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1. Real-world experience with CLAIRYG® 50 mg/mL (intravenous immunoglobulin) in children under 12 years with primary immunodeficiency or immmune thrombocytopenia: a post-approval safety study

Author: Nizar Mahlaoui, Fanny Fouyssac, Françoise Mazingue, Coralie Mallebranche, Malika Barthez-Toullec, Lamia Denti, Kalaivani Ruhier, Marie-Hélène André-Bonnet, Aude Marie-Cardine, Nathalie Aladjidi, and Jean-Louis Stephan
Subjects: immunoglobulin, primary immunodeficiency, Clairyg®, post-approval safety study, real-world experience, pediatrics, Pediatrics, RJ1-570
Abstract: IntroductionThis study presents the results of a real-life, multicenter, prospective, post-approval safety evaluation of Clairyg® 50 mg/mL, a 5% intravenous immunoglobulin (IVIg) liquid, in 59 children (aged
Published: 2023
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2. Risk factors in pediatric Malignant Peripheral Nerve Sheath Tumors (MPNST): Results from the French Pediatric Oncology Society (SFCE) cohort

Author: Jordane Chaix, Marie Karanian, Nadège Corradini, Maria Merched, Frédérique Larousserie, Louise Galmiche, Brigitte Lacour, Aude Marie-Cardine, Anne-Sophie Defachelles, Pablo Berlanga, Angélique Rome, Estelle Thébaud, Valérie Bernier-Chastagner, Hervé J. Brisse, Frédéric Hameury, Pierre Wolkenstein, Stéphane Ducassou, Daniel Orbach, and Cécile Vérité
Subjects: Malignant Peripheral Nerve Sheath Tumor, Child, Adolescent, Survival rate, Pathology review, Risk factors, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Introduction: Malignant Peripheral Nerve Sheath Tumors (MPNST) are very rare and aggressive tumors, which can affect children, adolescents, and young adults. These tumors are frequently associated with type 1 neurofibromatosis (NF1). This study aims to determine prognostic factors in unselected pediatric MPNST to specify the risk stratification strategy. Methods: A national multicenter retrospective study encompassing all French pediatric patients (0–18 years) treated for MPNST, confirmed by a pathology review, from 1995 to 2017. Results: Overall, 66 patients (median age 13.0 years [range, 0.1–18.0]) developed a MPNST located in the limbs (36%), trunk (27%), head and neck (21%) and para-vertebral area (15%). Forty-eight percent of patients had NF1, 50% had a histologic grade III tumor and 77% a large tumor (>5 cm), including 30% very large (>10 cm). Most patients (94%) had localized tumors. After a median follow-up of 7.6 years [range, 0.4–18.7], the 5-year overall (OS) and event-free (EFS) survivals were 46.7% [95%CI, 35.8–60.8] and 40.8% [95%CI, 30.3–54.9], respectively. On multivariate analysis were found to be associated with a worse outcome (OS): metastatic disease (HR (Hazard-Ratio) 6.4 [1.8; 22.0]), grade 3 FNCLCC (HR 4.77 [1.4; 15.8]),> 10-cm size (HR 2.3 [1.1; 4.8]) and the presence of NF1 (HR 2.2 [1.1; 4.4]). Histologic subtypes of MPNST (classical, malignant Triton or epithelioid tumor) were not correlated with outcome. Conclusion: The overall outcome of MPNST was poor in patients with NF1 and in high grade, very large and metastatic tumors. The identification of these risk factors allows us to define adapted risk stratification to propose new therapeutic strategies for high-risk cases.
Published: 2023
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3. Long term follow-up of pediatric-onset Evans syndrome: broad immunopathological manifestations and high treatment burden

Author: Thomas Pincez, Helder Fernandes, Thierry Leblanc, Gérard Michel, Vincent Barlogis, Yves Bertrand, Bénédicte Neven, Wadih Abou Chahla, Marlène Pasquet, Corinne Guitton, Aude Marie-Cardine, Isabelle Pellier, Corinne Armari-Alla, Joy Benadiba, Pascale Blouin, Eric Jeziorski, Frédéric Millot, Catherine Paillard, Caroline Thomas, Nathalie Cheikh, Sophie Bayart, Fanny Fouyssac, Christophe Piguet, Marianna Deparis, Claire Briandet, Eric Dore, Capucine Picard, Frédéric Rieux-Laucat, Judith Landman-Parker, Guy Leverger, and Nathalie Aladjidi
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Pediatric-onset Evans syndrome (pES) is defined by both immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) before the age of 18 years. There have been no comprehensive long-term studies of this rare disease, which can be associated to various immunopathological manifestations (IM). We report outcomes of the 151 patients with pES and more than 5 years of follow-up from the nationwide French prospective OBS’CEREVANCE cohort. Median age at final follow-up was 18.5 years (range, 6.8–50.0 years) and the median follow-up period was 11.3 years (range, 5.1–38.0 years). At 10 years, ITP and AIHA were in sustained complete remission in 54.5% and 78.4% of patients, respectively. The frequency and number of clinical and biological IM increased with age: at the age of 20 years, 74% had at least one clinical IM (cIM). A wide range of cIM occurred, mainly lymphoproliferation, dermatological, gastrointestinal/hepatic and pneumological IM. The number of cIM was associated with a subsequent increase in the number of second-line treatments received (other than steroids and immunoglobulins; hazard ratio 1.4, 95% Confidence Interval: 1.15–1.60, P=0.0002, Cox proportional hazards method). Survival at 15 years after diagnosis was 84%. Death occurred at a median age of 18 years (range, 1.7–31.5 years), and the most frequent cause was infection. The number of second-line treatments and severe/recurrent infections were independently associated with mortality. In conclusion, long-term outcomes of pES showed remission of cytopenias but frequent IM linked to high second-line treatment burden. Mortality was associated to drugs and/or underlying immunodeficiencies, and adolescents-young adults are a high-risk subgroup.
Published: 2021
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4. Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial

