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108 results on '"Yves Perel"'

1. The French paediatric cohort of Castleman disease: a retrospective report of 23 patients

Author: Charlotte Borocco, Claire Ballot-Schmit, Oanez Ackermann, Nathalie Aladjidi, Jeremie Delaleu, Vannina Giacobbi-Milet, Sarah Jannier, Eric Jeziorski, François Maurier, Yves Perel, Christophe Piguet, Eric Oksenhendler, Isabelle Koné-Paut, and Caroline Galeotti
Subjects: Paediatric Castleman disease, Unicentric, Multicentric, Tocilizumab, Medicine
Abstract: Abstract Background Castleman disease (CD) is a rare non-malignant lymphoproliferation of undetermined origin. Two major disease phenotypes can be distinguished: unicentric CD (UCD) and multicentric CD (MCD). Diagnosis confirmation is based on histopathological findings in a lymph node. We attempted to survey all cases of paediatric CD identified to date in France to set up a national registry aiming to improve CD early recognition, treatment and follow-up, within the context of a new national reference center ( http://www.castleman.fr ). Methods In 2016, we e-mailed a questionnaire to members of the French paediatric immunohaematology society, the paediatric rheumatology society and the Reference Centre for Castleman Disease to retrospectively collect cases of paediatric CD (first symptoms before age 18 years). Anatomopathological confirmation was mandatory. Results We identified 23 patients (12 girls) with a diagnosis of UCD (n = 17) and MCD (n = 6) between 1994 and 2018. The mean age at first symptoms was 11.47 ± 4.23 years for UCD and 8.3 ± 3.4 years for MCD. The mean diagnosis delay was 8.16 ± 10.32 months for UCD and 5.16 ± 5.81 years for MCD. In UCD, the initial symptoms were isolated lymph nodes (n = 10) or lymph node associated with other symptoms (n = 7); fever was present in 3 patients. Five patients with MCD presented fever. No patients had HIV or human herpesvirus 8 infection. Autoinflammatory gene mutations were investigated in five patients. One patient with MCD carried a K695R heterozygous mutation in MEFV, another patient with MCD and Duchenne myopathy carried two variants in TNFRSF1A and one patient with UCD and fever episodes carried two heterozygous mutations, in IL10RA and IL36RN, respectively. Treatment of UCD was mainly surgical resection, steroids, and radiotherapy. Treatment of MCD included tocilizumab, rituximab, anakinra, steroids, chemotherapy, and splenectomy. Overall survival after a mean of 6.1 ± 6.4 years of follow-up, was 100% for both forms. Conclusion Paediatric CD still seems underdiagnosed, with a significant diagnosis delay, especially for MCD, but new international criteria will help in the future. Unlike adult CD, which is strongly associated with HIV and human herpesvirus 8 infection, paediatric CD could be favored by primary activation of innate immunity and may affect life expectancy less.
Published: 2020
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2. Excellent prognosis of late relapses of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia: lessons from the FRALLE 93 protocol

Author: Virginie Gandemer, Sylvie Chevret, Arnaud Petit, Christiane Vermylen, Thierry Leblanc, Gérard Michel, Claudine Schmitt, Odile Lejars, Pascale Schneider, François Demeocq, Brigitte Bader-Meunier, Françoise Bernaudin, Yves Perel, Marie-Françoise Auclerc, Jean-Michel Cayuela, Guy Leverger, and André Baruchel
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background The prognosis of patients with relapses of ETV6/RUNX1-positive acute lymphoblastic leukemia remains to be evaluated, particularly with regards to the frequency of late relapses. We performed a long-term, follow-up retrospective study to address the outcome of patients with ETV6/RUNX1-positive leukemia relapses.Design and Methods Among the 713 children tested for ETV6/RUNX1 enrolled into the FRALLE 93 protocol, 43 ETV6/RUNX1-positive patients relapsed (19.4%). Most were initially stratified in the low or intermediate risk groups. The median follow-up after relapse was 54.2 months. All but three received second-line salvage therapy and 16 underwent allogeneic transplantation.Results ETV6/RUNX1 had a strong effect on overall survival after relapse (3-year survival= 64.7% for positive cases versus 46.5% for negative cases) (P=0.007). The 5-year cumulative incidence of relapse was 19.4% and testes were more frequently involved in ETV6/RUNX1-positive relapses (P=0.04). In 81.4% of cases the relapses were late, early combined or isolated extramedullary relapses. The 5-year survival rate of patients with ETV6-RUNX1-positive acute lymphoblastic leukemia relapses reached 80.8% when the relapse occurred after 36 months (versus 31.2% when the relapse occurred earlier). In univariate analysis, female gender was associated with a poor survival, whereas site of relapse, age at diagnosis, leukocytosis and consolidation strategy had no effect. In multivariate analysis, only the duration of first remission remained associated with outcome.Conclusions We found an excellent outcome for patients with ETV6/RUNX1-positive leukemia relapses that occurred more than 36 months after diagnosis. The duration of first complete remission may, therefore, be a guide to define the treatment strategy for patients with relapsed ETV6/RUNX1- positive leukemia. Key words: ETV6/RUNX1, childhood leukemia, acute lymphoblastic, prognosis, relapse.
Published: 2012
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3. Impact of genotype on survival of children with T-cell acute lymphoblastic leukemia treated according to the French protocol FRALLE-93: the effect of TLX3/HOX11L2 gene expression on outcome

Author: Paola Ballerini, Judith Landman-Parker, Jean Michel Cayuela, Vahid Asnafi, Myriam Labopin, Virginie Gandemer, Yves Perel, Gérard Michel, Thierry Leblanc, Claudine Schmitt, Sylvie Fasola, Anne Hagemejier, François Sigaux, Marie Françoise Auclerc, Luc Douay, Guy Leverger, and André Baruchel
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background The prognostic value of the ectopic activation of TLX3 gene expression, a major oncogenetic event associated with pediatric T-cell acute lymphoblastic leukemia, is controversial. Likewise, the frequency and the prognostic significance in pediatric T-cell acute lymphoblastic leukemia of the newly characterized NUP214-ABL1 fusion transcript is not yet clear.Design and Methods Two hundred children with T-cell acute lymphoblastic leukemia were treated in the French FRALLE-93 study from 1993 to 1999.The expression of TLX3, TLX1 and SILTAL1 genes was analyzed in samples from 92 patients by real-time quantitative reverse transcriptase polymerase chain reaction. Most of these samples were further studied for NUP214-ABL1 and CALM-AF10 fusion transcripts.Results The median follow-up was 7.9 years. At 5 years the overall survival (± standard deviation, %) was 62 (±3%) and leukemia-free survival was 58 (±3%). Patients with T-cell acute lymphoblastic leukemia positive for TLX3 had a poorer survival compared to those with T-ALL negative for TLX3 (overall survival: 45±11% vs. 57±5%, p=0.049). In multivariate analysis, TLX3 expression was an independent adverse risk factor predicting relapse with a hazard ratio of 2.44 (p=0.017) and an overall survival with a hazard ratio of 3.7 (p=0.001). NUP214-ABL1 was expressed in 16.6% of patients with TLX3-positive T-ALL (3 of 18); all of the patients with this association died before completion of the treatment. SILTAL expression did not significantly affect the prognosis of patients with T-cell acute lymphoblastic leukemia. Only three of 92 patients expressed the TLX1 gene and all three are alive.Conclusions TLX3 gene expression is an independent risk factor predicting poor survival in childhood T-cell acute lymphoblastic leukemia. When co-expressed with TLX3, NUP214-ABL1 transcripts may increase the risk of poor survival.
Published: 2008
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4. Rituximab therapy for childhood Evans syndrome

Author: Brigitte Bader-Meunier, Nathalie Aladjidi, Françoise Bellmann, Fabrice Monpoux, Brigitte Nelken, Alain Robert, Corinne Armari-Alla, Capucine Picard, Françoise Ledeist, Martine Munzer, Karima Yacouben, Yves Bertrand, Antoine Pariente, Arnaud Chaussé, Yves Perel, and Guy Leverger
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: The safety and efficacy of rituximab have been retrospectively assessed in 17 children with Evans syndrome. Patients received 4 or 3 weekly doses of rituximab (375 mg/m2 per dose) associated with prednisone, alone (14 patients) or associated with other immunosuppressive drugs. Complete or partial remission of at least one cytopenia was achieved in 13 out of the 17 patients (76%), and lasted in 11 of them with a mean follow-up of 2.4 years (range 0.5–7 years). Steroid therapy was stopped or tapered at 50–100% of the baseline dosage in all long-term responders. Moderate side effects and infection occurred only in 4 and 1 children respectively.
Published: 2007
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5. The French paediatric cohort of Castleman disease: a retrospective report of 23 patients

Author: Caroline Galeotti, Jérémie Delaleu, Claire Ballot-Schmit, Charlotte Borocco, Eric Jeziorski, Eric Oksenhendler, Isabelle Koné-Paut, Yves Perel, Sarah Jannier, Nathalie Aladjidi, Vannina Giacobbi-Milet, Oanez Ackermann, François Maurier, Christophe Piguet, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital JeanMinjoz, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CHU Tenon] (CeréMAIA), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pédiatrie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Hôpital de Hautepierre [Strasbourg], Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Hôpitaux Privés de Metz (HPMetz), Service de Pédiatrie médicale [CHU Limoges], CHU Limoges, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Michel-Avella, Amandine
Subjects: Adult, medicine.medical_specialty, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Splenectomy, lcsh:Medicine, Context (language use), Gene mutation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Internal medicine, Unicentric, medicine, Humans, Pharmacology (medical), Child, Genetics (clinical), Retrospective Studies, Anakinra, business.industry, Castleman disease, Castleman Disease, Interleukins, Research, Paediatric Castleman disease, lcsh:R, General Medicine, Pyrin, medicine.disease, MEFV, [SDV] Life Sciences [q-bio], chemistry, Multicentric, 030220 oncology & carcinogenesis, Rituximab, Female, France, Lymph Nodes, business, 030215 immunology, medicine.drug
Abstract: Background Castleman disease (CD) is a rare non-malignant lymphoproliferation of undetermined origin. Two major disease phenotypes can be distinguished: unicentric CD (UCD) and multicentric CD (MCD). Diagnosis confirmation is based on histopathological findings in a lymph node. We attempted to survey all cases of paediatric CD identified to date in France to set up a national registry aiming to improve CD early recognition, treatment and follow-up, within the context of a new national reference center (http://www.castleman.fr). Methods In 2016, we e-mailed a questionnaire to members of the French paediatric immunohaematology society, the paediatric rheumatology society and the Reference Centre for Castleman Disease to retrospectively collect cases of paediatric CD (first symptoms before age 18 years). Anatomopathological confirmation was mandatory. Results We identified 23 patients (12 girls) with a diagnosis of UCD (n = 17) and MCD (n = 6) between 1994 and 2018. The mean age at first symptoms was 11.47 ± 4.23 years for UCD and 8.3 ± 3.4 years for MCD. The mean diagnosis delay was 8.16 ± 10.32 months for UCD and 5.16 ± 5.81 years for MCD. In UCD, the initial symptoms were isolated lymph nodes (n = 10) or lymph node associated with other symptoms (n = 7); fever was present in 3 patients. Five patients with MCD presented fever. No patients had HIV or human herpesvirus 8 infection. Autoinflammatory gene mutations were investigated in five patients. One patient with MCD carried a K695R heterozygous mutation in MEFV, another patient with MCD and Duchenne myopathy carried two variants in TNFRSF1A and one patient with UCD and fever episodes carried two heterozygous mutations, in IL10RA and IL36RN, respectively. Treatment of UCD was mainly surgical resection, steroids, and radiotherapy. Treatment of MCD included tocilizumab, rituximab, anakinra, steroids, chemotherapy, and splenectomy. Overall survival after a mean of 6.1 ± 6.4 years of follow-up, was 100% for both forms. Conclusion Paediatric CD still seems underdiagnosed, with a significant diagnosis delay, especially for MCD, but new international criteria will help in the future. Unlike adult CD, which is strongly associated with HIV and human herpesvirus 8 infection, paediatric CD could be favored by primary activation of innate immunity and may affect life expectancy less.
Published: 2020
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6. An appraisal of the frequency and severity of noninfectious manifestations in primary immunodeficiencies: A study of a national retrospective cohort of 1375 patients over 10 years

Author: Mickaël Alligon, Nizar Mahlaoui, Virginie Courteille, Laurence Costes, Veronica Afonso, Philippe Randrianomenjanahary, Nathalie de Vergnes, Anja Ranohavimparany, Duy Vo, Inès Hafsa, Perrine Bach, Vincent Benoit, Nicolas Garcelon, Alain Fischer, Wadih Abou-Chahla, Daniel Adoue, Nathalie Aladjidi, Corinne Armari-Alla, Vincent Barlogis, Sophie Bayart, Yves Bertrand, Stéphane Blanche, Damien Bodet, Bernard Bonnotte, Raphaël Borie, Patrick Boutard, David Boutboul, Claire Briandet, Jean-Paul Brion, Jacques Brouard, Liana Carausu, Martin Castelle, Pascal Cathebras, Emilie Catherinot, Nathalie Cheikh, Morgane Cheminant, Sarah Cohen-Beaussant, Thibault Comont, Louis-Jean Couderc, Pierre Cougoul, Gérard Couillault, Lionel Crevon, Elisa Demonchy, Anne Deville, Catherine Devoldere, Eric Dore, Fabienne Dulieu, Isabelle Durieu, Natacha Entz-Werle, Claire Fieschi, Fanny Fouyssac, Pierre Frange, Vincent Gajdos, Lionel Galicier, Virginie Gandemer, Martine Gardembas, Catherine Gaud, Bernard Grosbois, Aurélien Guffroy, Corinne Guitton, Gaëlle Guillerm, Eric Hachulla, Mohamed Hamidou, Sophie Haro, Yves Hatchuel, Olivier Hermine, Cyrille Hoarau, Arnaud Hot, Sébastien Humbert, Arnaud Jaccard, Jean-Philippe Jais, Sarah Jannier, Serge Jacquot, Roland Jaussaud, Pierre-Yves Jeandel, Eric Jeziorski, Kamila Kebaili, Anne-Sophie Korganow, Olivier Lambotte, Fanny Lanternier, Claire Larroche, David Launay, Emmanuelle Le Moigne, Alain Le Quellec, Vincent Le Moing, Yvon Lebranchu, Marc Lecuit, Guillaume Lefèvre, Jean-Daniel Lelièvre, Richard Lemal, Valérie Li-Thiao-Te, Olivier Lortholary, Luminita Luca, Coralie Mallebranche, Marion Malphettes, Aude Marie-Cardine, Nicolas Martin-Silva, Agathe Masseau, Françoise Mazingue, Etienne Merlin, Gérard Michel, Frédéric Millot, Charline Miot, Béatrice Monlibert, Fabrice Monpoux, Despina Moshous, Luc Mouthon, Martine Münzer, Robert Navarro, Bénédicte Neven, Dalila Nouar, Raphaële Nove-Josserand, Eric Oksenhendler, Marie Ouachée-Chardin, Anne Pagnier, Marlène Pasquet, Isabelle Pellier, Yves Perel, Antoinette Perlat, Christophe Piguet, Dominique Plantaz, Sophie Rivière, Pascal Roblot, Pierre-Simon Rohrlich, Bruno Royer, Valéry Salle, Françoise Sarrot-Reynauld, Amélie Servettaz, Jean-Louis Stephan, Nicolas Schleinitz, Harry Sokol, Felipe Suarez, Laure Swiader, Sophie Taque, Caroline Thomas, Olivier Tournilhac, Caroline Thumerelle, Jean-Pierre Vannier, and Jean-François Viallard
Subjects: Inflammation, Neoplasms, Immunology, Hypersensitivity, Immunologic Deficiency Syndromes, Immunology and Allergy, Humans, Autoimmunity, Retrospective Studies
Abstract: Noninfectious manifestations-allergy, autoimmunity/inflammation, lymphoproliferation, and malignancies-are known to exist in many primary immunodeficiency diseases (PID) and to participate in prognosis.To obtain a global view on their occurrence, we retrieved data from a retrospective cohort of 1375 patients included in the French National Reference Center for Primary Immune Deficiencies (CEREDIH) for whom we had a 10-year follow-up since inclusion in the registry.These patients were followed for 10 years (2009-2018) by specialized centers in university hospitals. This study showed that 20.1% of patients without prior curative therapy (n = 1163) developed at least 1 manifestation (event) encompassing 277 events.Autoimmune/inflammatory events (n = 138) and malignancies (n = 85) affected all age classes and virtually all PID diagnostic groups. They were associated with a risk of death that occurred in 195 patients (14.2%) and were found to be causal in 43% of cases. Malignancies (odds ratio, 5.62; 95% confidence interval, 3.66-8.62) and autoimmunity (odds ratio, 1.9; 95% confidence interval, 1.27-2.84) were clearly identified as risk factors for lethality. Patients who underwent curative therapy (mostly allogeneic hematopoietic stem cell transplantation, with a few cases of gene therapy or thymus transplantation) before the 10-year study period (n = 212) had comparatively reduced but still detectable clinical manifestations (n = 16) leading to death in 9.4% of them.This study points to the frequency and severity of noninfectious manifestations in various PID groups across all age groups. These results warrant further prospective analysis to better assess their consequences and to adapt therapy, notably indication of curative therapy.
Published: 2021

