatrique (SHIP), a pour missions de structurer la filière de soins spécifique de l’adolescent. Patients et Méthodes Parmi les 345 enfants inclus dans la cohorte pédiatrique nationale prospective de suivi pour une AHAI, 52 avaient 13 ans ou plus au diagnostic initial. Résultats Ces adolescents (31 filles, 21 garçons) avaient des antécédents familiaux immunologiques (parents/fratrie) dans 27% des cas. Le test de Coombs était de type IgG/ IgG+C dans 82% des cas. L’AHAI était post infectieuse dans 11% des cas, associée à une maladie auto-immune ou un déficit immunitaire dans 48% des cas. Avec un suivi médian de 2,9 ans (0,1-9,1), 48% de ces jeunes, suivis par une équipe d’adultes, sont encore dépendants de traitements. Conclusion L’inclusion initiale des adolescents dans la cohorte pédiatrique permet de réaliser des études prospectives homogènes. Un relai de suivi dans une filière adulte est indispensable, compte tenu de la survenue parfois tardive d’une pathologie immunologique. Cette transition de l’enfant à l’adulte est effective dans plusieurs régions, grâce à une collaboration renforcée par le plan Maladies Rares.
    Archives de Pédiatrie 06/2010; 17(6):9-9. DOI:10.1016/S0929-693X(10)70247-5 · 0.41 Impact Factor
  • F. Monpoux · C. Dageville · P. Boutté ·

    Archives de Pédiatrie 03/2010; 17(3):299. DOI:10.1016/j.arcped.2009.11.018 · 0.41 Impact Factor
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    ABSTRACT: Objective: To evaluate clinical, immunological and virological consequences of CD4-guided antiretroviral therapy (ART) planned treatment interruptions (PTIs) compared with continuous therapy in children with chronic HIV infection in the Paediatric European Network for Treatment of AIDS 11 trial. Design: This was a multicentre, 72-week, open, randomized, phase 11 trial. Methods: One hundred and nine children with HIV-RNA below 50 copies/ml and CD4% of at least 30% (2-6 years) or at least 25% and CD4 cell count of at least 500 cells/mu l (7-15 years) were randomized to continuous therapy (53) or PTI (56). In PTI, ART was restarted if confirmed CD4% was less than 20% or more than 48 weeks had been spent off ART. The primary outcome was Centers for Disease Control and Prevention (CDC) stage C event, death or CD4% less than 15% (and CD4 cell count less than 200 cells/mu l for children aged 7-15years). Results: At baseline, median (interquartile range) age was 9 (6-12) years, CD4% 37% (33-41), CD4 cell count 966 (793-11258)cells/mu l, nadir CD41/0 before combination ART 18% (10-27), time on ART 6 (3-6) years and 26% were CDC stage C. After median (range) 130 (33-180) weeks of follow-up, 4 versus 48% of time was spent off ART in continuous therapy and PTI, respectively. No child died or had a new CDC stage C event; one (2%) continuous therapy versus four (7%) PTI children had a primary outcome based on CD4%/cell count (P=0.2). Lower nadir CD4% predicted faster CD4% decline after stopping ART. Younger age and higher nadir CD4% predicted being off ART for at least 48 weeks and better CD4% recovery following PTI. Conclusion: In this first paediatric trial of PTI, there were no serious clinical outcomes. Younger children had better CD4% recovery after PTIs. Immunology substudies and long-term follow-up in Paediatric European Network for Treatment of AIDS 11 trial are ongoing. Further research into the role of treatment interruption in children is required, particularly, as guidelines now recommend early ART for all infected infants. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
    AIDS 01/2010; 24(2):231-241. DOI:10.1097/QAD.0b013e328333d343 · 5.55 Impact Factor
  • F Monpoux · C Dageville · P Boutté ·

    Archives de Pédiatrie 01/2010; · 0.41 Impact Factor
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    A Appert-Flory · F Fischer · J Amiral · F Monpoux ·

    Thrombosis Research 12/2009; 126(2):e139-40. DOI:10.1016/j.thromres.2009.11.025 · 2.45 Impact Factor
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    ABSTRACT: Among the etiologies of anemia in the newborn, those related to mitochondrial cytopathies are rare. Pearson syndrome is mostly diagnosed during infancy and characterized by refractory sideroblastic anemia with vacuolization of marrow progenitor cells and exocrine pancreatic dysfunction. We describe two diagnosed cases of Pearson syndrome in the early neonatal period caused by severe macrocytic aregenerative anemia. Bone marrow aspiration revealed sideroblastic anemia and vacuolization of erythroblastic precursors. The diagnosis was confirmed by genetic analysis revealing a deletion in the mitochondrial DNA. These two newborns received monthly transfusions. Five other newborns suffering from Pearson syndrome with various clinical symptoms were found in literature. Pearson syndrome, rarely diagnosed in newborns, should be suspected in the presence of macrocytic aregenerative anemia and requires a bone marrow aspirate followed by a genetic analysis from a blood sample.
    Archives de Pédiatrie 11/2009; 17(1):38-41. DOI:10.1016/j.arcped.2009.10.006 · 0.41 Impact Factor
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    F Monpoux · P Puglièse · F Berthier · J Cottalorda · C Pradier ·
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    ABSTRACT: Prognosis of HIV-1 infection dramatically improved during the last decade. Meanwhile, treatment-induced virological success has always been different in adult and children patients. To compare 10 years of follow up in HIV-1 vertically infected children and adult patients. Monocentric retrospective longitudinal analysis of vertically HIV-1-infected children and adult patients followed in the Nice University Hospital between 1999 and 2008. Immunological, virological and antiretroviral treatment data were recorded. Forty children and 1752 adult patients were included. Between 1996 and 2008, the percentage of children receiving HAART increased from 3.2% to 91%. Mean CD4% in the paediatric group remained stable between 29 +/- 8.1% in 1998 and 30 +/- 9.4% in 2008. Mean adult CD4-cell count significantly increased from 410 in 1998 to 556 cells/mL in 2008. Logistic regression analysis showed that the children-to-adult difference for indetectability (HIV PCR-RNA below 400 copies/mL) was significant (p < 0.0001) with an odds ratio of 0.61 (CI(95th): 0.52-0.72). Year-to-patient interaction was also significant with a decreasing divergence over time (p: 0.038). Nowadays as in adult patients, the control of HIV-1 replication is achieved in nearly eight of 10 children and the percentage of patients with severe immunodeficiency dramatically decreased compared with the mid 1990s.
    Acta Paediatrica 09/2009; 98(11):1787-92. DOI:10.1111/j.1651-2227.2009.01440.x · 1.67 Impact Factor

Publication Stats

988 Citations
338.36 Total Impact Points


  • 2011
    • University of Nice-Sophia Antipolis
      Nice, Provence-Alpes-Côte d'Azur, France
  • 2002-2011
    • Centre Hospitalier Universitaire de Nice
      Nice, Provence-Alpes-Côte d'Azur, France
  • 2007
    • CHU de Lyon - Institut d'hématologie et d'oncologie pédiatrique
      Lyons, Rhône-Alpes, France
  • 1998
    • CHU de Lyon - Groupement Hospitalier Edouard Herriot
      Lyons, Rhône-Alpes, France
  • 1997
    • University of Leuven
      • Department of Human Genetics
      Louvain, Flanders, Belgium