Author: Chongsheng Qian, Arnaud Campidelli, Yingying Wang, Huili Cai, Véronique Venard, Hélène Jeulin, Jean Hugues Dalle, Cécile Pochon, Maud D’aveni, Benedicte Bruno, Catherine Paillard, Stéphane Vigouroux, Charlotte Jubert, Patrice Ceballos, Aude Marie-Cardine, Claire Galambrun, Clément Cholle, Isabelle Clerc Urmes, Nadine Petitpain, Marcelo De Carvalho Bittencourt, Véronique Decot, Loïc Reppel, Alexandra Salmon, Laurence Clement, and Danièle Bensoussan
Subjects: Adenovirus-specific T cells, Interferon-γ-based immunomagnetic isolation, Allogeneic stem cell transplantation, Umbilical cord blood transplantation, Third party haploidentical donor, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB). Methods Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. Results One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. Conclusions Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered).
Published: 2017
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5. Unrelated stem cell transplantation for severe acquired aplastic anemia: improved outcome in the era of high-resolution HLA matching between donor and recipient

Author: Sébastien Maury, Marie-Lorraine Balère-Appert, Zina Chir, Jean-Michel Boiron, Claire Galambrun, Karima Yakouben, Pierre Bordigoni, Aude Marie-Cardine, Noel Milpied, Judith Kanold, Natacha Maillard, Gérard Socié, and Gérard Socié on behalf of the French Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background and Objectives Severe acquired aplastic anemia (SAA) is a potentially fatal bone marrow failure syndrome occurring mainly in children and young adults. Immunosuppressive regimens and hematopoietic stem cell transplantation (HSCT) are the only two available curative treatments. Patients who lack an HLA-identical sibling donor may receive HSCT from an unrelated donor, a strategy historically associated with high mortality rates. Thus, for patients refractory to immunosuppressive regimens, the decision to transplant stem cells from unrelated donors is weighed against supportive care and often represents a dilemma for physicians. We aimed to determine whether outcome after unrelated HSCT has improved in recent years and, if so, to determine the factors responsible for the improvement.Design and Methods We analyzed the outcome of 89 patients (median age 17 years, range 0–52) with acquired SAA undergoing HSCT from an unrelated donor between 1989 and 2004. Cases were consecutively reported to the French Registry (SFGM-TC) by 25 centers.Results Patients transplanted during two successive time-periods (1989–1998 and 1999–2004) had different 5-year survival probabilities (±95% confidence interval): 29±7% and 50±7%, respectively (p
Published: 2007
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6. Mosaic PTEN alteration in the neural crest during embryogenesis results in multiple nervous system hamartomas

Author: Alice Goldenberg, Florent Marguet, Vianney Gilard, Aude-Marie Cardine, Adnan Hassani, François Doz, Sophie Radi, Stéphanie Vasseur, Jacqueline Bou, Maud Branchaud, Claude Houdayer, Stéphanie Baert-Desurmont, Annie Laquerriere, and Thierry Frebourg
Subjects: PTEN, Mosaics, Hamartomas, Central nervous system, Neural crest derivatives, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract The contribution of mosaic alterations to tumors of the nervous system and to non-malignant neurological diseases has been unmasked thanks to the development of Next Generation Sequencing (NGS) technologies. We report here the case of a young patient without any remarkable familial medical history who was first referred at 7 years of age, for an autism spectrum disorder (ASD) of Asperger type, not associated with macrocephaly. The patient subsequently presented at 10 years of age with multiple nodular lesions located within the trigeminal, facial and acoustic nerve ganglia and at the L3 level. Histological examination of this latter lesion revealed a glioneuronal hamartoma, exhibiting heterogeneous PTEN immunoreactivity, astrocyte and endothelial cell nuclei expressing PTEN, but not ganglion cells. NGS performed on the hamartoma allowed the detection of a PTEN pathogenic variant in 30% of the reads. The presence of this variant in the DNA extracted from blood and buccal swabs in 3.5 and 11% of the NGS reads, respectively, confirmed the mosaic state of the PTEN variant. The anatomical distribution of the lesions suggests that the mutational event affecting PTEN occurred in neural crest progenitors, thus explaining the absence of macrocephaly. This report shows that mosaic alteration of PTEN may result in multiple central and peripheral nervous system hamartomas and that the presence of such alteration should be considered in patients with multiple nervous system masses, even in the absence of cardinal features of PTEN hamartoma tumor syndrome, especially macrocephaly.
Published: 2019
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7. Impact of age at diagnosis, sex, and immunopathological manifestations in 886 patients with pediatric chronic immune thrombocytopenia

Author: Thomas Pincez, Helder Fernandes, Marlène Pasquet, Wadih Abou Chahla, Jérome Granel, Sébastien Héritier, Mony Fahd, Stéphane Ducassou, Caroline Thomas, Nathalie Garnier, Vincent Barlogis, Eric Jeziorski, Sophie Bayart, Pascal Chastagner, Nathalie Cheikh, Corinne Guitton, Catherine Paillard, Julien Lejeune, Frédéric Millot, Valérie Li‐Thiao Te, Coralie Mallebranche, Isabelle Pellier, Bénédicte Neven, Corinne Armari‐Alla, Liana Carausu, Christophe Piguet, Joy Benadiba, Claire Pluchart, Jean‐Louis Stephan, Marianna Deparis, Claire Briandet, Eric Doré, Aude Marie‐Cardine, Thierry Leblanc, Guy Leverger, and Nathalie Aladjidi
Subjects: Hematology
Published: 2023
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8. Nausées-vomissements induits par les traitements anticancéreux (NVITAC) en onco-hématologie pédiatrique : recommandations 2022 du Comité soins de support de la SFCE

Author: Sandrine Thouvenin-Doulet, Samia Mouffak, Amandine Bertrand, Aude Marie Cardine, Maïna Letort-Bertrand, Dominique Levy, Virginie Wiart-Monger, Cyril Lervat, and Marilyne Poirée
Subjects: Cancer Research, Oncology, Radiology, Nuclear Medicine and imaging, Hematology, General Medicine
Published: 2022
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9. Determinants of long-term outcomes of splenectomy in pediatric autoimmune cytopenias