7. Risk of autoimmune diseases and human papilloma virus (HPV) vaccines: Six years of case-referent surveillance

Author: Lamiae Grimaldi-Bensouda, Michel Rossignol, Isabelle Koné-Paut, Alain Krivitzky, Christine Lebrun-Frenay, Johanna Clet, David Brassat, Caroline Papeix, Marc Nicolino, Pierre-Yves Benhamou, Olivier Fain, Nathalie Costedoat-Chalumeau, Marie-France Courcoux, Jean-François Viallard, Bertrand Godeau, Thomas Papo, Patrick Vermersch, Isabelle Bourgault-Villada, Gerard Breart, Lucien Abenhaim, Firas Abbas, Abdelhakim Abdelmoumni, Pascal Hilliquin, Elisabeth Requeda, Daniel Adoue, Christian Agard, Agathe Masseau, Nathalie Aladjidi, Helder Fernandes, Gwendal Lemasson, Yves Perel, Isabelle Raymond, Olivier Richer, Anne Vital, Emma Allain-Launay, Marie Bru, Caroline Thomas, Jean-Jacques Altman, Daniel Amsallem, Nazmiye Aras, Latifato Boukari, Marie Dubrel, Edouard Letellier, Nadine Lucidarme, Arsène Mekinian, Anne-Sophie Morin, Jérôme Stirnemann, Catherine Atlan, Dominique Audry, Jérôme Augustin, Redouane Bakir, Pablo Bartolucci, Xavier Chevalier, Constance Guillaud, Mehdi Khellaf, Nicolas Limal, Valentine Lousteau, Matthieu Mahevas, Gayane Méliksetyan, Marc Michel, Mathilde Roumier, Sophie Bayart, Fabrice Bonnet, Olivier Decaux, Amine Bekherraz, Benoit Brihaye, Roger Dachez, Eric Daugas, Gilles Hayem, Olivier Meyer, Elisa Pasqualoni, Karim Sacre, Florence Travert, Hélène Bellon, Jacques Beltrand, François Lefrere, Albane Simon, Olivier Benveniste, Francis Bolgert, Raphael De Paz, Sophie Demeret, Bruno Fautrel, Sophie Jacqueminet, Céline Louapre, Elizabeth Maillart, Nathalie Morel, Julie Rigabert, Philippe Bensaid, Claire Berger, Patrick Berquin, Anne-Gaëlle Le Moing, Stéphane Berroir, Gérard Besson, Célia Boutte, Olivier Casez, Bernard Bonnotte, Sylvain Audia, Cécile Bossu-Estour, Anne Bourgarit, Alain Dupuy, Homa Keshmandt, Bertrand Bourre, Aude Brac, Agnès Perrin, Corinne Pondarré, Sylvie Villar-Fimbel, Isabelle Bruckert, Anne Cosson, Nadine Magy-Bertrand, Guillaume Tisserand, William Camu, Bertrand Carlander, Raul Juntas Morales, Claude Cances, Marlene Pasquet, Maria Angela Castilla Lievre, Stephanie Chabroux, Mamoud Charif, Emmanuel Chatelus, Jean Sibilia, Jacqueline Chevrant-Breton, Sylvaine Clavel, Françoise Bille-Turc, Jacques Cohen, Marie France Courcoux, Guy Leverger, Laurent Machet, Jean-Marie Cuisset, Pascale Cony-Makhoul, Paul Darsy, Sandrine Favre, Pierrick Giraud, Laurence Leitenschenck, Irène Monteiro, Chafika Morati, Jérôme DeSeze, Monica Dinulescu, Taher Dhaoui, Florence Dommange-Romero, Elisabeth Drevard, Clémentine Dupuis, Marie-Laure Dumuis, Jean-Marc Durand, Samia Farad, Pierre Lecomte, Peggy Pierre, Fanny Fouyssac, Philippe Gaudin, Alain Gautier, Justine Gellen-Dautremer, Irène Jarrin, Pascal Richette, Emilie Georget, Pierre Gras, Thibault Moreau, Eric Giraud, Maya Hacini, Anne Mayer, Cécile Guillaumat, Séverine Guillaume, Corinne Guitton, Isabelle Kone-Paut, Céline Marsaud, Linda Rossi, Marie-Hélène Guyot, Patrick Hassler, Claude Heimfert, Olivier Heinzlef, Brigitte Hillion, Catherine Hocquelet, Helene Husson, Pierre Ichai, Eric Jeziorski, Chantal Job Deslandre, Véronique Le Guern, Kamen Kamenov, Véronique Kerlan, Philippe Lemoine, Laurent Misery, Brigitte Pan-Petesch, Pierre Labauge, Michel Rodier, Chadi Lacade, Berthe Razafimahefa, Karim Lachgar, Marie-Pierre Larmarau, Thierry Leblanc, Patrick Lefèbvre, Philippe Lejoyeux, Charles Leske, Kim Ly, Laurent Magy, Sylvie Mansuy, Richard Marechaud, Marie-Laure Martin Negrier, Guilhem Sole, Jean Maupetit, Françoise Mazingue, Stéphanie Mochon, Blidi Moktar, Donald Morcamp, Nathalie Morlet-Barla, Guillaume Nicolas, Vivien Pautot, Isabelle Pellier, Jean-Luc Verret, Olivier Outteryck, Beatrice Pallot-Prades, Jean Michel Paquet, Xavier Puechal, Annie Sortais, Jean Pelletier, Audrey Rico, Dominique Pez, Bruno Stankoff, Philippe Quittet, Claude Rémy, Eléna Roba, Hélène Rosario, Nathalie Roudaut, Emmanuel Sonnet, Michel Ruel, Samuel Sebban, Pauline Schaepelynck, Marie-Jeanne Simonin, Christophe Vial, Jean-Francois Viallard, Isabelle Ladedan, Thierry Zenone, LASER ANALYTICA, Paris (LA-SER), Centre d'enseignement Cnam Paris (CNAM Paris), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre de référence des maladies auto-inflammatoires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), CHU Grenoble, Service de médecine interne [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], CHU Trousseau [APHP], Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département Hospitalo-Universitaire Fibrosis, Inflammation, Remodeling in cardiovascular, respiratory and renal diseases (Paris), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Claude Huriez [Lille], CHU Lille, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Ambroise Paré [AP-HP], Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), DHU Risques Et Grossesse, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Avicenne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Service d’oncologie hématologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Lille Inflammation Research International Center (LIRIC), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Ambroise Paré, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), and Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Risk, Pediatrics, medicine.medical_specialty, Adolescent, Immunology, HPV vaccines, Autoimmune Diseases, Autoimmune thyroiditis, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Autoimmune disease, Odds Ratio, medicine, Humans, Immunology and Allergy, Papillomavirus Vaccines, 030212 general & internal medicine, Family history, Young adult, Child, HPV vaccine, business.industry, Pharmacoepidemiology, Papillomavirus Infections, Odds ratio, medicine.disease, Thrombocytopenic purpura, Connective tissue disease, Confidence interval, 3. Good health, Population Surveillance, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Background Safety of HPV vaccines is still in question due to reports of autoimmune diseases (ADs) following HPV immunization. Objectives To assess the risk of ADs associated with HPV vaccination of female adolescents/young adults in France. Methods Systematic prospective case-referent study conducted to assess the risks associated with real-life use of HPV vaccines. Cases were female 11–25 years old with incident ADs [central demyelination/multiple sclerosis (CD/MS), connective tissue disease (CTD), Guillain-Barre syndrome (GBS), type-1 diabetes (T1D), autoimmune thyroiditis (AT), and idiopathic thrombocytopenic purpura (ITP)]. Cases were consecutively and prospectively identified at specialized centers across France (2008–2014) and individually matched by age and place of residence to referents recruited in general practice. Risk was computed using multivariate conditional logistic regression models adjusted for family history of ADs, living in France (north/south), co-medications and co-vaccinations. Results With a total of 478 definite cases matched to 1869 referents, all ADs combined were negatively associated to HPV vaccination with an adjusted odds ratio of 0.58 (95% confidence interval: 0.41–0.83). Similar results were obtained for CD/MS, AT, CT, and T1D, the last two not reaching statistical significance. No association was found for ITP and GBS. Sensitivity analyses combining definite and possible cases with secondary time window showed similar results. Conclusion Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.
Published: 2017
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8. SAT0488 THE FRENCH PAEDIATRIC COHORT OF CASTLEMAN DISEASE

Author: Oanez Ackermann, Claire Ballot-Schmit, Yves Perel, Caroline Galeotti, Vannina Giacobbi-Milet, Jérémie Delaleu, Christophe Piguet, Charlotte Borocco, François Maurier, Sarah Jannier, Nathalie Aladjidi, Eric Oksenhendler, Isabelle Koné-Paut, and Eric Jeziorski
Subjects: Abdominal pain, Pediatrics, medicine.medical_specialty, business.industry, Castleman disease, medicine.medical_treatment, Splenectomy, Context (language use), medicine.disease, MEFV, Rash, Failure to thrive, medicine, Rituximab, medicine.symptom, business, medicine.drug
Abstract: Background: Castleman disease (CD) is a very rare non-malignant lymphoproliferation of undetermined origin. CD diagnosis is difficult and often delayed because of insidious onset, low awareness and clinical heterogeneity. Two major disease phenotypes can be distinguished: unicentric CD (UCD) and multicentric CD (MCD). Diagnosis confirmation is based on histopathological findings on an involved lymph node. Objectives: We attempted to survey all cases of paediatric CD identified in France so far, in order to set up a national registry aimed to improve CD early recognition, treatment and follow-up, within the context of a new reference centre (http://www.castleman.fr). Methods: In 2016, we e-mailed a questionnaire to members of the French paediatric immunohaematology society, the French paediatric rheumatology society and the French Reference Centre for Castleman Disease to retrospectively collect cases of paediatric CD (first symptoms before age 18 years). Anatomopathological confirmation was mandatory. Results: We identified 23 patients (12 girls and 11 boys) diagnosed with UCD (n=17) and MCD (n=6) between 1994 and 2018 in 14 centres. The average age at first symptoms was 11.5 years for UCD and 8.3 years for MCD. The mean diagnosis delay was 8.2 months for UCD and 5.2 years for MCD. In UCD, the initial symptoms were: isolated lymph nodes (n = 10) or lymph node associated with other symptoms (n = 7), fever was present in 3 patients. Patients with MCD presented with fever (n=5), abdominal lymph nodes (n=5), failure to thrive (n=3), hepatomegaly and/or splenomegaly (n=3), arthralgia (n=2), abdominal pain (n=2), fatigue (n=2), facial oedema (n=1), isolated lymphadenopathy (n=1), trunk rash (n=1), vascular hepatopathy with oesophageal varicose veins (n=1), diarrhea (n=1) or cholestasis (n=1). One patient had a Duchenne muscular dystrophy. No patients had HIV or HHV8 infection. In MCD cases, one patient with recurrent fevers, had a heterozygous mutation in MEFV gene and another had a homozygous mutation in TNFRSF1A gene (P75L). A UCD patient experienced fever episodes and pericarditis two years after surgery. Genetic tests revealed one heterozygous mutation in IL10RA gene (V406L) and one in IL36RN gene (S113L). Nevertheless, our patient did not have any psoriasis or inflammatory bowel disease. Treatment of UCD was mainly surgical resection, steroids, and radiotherapy. Treatments of MCD were tocilizumab, rituximab, anakinra, steroids, chemotherapy and splenectomy. Overall survival after an average of 6 years of follow-up, was 100% for both unicentric and multicentric forms. Conclusion: Paediatric CD seems still underdiagnosed with a significant diagnosis delay specially for the MCD but new international criteria will help in future. In UCD, surgery is the main treatment. New drugs are used specially for the MCD, but more studies need to be conduct in children. The global survey is better in children than adults. Disclosure of Interests: Charlotte Borocco: None declared, Claire Ballot-Schmit: None declared, Oanez Ackermann: None declared, Nathalie Aladjidi: None declared, Jeremie Delaleu: None declared, Vannina Giacobbi-Milet: None declared, Sarah Jannier: None declared, Eric Jeziorski: None declared, Yves Perel: None declared, Francois Maurier: None declared, Christophe Piguet: None declared, Eric Oksenhendler: None declared, Isabelle Kone-Paut Grant/research support from: SOBI has supported drug product (anakinra) for the presented study, Consultant for: SOBI, Novartis, Pfizer, Abbvie, UCB, CHUGAI, ROCHE, Caroline Galeotti: None declared
Published: 2019
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9. Genetic diagnosis of primary immunodeficiencies: A survey of the French national registry

Author: Nizar Mahlaoui, Capucine Picard, Perrine Bach, Laurence Costes, Virginie Courteille, Anja Ranohavimparany, Alexandre Alcaïs, Jean-Philippe Jais, Alain Fischer, Christine Bellanné-Chantelot, Jacinta Bustamante, Sylvie Chollet-Martin, Christian Drouet, Véronique Fremeaux-Bacchi, Caroline Kannengiesser, Virginie Girardin, Nathalie Lambert, Valérie Proulle, Jérémie Rosain, Marie José Stasia, Dominique Stoppa Lyonnet, Ioannis Theodorou, Wadih Abou-Chahla, Daniel Adoue, Nathalie Aladjidi, Zahir Amoura, Corinne Armari-Alla, Brigitte Bader-Meunier, Vincent Barlogis, Sophie Bayart, Yves Bertrand, Stéphane Blanche, Damien Bodet, Bernard Bonnotte, Raphaël Borie, Patrick Boutard, Claire Briandet, Jean-Paul Brion, Jacques Brouard, Liana Carausu, Emilie Catherinot, Nathalie Cheikh, Sarah Cohen-Beaussant, Louis-Jean Couderc, Pierre Cougoul, Gérard Couillault, Geneviève de Saint Basile, Catherine Devoldere, Anne Deville, Eric Dore, Fabienne Dulieu, Isabelle Durieu, Natacha Entz Werle, Claire Fieschi, Fanny Fouyssac, Pierre Frange, Vincent Gajdos, Lionel Galicier, Virginie Gandemer, Martine Gardembas, Catherine Gaud, Bernard Grosbois, Aurélien Guffroy, Corinne Guitton, Gaelle Guillerm, Eric Hachulla, Mohamed Hamidou, Sophie Haro, Yves Hatchuel, Olivier Hermine, Cyrille Hoarau, Bruno Hoen, Arnaud Hot, Sébastien Humbert, Arnaud Jaccard, Serge Jacquot, Rolland Jaussaud, Pierre-Yves Jeandel, Eric Jeziorski, Kamila Kebaili, Anne-Sophie Korganow, Olivier Lambotte, Fanny Lanternier, Claire Larroche, Alain Le Quellec, Emmanuelle Le Moigne, Vincent Le Moing, David Launay, Yvon Lebranchu, Marc Lecuit, Guillaume Lefevre, Richard Lemal, Valérie Li-Thiao-Te, Olivier Lortholary, Marion Malphettes, Aude Marie-Cardine, Nicolas Martin Silva, Agathe Masseau, Christian Massot, Françoise Mazingue, Etienne Merlin, Gérard Michel, Frédéric Millot, Béatrice Monlibert, Fabrice Monpoux, Despina Moshous, Luc Mouthon, Martine Munzer, Bénédicte Neven, Raphaëlle Nove-Josserand, Dalila Nouar, Eric Oksenhendler, Marie Ouachée-Chardin, Anne Pagnier, Marlène Pasquet, Isabelle Pellier, Yves Perel, Antoinette Perlat, Christophe Piguet, Dominique Plantaz, Pierre Quartier, Frédéric Rieux-Laucat, Pascal Roblot, Pierre-Simon Rohrlich, Bruno Royer, Valéry Salle, Françoise Sarrot-Reynauld, Amélie Servettaz, Jean-Louis Stephan, Nicolas Schleinitz, Felipe Suarez, Laure Swiader, Sophie Taque, Caroline Thomas, Olivier Tournilhac, Caroline Thumerelle, Jean-Pierre Vannier, Jean-François Viallard, IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Service de Biostatistique et Informatique Médicale, Université Paris Descartes - Paris 5 (UPD5), Service d'immuno-hématologie pédiatrique [CHU Necker], Collège de France - Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Immunologie 'Autoimmunité et Hypersensibilités' [AP-HP Hôpital Bichat, Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe de Recherche et d'Etude du Processus Inflammatoire (GREPI), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'immunologie [HEGP, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), the Study Center of Primary Immunodeficiencies, CHU Necker - Enfants Malades [AP-HP], Hémostase et biologie vasculaire, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital de la Tronche, Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hématogoie pédiatrique, hôpital Sud, SIGNAL-IMAGE-COMMUNICATION (SIC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Pneumologie et Centre de Compétence des Maladies Pulmonaires Rares [AP-HP Hôpital Bichat, Paris], Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Pédiatrie Enfants - Hématologie Oncologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service des Maladies Infectieuses, CHU Grenoble, Service de Pédiatrie Médicale [Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Foch [Suresnes], Service de pédiatrie (CHU de Dijon), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Immunologie clinique [CHU St-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Service d'Immunologie Clinique et de Médecine Interne, Centre National de Référence des Maladies Auto-immunes Rares, Hôpitaux Universitaires de Strasbourg, Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service Hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Claude Huriez [Lille], CHU Lille, Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), 'Personal Protection Against Vectors' working group (PPAV), PPAV working group, cellules dendritiques et greffes (JE 2448), Université de Tours (UT), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Service de Médecine Interne, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Médecine interne, maladies infectieuses, immunologie clinique, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut d’Hémato-Oncologie Pédiatrique, INSERM U1012, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Internal Medicine, Paris, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Laboratoire de Génie Electrique de Grenoble (G2ELab), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU Clermont-Ferrand, Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Dept of Physiology, McGill University = Université McGill [Montréal, Canada], Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], American Memorial Hospital, American Memory Hospital, Department of Clinical Immunology, Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service Immuno Hémato-Onco Pédiatrique, Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Service Hématologie Infantile, CHU Amiens-Picardie, Clinique de médecine interne, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Département de Médecine Interne, Immunologie clinique et maladies infectieuses [CHU Reims], Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de médecine de l'enfant et de l'adolescent [CHU Rennes], Clinical Haematology, CHU Hôtel-Dieu, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], French Ministry of Health, LFB, GlaxoSmithKlineGlaxoSmithKline, CSL BehringCSL Behring, ShireShire, Octapharma, Binding Site, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Chaire Médecine expérimentale (A. Fischer), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), GREPI, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématologie pédiatrique, CHU Toulouse [Toulouse], CHU Saint-Etienne, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service de médecine de l'enfant et de l'adolescent, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Sud, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), CIC - Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Apoptose et Progression tumorale (CRCNA / Equipe 9), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), Service de médecine interne, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest], Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Tours, Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], McGill University, Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche sur le Cancer Nantes-Angers (LUNAM), Université d'Angers (UA)-Université de Nantes (UN), Centre Hospitalier Universitaire d'Amiens (CHU), centre hospitalier universitaire amiens, CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC)
Subjects: 0301 basic medicine, Primary Immunodeficiency Diseases, medicine.medical_treatment, Genetic counseling, Immunology, Genomics, Bioinformatics, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Genotype, Humans, Immunology and Allergy, Medicine, Genetic Testing, Registries, Retrospective Studies, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], business.industry, Common variable immunodeficiency, Retrospective cohort study, medicine.disease, Phenotype, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030104 developmental biology, Identification (biology), France, business, 030215 immunology
Abstract: International audience; To the Editor:Since the mid-1980s, continuous progress in genetics and genomics has accelerated the rapid identification of causative genetic variants leading to primary immunodeficiencies (PIDs; >300 genes),1 with the noticeable exception of B-cell disorders, such as common variable immunodeficiency (CVID). The identification of these mutations not only validates a clinical diagnosis but also is useful in several other respects (more accurate prognosis on phenotype/genotype correlation, targeted therapy, and genetic counseling). [...]
Published: 2019
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10. Consultations d’oncogénétique pédiatrique : Quelles indications et quelles pratiques dans un service spécialisé de cancérologie pédiatrique ? Enquête dans le centre spécialisé du CHU de Bordeaux en 2011–2012

Author: Yves Perel, S. Gourdon, Yves Reguerre, Stéphane Ducassou, V. Bubien, B. Doray, and D. Lacombe
Subjects: 03 medical and health sciences, 0302 clinical medicine, Oncology, 030225 pediatrics, 030220 oncology & carcinogenesis, Pediatrics, Perinatology and Child Health, Hematology
Abstract: Introduction : Les predispositions genetiques au cancer de l’enfant sont rares avec une proportion de 10% des cas retenue actuellement. La mise en evidence de ces predispositions fait partie des « indispensables » pour ameliorer la prise en charge de ces patients. Pour porter des indications justes, il convient de repertorier precisement les points d’appel qui permettent de s’interroger sur une predisposition genetique au cancer. Problematique : Devant la necessite de tester les enfants les plus a risque de predisposition en priorite, un outil d’aide a l’orientation pourrait etre utile au depistage des facteurs de risque dans un service d’oncologie pediatrique generaliste. La description et la quantification de ces situations a risque genetique ainsi que leur modalite de prise en charge, permettra de creer cet outil. Materiels et methodes : Ce travail a ete realise dans le centre specialise du CHU de Bordeaux sur tous les enfants pris en charge avec un diagnostic de cancer entre 2011 et 2012. Les facteurs de risque utilises, comprenait l’âge de moins d’un an au diagnostic, la multifocalite des lesions, le type de cancer presente (specifique de syndrome de predisposition), le caractere secondaire de la tumeur, l’histoire familiale de cancer et enfin les points d’appels de l’examen clinique. Resultats : 223 patients avec un diagnostic de cancer ont ete pris en charge au centre specialise du CHU de Bordeaux entre 2011 et 2012. Pour 76 patients soit 33,9%, il existait au moins un facteur de risque de predisposition genetique au cancer. Les 2 facteurs de risques les plus rencontres etaient l’âge de moins d’un an au diagnostic (26 soit 34,2%) et une histoire familiale de cancer (37 soit 48,7%). Pour 65,8% des patients presentant un risque de predisposition, celui-ci etait porte sur un seul facteur de risque. Au total 23 patients ont ete pris en charge en oncogenetique soit 30% des patients avec facteur de risque. Il s’agissait en priorite des patients avec une atteinte multifocale ou plusieurs facteurs de risque. Conclusion : Il existe une large proportion (33,9%) de patients pour qui une consultation d’oncogenetique serait necessaire. Ceci justifie pleinement la mise en place d’une consultation dediee d’oncogenetique pediatrique. Les consultations d’oncogenetique ont ete realisees chez des patients presentant des criteres visibles pour le clinicien. Une fiche systematique de recueil de donnees a mettre dans les dossiers des patients pour ameliorer l’acces a cette prise en charge faciliterait le depistage de ces patients a risque.
Published: 2016
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11. Abstract CT136: Phase I study with rapamycin combined with irinotecan, the SFCE RAPIRI I trial, a new way to target tumor hypoxia in pediatric refractory cancers

Author: Florence Vincent, Natacha Entz-Werle, Véronique Kemmel, Benoit Lhermitte, Sarah Jannier, Pierre Leblond, Consuelo Sebastia, Agathe Chammas, Amelia-Naomi Sabo, Anne Isabelle Bertozzi, Nicolas André, Birgit Geoerger, Françoise Farace, Isabelle Aerts, Yves Perel, Didier Frappaz, Erwan Pencreach, and Nadège Corradini
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Tumor hypoxia, business.industry, medicine.medical_treatment, Cancer, medicine.disease, Irinotecan, Cytokine, Pharmacokinetics, Tumor progression, Pharmacodynamics, Internal medicine, Clinical endpoint, Medicine, business, medicine.drug
Abstract: Background: Hypoxic environment is a pejorative prognostic factor in pediatric solid tumors (ST). It is favoring neoangiogenesis, tumor progression and resistance to treatments through the activation of mTor and HIF-1α pathways. Those hypoxic markers can be targeted by rapamycin and irinotecan, respectively. Therefore, we designed a dose-escalation phase I trial combining both drugs to inhibit tumor hypoxic mechanisms present in several pediatric refractory/relapsing ST. Procedure: Patients were enrolled in this 3+3 escalation trial with ten dose levels. The primary endpoint was to determine the maximum tolerated dose (MTD) of rapamycin when combined with irinotecan. Rapamycin was administered orally once daily in a 28-day cycle (1 to 2.5 mg/m2/day) and associated biweekly with intravenous irinotecan (125 to 240 mg/m2/dose). Toxicities, pharmacokinetics (PK), efficacy analyses and pharmacodynamics (UGT1A1 status, cytokines/chemokines assessment, MRI markers and proteins' expression) were evaluated. Results: 42 patients were treated and had mild to moderate reversible toxicities. No MTD was present up to the tenth level. The PK were highly variable. Nevertheless, the usually targeted concentrations of rapamycin over time were reached at 1.5 mg/m2/day dose. When looking to the 2 partial responses (PR) and 19 stable diseases (SD) in 31 assessable patients, the mean irinotecan AUC was 363 min.mg/L and the mean D8 rapamycin AUC was 9.3 min.mg/L. No significant relationship was observed between dose escalation and response, but progressive tumors' subgroup (PD) had slightly lower mean irinotecan AUC (321 min.mg/L) and D8 rapamycin AUC (6.5 min.mg/L). The two main tumor groups were brain tumors (BTs) and sarcomas. A high proportion of those patients experienced tumor responses (3/4 ependymomas, 2/3 medulloblastomas, 1 rhabdoid tumor, 2/3 high-grade gliomas and 5/6 osteosarcomas). In all 17 assessable patients for immunohistochemistry, the two targeted proteins, mTor and HIF-1α, were expressed, but the resistance to this double strategy was significantly linked to the HIF-2α protein hyperexpression. In the BTs, lower ADC values in MRI were also a prerequisite for tumor responsiveness. Cytokine analyses, distinguished specific proinflammatory and angiogenic signatures during first course of treatment: PR patients had an increase of TNF, associated to a stable PIGF and a decrease of VEGF-C; the SD subgroup had a significant increase of VEGF-D and a stable or increase of sFLT1 and PD group had a constant increase of IL8 and VEGF-D. Conclusion: Despite no MTD, we can propose a next phase II trial with rapamycin dose of 1.5 mg/m2/day associated with 125 mg/m2 irinotecan in STs not expressing HIF-2α protein. A precise PK follow-up will be used to reach an irinotecan AUC up to 360 min.mg/L and a D8 rapamycin blood concentration of 10 µg/L. The cytokine evaluation will help us to predict during first cycle the potential tumor response. Citation Format: Sarah Jannier, Veronique Kemmel, Consuelo Sebastia, Agathe Chammas, Amelia-Naomi Sabo, Erwan Pencreach, Françoise Farace, Benoit Lhermitte, Birgit Geoerger, Isabelle Aerts, Didier Frappaz, Pierre Leblond, Nicolas Andre, Yves Perel, Nadège Corradini, Anne Isabelle Bertozzi, Florence Vincent, Natacha Entz-Werle. Phase I study with rapamycin combined with irinotecan, the SFCE RAPIRI I trial, a new way to target tumor hypoxia in pediatric refractory cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT136.
Published: 2020
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12. Non syndromic childhood onset congenital sideroblastic anemia: A report of 13 patients identified with an ALAS2 or SLC25A38 mutation

Author: Thierry Leblanc, Hana Manceau, Fanny Fouyssac, J.F. Guichard, Nadja Jäkel, Patrick Lutz, Jean-Pierre Vannier, Cyrielle Fouquet, Fabienne Toutain, Mohamed Touati, Christiane Vermylen, Yves Perel, Marie-Amelyne Le Rouzic, Karim Maloum, Caroline Kannengiesser, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université de Bordeaux (UB), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Génétique Hématologique, Clinique Universitaire Saint-Luc, de Duve Institute, UCL, Médecine Interne-Pathologie Vasculaire - Immunologie Clinique, Hôpital Sainte Blandine, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Pontchaillou [Rennes], Hôpital Civil, Hopital Civil, Service d'hématologie pédiatrique et oncologie, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Micro-Environnement et Régulation Cellulaire Intégrée (MERCI), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), California Institute of Technology (CALTECH)-NASA, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN)
Subjects: Pathology, medicine.medical_specialty, Pediatrics, Iron Overload, [SDV]Life Sciences [q-bio], Mitochondrial Membrane Transport Proteins, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, medicine, Humans, Chelation therapy, Child, Adverse effect, Molecular Biology, Congenital sideroblastic anemia, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, business.industry, Cell Biology, Hematology, ALAS2, Anemia, Sideroblastic, 3. Good health, Phenotype, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Molecular Medicine, business, Non syndromic, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 5-Aminolevulinate Synthetase, 030215 immunology
Abstract: The most frequent germline mutations responsible for non syndromic congenital sideroblastic anemia are identified in ALAS2 and SLC25A38 genes. Iron overload is a key issue and optimal chelation therapy should be used to limit its adverse effects on the development of children. Our multicentre retrospective descriptive study compared the strategies for diagnosis and management of congenital sideroblastic anemia during the follow-up of six patients with an ALAS2 mutation and seven patients with an SLC25A38 mutation. We described in depth the clinical, biological and radiological phenotype of these patients at diagnosis and during follow-up and highlighted our results with a review of available evidence and data on the management strategies for congenital sideroblastic anemia. This report confirms the considerable variability in manifestations among patients with ALAS2 or SLC25A38 mutations and draws attention to differences in the assessment and the monitoring of iron overload and its complications. The use of an international registry would certainly help defining recommendations for the management of these rare disorders to improve patient outcome.
Published: 2017
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13. Auteurs

Author: Antoine, Bourrillon, Grégoire, Benoist, Brigitte, Chabrol, Gérard, Chéron, Emmanuel, Grimprel, Marianne, Alison, Justine, Bacchetta, Alexandre, Belot, Dominique, Brémond-Gignac, Alain, Chantepie, Régis, Coutant, Christophe, Delacourt, Stéphane, Ducassou, Philippe, Duverger, Albert, Faye, Erik, Hervieux, Paul, Jacquin, Pierre-Henri, Jarreau, Thierry, Lamireau, Nicolas, Leboulanger, Joël, Lechevallier, Gérard, Lorette, Stéphanie, Mallet, Gérard, Michel, Yves, Pérel, Sophie, Achard, Alessandro, Amaddeo, Florent, Amatore, Jessica, Amsellem-Jager, Guillaume, Aubertin, Vincent, Audard, Frédérique, Audic, Manon, Bachy, Ananda, Banerjee, Pascal, Barat, Mélisande, Baravalle-Einaudi, Romain, Basmaci, Véronique, Baudouin, Pierre, Bégué, Gérard, Beley, Valérie, Bélien Pallet, Étienne, Bérard, Sophie, Bernard, Isabelle, Bernardini, Patrick, Berquin, Étienne, Bidat, Renaud, Blondé, Nathalie, Bodak, Émilie, Bois, Marie, Bon Saint Côme, Nicolas, Bonnet, Adeline, Boucheron, Bernard, Boudailliez, Natacha, Bouhours Nouet, Claire, Bouvattier, Olivia, Boyer, Étienne, Branchereau, Violaine, Bresson, Guillaume, Bronsard, Apoline, Cailliez, Aline, Cano, Ricardo, Carbajal, Charlotte, Celerier, Hervé, Chambost, Bertrand, Chevallier, Christine, Chiaverini, Isabelle, Claudet, Héloïse, Clerc, Robert, Cohen, François, Corrard, Vincent, Couloigner, Céline, Cudejko, Hélène, De Leersnyder, Renaud, De Tournemire, Dominique, Debray, Chantal, Delafosse, Delphine, Demède, Antoine, Deschildre, Isabelle, Desguerre, Marine, Desjonqueres, Béatrice, Desnous, Chloé, Di Meglio, Jean, Donadieu, Aurélie, Donzeau, Claire, Dossier, Laurence, Dubourg, Jean-Christophe, Dubus, Hubert, Ducou Le Pointe, Véronique, Dufour, Raphaël, Enaud, Brigitte, Fauroux, Marc, Fila, Valérie, Flaum, Daniel, Floret, Pierre, Foucaud, Martine, François, Caroline, Freychet, Marilyn, Fuger, Mathieu, Fusaro, Olivier, Gall, Solène, Ganousse, Joël, Gaudelus, Maxime, Gérard, Muriel, Girard, Thomas, Girard, Christèle, Gras-Le Guen, Lucie, Griffon, Vincent, Guigonis, Myriam, Hazan, Floriane, Hemery, Véronique, Hentgen, Julien, Hogan, Gaëlle, Hubert, Églantine, Hullo, Brice, Ilharreborde, Patrick, Imbert, Béatrice, Jouret, Chantal, Karila, Elsa, Kermorvant, Philippe, Labrune, Marion, Lajus, Anne-Sophie, Lambert, Rémi, Laporte, Élise, Launay, Pierre, Le Coz, Claire, Leblanc, Sophie, Leducq, Bruno, Lefort, Karine, Levieux, Guillaume, Lezmi, Agnès, Linglart, Mathie, Lorrot, Mathilde, Louvigné, Fouad, Madhi, Emmanuel, Mahé, Nausicaa, Malissen, Valérie, Marcou, Christophe, Marguet, Alain, Martinot, Annabel, Maruani, Emmanuel, Mas, Caroline, Maurin, Julie, Mazenq, Anne-Pascale, Michard-Lenoir, Mathieu, Milh, Philippe, Minodier, Florence, Moulin, Olivier, Mouterde, Javotte, Nancy, Valérie, Nouyrigat, Alexandra, Ntorkou, Hayat, Ouaziz, Fabienne, Pangrani, Sophie, Parat, Marine, Parodi, Juliana, Patkai, Géraldine, Patteau, Grégoire, Pech Gourg, Justine, Perrin, Capucine, Picard, Georges, Picherot, Christine, Pietrement, Pierre, Quartier, Béatrice, Quinet, Bruno, Ranchin, Rachel, Reynaud, Estelle, Riblier, Élise, Riquin, Jérémie, Rosain, Sébastien, Rouget, Isabelle, Rouillon, Stéphanie, Rouleau, Caroline, Rousset-Rouvière, Gwenaëlle, Roussey, Catherine, Salinier, Paul, Saultier, Isabelle, Sermet-Gaudelus, Frédéric, Sorge, Nathalie, Soulé, Chantal, Stheneur, Aline, Tamalet, Corentin, Tanné, Maïthé, Tauber, Natacha, Teissier, Briac, Thierry, Guillaume, Thouvenin, Sandra, Timsit, Julie, Toubiana, Michel, Tsimaratos, Dominique, Turck, Diego, Urbina, Amélie, Vadot, de Moulliac Jérôme, Valleteau, Vanessa, Vautier, Sarah, Ventéjou, Raphaël, Vialle, le Sage François, Vié, Nathalie, Villeneuve, Bénédicte, Vrignaud, Isabelle, Vrillon, Armelle, Wastiaux, Ariane, Zaloszyc, and Hyacinthe, Zokou
Published: 2020
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14. Impact of shared care program in follow-up of childhood cancer survivors: An intervention study

Author: Maïté Chipi, Mélanie Afonso, Gérard Ducos, Jean-Louis Demeaux, Stéphane Ducassou, Sophie Ansoborlo, Aurélie Pouyade, and Yves Perel
Subjects: Male, medicine.medical_specialty, Adolescent, Childhood cancer, Special needs, 03 medical and health sciences, 0302 clinical medicine, General Practitioners, Early Medical Intervention, Neoplasms, medicine, Pediatric oncology, Humans, 030212 general & internal medicine, Survivors, Child, Shared care, Accountable Care Organizations, business.industry, Infant, Newborn, Cancer, Infant, Hematology, Continuity of Patient Care, medicine.disease, Prognosis, Intervention studies, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Family medicine, Child, Preschool, Pediatrics, Perinatology and Child Health, Cohort, Physical therapy, Female, business, Delivery of Health Care, Follow-Up Studies
Abstract: Background With the growing rate of childhood cancer cure and the risks of sequelae, long-term follow-up (FU) of survivors is a central issue. Several models have been proven far from satisfactory. Shared care FU is the result of collaboration between general practitioners (GPs) and cancer centers. We sought to demonstrate the feasibility of setting up a shared care program based on the patient-centered education of GPs and to evaluate the impact of this model in an intervention study. Methods We compared the FU care achievement in two childhood cancer survivor cohorts in the same pediatric oncology center, (i) control group (n = 134) and (ii) intervention study cohort (n = 137), after setting up the program. Results The rate of survivors answering the survey and the rate of patients involved in FU by their GPs were higher in intervention study cohort than in baseline one (132/137 vs. 72/134 and 110/132 vs. 13/72; P ≤ 0.0001). The lack of any FU was definitely lower (10/132 vs. 18/72; P = 0.001) in the intervention study cohort. Conclusion In this shared care program, survivors overcame distrust in their GP's knowledge and entered the FU program after their GPs had been involved in patient-centered education. Personalized and incentive-based guidance was very useful in helping survivors to adhere to FU. Support of a dedicated long-term FU team was very useful. A nationwide organization, consideration of special needs in subgroups of survivors and sustained funding are needed to adjust the program in the very long term.
Published: 2016