Author: Thomas Pincez, Nathalie Aladjidi, Sébastien Héritier, Nathalie Garnier, Mony Fahd, Wadih Abou Chahla, Helder Fernandes, Claire Dichamp, Stéphane Ducassou, Marlène Pasquet, Sophie Bayart, Despina Moshous, Nathalie Cheikh, Catherine Paillard, Dominique Plantaz, Eric Jeziorski, Caroline Thomas, Corinne Guitton, Marianna Deparis, Aude Marie Cardine, Jean-Louis Stephan, Isabelle Pellier, Eric Doré, Joy Benadiba, Claire Pluchart, Claire Briandet, Vincent Barlogis, Guy Leverger, and Thierry Leblanc
Subjects: Cohort Studies, Immunology, Splenectomy, Humans, Anemia, Hemolytic, Autoimmune, Cell Biology, Hematology, Child, Thrombocytopenia, Biochemistry
Abstract: Splenectomy is effective in ∼70% to 80% of pediatric chronic immune thrombocytopenia (cITP) cases, and few data exist about it in autoimmune hemolytic anemia (AIHA) and Evans syndrome (ES). Because of the irreversibility of the procedure and the lack of predictions regarding long-term outcomes, the decision to undertake splenectomy is difficult in children. We report here factors associated with splenectomy outcomes from the OBS’CEREVANCE cohort, which prospectively includes French children with autoimmune cytopenia (AIC) since 2004. The primary outcome was failure-free survival (FFS), defined as the time from splenectomy to the initiation of a second-line treatment (other than steroids and intravenous immunoglobulins) or death. We included 161 patients (cITP, n = 120; AIHA, n = 19; ES, n = 22) with a median (minimum-maximum) follow-up of 6.8 years (1.0-33.3) after splenectomy. AIC subtype was not associated with FFS. We found that immunopathological manifestations (IMs) were strongly associated with unfavorable outcomes. Diagnosis of an IM before splenectomy was associated with a lower FFS (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.21-0.72, P = .003, adjusted for AIC subtype). Diagnosis of an IM at any timepoint during follow-up was associated with an even lower FFS (HR, 0.22; 95% CI, 0.12-0.39; P = 2.8 × 10−7, adjusted for AIC subtype) as well as with higher risk of recurrent or severe bacterial infections and thrombosis. In conclusion, our results support the search for associated IMs when considering a splenectomy to refine the risk-benefit ratio. After the procedure, monitoring IMs helps to identify patients with higher risk of unfavorable outcomes.
Published: 2022
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10. Extracranial rhabdoid tumours: Results of a SFCE series of patients treated with a dose compression strategy according to European Paediatric Soft tissue sarcoma Study Group recommendations

Author: Maxime Enault, Véronique Minard-Colin, Nadège Corradini, Guy Leverger, Estelle Thebaud, Angélique Rome, Stéphanie Proust, Aude Marie-Cardine, Anne-Sophie Defachelles, Sabine Sarnacki, Pascale Philippe-Chomette, Olivier Delattre, Julien Masliah-Planchon, Brigitte Lacour, Andrea Ferrari, Bernadette Brennan, Daniel Orbach, and Franck Bourdeaut
Subjects: Europe, Male, Cancer Research, Oncology, Child, Preschool, Infant, Newborn, Humans, Infant, Female, Sarcoma, Soft Tissue Neoplasms, Rhabdoid Tumor, Retrospective Studies
Abstract: Extracranial malignant rhabdoid tumours are tumours that mainly affect young children and have a poor prognosis. In 2014, the European Paediatric Soft-tissue sarcoma Study Group developed treatment recommendations consisting in intensive dose chemotherapy every 2 weeks using vincristine-doxorubicin-cyclophosphamide (VDCy) and ifosfamide-etoposide (IE) associated with early surgery and irradiation of tumour sites.A retrospective study was conducted on children treated in France by these new recommendations up to January 2019.Thirty-five patients were identified. The primary tumour was in miscellaneous soft parts for 18 patients, in the kidney for 11 and in the liver for six. The median age at diagnosis was 17.5 months (range 1.2-198.2). Distant locations (metastatic or synchronous tumours) were present in 37.1% at diagnosis. SMARCB1 germline pathogenic variant was detected in 17.1% of patients. Overall tolerance was good, with 87-97% of theoretical chemotherapy cumulative doses actually delivered. The median interval between two courses was 18 days. Surgical resection was performed in 83% (19 R0, 7 R1 and 3 R2) and local radiotherapy in 49% of patients. After a median follow-up of 50.4 months (range 16.5-134.1), the 2-year overall and event-free survivals were 47.6% (95% confidence interval [CI] 30.2-63.1) and 42.9% (95% [CI] 26.5-58.3), respectively. On univariate analyses, localised disease and gross total resection were significantly associated with favourable outcomes.Intensive dose chemotherapy with VDCy/IE can be administrated with no remarkable short-term toxicity, including in infants. However, the outcome remains poor for patients without gross total resection and with metastatic or multifocal disease. These patients could be stratified into a high-risk group that requires a new immediate therapeutic approach such as targeted agents combined with multimodal therapy.
Published: 2022
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11. The French FRACTURE database: A way to improve knowledge on management of children with very rare tumors