15. Childhood immune thrombocytopenia: A nationwide cohort study on condition management and outcomes

Author: Lamiae, Grimaldi-Bensouda, Clémentine, Nordon, Thierry, Leblanc, Lucien, Abenhaim, Slimane, Allali, Corinne, Armari-Alla, Claire, Berger, Mary-France, Courcoux, Fanny, Fouyssac, Cécile, Guillaumat, Corinne, Guitton, Philippe, Le Moine, Françoise, Mazingue, Corinne, Pondarré, Caroline, Thomas, Marlène, Pasquet, Yves, Perel, Guy, Leverger, and Nathalie, Aladjidi
Subjects: Cohort Studies, Male, Purpura, Thrombocytopenic, Idiopathic, Treatment Outcome, Adolescent, Platelet Count, Child, Preschool, Odds Ratio, Humans, Infant, Female, France, Child
Abstract: Nationwide prospective cohort study exploring (i) the factors associated with treatment initiation (vs. watchful waiting) in children with primary immune thrombocytopenia (ITP) followed in routine clinical practice and (ii) the predictors of chronicity at 12 months.Between 2008 and 2013, 23 centers throughout France consecutively included 257 children aged 6 months-18 years and diagnosed with primary ITP over a 5-year period. Data on ITP clinical features along with medical management were collected at baseline and 12 months. Multivariate logistic regressions were used to determine (i) and (ii) as defined above, providing odds ratio (OR) with 95% confidence interval (95% CI).One hundred thirty-seven (53%) children were males, median age was 4.6 years, median platelet count was 7 × 109/l, and 214 (81%) patients initiated medication. Factors independently associated with treatment initiation included platelet counts10 × 109/l (P0.0001) and mucocutaneous bleeding symptoms at baseline (P0.001). At 12 months, data were available for 211 (82%) children, of whom 160 (74%) had recovered. Predictors of chronicity included female gender (OR = 2.2; 95% CI = 1.0-4.8), age ≥10 years (OR = 2.6; 95% CI = 1.1-6.0), and platelet counts ≥10 × 10In routine clinical practice, the decision to apply a watchful waiting strategy seems to be driven by platelet counts even in the absence of bleeding symptoms, resulting in treatment being initiated in more than 80% of the children surveyed. Overall, younger children with ITP showed good prognosis, with lower platelet counts and, to a lesser extent, male gender predicting more favorable outcomes.
Published: 2016

16. Présentation atypique d’un lymphome pédiatrique : hypermétabolisme ostéo-médullaire isolé en TEP/TDM au 18F-FDG

Author: S. Dulucq, N. Aladjidi, A. Tiphaine, R. Schollhammer, C. Jubert, M.C. Parrens, Yves Perel, M. Meyer, P. Fernandez, and H. De Clermont
Subjects: Radiological and Ultrasound Technology, Biophysics, Radiology, Nuclear Medicine and imaging
Abstract: Objectifs Le lymphome est une hemopathie maligne rare chez l’enfant, habituellement suspecte devant un tableau associant syndrome tumoral ganglionnaire, fievre au long cours et alteration de l’etat general. La precocite du diagnostic histologique precis conditionne la strategie therapeutique. Nous rapportons ici une presentation atypique de lymphome T chez un enfant de 9 ans, se presentant avec une fievre a 40 °C evoluant depuis 15 jours et une discrete pancytopenie avec activation macrophagique, sans syndrome tumoral ni contexte infectieux associe. Materiels et methodes L’echographie abdominale et la radiographie thoracique sont normales. Plusieurs myelogrammes objectivent une hypoplasie granuleuse et erythroblastique avec 15–20 % de lymphocytes CD8+ et CD30+. Le bilan est complete par une biopsie osteo-medullaire (BOM) et une TEP/TDM au 18F-FDG (TEP). Resultats La BOM revele une infiltration medullaire par une lymphoproliferation clonale T CD8+, CD30+, ALK−. La TEP initiale montre un hypermetabolisme osteo-medullaire intense et diffus tres inhabituel (SUVmax = 13), predominant sur le squelette peripherique, sans atteinte morphologique osseuse, syndrome tumoral ni cible ganglionnaire. Les bilans infectieux et immunitaire sont negatifs. Une atteinte medullaire reactionnelle inflammatoire est initialement evoquee. Apres echec de plusieurs antibiotherapies d’epreuve, la corticotherapie est efficace sur la fievre et les signes biologiques, recidivant des l’arret, avec atteinte cutanee associee montrant la meme lymphoproliferation T CD8. Une nouvelle TEP est realisee, mettant en evidence une progression metabolique de l’atteinte osteo-medullaire plus heterogene et l’apparition d’adenopathies hypermetaboliques sus et sous-diaphragmatiques. La biopsie ganglionnaire retrouve l’infiltrat T CD8. La confrontation de l’analyse anatomopathologique et de l’evolution clinique et morpho-metabolique retient finalement le diagnostic de lymphome T CD8 cytotoxique inclassable, initialement osteo-medullaire. L’enfant est actuellement en remission au decours d’une chimiotherapie conventionnelle, suivie d’une allogreffe de moelle osseuse. Conclusion Le bilan d’extension d’un lymphome inclut de facon standardisee la TEP dans l’evaluation initiale. Un hypermetabolisme osteo-medullaire isole, intense et diffus, sans syndrome tumoral ou atteinte morphologique osseuse associee, n’avait pas ete jusque-la rapporte dans la litterature, et doit faire evoquer precocement un lymphome.
Published: 2017
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17. A dose-intensive approach (NB96) for induction therapy utilizing sequential high-dose chemotherapy and stem cell rescue in high-risk neuroblastoma in children over 1 year of age

Author: Olivier Hartmann, François Demeocq, Sylvie Monnereau-Laborde, Dominique Valteau-Couanet, Carole Coze, Hervé Rubie, Caroline Munzer, Sophie Ansoborlo, Yves Perel, Pascal Chastagner, and Jean-Louis Stephan
Subjects: Chemotherapy, medicine.medical_specialty, Autologous Stem Cell Rescue, Cyclophosphamide, business.industry, medicine.medical_treatment, Hematology, Carboplatin, Surgery, Transplantation, chemistry.chemical_compound, Regimen, Oncology, chemistry, Pediatrics, Perinatology and Child Health, medicine, business, Survival analysis, Etoposide, medicine.drug
Abstract: Background To improve outcome and overall survival (OS) in high-risk neuroblastoma, NB96 induction therapy was intensified using sequential high-dose chemotherapy and autologous stem cell rescue. Procedure Twenty children were included in this pilot study undertaken at seven reference centers in France, between May 1995 and October 1996. Induction began with one cycle of conventional chemotherapy followed by six sequential cycles of high-dose chemotherapy comprising two cycles of etoposide 800 mg/m2/day over 3 days, two cycles of cyclophosphamide 2,000 mg/m2/day over 3 days, and two cycles of carboplatin 400 mg/m2/day over 5 days, followed by stem cell rescue. Results Thirteen patients (13/20) received this induction with acceptable toxicity and adequate stem cell harvest. Of these, nine (9/13) underwent surgery according to the protocol, while one patient was given a consolidation regimen prior to surgery. No toxic death was recorded. At the end of induction, complete remission was achieved in 10 cases (50%), with six still alive in July 2009. The 5-year event-free survival and OS were 35 ± 11% and 40 ± 11%, respectively. Conclusion NB96 therapy is feasible and tolerated without lethal toxicity. Nevertheless, given the small sample size and absence of randomization in our study, the effectiveness of this strategy based on metastasis complete response rates and long-term outcome was not superior to other intensive chemotherapy regimens. Pediatr Blood Cancer 2011; 57: 965–971. © 2011 Wiley-Liss, Inc.
Published: 2011
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18. Road Traffic and Childhood Leukemia: The ESCALE Study (SFCE)

Author: Laurent Orsi, Guy Leverger, Pierre Bordigoni, Francoise Mechinaud, Jacqueline Clavel, Denis Hémon, Yves Bertrand, Gérard Michel, Alain Robert, Brigitte Nelken, Claire Sermage-Faure, André Baruchel, Geneviève Margueritte, Alicia Amigou, and Yves Perel
Subjects: Childhood leukemia, Health, Toxicology and Mutagenesis, Nitrogen Dioxide, Risk Assessment, benzene, children, Air Pollution, Environmental health, Humans, Medicine, Children’s Health, acute leukemia, Registries, Child, Road traffic, Vehicle Emissions, Air Pollutants, Inhalation Exposure, Leukemia, business.industry, Research, Public Health, Environmental and Occupational Health, road traffic, Infant, medicine.disease, Child, Preschool, epidemiology, National registry, business, environment, Automobiles
Abstract: Background Traffic is a source of environmental exposures, including benzene, which may be related to childhood leukemia. Objectives A national registry–based case–control study [ESCALE (Etude Sur les Cancers et les Leucémies de l’Enfant, Study on Environmental and Genetic Risk Factors of Childhood Cancers and Leukemia)] carried out in France was used to assess the effect of exposure to road traffic exhaust fumes on the risk of childhood leukemia. Methods Over the study period, 2003–2004, 763 cases and 1,681 controls < 15 years old were included, and the controls were frequency matched with the cases on age and sex. The ESCALE data were collected by a standardized telephone interview of the mothers. Various indicators of exposure to traffic and pollution were determined using the geocoded addresses at the time of diagnosis for the cases and of interview for the controls. Indicators of the distance from, and density of, main roads and traffic nitrogen dioxide (NO2) concentrations derived from traffic emission data were used. Odds ratios (ORs) were estimated using unconditional regression models adjusted for potential confounders. Results Acute leukemia (AL) was significantly associated with estimates of traffic NO2 concentration at the place of residence > 27.7 μg/m3 compared with NO2 concentration < 21.9 μg/m3 [OR = 1.2; confidence interval (CI), 1.0–1.5] and with the presence of a heavy-traffic road within 500 m compared with the absence of a heavy-traffic road in the same area (OR = 2.0; 95% CI, 1.0–3.6). There was a significant association between AL and a high density of heavy-traffic roads within 500 m compared with the reference category with no heavy-traffic road within 500 m (OR = 2.2; 95% CI, 1.1–4.2), with a significant positive linear trend of the association of AL with the total length of heavy-traffic road within 500m. Conclusion This study supports the hypothesis that living close to heavy-traffic roads may increase the risk of childhood leukemia.
Published: 2011
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19. New insights into childhood autoimmune hemolytic anemia: a French national observational study of 265 children

Author: Julien Jeanpetit, André Baruchel, Virginie Gandemer, Gérard Michel, Brigitte Nelken, Yves Bertrand, Geneviève Chêne, Alain Robert, Caroline Thomas, Jean Louis Stephan, Guy Leverger, Alain Fischer, Thierry Leblanc, Nathalie Aladjidi, Brigitte Bader-Meunier, Fanny Fouyssac, Hélène Savel, Marie Quitterie Picat, Yves Perel, Pierre Rohrlich, Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie-Oncologie Pédiatrique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Hématogoie pédiatrique, Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service d'hématologie-immunologie-oncologie pédiatrique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 )
Subjects: Male, Hemolytic anemia, Pediatrics, medicine.medical_specialty, Evans syndrome, Anemia, [SDV]Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Autoimmune disease, [ SDV ] Life Sciences [q-bio], business.industry, Hazard ratio, Original Articles, Hematology, medicine.disease, Thrombocytopenic purpura, 3. Good health, 030220 oncology & carcinogenesis, Cohort, Immunology, Female, Anemia, Hemolytic, Autoimmune, Autoimmune hemolytic anemia, business, 030215 immunology
Abstract: Background Autoimmune hemolytic anemia is a rare condition in children. Little is known about its initial presentation and the subsequent progression of the disease. Design and Methods Since 2004, a national observational study has been aiming to thoroughly describe cases and identify prognostic factors. Patients from all French hematologic pediatric units have been included if they had a hemoglobin concentration less than 11 g/dL, a positive direct antiglobulin test and hemolysis. Evans’ syndrome was defined by the association of autoimmune hemolytic anemia and immunological thrombocytopenic purpura. Data from patients’ medical records were registered from birth to last follow-up. Autoimmune hemolytic anemia was classified as primary or secondary. Remission criteria, qualifying the status of anemia at last follow-up, were used with the aim of identifying a subgroup with a favorable prognosis in continuous complete remission. Results The first 265 patients had a median age of 3.8 years at diagnosis. In 74% of cases the direct antiglobulin test was IgG/IgG+C3d. Consanguinity was reported in 8% of cases and first degree familial immunological diseases in 15% of cases. Evans’ syndrome was diagnosed in 37% of cases. Autoimmune hemolytic anemia was post-infectious in 10%, immunological in 53% and primary in 37% of cases. After a median follow-up of 3 years, 4% of children had died, 28% were still treatment-dependent and 39% were in continuous complete remission. In multivariate analysis, IgG and IgG+C3d direct antiglobulin tests were associated with a lower rate of survival with continuous complete remission (adjusted hazard ratio, 0.43; 95% confidence interval, 0.21–0.86). Conclusions This nationwide French cohort is the largest reported study of childhood autoimmune hemolytic anemia. The rarity of this condition is confirmed. Subgroups with genetic predisposition and underlying immune disorders were identified.
Published: 2011
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20. Ectopic Cushing’s Syndrome due to an Adrenal Ganglioneuroma

Author: Colette Deminiere, Jean-Benoît Corcuff, Pascal Barat, Olivier Puel, Jacqueline Trouillas, Yves Perel, Psychoneuroimmunologie, nutrition et génétique, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire, CHU Bordeaux [Bordeaux], Service de pathologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Cancéropôle du Grand Sud-Ouest, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie, and CHU Bordeaux [Bordeaux]-Centre de référence des maladies rénales rares (SORARE)
Subjects: endocrine system, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, CUSHING’S SYNDROME, Endocrinology, GANGLIONEUROME SURRENALIEN, Adrenocorticotropic Hormone, Internal medicine, Adrenal Glands, medicine, Humans, Ganglioneuroma, Cushing Syndrome, S syndrome, business.industry, SYNDROME DE CUSHING, medicine.disease, Adrenal Cortex Neoplasms, Hormones, Ectopic, Pediatrics, Perinatology and Child Health, Female, business, hormones, hormone substitutes, and hormone antagonists
Abstract: Background: Cushing’s syndrome (CS), rare in children, is due to pituitary or, less frequently, to adrenocortical tumors. Ectopic adrenocorticotropin (ACTH) secretion is exceptional. Method: A case of apparently ACTH-independent CS in a child is reported. Results: CS was due to an adrenal ganglioneuroma where neuroendocrine cells were immunopositive for ACTH responsible for the syndrome through a paracrine effect. Cortical cell hyperplasia was observed. Conclusion: Benign and differentiated tumors of the neural crest such as ganglioneuromas may be responsible for CS.
Published: 2010
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21. Acute childhood leukaemia and residence next to petrol stations and automotive repair garages: the ESCALE study (SFCE)

Author: Denis Hémon, Jérémie Rudant, Alain Robert, Brigitte Nelken, Jacqueline Clavel, André Baruchel, Yves Perel, Pierre Bordigoni, Francoise Mechinaud, Geneviève Margueritte, Guy Leverger, Laurent Orsi, Gérard Michel, Yves Bertrand, and Pauline Brosselin
Subjects: Male, medicine.medical_specialty, Adolescent, Childhood leukemia, Population, Age Distribution, Residence Characteristics, Environmental health, Epidemiology, medicine, Humans, Sex Distribution, Child, education, Air Pollutants, Acute leukemia, education.field_of_study, Leukemia, business.industry, Infant, Newborn, Public Health, Environmental and Occupational Health, Infant, Benzene, Environmental Exposure, Odds ratio, medicine.disease, Carcinogens, Environmental, Social Class, Telephone interview, El Niño, Case-Control Studies, Child, Preschool, Acute Disease, Epidemiological Monitoring, Educational Status, Female, Residence, France, business, Gasoline, Environmental Monitoring
Abstract: The association between acute childhood leukaemia and residing next to petrol stations and automotive repair garages was analysed in a national registry-based case-control study carried out in France in 2003-2004.Population controls were frequency matched with cases on age and gender. Data were collected by standardised telephone interview with the mothers. The latter were asked to report the proximity of their homes to petrol stations, automotive repair garages and other businesses from the conception of the index child to the diagnosis (for cases) or interview (for controls). Odds ratios were estimated using unconditional regression models adjusted for age, gender, number of children under 15 years of age in the household, degree of urbanisation and type of housing.765 cases of acute leukaemia and 1681 controls were included. Acute leukaemia was significantly associated with residence next to petrol stations or automotive repair garages (OR 1.6, 95% CI 1.2 to 2.2) and next to a petrol station (OR 1.9, 95% CI 1.2 to 3.0). The OR showed no tendency to increase with duration of exposure. The results were not modified by adjustment for potential confounding factors including urban/rural status and type of housing.The results support the findings of our previous study and suggest that living next to a petrol station may be associated with acute childhood leukaemia. The results also suggest that the role of low-level exposure to benzene in acute childhood leukaemia deserves further evaluation.
Published: 2009
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22. Prognostic Factors for Leukemic Induction Failure in Children With Acute Lymphoblastic Leukemia and Outcome After Salvage Therapy: The FRALLE 93 Study