Author: Coralie Mallebranche, Yves Reguerre, Brice Fresneau, Nicolas Andre, Claire Berger, Claire Briandet, Marie‐Pierre Castex, Anne‐Sophie Defachelles, Cécile Faure‐Conter, Julien Lejeune, Sébastien Klein, Guy Leverger, Aude Marie‐Cardine, Caroline Oudot, Claire Freycon, Stéphanie Proust, Marianne Roumy, Estelle Thebaud, Cécile Verite, Brigitte Lacour, Daniel Orbach, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Unité d'Immuno-Hémato-Oncologie Pédiatrique [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Service d'hémato-immuno-oncologie pédiatrique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), 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)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'Immunologie Hématologie et Oncologie pédiatriques [CHU Angers], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Pellegrin Tripode, Equipe 7 : EPICEA - Epidémiologie des cancers de l'enfant et de l'adolescent (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), 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)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Registre National des Tumeurs Solides de l'Enfant (RNTSE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Institut Curie [Paris]
Subjects: very rare tumors, Adolescent, Databases, Factual, Incidence, [SDV]Life Sciences [q-bio], Hematology, FRACTURE database, national registry, childhood malignancies, Oncology, Neoplasms, Pediatrics, Perinatology and Child Health, Humans, Registries, France, Child
Abstract: International audience; Introduction: Very rare pediatric tumors (VRTs), defined by an annual incidence ≤2 per million inhabitants, represent a heterogeneous group of cancers. Due to their extremely low incidence, knowledge on these tumors is scant. Since 2012, the French Very Rare Tumors Committee (FRACTURE) database has recorded clinical data about VRTs in France. This study aims: (a) to describe the tumors registered in the FRACTURE database; and (b) to compare these data with those registered in the French National Registry of Childhood Cancer (RNCE).Methods: Data recorded in the FRACTURE database between January 1, 2012 and December 31, 2018 were analyzed. In addition, these data were compared with those of the RNCE database between 2012 and 2015 to evaluate the completeness of the documentation and understand any discrepancies.Results: A total of 477 patients with VRTs were registered in the FRACTURE database, representing 97 histological types. Of the 14 most common tumors registered in the RNCE (772 patients), only 19% were also registered in the FRACTURE database. Total 39% of children and adolescent VRTs registered in the RNCE and/or FRACTURE database (323 of a total of 828 patients) were not treated in or linked to a specialized pediatric oncology unit.Conclusion: VRTs represent many different heterogenous entities, which nevertheless account for 10% of all pediatric cancers diagnosed each year. Sustainability in the collection of these rare tumor cases is therefore important, and a regular systematic collaboration between the FRACTURE database and the RNCE register helps to provide a more exhaustive picture of these VRTs and allow research completeness for some peculiar groups of patients.
Published: 2022
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12. Potential Benefit of New Target Inhibitors in Neurotrophic Tropomyosin Receptor Kinase Fusion Positive Tumors: A Historical Cohort Analysis

Author: Lauriane Lemelle, Delphine Guillemot, Anne-Laure Hermann, Arnaud Gauthier, Matthieu Carton, Nadège Corradini, Angélique Rome, Pablo Berlanga, Anne Jourdain, Aude Marie Cardine, Sarah Jannier, Hélène Boutroux, Anne-Sophie Desfachelles, Isabelle Aerts, Birgit Geoerger, Marie Karanian, François Doz, Hervé J. Brisse, Gudrun Schleiermacher, olivier delattre, Gaelle Pierron, and Daniel Orbach
Subjects: History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published: 2022
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13. Unrelated Cord Blood Transplantation in Children, Adolescents, and Young Adults with Acute Leukemia or Myelodysplastic Syndrome: A Retrospective Comparative Study from the French Society for Bone Marrow Transplantation and Cellular Therapy Between Real-World Data and Previously Reported Results of a Randomized Clinical Trial

Author: Anne-Charlotte Teyssier, Gérard Michel, Charlotte Jubert, Fanny Rialland, Sandrine Visentin, Marie Ouachée, Karin Bilger, Virginie Gandemer, Yves Beguin, Aude Marie-Cardine, Yves Chalandon, Marc Ansari, Karine Baumstarck, Anderson Loundou, Jean-Hugues Dalle, Anne Sirvent, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Bordeaux [Bordeaux], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM], Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), Institut de Cancérologie de Strasbourg Europe (ICANS), CHU Pontchaillou [Rennes], 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 ), Centre Hospitalier Universitaire de Liège (CHU-Liège), CHU Rouen, Normandie Université (NU), Hôpitaux Universitaires de Genève (HUG), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Faculté de médecine [Genève], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital Robert Debré Paris, Hôpital Robert Debré, and Supported by the French Society for Bone Marrow Transplantation and Cellular Therapy.
Subjects: Acute leukemia, Transplantation, Transplantation Conditioning, Adolescent, [SDV]Life Sciences [q-bio], Stem cell transplantation, Cord blood unit, Cell Biology, Hematology, Young Adult, Leukemia, Myeloid, Acute, Conditioning regimen, Myelodysplastic Syndromes, Acute Disease, Humans, Molecular Medicine, Immunology and Allergy, Cord Blood Stem Cell Transplantation, Child, Children, Bone Marrow Transplantation, Young adults
Abstract: International audience; We previously reported results of a French randomized clinical trial (RCT) comparing the risk of transplantation failure (including transplant-related mortality [TRM], engraftment failure, and autologous recovery) in single and double unrelated cord blood (UCB) transplantation in children and young adults with hematologic malignancies. We concluded that single-UCB transplantation with an adequate cell dose is the standard of care, leading to a 70% two-year overall survival (OS). It remains unclear, however, whether RCT participants have better outcomes than comparable patients not treated in the setting of a clinical trial. We compared the characteristics and outcomes of RCT participants (n = 137) to a Francophone population-based registry of patients (real-world [RW] group) fulfilling the eligibility criteria used in our RCT and transplanted with 1 or 2 UCB units after a myeloablative conditioning (MAC) regimen between March 2015 (end of inclusion in the RCT) and February 2019 (n = 141). The primary endpoint was the 2-year cumulative incidence (CI) of transplantation strategy failure as defined in our RCT. The 2 groups were comparable in terms of age, disease distribution, hematologic status at transplantation, follow-up, and HLA compatibility. Patients in the RW group were more likely to be transplanted with a single-unit UCB (87.9% versus 49.6%, P< .001) and to receive a radiation-free regimen (39.0% versus 60.6%, P< .001). The 2-year CI of transplantation strategy failure, TRM, and the 2-year probability of OS were similar between the 2 groups, although the relapse risk was higher in the RW group (31.2% ± 7.7% versus 20.4% ± 6.8%, P= .01), resulting in a significantly lower disease-free survival (DFS) (59.2% ± 8.4% versus 69.3% ± 8.0%, P= .047). This difference remained statistically significant only in the group of patients with acute lymphoid leukemia (ALL) who did not receive the conditioning regimen recommended by the RCT (fludarabine 75 mg/m2, total body irradiation 12 Gy, cyclophosphamide 120 mg/kg). The results of our RCT appear to be reproducible in real-world conditions, provided that the same cord blood selection criteria and conditioning regimen are used.
Published: 2022
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14. Recurrent bacterial infections, but not fungal infections, characterise patients with ELANE-related neutropenia: a French Severe Chronic Neutropenia Registry study