Author: Claudine Schmitt, Marie-Françoise Auclerc, Jean-Michel Cayuela, Gérard Michel, André Baruchel, Guy Leverger, Marianne Debré, Yves Perel, Brigitte Pautard, Thierry Leblanc, Gérard Socié, Raphaël Porcher, Caroline Oudot, Christophe Piguet, Virginie Gandemer, Vincent Levy, Claire Berger, Christiane Vermylen, Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Service d'hématologie pédiatrique, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre d'Investigations Cliniques 9504, Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Biostatistique et Informatique Médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Sain-Louis, Service d'onco-hématologie pédiatrique, hôpital Sud, Service de Pédiatrie Oncologie, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'hématologie pédiatrique, Université Catholique de Louvain = Catholic University of Louvain (UCL), CHU Amiens-Picardie, Service d'Hématologie et Oncologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Unité d'hématologie et de transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 ( UPD7 ) -CHU Saint Louis [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Sain-Louis, Hôpital Sud, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Catholique de Louvain ( UCL ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Service d'hématologie-immunologie-oncologie pédiatrique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], and De Villemeur, Hervé
Subjects: Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Oncology, MESH: Remission Induction, Cancer Research, MESH : Antineoplastic Combined Chemotherapy Protocols, MESH: Treatment Failure, Lymphoblastic Leukemia, MESH : Prospective Studies, Salvage therapy, MESH : Analysis of Variance, MESH: Logistic Models, MESH : Child, Preschool, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH : Child, Risk Factors, MESH: Risk Factors, MESH: Child, Antineoplastic Combined Chemotherapy Protocols, MESH : Precursor Cell Lymphoblastic Leukemia-Lymphoma, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, MESH : Female, Prospective Studies, Treatment Failure, Child, Prospective cohort study, 0303 health sciences, MESH : Prognosis, Remission Induction, MESH : Infant, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH : Adult, Prognosis, MESH : Risk Factors, MESH: Infant, MESH: Salvage Therapy, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, Child, Preschool, 030220 oncology & carcinogenesis, Female, France, Adult, medicine.medical_specialty, Adolescent, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Prognosis, Risk category, 03 medical and health sciences, MESH : Treatment Failure, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH : Adolescent, MESH: Analysis of Variance, Internal medicine, Acute lymphocytic leukemia, medicine, Humans, MESH : France, 030304 developmental biology, Salvage Therapy, MESH: Adolescent, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, Analysis of Variance, MESH : Remission Induction, MESH: Humans, business.industry, MESH : Humans, MESH: Child, Preschool, Infant, Cancer, MESH: Adult, medicine.disease, MESH: Male, MESH: Prospective Studies, Surgery, MESH: France, Clinical trial, Logistic Models, Multicenter study, MESH : Salvage Therapy, business, MESH: Female, MESH : Logistic Models
Abstract: Purpose To identify prognostic factors and to evaluate the outcome of children with acute lymphoblastic leukemia (ALL) failure after induction therapy. Patients and Methods Between June 1993 and December 1999, 1,395 leukemic children were included in the French Acute Lymphoblastic Leukemia 93 study. Results Fifty-three patients (3.8%) had a leukemic induction failure (LIF) after three- or four-drug induction therapy. In univariate analysis, high WBC count (P = .001), mediastinal mass (P = .017), T-cell phenotype (T-ALL; P = .001), t(9;22) translocation (P = .001), and a slow early response (at day 8 and/or on day 21, P = .001) were predictive of LIF. The following three prognostic groups for LIF were identified by multivariate analysis: a low-risk group with B-cell progenitor (BCP) ALL without t(9;22) (odds ratio [OR] = 1), an intermediate-risk group with T-ALL and a mediastinal mass (OR = 7.4, P < .0001), and a high-risk group with BCP-ALL and t(9;22) or T-ALL without a mediastinal mass (OR = 28.4, P < .0001). Complete remission (CR) was subsequently obtained in 43 patients (81%). The 5-year overall survival (OS) rate of the 53 patients was 30% ± 6%. The 5-year OS rate among allogeneic graft recipients, autologous graft recipients, and after chemotherapy were 30.4% ± 9.6% (50% ± 26% after genoidentical transplantation), 50% ± 17.7%, and 41.7% ± 14.2%, respectively (P = .18). Fourteen patients (26%) were still in first CR after a median of 83 months (range, 53 to 117 months). Conclusion Three risk categories for LIF in children with ALL were identified. Approximately one third of patients with LIF can be successfully treated with salvage therapy overall. Subsequent CR after LIF is mandatory for cure.
Published: 2008
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23. Abstract CT113: A phase III, multicenter, randomized study evaluating the efficacy and safety and efficacy of erythrocyte encapsulated l-asparaginase (Ery001) versus native l-asparaginase (L-asp) in combination with COOPRALL regimen in patients with first relapse of acut

Author: Virginie Gandemer, André Baruchel, Emmanuelle Tavernier, Nicolas Blin, Yves Perel, Yves Bertrand, Norbert Vey, Iman El-Hariry, Xavier Thomas, Yann Godfrin, Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), Service d'hématologie et immunologie pédiatrique, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Pediatric Onco-Hematology Unit, CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Cancer Research, medicine.medical_specialty, Asparaginase, business.industry, Incidence (epidemiology), [SDV]Life Sciences [q-bio], Gastroenterology, 3. Good health, Surgery, law.invention, Regimen, chemistry.chemical_compound, Oncology, Pharmacokinetics, chemistry, Tolerability, Randomized controlled trial, Refractory, law, Internal medicine, medicine, business, Adverse effect
Abstract: Asparaginases are a cornerstone in the treatment of ALL, but their utility is limited by toxicities including hypersensitivity. ERY001 improves pharmacokinetics and tolerability, while maintaining circulating asparaginase (ASPA) activity due to the protective barrier of the erythrocyte membrane. This phase III study enrolled pts with primary relapsed/refractory Ph- ALL. The co-primary endpoints were the duration of ASPA activity equal or greater than 100IU/L and the incidence of ASPA hypersensitivity during induction. Patients, aged 1-55 years, without prior ASPA hypersensitivity were randomized to ERY001 (150 IU/kg) or L-ASP(10.000IU/m2) in combination with COOPRALL. The patients with prior ASPA hypersensitivity received ERY001. ERY001 significantly reduced the incidence of ASPA hypersensitivity (0% vs 43%; p100IU/l significantly longer than L-ASP (20.5±5.2 vs 9.2±7.5 days; p These highly encouraging results show that ERY001 is a suitable option for patients with relapsed ALL maintaining ASPA efficacy with improved tolerability. Citation Format: Yves Bertrand, Andre Baruchel, Xavier Thomas, Nicolas Blin, Emmanuelle Tavernier, Yves Perel, Norbert Vey, Virginie Gandemer, Iman ElHariry, Yann Godfrin. A phase III, multicenter, randomized study evaluating the efficacy and safety and efficacy of erythrocyte encapsulated l-asparaginase (Ery001) versus native l-asparaginase (L-asp) in combination with COOPRALL regimen in patients with first relapse of acut [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT113. doi:10.1158/1538-7445.AM2015-CT113
Published: 2015
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24. Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children

Author: M. D. Tabone, P Levy, J.-P. Vannier, Marie-Françoise Auclerc, G. Michel, Virginie Gandemer, F. Demeocq, Gérard Couillault, Guy Leverger, Thierry Leblanc, C. Schmitt, Judith Landman-Parker, Yves Perel, André Baruchel, M N Dufourg, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Bordeaux 2 Laboratoire de Psychologie EA «Santé et qualité de vie», Université Bordeaux Segalen - Bordeaux 2, Georgia Institute of Technology [Lorraine, France], Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pediatric Hematology and Oncology, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Service d'hématologie pédiatrique, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Dufourg MN, Landman-Parker J, Michel G, Levy P, Couillault G, Gandemer V, Tabone MD, Demeocq F, Vannier JP, Leblanc T, Leverger G, Baruchel A., Auclerc MF, Schmitt C, Perel Y, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, MESH: Combined Modality Therapy, Cancer Research, MESH: Risk Assessment, Gastroenterology, MESH: Dose-Response Relationship, Drug, chemistry.chemical_compound, 0302 clinical medicine, Maintenance therapy, MESH: Child, Child, MESH: Antimetabolites, Antineoplastic, Acute leukemia, Brain Diseases, Metabolic, Age Factors, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Combined Modality Therapy, MESH: Infant, 3. Good health, MESH: Methotrexate, Oncology, Methylprednisolone, Child, Preschool, 030220 oncology & carcinogenesis, Antifolate, Female, medicine.drug, Antimetabolites, Antineoplastic, medicine.medical_specialty, Adolescent, Neurotoxins, Encephalopathy, MESH: Brain Diseases, Metabolic, Risk Assessment, 03 medical and health sciences, Acute lymphocytic leukemia, Internal medicine, medicine, Humans, MESH: Neurotoxins, MESH: Adolescent, MESH: Age Factors, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Humans, Dose-Response Relationship, Drug, business.industry, MESH: Child, Preschool, Infant, medicine.disease, MESH: Male, Surgery, Methotrexate, chemistry, Cytarabine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)+/-high-dose methotrexate (HD MTX) in children with acute lymphoblastic leukemia (ALL). 1395 children were enrolled on FRALLE 93 protocol from 1993 to 1999. Lower-risk group (LR, n=182) were randomized to weekly low-dose MTX at 25 mg/m(2)/week (LD MTX, n=81) or HD MTX at 1.5 g/m(2)/2 weeks x 6 (n=77). Intermediate-risk group (IR, n=672) were randomized to LD MTX (n=290) or HD MTX at 8 g/m(2)/2 weeks x 4 (n=316). Higher-risk group (HR, n=541) prednisone-responder patients received LD MTX and cranial radiotherapy. HR group steroid resistant cases were grafted (autologous or allogenic). TIT (MTX, cytarabine and methylprednisolone) was given every 2 weeks during 16-18 weeks and every 3 months during maintenance therapy in LR and IR patients. 52 patients (3.7%) developed neurotoxicity. Isolated seizures: n=15 (1.1%), peripheral and spinal neuropathy: n=17 (1.2%) and encephalopathy: n=20 (1.4%). Age >10 years was significantly associated with neurotoxicity (P=0.01) and use of HD MTX is associated with encephalopathy (P=0.03). Sequels are reported respectively in 60 and 33% of spinal neuropathy and encephalopathy cases. Current strategies tailoring risk of neurological sequels has to be defined.
Published: 2006
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25. Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit – multicenter studies of the French LAME (Leucémie Aiguë Myéloblastique Enfant) Cooperative Group

Author: G. Michel, Virginie Gandemer, Anne Auvrignon, J.-H. Dalle, Judith Landman-Parker, Brigitte Pautard, I. Thuret, Thierry Leblanc, Yves Reguerre, J.-P. Vannier, Francoise Mechinaud, Yves Perel, O Lejars, André Baruchel, Gérard Couillaud, Christophe Piguet, Guy Leverger, N. Aladjidi, and C. Schmitt
Subjects: Cancer Research, medicine.medical_specialty, Asparaginase, Adolescent, Risk Assessment, chemistry.chemical_compound, Maintenance therapy, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Child, Bone Marrow Transplantation, Mitoxantrone, Acute leukemia, Dose-Response Relationship, Drug, business.industry, Remission Induction, Infant, Newborn, Antineoplastic Protocols, Infant, Induction chemotherapy, Hematology, Survival Analysis, Surgery, Transplantation, Leukemia, Myeloid, Acute, Regimen, Treatment Outcome, Oncology, chemistry, Child, Preschool, Cytarabine, France, business, Follow-Up Studies, medicine.drug
Abstract: From 1989 to 1998, 341 children were included in the French multicentric LAME (Leucémie Aiguë Myéloblastique Enfant) trials. A total of 309 children were registered in the LAME 89/91 protocol. This intensive regimen included an induction phase (mitoxantrone plus cytarabine), two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine; 276 (90%) achieved a CR. The 5-year overall survival (OS) and event-free survival (EFS) were 60+/-4 and 48+/-4%, respectively. From 1997, timed-sequencing of the LAME SP induction chemotherapy led to an unacceptable frequency of consolidation delay; future improvements are unlikely to come from further increases in intensity. The role of allogenic bone-marrow transplantation from an HLA-identical sibling in CR1 was examined. The disease-free survival (DFS) was 52+/-4% for non-allografted patients and 57+/-7% for allografted patients (P=NS); a better OS for allografted patients was shown and could be related either to allo-BMT early in CR1 or to a second allo-BMT in CR2. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no maintenance therapy (MT-) than in patients randomized for MT (77.6+/-8 vs 59+/-8%; P=0.05), while the 5-year DFS was not significantly different. Exposure to low-dose MT might contribute to clinical drug resistance and treatment failure in relapsing patients.
Published: 2005
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26. Que sont les enfants devenus… ?

Author: Stéphane Ducassou and Yves Perel
Subjects: 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Pediatrics, Perinatology and Child Health, 030212 general & internal medicine, Hematology
Abstract: Revue d'oncologie hematologie pediatrique - Sous presse. Epreuves corrigees par l'auteur. Disponible en ligne depuis le mercredi 27 juillet 2016
Published: 2016
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27. Further delineation of the congenital form of X-linked dyskeratosis congenita (Hoyeraal-Hreidarsson syndrome)

Author: Inderjeet Dokal, Tomy Vulliamy, Jean-François Segura, Didier Lacombe, Hubert Journel, Yves Sznajer, Jean-Pierre Cezard, Clarisse Baumann, Alain Verloes, Yves Perel, Michel Peuchmaur, Albert David, and Pascale Blouin
Subjects: Diarrhea, Male, Pathology, medicine.medical_specialty, Microcephaly, Hyperkeratosis, Mutation, Missense, Cell Cycle Proteins, Hoyeraal-Hreidarsson syndrome, Dyskeratosis Congenita, Dyskerin, medicine, Humans, Missense mutation, Esophageal Motility Disorders, Intestinal Mucosa, Cerebellar hypoplasia, X chromosome, business.industry, Infant, Newborn, Nuclear Proteins, Syndrome, medicine.disease, Pediatrics, Perinatology and Child Health, business, Dyskeratosis congenita
Abstract: Hoyeraal-Hreidarsson syndrome represents a severe variant of dyskeratosis congenita (Zinsser-Cole-Engman syndrome). This X-linked recessive, progressive, multisystemic disorder reported so far in 12 pedigrees is characterised by intrauterine growth retardation, microcephaly, cerebellar hypoplasia, mental retardation, progressive combined immune deficiency and aplastic anaemia. Mutations in the DKC1gene on Xq28 have been identified in the X-linked form of dyskeratosis congenita and in some Hoyeraal-Hreidarsson syndrome patients. We report on two sibs and two other unrelated patients with the striking clinical features of Hoyeraal-Hreidarsson syndrome. Noticeably, all four had early digestive problems, with chronic, bloody diarrhoea and feeding problems causing one of the most difficult problems in the supportive treatment of this uniformly lethal condition. Pathological changes in the proliferative compartment of the digestive mucosa included alterations of the glandular architecture and focal rarefaction of the glands. This aspect seems consistent with altered telomerase function associated with a dyskerin mutation which may decrease the proliferative capacity of digestive epithelial cells. A missense mutation 146 C-->T (Thr49Met) in the DKC1gene was found in two unrelated patients, whereas mutation screening was negative for one single case. The absence of mutations of the DKC1gene in patients with Hoyeraal-Hreidarsson syndrome emphasises the probable implication of one or more other loci.
Published: 2003
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28. Lymphocyte-Predominant Hodgkin’s Lymphoma in Children: Therapeutic Abstention After Initial Lymph Node Resection—A Study of the French Society of Pediatric Oncology

Author: Odile Oberlin, M.J. Terrier-Lacombe, Christine Edan, J P Vannier, Yves Bertrand, Annie Babin-Boilletot, B. Pellegrino, C. Lambilliote, Thierry Leblanc, C. Beard, Isabelle Thuret, Dominique Plantaz, Georges Delsol, Guy Leverger, Gérard Couillault, F. Demeocq, H. Pacquement, Yves Perel, Judith Landman-Parker, and Claudine Schmitt
Subjects: Male, Cancer Research, medicine.medical_specialty, Adolescent, medicine.medical_treatment, medicine, Humans, Prospective Studies, Stage (cooking), Child, Prospective cohort study, Chemotherapy, business.industry, Standard treatment, Remission Induction, medicine.disease, Hodgkin's lymphoma, Combined Modality Therapy, Hodgkin Disease, Survival Analysis, Lymphoma, Surgery, Treatment Outcome, Oncology, Child, Preschool, Lymph Node Excision, Female, Lymphadenectomy, Neoplasm Recurrence, Local, business, Adenectomy
Abstract: Purpose: To clarify treatment strategy for lymphocyte-predominant Hodgkin’s lymphoma (LPHL), the French Society of Pediatric Oncology initiated a prospective, nonrandomized study in 1988. Patients received either standard treatment for Hodgkin’s lymphoma or were not treated beyond initial adenectomy. Patients and Methods: From 1988 to 1998, 27 patients were available for study. Twenty-four patients were male, and median age was 10 years (range, 4 to 16 years). Twenty-two, two, and three patients had stage I, II, and III disease, respectively. Thirteen patients (stage I, n = 11; stage III, n = 2) received no further treatment after initial surgical adenectomy (SA). Fourteen patients received combined treatment (CT; n = 10), involved-field radiotherapy alone (n = 1), or chemotherapy alone (n = 3). The two groups were comparable for clinical status, treatment, and follow-up. Results: Twenty-three of 27 patients achieved complete remission (CR). With a median follow-up time of 70 months (range, 32 to 214 months), overall survival to date is 100%, and overall event-free survival (EFS) is 69% ± 10% (SA, 42% ± 16%; CT, 90% ± 8.6%; P < .04). If we considered only the patients in CR after initial surgery (n = 12), EFS was no longer significantly different between the two groups. Patients with residual mass after initial surgery (n = 15) had worse EFS if they did not receive complementary treatment (P < .05). Conclusion: Although based on a small number of patients, our study showed that (1) no further therapy is a valid therapeutic approach in LPHL patient in CR after initial lymph node resection, and (2) complementary treatment diminishes relapse frequency but has no impact on survival.
Published: 2003
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29. A 22-year French Experience with Solid Tumors in Children with Down Syndrome

Author: Danièle Sommelet, Michel Vekemans, Hélène Martelli, Justine Kanold, Daniel Orbach, Daniel Satgé, Bernard Roullet, Christophe Bergeron, Fréderic Bernard, Yves Bertrand, Agnès Chompret, Brigitte Nelken, Francoise Mechinaud, Annie J. Sasco, Anne-Isabelle Bertozzi, Didier Lacombe, Pascal Monteil, Martine Munzer, Yves Perel, and Brigitte Lacour
Subjects: Adult, Male, Down syndrome, Pathology, medicine.medical_specialty, Pediatrics, Adolescent, Aneuploidy, Neoplasms, Epidemiology, Humans, Medicine, Child, Retrospective Studies, business.industry, Infant, Hematology, Neoplasms, Germ Cell and Embryonal, medicine.disease, Combined Modality Therapy, Oncology, El Niño, Child, Preschool, Hematologic Neoplasms, Pediatrics, Perinatology and Child Health, Female, France, Germ cell tumors, Down Syndrome, Congenital disease, business
Abstract: Malignant solid tumors have rarely been reported in children with Down syndrome (DS) and are not well known. The authors collected from 1980 to 2001 all cases of solid tumors observed in DS patients aged from birth to 19 years within the network of the Société Française d'Oncologie Pédiatrique (SFOP). Only 21 cases were observed, with a peculiar distribution: a lack of intracranial tumors and embryonal neoplasms combined with an overrepresentation of lymphomas and germ cell tumors. The treatment of solid tumors in DS is difficult, due to physical and psychological impairments, different pharmacogenetic profile, and associated malformations.
Published: 2003
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30. Impact of Addition of Maintenance Therapy to Intensive Induction and Consolidation Chemotherapy for Childhood Acute Myeloblastic Leukemia: Results of a Prospective Randomized Trial, LAME 89/91

Author: Brigitte Nelken, Anne Auvrignon, Yves Perel, Jean-Pierre Vannier, Judith Landman-Parker, Isabelle Thuret, Lionel de Lumley, Schaison G, André Baruchel, Gérard Michel, Brigitte Bader-Meunier, Thierry Leblanc, Gérard Couillaud, Jean-Hugues Dalle, Jean-Pierre Lamagnere, Virginie Gandemer, and Claudine Schmitt
Subjects: Cancer Research, Chemotherapy, medicine.medical_specialty, Mitoxantrone, business.industry, medicine.medical_treatment, Childhood Acute Myeloid Leukemia, Consolidation Chemotherapy, Mercaptopurine, Surgery, Regimen, Oncology, Maintenance therapy, Internal medicine, medicine, Cytarabine, business, medicine.drug
Abstract: PURPOSE: To determine whether the use of maintenance therapy (MT) delivered after intensive induction and consolidation therapy confers any advantage in childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: A total of 268 children with AML were registered in the Leucámie Aiquë Myéloïde Enfant (LAME) 89/91 protocol. This regimen included an intensive induction phase (mitoxantrone plus cytarabine) and, for patients without allograft, two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase, and amsacrine. In the LAME 89 pilot study, patients were given an additional MT consisting of mercaptopurine and cytarabine for 18 months. In the LAME 91 trial, patients were randomized to receive or not receive MT. RESULTS: A total of 241 (90%) of 268 patients achieved a complete remission. The overall survival and event-free survival at 6 years were 60% ± 6% and 48% ± 6%, respectively. For the complete responders after consolidation therapy, the 5-year disease-free survival was not significantly different in MT-negative and in MT-positive randomized patients (respectively, 60% ± 19% v 50% ± 15%; P = .25), whereas the 5-year overall survival was significantly better in MT-negative randomized patients (81% ± 13% v 58% ± 15%; P = .04) due to a higher salvage rate after relapse. CONCLUSION: More than 50% of patients can be cured of AML in childhood. Either drug intensity or each of the induction and postremission phases may have contributed to the outstanding improvement in outcome. Low-dose MT is not recommended. Exposure to this low-dose MT may contribute to clinical drug resistance and treatment failure in patients who experience relapse.
Published: 2002
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31. Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies

Author: Alain Fischer, Johan Provot, Jean-Philippe Jais, Alexandre Alcais, Nizar Mahlaoui, Daniel Adoue, Nathalie Aladjidi, Zahir Amoura, Philippe Arlet, Corinne Armari-Alla, Brigitte Bader-Meunier, Vincent Barlogis, Sophie Bayart, Beatrice Beaurain, Yves Bertrand, Boris Bienvenu, Stéphane Blanche, Damien Bodet, Bernard Bonnotte, Raphaël Borie, Patrick Boutard, Claire Briandet, Jean-Paul Brion, Carolina Brito, Jacques Brouard, Emilie Catherinot, Olivia Chandesris, Sarah Cohen-Beaussant, Hélène Coignard-Biehler, Laurence Costes, Louis-Jean Couderc, Gérard Couillault, Virginie Courteille, Elodie Curlier, Geneviève de Saint Basile, François Demeocq, Nathalie de Vergnes, Catherine Devoldere, Anne Deville, Jean Donadieu, Eric Dore, Fabienne Dulieu, Isabelle Durieu, Christine Edan, Natacha Entz Werle, Claire Fieschi, Fanny Fouyssac, Pierre Frange, Vincent Gajdos, Lionel Galicier, Virginie Gandemer, Martine Gardembas, Catherine Gaud, Bernard Grosbois, Gaelle Guillerm, Eric Hachulla, Mohamed Hamidou, Sébastien Héritier, Olivier Hermine, Cyrille Hoarau, Bruno Hoen, Arnaud Hot, Sébastien Humbert, Arnaud Jaccard, Serge Jacquot, Rolland Jaussaud, Pierre-Yves Jeandel, Eric Jeziorski, Kamila Kebaili, Anne-Sophie Korganow, Philippe Labrune, Olivier Lambotte, Fanny Lanternier, Claire Larroche, Alain Le Quellec, Emmanuelle Le Moigne, Vincent Le Moing, Yvon Lebranchu, Marc Lecuit, Guillaume Lefevre, Richard Lemal, Philippe Le Moine, Valérie Li Thiao Te, Olivier Lortholary, Patrick Lutz, Aude Magerus-Chatinet, Marion Malphettes, Aude Marie-Cardine, Nicolas Martin Silva, Agathe Masseau, Christian Massot, Françoise Mazingue, Etienne Merlin, Gérard Michel, Frédéric Millot, Odile Minckes, Béatrice Monlibert, Fabrice Monpoux, Despina Moshous, Luc Mouthon, Martine Munzer, Bénédicte Neven, Raphaëlle Nove-Josserand, Eric Oksenhendler, Marie Ouachée-Chardin, Anne Pagnier, Jean-Louis Pasquali, Marlène Pasquet, Isabelle Pellier, Yves Perel, Antoinette Perlat, Capucine Picard, Christophe Piguet, Dominique Plantaz, Pierre Quartier, Frédéric Rieux-Laucat, Pascal Roblot, Pierre-Marie Roger, Pierre-Simon Rohrlich, Bruno Royer, Valéry Salle, Françoise Sarrot-Reynauld, Amélie Servettaz, Jean-Louis Stephan, Nicolas Schleinitz, Felipe Suarez, Laure Swiader, Sophie Taque, Caroline Thomas, Olivier Tournilhac, Caroline Thumerelle, Jean-Pierre Vannier, Jean-François Viallard, Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immuno-hématologie pédiatrique [CHU Necker], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collège de France - Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collège de France (CdF), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chaire Médecine expérimentale (A. Fischer), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Risk, 0301 basic medicine, Primary immunodeficiencies, Adolescent, T-Lymphocytes, Immunology, Population, Context (language use), medicine.disease_cause, Inflammatory bowel disease, Autoimmunity, Young Adult, 03 medical and health sciences, Prevalence, medicine, Humans, Immunology and Allergy, Age of Onset, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Child, education, Aged, Retrospective Studies, Aged, 80 and over, Autoimmune disease, Purpura, Thrombocytopenic, Idiopathic, education.field_of_study, business.industry, Common variable immunodeficiency, Autoimmune Cytopenia, autoimmunity, Immunologic Deficiency Syndromes, Infant, Middle Aged, Inflammatory Bowel Diseases, Prognosis, medicine.disease, Survival Analysis, 3. Good health, 030104 developmental biology, inflammation, Child, Preschool, Primary immunodeficiency, Female, France, business
Abstract: International audience; BACKGROUND:Primary immunodeficiencies (PIDs) are inherited diseases associated with a considerable increase in susceptibility to infections. It is known that PIDs can also predispose to cancer and immune diseases, including allergy, autoimmunity, and inflammation.OBJECTIVE:We aimed at determining the incidence of autoimmunity and inflammation in patients with PIDs.METHODS:We have retrospectively screened 2183 consecutive cases of PID in the Centre de Référence Déficits Immunitaires Héréditaires registry (CEREDIH; the French national PID registry) for the occurrence of autoimmunity and inflammation.RESULTS:One or more autoimmune and inflammatory complications were noted in 26.2% of patients, with a risk of onset throughout the patient's lifetime. The risk of autoimmune cytopenia was at least 120 times higher than in the general population, the risk of inflammatory bowel disease in children was 80 times higher, and the risk of other autoimmune manifestations was approximately 10 times higher. Remarkably, all types of PIDs were associated with a risk of autoimmune and inflammatory complications, although the greatest risk was associated with T-cell PIDs and common variable immunodeficiency. The occurrence of autoimmune disease is a negative prognostic factor for survival.CONCLUSIONS:Our results provide the basis for a detailed prospective evaluation of autoimmunity and inflammation in the context of PIDs, with a view to accurately assessing these risks and describing the possible effect of medical intervention.
Published: 2017
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32. Anémie hémolytique aiguë de l’enfant̊: quand et comment transfuser dans l’urgence̊?

Author: Muriel Bouton, Nathalie Aladjidi, Guy Leverger, Yves Perel, Helder Fernandez, and Hélène Petit
Subjects: Biochemistry (medical), Clinical Biochemistry, Hematology
Abstract: L’anemie hemolytique auto-immune (AHAI) de l’enfant est une maladie rare qui atteint moins de 50 enfants par an en France. Elle constitue souvent une urgence vitale immediate par la brutalite et la profondeur de l’anemie, necessitant une discussion de transfusion de culot globulaire (CGR), malgre les risques d’allo-immunisation masquee ou d’exacerbation de l’hemolyse. La cohorte prospective nationale observationnelle OBS’CEREVANCE est coordonnee depuis 2004 a Bordeaux, et inclut en mars 2017, 385 enfants atteints d’une AHAI isolee: âge median: 3,8 ans (0,1–17,4), signes de gravite clinique de l’anemie pour 66 %, mediane du taux d’hemoglobine 5,7 g/dL (1,8–12,2) et de reticulocytes 148 G/L (1–805), test de Coombs IgG/IgG + complement dans 63 % des cas, suivi median 2,4 ans (0,0–27,5). Une corticotherapie a ete debutee dans la semaine du diagnostic chez 74 % des enfants. Une ou plusieurs transfusions de CGR ont ete necessaires pour 55 % des enfants, avec une tolerance le plus souvent bonne. Aucun des 7 deces n’a ete directement relie a l’anemie. La decision d’un support transfusionnel repose sur la tolerance clinique de l’anemie, sa brutalite, le taux d’hemoglobine, voire l’absence d’hyperreticulocytose. La corticotherapie est indiquee precocement pour attenuer l’hemolyse. Pour assurer la securite transfusionnelle, les examens immuno-hematologiques necessitent du temps en raison de la presence de l’auto-anticorps et le choix d’un CGR compatible est difficile, voire parfois impossible. Un dialogue entre le clinicien et le medecin de l’etablissement de transfusion est donc indispensable afin d’evaluer le ratio benefice/risque et le degre d’urgence clinique de la transfusion.
Published: 2017
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33. Atypical hematologic and renal manifestations in neurofibromatosis type I: coincidence or pathophysiological link?

Author: Charlotte Jubert, Brigitte Llanas, Cyril Goizet, Dominique Vidaud, Julien Van-Gils, Jérôme Harambat, Yves Perel, and Didier Lacombe
Subjects: Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Nephrotic Syndrome, Neurofibromatosis 1, Adolescent, Mutation, Missense, Proto-Oncogene Mas, Pallor, Nephritic syndrome, Internal medicine, Genetics, Medicine, Missense mutation, Humans, Neurofibromatosis, Child, neoplasms, Genetics (clinical), Neurofibromatosis type I, Neurofibromin 1, biology, business.industry, Cafe-au-Lait Spots, Axillary freckling, General Medicine, medicine.disease, Dermatology, Pedigree, Endocrinology, biology.protein, medicine.symptom, business, Nephrotic syndrome
Abstract: Neurofibromatosis type 1 (NF1) is an autosomal dominant, multi-system, neurocutaneous disorder that predisposes to the development of benign and malignant tumors with a birth incidence rate of 1 in 2500–3000. 50% of cases are sporadic. The diagnosis is exclusively based on clinical assessment with clinical diagnostic criteria such as cafe-au-lait spots, neurofibromas, axillary or groin freckling, Lisch nodules, optic pathway glioma, bony dysplasia and first-degree relative with NF1. We report a family with NF1 in which two members presented atypical clinical features in addition to the classical diagnostic criteria. Three relatives affected by NF1, a father and two of his three sons, are described. The clinical diagnosis was originally worn in all three cases, with the association many spots cafe-au –lait over the entire body and some axillary freckling as well as first-degree relative. One case presented an Acute Myeloid Leukemia (AML) type 2 at 10 years of age diagnosed before the revelation of bicytopenia associated pallor and isolated asthenia. A second case presented a nephrotic syndrome at 4 years of age due to the association of hydrops with headache and asthenia. Direct sequencing of NF1 led to identify the familial mutation, a previously unreported heterozygous missense mutation c.3443C > A, p.Ala1148Glu in exon 20 which segregated with all three affected patients. The family described in this report confirms the high clinical variability of NF1, even intrafamilial, and raises the question as to whether rare features such as AML and nephrotic syndrome are associated with NF1. Some NF1 patients presenting glomerular diseases or AML have rarely been reported, but due to the small number of cases described the mechanisms underlying these associations are poorly understood. However, it seems important to be aware of the possible occurrence of nephritic syndrome and/or malignant blood diseases in NF1 patients.
Published: 2014

34. The Societe Francaise d'Oncologie Pediatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia

Author: Patrick Lutz, Guy Leverger, Anne Auperin, Didier Frappaz, Martine Raphael, Marie-Josée Terrier-Lacombe, Jean Michon, Yves Perel, Carole Coze, Henk Behrendt, Catherine Patte, and Faculteit der Geneeskunde
Subjects: Male, medicine.medical_specialty, Vincristine, Lymphoma, B-Cell, Adolescent, Hydrocortisone, Cyclophosphamide, Immunology, Leucovorin, Biochemistry, Gastroenterology, Recurrence, Internal medicine, Acute lymphocytic leukemia, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Child, Survival rate, Etoposide, Neoplasm Staging, business.industry, Remission Induction, Cytarabine, Large-cell lymphoma, Infant, Cell Biology, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, medicine.disease, Chemotherapy regimen, Confidence interval, Lymphoma, Surgery, Survival Rate, Methotrexate, Doxorubicin, Child, Preschool, Prednisone, Female, business, medicine.drug
Abstract: This study was undertaken to show that a high survival rate can be obtained in B-cell (Burkitt and large B-cell) lymphoma and L3 leukemia with multiagent chemotherapy adapted to the tumor burden (stage, resection status, percentage of blasts in bone marrow, and central nervous system [CNS] involvement) and early response to chemotherapy, to investigate actual prognostic factors, and to see if large B-cell lymphoma can be treated with the same regimen as Burkitt lymphoma. Patients were classified into 3 risk groups. Group A (resected stage I and abdominal stage II) received 2 courses of vincristine, cyclophosphamide, doxorubicin, and prednisone. Group B (patients not eligible for groups A or C) received 5 courses of chemotherapy with, in addition, high-dose methotrexate, 3 g/m(2) over 3 hours; infusional cytarabine; and intrathecal (IT) methotrexate. Group C (patients with CNS involvement and acute lymphoblastic leukemia with at least 70% of blasts in bone marrow) received 8 courses with, in addition, high-dose methotrexate, 8 g/m(2); high-dose cytarabine; etoposide; and triple IT. Except in group A, treatment started with a prephase (COP, low-dose vincristine and cyclophosphamide). It was intensified for patients who did not respond to COP in group B and any patient with residual viable cells after the consolidation phase. A total of 561 patients were enrolled in the SFOP LMB89 protocol (July 1989-June 1996). Five-year survival is 92.5% (95% confidence interval [CI], 90%-94%) and event-free survival (EFS) 91% (95% CI, 89%-93%). EFS is 98% (95% CI, 90%-100%), 92% (95% CI, 89%-95%), and 84% (95% CI, 77%-90%) for group A, B, and C, respectively. In group B, multivariate analysis of prognostic factors showed that a lactate dehydrogenase level more than 2-fold the normal value, no response after COP, and age of at least 15 years were associated with a lower EFS. CNS involvement was the only prognostic factor in group C. (Blood. 2001;97:3370-3379)
Published: 2001
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35. Pharmacokinetics of Itraconazole Oral Solution in Neutropenic Children during Long-Term Prophylaxis