Author: Aude Marie-Cardine, Flore Sicre de Fontbrune, Stéphane Blanche, Despina Moushous, Thierry Leblanc, Christine Bellanné-Chantelot, Fanny Rialland, Nathalie Aladjidi, Claire Freycon, Virginie Gandemer, Catherine Paillard, Blandine Beaupain, Marlène Pasquet, French Severe Chronic Neutropenia Registry, Marie-Gabrielle Vigue, Wadih Abou-Chahla, Christophe Piguet, Frédéric Millot, Martin Biosse-Duplan, Pacifique Lévy, Cecile Renard, Jean Donadieu, Gioacchino Andrea Rotulo, Geneviève Plat, Vincent Barlogis, Claire Fieschi, Therapeia Rehabilitation Center, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Registre des neutropénies chroniques [CHU Trousseau], 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)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital des Enfants, CHU Toulouse [Toulouse], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Robert Debré, Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Universitaire [Grenoble] (CHU), 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 ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Rouen, Normandie Université (NU), CHU Strasbourg, CHU Bordeaux [Bordeaux], Hôpital Bretonneau, Amgen SAS, Chugai SA, Inserm, Association Sportive de Saint-Quentin–Fallavier, Société d’Hémato-Immunologie Pédiatrique, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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: Adult, medicine.medical_specialty, Neutropenia, Adolescent, severe congenital neutropenia, [SDV]Life Sciences [q-bio], Disease, medicine.disease_cause, 03 medical and health sciences, Cyclic neutropenia, Young Adult, 0302 clinical medicine, Recurrence, Internal medicine, medicine, Humans, Registries, Child, 030304 developmental biology, 0303 health sciences, ELANE-related neutropenia, business.industry, Elastase, Hematopoietic Stem Cell Transplantation, Genetic Variation, Infant, Hematology, Bacterial Infections, medicine.disease, opportunistic infections, 3. Good health, Transplantation, Pneumonia, Mycoses, Staphylococcus aureus, 030220 oncology & carcinogenesis, Cellulitis, France, business, Leukocyte Elastase, Follow-Up Studies
Abstract: International audience; Among 143 patients with elastase, neutrophil-expressed (ELANE)-related neutropenia enrolled in the French Severe Chronic Neutropenia Registry, 94 were classified as having severe chronic neutropenia (SCN) and 49 with cyclic neutropenia (CyN). Their infectious episodes were classified as severe, mild or oral, and analysed according to their natural occurrence without granulocyte-colony stimulating factor (G-CSF), on G-CSF, after myelodysplasia/acute leukaemia or after haematopoietic stem-cell transplantation. During the disease’s natural history period (without G-CSF; 1913 person-years), 302, 957 and 754 severe, mild and oral infectious events, respectively, occurred. Among severe infections, cellulitis (48%) and pneumonia (38%) were the most common. Only 38% of episodes were microbiologically documented. The most frequent pathogens were Staphylococcus aureus (37·4%), Escherichia coli (20%) and Pseudomonas aeruginosa (16%), while fungal infections accounted for 1%. Profound neutropenia (3000/mm(3) ) and neutropenia subtype were associated with high risk of infection. Only the p.Gly214Arg variant (5% of the patients) was associated with infections but not the overall genotype. The first year of life was associated with the highest infection risk throughout life. G-CSF therapy achieved lower ratios of serious or oral infectious event numbers per period but was less protective for patients requiring >10 µg/kg/day. Infections had permanent consequences in 33% of patients, most frequently edentulism.
Published: 2021
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15. Pediatric-Onset Evans Syndrome Is Associated with Broad Immunopathological Manifestations, High Treatment Burden and Mortality in Long-Term Follow-up