Author: Jean-Pierre le Moing, Jean-Claude Levron, Claudine Schmitt, Elisabeth Chwetzoff, Sophie Lemerle, Yves Perel, and Jean-luc Harousseau
Subjects: medicine.medical_specialty, Antifungal Agents, Neutropenia, Itraconazole, medicine.medical_treatment, Administration, Oral, Pharmacology, Gastroenterology, Pharmacokinetics, Oral administration, Internal medicine, medicine, Humans, Pharmacology (medical), Antibiotic prophylaxis, Child, Chemotherapy, Leukopenia, business.industry, Antibiotic Prophylaxis, medicine.disease, Long-Term Care, Infectious Diseases, Child, Preschool, Toxicity, medicine.symptom, business, medicine.drug
Abstract: We investigated the pharmacokinetics and safety of an oral solution of itraconazole in two groups of neutropenic children stratified by age. Effective concentrations of itraconazole in plasma were reached quickly and maintained throughout treatment. The results indicate a trend toward higher concentrations of itraconazole in plasma in older children.
Published: 2001
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36. Pharmacokinetics of liposomal daunorubicin (DaunoXome) during a phase I-II study in children with relapsed acute lymphoblastic leukaemia

Author: Anne Auvrignon, Guy Leverger, Yves Bertrand, Thierry Leblanc, André Baruchel, Yves Perel, Virginie Gandemer, Jérôme Vernois, Patrice Bellenger, Jacques Robert, Francoise Mechinaud, and Ricardo Bellott
Subjects: Male, Cancer Research, Time Factors, Adolescent, Daunorubicin, medicine.medical_treatment, Pharmacology, Toxicology, Pharmacokinetics, Recurrence, Acute lymphocytic leukemia, Blood plasma, medicine, Humans, Pharmacology (medical), Child, Volume of distribution, Drug Carriers, Chemotherapy, Liposome, Antibiotics, Antineoplastic, business.industry, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Liposomal daunorubicin, Oncology, Child, Preschool, Anesthesia, Liposomes, Female, business, Half-Life, medicine.drug
Abstract: Purpose: The pharmacokinetics of DaunoXome were studied during a multicentric phase I-II study performed in children suffering from relapsed acute lymphoblastic leukaemia and treated on a weekly schedule. Patients and methods: A group of 18 patients were studied during the first course of treatment at dose levels between 40 and 120 mg/m2. Blood samples were obtained up to 72 h after infusion. The liposomal and free forms of daunorubicin, as well as daunorubicinol, were separated and quantified by HPLC using fluorometric detection, and data were analysed using a model-independent approach. Results: Unchanged liposomal daunorubicin disappeared from plasma following a monoexponential decay. Its AUC represented 95.8% of the total fluorescent species found in plasma and increased linearly with the dose administered. The elimination half-life was 5.23 h, total plasma clearance 0.344 l/h per m2, and volume of distribution at steady state 2.08 l/m2. Free daunorubicin and daunorubicinol were detected in plasma at all time-points studied. Their AUCs represented, respectively, 2.53% and 1.70% of total fluorescent species and their elimination half-lives were, respectively, 16.6 h and 22.3 h. The daunorubicinol/daunorubicin AUC ratio was 0.82%. Conclusions: This study is the first to demonstrate that free daunorubicin is present in plasma after DaunoXome administration and that it originates from in vivo release from the liposomes. The pharmacokinetics of free daunorubicin appeared to be comparable to those observed after conventional administration. However, the concentration of daunorubicinol appeared to be lower than that found after conventional administration of daunorubicin.
Published: 2000
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37. Localized Childhood Hodgkin’s Disease: Response-Adapted Chemotherapy With Etoposide, Bleomycin, Vinblastine, and Prednisone Before Low-Dose Radiation Therapy—Results of the French Society of Pediatric Oncology Study MDH90

Author: Schaison G, Guy Leverger, Annie Robert, Isabelle Thuret, Yves Bertrand, Jean Lemerle, Carole Coze, Judith Landman-Parker, Jean Donadieu, Odile Oberlin, M.J. Terrier-Lacombe, H. Pacquement, Yves Perel, Jean-Louis Habrand, and Thierry Leblanc
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Vincristine, Adolescent, Anthracycline, Dacarbazine, medicine.medical_treatment, Vinblastine, Procarbazine, Disease-Free Survival, Bleomycin, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Child, Etoposide, Chemotherapy, business.industry, Radiotherapy Dosage, Combined Modality Therapy, Hodgkin Disease, Chemotherapy regimen, Surgery, Treatment Outcome, ABVD, Doxorubicin, Child, Preschool, Prednisone, Female, business, medicine.drug
Abstract: PURPOSE: The French Society of Pediatric Oncology MDH82 study demonstrated the effectiveness of 20 Gy irradiation of involved fields after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, vincristine, procarbazine, and prednisone/ABVD chemotherapy in children with localized Hodgkin’s disease (HD). The response to primary chemotherapy was the only predictor of survival. To reduce long-term treatment complications without compromising efficacy, the MDH90 study was based on a new chemotherapy regimen devoid of both alkylating agents and anthracycline, followed by 20 Gy of radiotherapy (RT) for good responders. PATIENTS AND METHODS: From January 1990 to July 1996, 202 children were enrolled from 30 institutions. Good responders to four cycles of vinblastine, bleomycin, etoposide (VP16), and prednisone (VBVP) were given 20 Gy of RT and no further therapy. Poor responders were given vincristine, procarbazine, prednisone, and doxorubicin. After a second evaluation, good responders were given 20 Gy of RT, and poor responders were given 40 Gy of RT. RESULTS: One hundred seventy-one patients (85%) were good responders to VBVP, 27 (15%) were poor responders, and four did not respond. With a median follow-up of 74 months (range, 25 to 117 months), the 5-year overall survival rate (mean ± SD) is 97.5% ± 2.1%, and the event-free survival rate (mean ± SD) is 91.1% ± 1.8%. Significant predictors of worse event-free survival in multivariate analysis were hemoglobin < 10.5 g/L, “b” biologic class, and nodular sclerosis. CONCLUSION: These results suggest that most children with clinical stage I and II HD can be treated with chemotherapy devoid of alkylating agents and anthracycline, followed by low-dose RT.
Published: 2000
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38. Use of Recombinant Human Granulocyte Colony-Stimulating Factor to Increase Chemotherapy Dose-Intensity: A Randomized Trial in Very High-Risk Childhood Acute Lymphoblastic Leukemia

Author: E. Legall, Anne Auvrignon, Christian Berthou, Gérard Michel, Yves Perel, André Baruchel, Guy Leverger, F. Demeocq, F. Bauduer, Pascale Schneider, Brigitte Pautard, Pierre Bordigoni, C. Mathey, Jean-Pierre Lamagnere, Marie-Françoise Auclerc, Schaison G, Judith Landman-Parker, and Thierry Leblanc
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Vincristine, Neutropenia, Adolescent, Cyclophosphamide, Dexamethasone, Acute lymphocytic leukemia, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Granulocyte Colony-Stimulating Factor, medicine, Humans, Child, Childhood Acute Lymphoblastic Leukemia, Etoposide, Dose-Response Relationship, Drug, business.industry, Cytarabine, Infant, Newborn, Infant, Consolidation Chemotherapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Thrombocytopenia, Recombinant Proteins, Surgery, Granulocyte colony-stimulating factor, Methotrexate, Treatment Outcome, Doxorubicin, Child, Preschool, Absolute neutrophil count, Prednisone, Female, business, medicine.drug
Abstract: PURPOSE: To determine whether the use of a recombinant human granulocyte colony-stimulating factor ([G-CSF] lenogastrim) can increase the chemotherapy dose-intensity (CDI) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Sixty-seven children with very high-risk ALL were randomized (slow early response to therapy, 55 patients; translocation t(9;22) or t(4;11), 12 patients). Consolidation consisted of six courses of chemotherapy; the first, third, and fifth courses were a combination of high-dose cytarabine, etoposide, and dexamethasone (R3), whereas the second, fourth, and sixth courses included vincristine, prednisone, cyclophosphamide, doxorubicin, and methotrexate (COPADM). G-CSF was given after each course, and the next scheduled course was started as soon as neutrophil count was > 1 × 109/L and platelet count was > 100 × 109/L. CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course (100% CDI = 105-day interval). RESULTS: CDI was significantly increased in the G-CSF group compared with the non–G-CSF group (mean ± 95% confidence interval, 105 ± 5% v 91 ± 4%; P < .001). This higher intensity was a result of shorter post-R3 intervals in the G-CSF group, whereas the post-COPADM intervals were not statistically reduced. After the R3 courses, the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF, whereas reductions observed after COPADM were not statistically significant. Duration of granulocytopenia was reduced in the G-CSF group, but thrombocytopenia was prolonged, and the number of platelet transfusions was increased. Finally, the 3-year probability of event-free survival was not different between the two groups. CONCLUSION: G-CSF can increase CDI in high-risk childhood ALL. Its effects depend on the chemotherapy regimen given before G-CSF administration. In our study, a higher CDI did not improve disease control.
Published: 2000
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39. Relapses of childhood anaplastic large-cell lymphoma: Treatment results in a series of 41 children - a report from the French Society of Pediatric Oncology

Author: Laurence Brugières, M.C. Le Deley, Georges Delsol, Olivier Hartmann, P. Quartier, Christophe Bergeron, Catherine Patte, M.J. Terrier-Lacombe, Hélène Pacquement, J. Landmann, Claudine Schmitt, and Yves Perel
Subjects: Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Vinblastine, Transplantation, Autologous, Disease-Free Survival, Childhood Anaplastic Large Cell Lymphoma, Bleomycin, Lomustine, Recurrence, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Asparaginase, Humans, Transplantation, Homologous, Child, Cyclophosphamide, Survival rate, Anaplastic large-cell lymphoma, Bone Marrow Transplantation, Retrospective Studies, Univariate analysis, Chemotherapy, business.industry, Cytarabine, Infant, Hematology, medicine.disease, Chemotherapy regimen, Surgery, Survival Rate, Transplantation, Methotrexate, Oncology, Doxorubicin, Vincristine, Child, Preschool, Prednisone, Female, France, Lymphoma, Large B-Cell, Diffuse, business, Follow-Up Studies, medicine.drug
Abstract: 9Pathology, CHUPurpan, Toulouse, France Summary Purpose: to study response to chemotherapy and the outcome of children treated for a relapsed anaplastic large-cell lymphoma (ALCL) and to evaluate the role of bone marrow transplantation (BMT) in these patients. Patients and methods: Clinical data concerning the 41 relapses that occurred in 119 patients with ALCL enrolled in 3 consecutive studies since 1975 were analysed. First-line treatment consisted of intensive chemotherapy according to the COPAD protocol for the first series of 12 patients treated between 1975 and 1989 and to the SFOP (French Society of Pediatric Oncology) HM protocols for the 30 patients treated between 1989 and 1997. Twenty-eight patients were treated with CV(B)A (CCNU, vinblastine, ara-C with or without bleomycin), and the others with miscellaneous protocols for recurrent disease. Fifteen patients underwent autologous BMT and 1 allogeneic BMT while in CR2. Results: Thirty-six of forty-one (88%) patients achieved CR2. With a median follow-up of 5 years, 12 patients died, 9 of their disease and 29 patients are alive in CR2 (20 patients), CR3 (5 patients), CR4 (2 patients), CR5 (1 patient) or CR6 (1 patient). Overall and disease-free survival are respectively 69% (53%-82%) and 44% (29%-61%) at three years. In univariate analysis, patients treated with ABMT while in CR2 did not appear to have a better outcome than the other. Remarkably, a long-lasting remission was obtained in 8 of 13 patients treated with weekly vinblastine for a relapse including 6 relapses occurring after ABMT. Conclusions: Relapsed ALCL are highly chemosensitive but over 40% of the patients experience several relapses. Prolonged conventional chemotherapy based on vinblastine might, in some cases, be as efficient as short intensive treatment with ABMT.
Published: 2000
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40. Second thyroid neoplasms after prophylactic cranial irradiation for acute lymphoblastic leukemia

Author: Yves Perel, Sophie Ansoborlo, Erea Noel Garabedian, Anne Carrere, Michel Caudry, Guy Leverger, and P. Vergnes
Subjects: Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Pathogenesis, Thyroid carcinoma, Acute lymphocytic leukemia, medicine, Carcinoma, Humans, Thyroid Neoplasms, business.industry, Thyroid, Infant, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Surgery, Radiation therapy, medicine.anatomical_structure, Child, Preschool, Female, Radiology, Cranial Irradiation, Prophylactic cranial irradiation, business, Complication
Abstract: An understanding of the pathogenesis of second cancers may help in their prevention. We report on two children who were treated for acute lymphoblastic leukemia (ALL), with an exclusively cranial prophylactic irradiation (18 Gy) and who presented with a thyroid carcinoma (TC) 12 and 13 years later. From a thorough review of the literature of TC after ALL and of radiation-induced TC, a strong case can be made that these tumors are caused by late effects of scattered radiation. The risk is at its highest in small children. After cranial irradiation, patients require clinical monitoring of the thyroid and cervical area for nodules, continued indefinitely. We suggest that, in most cases, an alternative form of neuromeningeal prophylaxis should be offered in small children with ALL.
Published: 1998
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41. Immune Thrombocytopenic Purpura after Recombinant Hepatitis B Vaccine: Retrospective Study of Seven Cases

Author: M. Longy-Boursier, J.M. Guillard, Jean-Marie Ragnaud, Maggy Michaud, Yves Perel, Didier Neau, and Fabrice Bonnet
Subjects: Male, Microbiology (medical), Adolescent, Thrombotic thrombocytopenic purpura, Immune system, Adrenal Cortex Hormones, Risk Factors, medicine, Humans, Hepatitis B Vaccines, Child, Retrospective Studies, Purpura, Thrombocytopenic, Idiopathic, Vaccines, Synthetic, General Immunology and Microbiology, biology, business.industry, Incidence, Immunization, Passive, General Medicine, Hepatitis B, Prognosis, medicine.disease, Thrombocytopenic purpura, Vaccination, Infectious Diseases, Immunization, Child, Preschool, Immunology, biology.protein, Female, France, Viral disease, Antibody, business
Abstract: Recombinant hepatitis B vaccine is usually well tolerated. Clinical and laboratory test manifestations with immunologic mechanisms have nonetheless been described following use of this vaccine. We retrospectively report 7 cases of thrombocytopenia occurring within 3 months (7 weeks on the average) of 1 or following injections of recombinant hepatitis B vaccine. Four boys and 3 girls, average age 12 y, were involved. Three had a history of immune thrombocytopenic purpura. Four had haemorrhagic manifestations. The haemogram showed thrombocytopenia (24 x 10(9)/l on the average) without alterations of the other lines. Infectious and immune aetiologies were excluded in all cases. The course varied after treatment by corticosteroids, high-dose intravenous immunoglobulin, or both. After describing the different manifestations subsequent to recombinant hepatitis B vaccination, we discuss post-vaccinal thrombocytopenias (vaccines in question, mechanisms) and the reality of this entity.
Published: 1998
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42. Nephrotic syndrome and Hodgkin disease in children: a report of five cases

Author: Odile Lejars, J P Lamagnères, M Brunat-Mentigny, Georges Deschênes, Brigitte Bader-Meunier, Jean-Louis Stephan, and Yves Perel
Subjects: Male, Pediatrics, medicine.medical_specialty, Nephrotic Syndrome, Adolescent, Disease, Pathogenesis, immune system diseases, hemic and lymphatic diseases, Biopsy, medicine, Humans, Child, Proteinuria, medicine.diagnostic_test, business.industry, Complement C1q, Biopsy, Needle, Remission Induction, Glomerulonephritis, Complement C3, medicine.disease, Combined Modality Therapy, Hodgkin Disease, Glomerular Mesangium, Lymphoma, Immunoglobulin M, Pediatrics, Perinatology and Child Health, Immunology, Female, medicine.symptom, business, Nephrotic syndrome, Kidney disease
Abstract: This report documents the occurrence of a nephrotic syndrome in five children with Hodgkin disease. In two cases the nephrotic syndrome predated the diagnosis of lymphoma by 6 months and 12 months respectively, while in the other three, the two disorders occurred simultaneously. The nephrotic syndrome resolved in four cases during effective treatment for active Hodgkin disease, while proteinuria remained unchanged in the fifth case with partial control of the lymphoma. The occurrence of a nephrotic syndrome as a manifestation of active Hodgkin disease suggests that some immunological abnormalities play a role in the pathogenesis of the association.The possibility of glomerular dysfunction although rare must be considered and actively looked for in all cases of Hodgkin disease. Similarly, any unusual sign or symptom noted in patients with nephrotic syndrome, particularly receiving or having received immunosuppressants, requires thorough investigation to determine the presence or absence of lymphoma.
Published: 1997
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43. Paediatric anaplastic large cell lymphoma with leukaemic presentation in children: a report of nine French cases

Author: Patrick Lutz, Dominique Plantaz, Alexandra Spiegel, Stéphane Ducassou, Catherine Paillard, Laurence Brugières, Laurence Lamant, Marion Strullu, Alice Eischen, Marie-Cécile Le Deley, and Yves Perel
Subjects: Central Nervous System, Male, medicine.medical_specialty, Pathology, Adolescent, Leukocytosis, Biopsy, Lymph node biopsy, Ki-1 Antigen, Gastroenterology, Diagnosis, Differential, Immunophenotyping, Bone Marrow, Recurrence, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Medicine, Anaplastic lymphoma kinase, Humans, Anaplastic Lymphoma Kinase, Child, Anaplastic large-cell lymphoma, Skin, Leukemia, medicine.diagnostic_test, biology, business.industry, Infant, Receptor Protein-Tyrosine Kinases, Hematology, Protein-Tyrosine Kinases, medicine.disease, Lymphoma, Transplantation, Treatment Outcome, Child, Preschool, biology.protein, Neoplastic Stem Cells, Lymphoma, Large-Cell, Anaplastic, Female, France, Lymph Nodes, Stem cell, Antibody, Symptom Assessment, business
Abstract: Summary This study aimed to describe the clinical features and outcome of anaplastic large cell lymphoma (ALCL) with leukaemic presentation in children. Among 267 patients included in the French paediatric ALCL database between 1989 and 2012, nine (3%) were described as having cytologically detectable circulating tumour cells. Clinical features combined fever (8/9), nodal and extra-nodal disease (9/9), including hepato-splenic (9/9) and lung involvement (7/9). The level of hyperleucocytosis ranged from 30 to 120 × 109/l, with 12–90% of tumour cells. Diagnosis relied on a lymph node biopsy, with a positive ALK+ antibody immunostain in all nine cases, a T-cell immunophenotype in 7/9 cases and CD3 positivity in 5/9 cases. A small cell component was present in 6/9 cases. Only four patients achieved a complete remission with first-line therapy and 3/4 relapsed. Four patients are alive with a median follow-up of 31 months, two of them after allogeneic haematopoietic stem cell transplantation (HSCT), and five patients died, two of them of disease. In conclusion, ALCL with leukaemic presentation is very unusual and should be considered as high-risk lymphoma requiring new therapeutic strategies. The respective role of new agents and allogeneic HSCT in first complete remission still has to be assessed.
Published: 2013

44. Screening for G-CSF receptor mutations in patients with secondary myeloid or lymphoid transformation of severe congenital neutropenia. A report from the French neutropenia register

Author: A. Notz-Carrere, Christine Bellanné-Chantelot, Bruno Cassinat, Thierry Leblanc, M L Menot, Christine Chomienne, Marguerite Micheau, Yves Perel, J. Donadieu, Christelle Vaury, and Brigitte Bader-Meunier
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Myeloid, business.industry, macromolecular substances, Hematology, Neutropenia, medicine.disease, Transformation (genetics), medicine.anatomical_structure, hemic and lymphatic diseases, Internal medicine, Immunology, Medicine, In patient, business, Receptor, Congenital Neutropenia
Abstract: Screening for G-CSF receptor mutations in patients with secondary myeloid or lymphoid transformation of severe congenital neutropenia. A report from the French neutropenia register
Published: 2004
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45. Safety and Efficacy of Blinatumomab Used in Children with B-Precursor Acute Lymphoblastic Leukemia (ALL) Treated in French Hematological Centers

Author: Fanny Rialland, Benoit Brethon, Virginie Gandemer, Arnaud Petit, Yves Perel, André Baruchel, Odile Minckes, Anne-Flore Derache, Gérard Michel, and Pascale Blouin
Subjects: medicine.medical_specialty, education.field_of_study, Pediatrics, business.industry, Immunology, Population, Retrospective cohort study, Cell Biology, Hematology, medicine.disease, Biochemistry, Minimal residual disease, Clinical trial, Cytokine release syndrome, Internal medicine, Monoclonal, medicine, Blinatumomab, Adverse effect, business, education, medicine.drug
Abstract: Blinatumomab is a monoclonal bispecific antibody, combining two binding sites: a CD3 site for T cells and a CD19site for the target B cells. Blinatumomab has demonstrated efficacy and safety in adult relapsed/refractory B-precursor ALL (R/R ALL) populations, but also in the pediatric R/R ALL population as shown by interim results from the Phase 1b/2 study MT103-205 (Gore L et al, ASH 2014). Patients and methods: this retrospective study aims to evaluate safety and efficacy of Blinatumomab in 17 pediatric pts with B-precursor ALL treated in 4 french hematological centers between April 2013 and December 2015 within a compassionate use frame. These 17 pts represent the whole population of French children treated with Blinatumomab outside a clinical trial but under a Temporary Authorization for Use (ATU) given by the French Regulatory Agency (ANSM) within this period. Median age was 6.6 years (8 months - 16.6 years). Results: 1)7 pts (41%) received Blinatumomab at a dose of 15 mcg/m2/day for 28 days/cycle in first or second complete remission for minimal residual disease (MRD) persistence. Six of those 7 pts had a molecular remission (MRD Enterococcus faecalis, n=1 and Staphylococcus haemolyticus, n=1). One patient had a grade 3 soft tissue mucormycosis. Three pts (18%) had hepatic toxicity (≥ grade 3 increased ALAT, n=2). One patient had a grade 4 pericarditis without documented infection. No neurological event was observed. Conclusion: Although our numbers are small 1) Blinatumomab is an effective bridge to HSCT for pts with persisting high MRD after intensive chemotherapy. 2) A 40% MRD response rate has been found for R/R pts but with a dismal final outcome. 3) Toxicity is manageable with a low neurological event rate (none in this study). Blinatumomab should be developed in less advanced B lineage ALL in children. Disclosures Baruchel: Amgen: Consultancy. Brethon:Amgen: Consultancy.
Published: 2016
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46. Pédiatrie

Author: Antoine Bourrillon, Joël Lechevallier, Gérard Lorette, Juliane Léger, Yves Perel, Michel Rybojad, Guy Sebag, Thierry Van Den Abbeele, Dominique Bremond-Gignac, Brigitte Chabrol, Alain Chantepie, Albert Faye, Christèle Gras Le Guen, Pierre-Henri Jarreau, Philippe Labrune, Marie-France Le Heuzey, Jean-Pierre Chouraqui, Georges Deschênes, Chantal Job-Deslandre, Laure BESSON, Claire GUILABERT, Antoine Bourrillon, Joël Lechevallier, Gérard Lorette, Juliane Léger, Yves Perel, Michel Rybojad, Guy Sebag, Thierry Van Den Abbeele, Dominique Bremond-Gignac, Brigitte Chabrol, Alain Chantepie, Albert Faye, Christèle Gras Le Guen, Pierre-Henri Jarreau, Philippe Labrune, Marie-France Le Heuzey, Jean-Pierre Chouraqui, Georges Deschênes, Chantal Job-Deslandre, Laure BESSON, and Claire GUILABERT
Subjects: Pediatrics, Children--Diseases
Abstract: Les pédiatres et les médecins généralistes s'interrogent et sont eux-mêmes interrogés dans leur pratique quotidienne par les familles à propos d'un diagnostic, d'un traitement, ou d'une orientation spécialisée concernant leurs enfants. Cet ouvrage, s'appuyant sur l'expérience conjointe de médecins de l'enfant, de généralistes et de spécialistes, a été pensé pour répondre à ces questionnements. Réalisé par un collectif d'auteurs de toutes disciplines issues de la spécialité pédiatrique, ce livre assure pour chaque chapitre, une analyse des mécanismes physiopathologiques, une approche diagnostique en pratique clinique, une évaluation pour chaque cas des signes de sévérité et des examens complémentaires éventuels, des précisions thérapeutiques rationnelles et actualisées. Cette 6e édition, complètement renouvelée, bénéficie d'une riche iconographie en couleur. De nombreux chapitres ont entièrement été réécrits et constituent de véritables monographies autonomes au sein de ce traité : néonatologie, urgences, maladies infectieuses, dermatologie, orthopédie… Pratique et didactique, facile d'utilisation grâce à de nombreux arbres décisionnels et à un index détaillé, cet outil indispensable s'articule en trois grandes parties : – la prise en charge du nouveau-né normal et pathologique depuis la naissance jusqu'à la fin du premier mois ; – l'évaluation des acquisitions de l'enfant normal, de ses besoins (nutritionnels, psychoaffectifs, éducatifs), mais aussi des risques liés à son environnement ; – la pathologie pédiatrique traitée en vingt-quatre chapitres et classée par discipline.Nouvelle édition entièrement actualisée → Rédigé par près de 160 auteurs → La prise en charge du nouveau-né normal et pathologique depuis la naissance jusqu'à la fin du premier mois → L'évaluation des acquisitions de l'enfant normal, de ses besoins (nutritionnels, psychoaffectifs, éducatifs), mais aussi des risques liés à son environnement → La pathologie pédiatrique classée par discipline → Pour chaque chapitre : - une analyse des mécanismes physiopathologiques ; - une approche diagnostique en pratique clinique ; - une évaluation pour chaque cas des signes de sévérité et des examens complémentaires éventuels ; - des précisions thérapeutiques rationnelles et actualisées. → De nombreux arbres décisionnels et illustrations en couleur
Published: 2011

47. EPT-13RAPIRI I – PHASE I STUDY OF DAILY ORAL RAPAMYCIN AND INTRAVENOUS IRINOTECAN IN CHILDREN WITH A RECURRENT/REFRACTORY MALIGNANT SOLID TUMOR: GOOD TOLERANCE AND PROMISING RESULTS IN BRAIN TUMORS - A REPORT FROM THE SOCIÉTÉ FRANÇAISE DES CANCERS ET LEUCÉMIES DE L'ENFANT ET DE L'ADOLESCENT (SFCE)

Author: Nadège Corradini, Françoise Farace, Erwan Pencreach, Yves Perel, Natacha Entz-Werle, Mériam Koob, Nicolas André, Cécile Faure-Conter, Véronique Kemmel, Sarah Jannier, Pierre Leblond, Birgit Geoerger, Anne Isabelle Bertozzi, and Isabelle Aerts
Subjects: Oncology, Solid tumour, Cancer Research, medicine.medical_specialty, business.industry, Brain tumor, Cancer, medicine.disease, Irinotecan, Abstracts, Refractory, Internal medicine, medicine, Neurology (clinical), Solid tumor, business, medicine.drug
Published: 2016
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48. Intérêt de la TEP-FDG dans une pathologie rare : la neurolymphomatose de l’enfant. À propos d’un cas

Author: Jean-François Chateil, C. De Vaugelade, P. Fernandez, Alice Benjamin, Yves Perel, H. De Clermont, and A. My Duyen Tiphaine
Subjects: Radiological and Ultrasound Technology, Biophysics, Radiology, Nuclear Medicine and imaging
Abstract: Objectifs La neurolymphomatose est une manifestation rare du lymphome non hodgkinien, en particulier chez les enfants. Elle est souvent diagnostiquee tardivement, et le succes de la prise en charge repose sur la reconnaissance precoce de cette complication neurologique. Cas clinique : un garcon de huit ans est adresse aux urgences pour l’apparition progressive de douleurs dorsales et des membres inferieurs, puis apparait une paresie des membres superieur et inferieur gauches. Une premiere ponction lombaire est d’abord en faveur d’une meningite lymphocytaire devant la presence de lymphoblastes sans germe identifie. A ce stade, un processus infectieux, un syndrome de Guillain-Barre ou une hemopathie maligne etaient envisages. Une seconde ponction lombaire realisee une semaine plus tard met en evidence des cellules tumorales malignes dont l’immunophenotypage est en faveur d’un lymphome B de haut grade, avec un profil immunohistochimique CD20+ CD5−. Materiels et methodes Examens complementaires : le bilan d’extension est complete par un TDM thoraco-abdomino-pelvien negatif, une IRM cerebrale et medullaire montrant une infiltration des racines cervicales, sacrees et de la queue de cheval. Une TEP au 18F-FDG est demandee pour finaliser le bilan. Resultats La TEP-FDG confirme l’infiltration hypermetabolique intense des racines cervicales et lombo-sacrees, mais identifie egalement une fixation de l’emergence des nerfs crâniens IX, X et XI a la sortie du foramen jugulaire passee inapercue sur l’IRM ainsi que de multiples foyers osseux hypermetaboliques dissemines du squelette axial et peripherique. La realisation d’un premier cycle de chimiotherapie par COP permet une reponse clinique complete avec disparition des douleurs et des symptomes neurologiques. La reponse radiologique est alors nette mais partielle. Enfin, la TEP de suivi a 5 cures montre une reponse metabolique complete. Conclusions Les neurolymphomatoses sont des presentations rares de LMNH surtout chez l’enfant. La TEP FDG est utile dans leur staging en montrant des lesions nerveuses passees inapercues a l’IRM ou des localisations secondaires non identifiees. Son utilite a aussi ete montree dans l’evaluation de la reponse therapeutique du lymphome primaire epidural spinal en detectant une reponse plus precoce que l’IRM.
Published: 2016
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49. Excellent prognosis of late relapses of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia: lessons from the FRALLE 93 protocol

Author: Sylvie Chevret, Guy Leverger, Brigitte Bader-Meunier, Yves Perel, Gérard Michel, André Baruchel, Pascale Schneider, Odile Lejars, Claudine Schmitt, Thierry Leblanc, Arnaud Petit, Françoise Bernaudin, Virginie Gandemer, Christiane Vermylen, Marie-Françoise Auclerc, François Demeocq, Jean-Michel Cayuela, and UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique
Subjects: Male, Oncogene Proteins, Fusion, Salvage therapy, 0302 clinical medicine, Recurrence, Risk Factors, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Cumulative incidence, Anthracyclines, Child, Hematopoietic Stem Cell Transplantation, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, humanities, 3. Good health, Survival Rate, Leukemia, Vincristine, 030220 oncology & carcinogenesis, Child, Preschool, embryonic structures, Core Binding Factor Alpha 2 Subunit, Female, medicine.drug, Adult, medicine.medical_specialty, Childhood leukemia, Adolescent, education, Disease-Free Survival, 03 medical and health sciences, Internal medicine, mental disorders, medicine, Asparaginase, Humans, Transplantation, Homologous, Survival rate, Childhood Acute Lymphoblastic Leukemia, Retrospective Studies, business.industry, medicine.disease, Surgery, Transplantation, Cortisone, Original Articles and Brief Reports, business, 030215 immunology, Follow-Up Studies
Abstract: The prognosis of patients with relapses of ETV6/RUNX1-positive acute lymphoblastic leukemia remains to be evaluated, particularly with regards to the frequency of late relapses. We performed a long-term, follow-up retrospective study to address the outcome of patients with ETV6/RUNX1-positive leukemia relapses.Among the 713 children tested for ETV6/RUNX1 enrolled into the FRALLE 93 protocol, 43 ETV6/RUNX1-positive patients relapsed (19.4%). Most were initially stratified in the low or intermediate risk groups. The median follow-up after relapse was 54.2 months. All but three received second-line salvage therapy and 16 underwent allogeneic transplantation.ETV6/RUNX1 had a strong effect on overall survival after relapse (3-year survival= 64.7% for positive cases versus 46.5% for negative cases) (P=0.007). The 5-year cumulative incidence of relapse was 19.4% and testes were more frequently involved in ETV6/RUNX1-positive relapses (P=0.04). In 81.4% of cases the relapses were late, early combined or isolated extramedullary relapses. The 5-year survival rate of patients with ETV6-RUNX1-positive acute lymphoblastic leukemia relapses reached 80.8% when the relapse occurred after 36 months (versus 31.2% when the relapse occurred earlier). In univariate analysis, female gender was associated with a poor survival, whereas site of relapse, age at diagnosis, leukocytosis and consolidation strategy had no effect. In multivariate analysis, only the duration of first remission remained associated with outcome.We found an excellent outcome for patients with ETV6/RUNX1-positive leukemia relapses that occurred more than 36 months after diagnosis. The duration of first complete remission may, therefore, be a guide to define the treatment strategy for patients with relapsed ETV6/RUNX1- positive leukemia.
Published: 2012

50. Outcome of children and adolescents with recurrent/refractory classical Hodgkin lymphoma, a study from the Société Française de Lutte contre le Cancer des Enfants et des Adolescents (SFCE)

Author: Judith Landman-Parker, Christine Edan, Alain Robert, Martine Munzer, Catherine Paillard, Caroline Thomas, Patrick Lutz, Florence Dommange, Hélène Pacquement, Odile Oberlin, Sophie Ansoborlo, Jean Donadieu, Anne Lambilliotte, Gérard Michel, Thierry Leblanc, Stephanie Gorde-Grosjean, Jean-Louis Stephan, Claudine Schmitt, Mathias Schell, and Yves Perel
Subjects: Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Salvage therapy, Disease-Free Survival, Autologous stem-cell transplantation, Refractory, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Autologous transplantation, Humans, Child, Retrospective Studies, Salvage Therapy, Chemotherapy, business.industry, Cancer, Retrospective cohort study, Hematology, medicine.disease, Combined Modality Therapy, Hodgkin Disease, Surgery, Radiation therapy, Treatment Outcome, Child, Preschool, Disease Progression, Female, France, Neoplasm Recurrence, Local, business, Stem Cell Transplantation
Abstract: There is little data available regarding children and adolescents with Hodgkin lymphoma (HL) who relapse after combined-modality treatment, even though they have a substantial chance of cure. The purpose of this national retrospective study was to evaluate the outcome of patients with recurrent/refractory HL and determine adverse prognostic factors. From 1990 to 2006, 70 patients (median age 13·9 years) with refractory (n = 31) or first relapse (n = 39) HL were identified. Median time from end of treatment to relapse was 6 months (3-56). Relapses occurred in irradiated areas in 43/70 patients. Salvage therapy consisted of chemotherapy and 50 patients received high-dose chemotherapy with autologous stem cell transplantation. Radiotherapy was performed in 29 cases, tandem autologous transplantation in five and allograft in three. With a median follow-up of 40 months (2-140), significant prognostic factors were time to progression/relapse and response to therapy before autograft. Event-free survival and overall survival in patients with refractory disease, early relapse and late relapse were 35 ± 9%, 67 ± 11%, 76 ± 10% and 48 ± 11%, 89 ± 7% and 80 ± 10%, respectively. As progression3 months was a major adverse prognostic factor, novel therapeutic approaches are needed for this group of patients. By contrast, patients have substantial chance of long term second remission in case of relapse3 months.
Published: 2011

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