Author: Eric Jeziorski, Frédéric Millot, Wadih Abou Chahla, Joy Benadiba, Corinne Armari-Alla, Nathalie Aladjidi, Thierry Leblanc, Helder Fernandes, Claire Briandet, Sophie Bayard, Fanny Fouyssac, Thomas Pincez, Christophe Piguet, Yves Bertrand, Marlène Pasquet, Caroline Thomas, Judith Landman-Parker, Isabelle Pellier, Bénédicte Neven, Pascale Blouin, Corinne Guitton, Vincent Barlogis, E. Dore, Catherine Paillard, Aude Marie-Cardine, Gérard Michel, Nathalie Cheikh, Mariana Deparis, and Guy Leverger
Subjects: Pediatrics, medicine.medical_specialty, Evans syndrome, Long term follow up, business.industry, Pediatric onset, Immunology, Treatment burden, Cell Biology, Hematology, medicine.disease, Biochemistry, medicine, business
Abstract: Introduction Pediatric-onset Evans syndrome (pES) is defined by the association between immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) before the age of 18 years and may be associated to various immunopathological manifestations (IMs). No comprehensive study of this rare disease exists, and its long-term outcomes are poorly described. Methods Patients from the nationwide French prospective OBS'CEREVANCE cohort with pES and more than 5 years of follow-up were included (excepted pES secondary to bone marrow transplantation or primary immunodeficiencies known at the inclusion). All patients, including those with less than 5 years of follow-up, were included in survival analyses. Multivariate Cox proportional hazards model was used to analyze factors associated with time-dependent variables. Results Of the 216 patients with pES in the cohort, 151 (88 males and 63 females) were included with a median (min-max) follow-up time after first cytopenia diagnosis of 11.3 (5.1-38) years. Median age at final follow-up was 18.5 (6.8-50.0) years. The proportion of patients achieving a sustained complete response (i.e. persisting until final follow-up) increased after cytopenia onset (Fig. 1A). ITP and AIHA were in complete remission in 40.5% and 54.5%, 74.1% and 62.3%, and 78.4% and 86% of patients at 5, 10, and 15 years, respectively. Clinical IMs (cIMs) developed in 100/151 patients (66%), before the first diagnosis of cytopenia in 21/100 cases. The number of cIMs increased over time (Fig. 1B). The proportions of patients with one and more than one cIM were 50% and 14%, 57% and 19%, and 81% and 44% at 5, 10, and 15 years after the first cytopenia diagnosis, respectively. A broad spectrum of cIMs were present, lymphoproliferation (n = 71), dermatological (n = 26), gastrointestinal/hepatic (n = 23), and pneumological manifestations (n = 16) being the most common. Three patients had a hematological malignancy. Biological IMs (bIMs) were diagnosed in 101/151 patients (67%) and also increased over time, with hypogammaglobulinemia (n = 54) being the most common. Autoimmune neutropenia developed in 43 patients (28.5%) and was independently associated with the number of cIMs (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.5-3.8; p = 0.0002). Severe or recurrent infections were present in 53 patients (35%). The number of second-line treatments received (i.e. other than steroids and immunoglobulins) increased over time without reaching a plateau (Fig. 1C). Half of the patients had received at least one, two, and three different treatments at 2.7, 10.5, and 14.7 years after the first cytopenia diagnosis, respectively. The number of cIMs was independently associated with the number of second-line treatments received (HR, 1.3; 95% CI, 1.08-1.6; p = 0.006). Systemic lupus erythematosus (SLE) was diagnosed in 11/151 patients (7.3%, 1/88 males and 10/63 females) and autoimmune lymphoproliferative syndrome (ALPS) in six (4.0%). Sixteen of the 151 patients followed for more than 5 years (10.6%) died, and seven died before the fifth year of follow-up (23 deaths in total). Survival at 5, 10, and 15 years after the first cytopenia was 97%, 92%, and 84%, respectively (Fig. 1D). Deaths occurred regularly throughout the follow-up period, at a median age of 18.0 (1.7-31.5) years. The most frequent cause of death was infections (n = 12, 52%). Four patients (18%) died of hemorrhage, all were less than 13 years old. The numbers of second-line treatments (HR, 1.3; 95% CI, 1.1-1.6; p = 0.004) and severe or recurrent infections (HR, 3.4; 95% CI, 1.2-9.7; p = 0.02) were independently associated with mortality after 5 years of follow-up. Overall, 20-year-old compared to 10-year-old patients more frequently showed a sustained complete response for AIHA (72% vs. 30%) and ITP (50% vs. 26%), but more frequently had cIMs (74% vs. 37%), bIMs (75% vs. 39%), and ongoing second-line treatments (88% vs. 47%; p < 0.001 for all comparisons). Conclusions Long-term outcomes of pES were associated to IMs and second-line treatment burden, not active cytopenia. The significant mortality rates, mostly among adolescents and young adults, were linked to drug-induced and/or constitutive immunodeficiencies. Few cases were associated with SLE or ALPS, which is consistent with a heterogeneous genetic background. These results highlight the importance of multidisciplinary care during the transition from childhood to adulthood. Figure 1 Disclosures No relevant conflicts of interest to declare.
Published: 2020
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16. 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

17. X-linked Agammaglobulinemia of incidental finding

Author: Pauline Treguier, Aude Marie-Cardine, Nizar Mahlaoui, Vincent Langlois, Pascale Schneider, and Ioannis Theodorou
Subjects: biology, medicine.diagnostic_test, business.industry, X-linked agammaglobulinemia, medicine.disease, Asymptomatic, medicine.anatomical_structure, Immunology, biology.protein, medicine, Primary immunodeficiency, Bruton's tyrosine kinase, Missense mutation, Antibody, medicine.symptom, business, B cell, Genetic testing
Abstract: X-linked agammagobulinemia (XLA) is a primary immunodeficiency disorder caused by a mutation in the Bruton Tyrosine Kinase (BTK). Usually, patients present severe infections before the age of 2, and require immunoglobulin replacement therapy during all their life. We present the case of a 16-years-old male for whom the diagnosis was incidental. He did not present any infection since childhood. At the age of 4, immunoglobulin assay was performed because he had recurrent fever episodes. A panhypogammaglobulinemia was identified, but the boy became asymptomatic and explorations were stopped. At the age of 16, the patient’s parents suggested a control of the deficit which was confirmed. Genetic testing revealed a novel mutation on BTK, located in the pleckstrin homology domain [c.70A>C, p.(Asn24His)]. Initially, he received immunoglobulin substitution at the rate of one subcutaneous injection per week but stopped it after 2 years of treatment by immunoglobulin and continued to present no symptom. We thereafter report the case of an asymptomatic patient presenting a novel missense mutation of BTK. The patient doesn’t have circulant B cell. He doesn’t receive immunoglobulin substitution and doesn’t present infectious diseases.
Published: 2020
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18. Uptake of Pineal Gland Visible on 18F-DOPA PET/CT With Last Generation of SiPM PET/CT

Author: Pierre Vera, Olivier Humbert, Sébastien Hapdey, Aude Marie-Cardine, Pierre Decazes, Service de médecine nucléaire [Rouen], CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU), Laboratoire d'Electronique, d'Informatique et d'Image [EA 7508] (Le2i), Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Rouen], Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), and ANR-19-P3IA-0002,3IA@cote d'azur,3IA Côte d'Azur(2019)
Subjects: Movement disorders, Adolescent, [SDV]Life Sciences [q-bio], Partial volume, Astrocytoma, Pineal Gland, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Pineal gland, 0302 clinical medicine, Silicon photomultiplier, Positron Emission Tomography Computed Tomography, Medicine, Humans, Radiology, Nuclear Medicine and imaging, ComputingMilieux_MISCELLANEOUS, PET-CT, Pilocytic astrocytoma, business.industry, Biological Transport, General Medicine, medicine.disease, Dihydroxyphenylalanine, 18f dopa, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, business, Nuclear medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, DOPA decarboxylase activity
Abstract: A 17-year-old girl underwent an F-DOPA brain PET/CT on a new high-resolution digital SiPM PET/CT (Vision600 Siemens) to explore a suspicion of recurrence of a pilocytic astrocytoma. This study showed a local recurrence, but a second intense focal uptake was visible above, more intense than striata. On fused MRI, this was the pineal gland considered as physiological. This physiological uptake, due to a pineal DOPA decarboxylase activity, has also been observed with this PET system in other patients with F-DOPA to explore movement disorders. New high-resolution PET can show uptake of small structures by being less dependent to partial volume effect.
Published: 2020
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19. Tag-n-trak study: Preliminary analysis of an unselected biobank tumors with NTRK fusion transcript, the French SFCE society contribution

Author: Anne Jourdain, Delphine Guillemot, Arnaud Gauthier, Marie Karanian, Gaëlle Pierron, Nadège Corradini, Angélique Rome, Sarah Jannier, Anne-Sophie Defachelles, Aude Marie Cardine, Marie Pierre Castex, Matthieu Carton, Anne-Laure Hermann, Daniel Orbach, Lauriane Lemelle, Isabelle Aerts, Hélène Boutroux, Hervé Brisse, Olivier Delattre, and Francois P. Doz
Subjects: Cancer Research, TRAK, biology, business.industry, Biobank, Receptor tyrosine kinase, Preliminary analysis, Oncology, Fusion transcript, biology.protein, Cancer research, Medicine, Infantile Fibrosarcoma, business, Neurotrophin
Abstract: 10540 Background: NTRK ( Neurotrophic receptor tyrosine kinase) fusion transcript was initially described in infantile fibrosarcoma (IFS) and is now known to be present in many other rare types of tumor with a lower incidence. The main objective of the study is to describe the presentation and outcome of unselected tumors with NTRK fusion transcript (NTRK-FTT) to better consider the role of TRK inhibitors (TRKi) in such entities. Methods: We selected patients (pts) from the Institut Curie biobank (adults and children) with NTRK-FTT and which were assessed by RT-qPCR then RNA sequencing in a prospective or retrospective process, between 2001 and 2019. Results: We identified 62 NTRK-FTT among 2119 screened tumors (2.2 cases/year with RT-qPCR and 6.9 cases/year with RNA seq after 2016), NTRK3 (44 cases) (including 41 NTRK3-ETV6), NTRK2 (9) or NTRK1 (9). Most of pts had under 2 years (y) (74%) and only 7 pts were adults. We report preliminary analysis of clinical observation for the first 27 pts. Median age was 0.4 y [0-60.2]. Pathologic diagnosis was IFS (12 cases), various CNS tumors (4), atypical teratoid rhabdoid tumor (1), myofibroblastic inflammatory tumor (2), benign tumors (3), cellular congenital mesoblastic nephroma (2), lipofibromatosis like neural tumor, myxoïd liposarcoma, unclassifiable sarcoma (1 each). Two pts had metastatic tumors. Among all, 22 had surgery (1 mutilating), 15 chemotherapy, 4 radiotherapy, and 5 received TRKi, as second line treatment (2 pts) or ≥ third line (3 pts). After a median follow-up of 50 months [range, 1-155], 20/27 pts remained in complete remission, 3 had stable residue, and 4 had progressive disease (associated to 1 disease-related and 1 toxic deaths). Five-year OS is 88% [95%CI, 73.5-100] and 5y-EFS 59.5% [95%CI, 41.7-84.9]. Conclusions: This descriptive study showed that NTRK-FTT is rare (2.9%), encompasses a variety of different histotypes (n = 14). Systematic RNA sequencing allowed to depict 3.5 times more NTRK-FTT than targeted RT-qPCR. Overall outcome is favorable despite frequent tumor events. According to tumor type and the uncertainties regarding the long-term side effects of TRKi, the benefit/risk ratio must be carefully evaluated before using these drugs in first line.
Published: 2020
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20. 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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21. MOESM1 of Mosaic PTEN alteration in the neural crest during embryogenesis results in multiple nervous system hamartomas

Author: Goldenberg, Alice, Marguet, Florent, Gilard, Vianney, Aude-Marie Cardine, Hassani, Adnan, Doz, François, Radi, Sophie, Vasseur, Stéphanie, Bou, Jacqueline, Branchaud, Maud, Houdayer, Claude, Baert-Desurmont, Stéphanie, Laquerriere, Annie, and Frebourg, Thierry
Abstract: Additional file 1. Molecular assays.
Published: 2019
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22. Possible role of CYP2B6 genetic polymorphisms in ifosfamide-induced encephalopathy: report of three cases

Author: Jeremy Bellien, Céline Verstuyft, Bruno Filhon, Thomas Duflot, Fabien Lamoureux, Robinson Joannides, Tony Pereira, Nathalie Massy-Guillemant, Aude Marie-Cardine, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Hôpital Charles Nicolle [Rouen], CHU Rouen, 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), Barrière et passage des médicaments, Université Paris-Sud - Paris 11 (UP11)-IFR141, Endothélium, valvulopathies et insuffisance cardiaque (EnVI), and TAN, Yossan-Var
Subjects: CYP2B6, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Encephalopathy, Pharmacology, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, parasitic diseases, Genotype, medicine, Pharmacology (medical), Allele, Genotyping, ComputingMilieux_MISCELLANEOUS, Ifosfamide, CYP3A4, business.industry, bacterial infections and mycoses, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Pharmacogenetics, medicine.drug
Abstract: Ifosfamide (IFA) is a potent alkylating antitumoral agent, but its use is limited by neurological side effects. IFA is a racemic mixture of two enantiomeric forms, R-IFA and S-IFA with a stereoselective metabolism by CYP3A4 and CYP2B6, leading either to bioactive or to toxic pathways. In three consecutive cases of pediatric patients who exhibited IFA-induced encephalopathy (IIE), genotyping of clinically relevant single-nucleotide polymorphisms associated with decreased CYP3A4 and CYP2B6 activities was performed. Genetic investigations revealed the presence of CYP2B6 rs4803419 (C>T) in one patient while the two others carried the CYP2B6*6 allelic variant. All patients carried CYP3A4 wild-type genotype (CYP3A4*1/*1). Because CYP2B6-deficient alleles may be responsible for an increased conversion of S-IFA into neurotoxic metabolites, screening for CYP2B6 polymorphisms may help to avoid IIE and improve clinical outcomes.
Published: 2018
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23. Rhabdomyosarcomas in children with neurofibromatosis type I: A national historical cohort

Author: Wilfrid Richer, Daniel Orbach, Nadège Corradini, Laurence Brugières, Christophe Bergeron, Veronique Minard-Colin, Dominique Ranchère-Vince, Pauline Girard, Brigitte Lacour, Aude Marie-Cardine, Martine Munzer, Sabine Sarnacki, Franck Bourdeaut, Jean-Louis Stephan, and Anne Crucis
Subjects: Neurofibromatosis type I, Oncology, 0303 health sciences, medicine.medical_specialty, Pathology, business.industry, Cancer, Context (language use), Hematology, medicine.disease, 3. Good health, Loss of heterozygosity, 03 medical and health sciences, 0302 clinical medicine, Costello syndrome, 030220 oncology & carcinogenesis, Internal medicine, Pediatrics, Perinatology and Child Health, Medicine, Noonan syndrome, Neurofibromatosis, business, Rhabdomyosarcoma, 030304 developmental biology
Abstract: Background Rhabdomyosarcoma (RMS) occasionally occurs in a context of a predisposition syndrome. The most common predisposition syndromes include germline TP53 mutations and constitutive alterations in RAS pathway activation, such as Costello syndrome, Noonan syndrome and neurofibromatosis type 1. We report a national retrospective series of 16 RMS occurring in neurofibromatosis type 1 (NF1) patients during childhood, within a 20-year period. Results The mean age at diagnosis of the cancer was 2.5 years. All were embryonal subtype. Most tumours developed in the pelvis. One was metastatic. Chemotherapy and radiotherapy were normally scheduled without any specific toxicity. The 5-year event-free survival and overall survival were 67% and 87%, respectively. Long-term sequel related to chemotherapy consisted in two chronic tubulopathies, hence not obviously different from non-NF1 patients. No second cancer was reported so far with a median follow-up of 9.7 years. The genomic analysis performed on six samples revealed the abnormalities commonly observed in sporadic RMS: gain of chromosome 2 (5/6), 8 (6/6) and chromosome 11p loss of heterozygosity (5/6). Interestingly, we identified small deletions in tumour suppressor genes that may synergize with NF1 inactivation. Conclusions Patients with neurofibromatosis are prone to develop embryonal-type RMS that require the same treatment as sporadic cases. Pediatr Blood Cancer 2015;62:1733–1738. © 2015 Wiley Periodicals, Inc.
Published: 2015
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24. Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial

Author: Yingying Wang, Chongsheng Qian, Bénédicte Bruno, Isabelle Clerc Urmes, Huili Cai, Patrice Ceballos, Cécile Pochon, Jean Hugues Dalle, Arnaud Campidelli, Marcelo De Carvalho Bittencourt, Nadine Petitpain, Danièle Bensoussan, Maud D'Aveni, Catherine Paillard, Hélène Jeulin, Loïc Reppel, Charlotte Jubert, Clément Cholle, Aude Marie-Cardine, Véronique Decot, Stephane Vigouroux, Claire Galambrun, Véronique Venard, Alexandra Salmon, Laurence Clement, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Unité de Thérapie Cellulaire et Tissulaire [CHU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Immunologie [CHRU Nancy], Service de Virologie [CHRU Nancy], Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Hôpital Jeanne de Flandre [Lille], Hôpital de Hautepierre [Strasbourg], Dpt hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Département d’Hématologie Clinique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Charles Nicolle [Rouen], Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Faculté de Pharmacie [Nancy], and Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine)
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, [SDV]Life Sciences [q-bio], viruses, medicine.medical_treatment, Graft vs Host Disease, T-Cell Antigen Receptor Specificity, Hematopoietic stem cell transplantation, Immunotherapy, Adoptive, Adenovirus Infections, Human, 0302 clinical medicine, T-Lymphocyte Subsets, Child, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, lcsh:Diseases of the blood and blood-forming organs, Hematology, Viral Load, Allografts, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Tissue Donors, 3. Good health, Treatment Outcome, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Interferon-γ-based immunomagnetic isolation, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cord Blood Stem Cell Transplantation, Viral load, Immunosuppressive Agents, Adult, Third party haploidentical donor, medicine.medical_specialty, Adolescent, T cell, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, lcsh:RC254-282, Interferon-gamma, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Leukapheresis, Viremia, Adenovirus infection, Molecular Biology, Umbilical cord blood transplantation, Immunomagnetic Separation, lcsh:RC633-647.5, business.industry, Umbilical Cord Blood Transplantation, Research, Adenoviruses, Human, medicine.disease, Allogeneic stem cell transplantation, Transplantation, 030104 developmental biology, Graft-versus-host disease, Transplantation, Haploidentical, Immunology, Virus Activation, Adenovirus-specific T cells, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB). Methods Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. Results One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. Conclusions Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered). Electronic supplementary material The online version of this article (doi:10.1186/s13045-017-0469-0) contains supplementary material, which is available to authorized users.
Published: 2017
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25. Alemtuzumab as First Line Treatment in Children with Familial Lymphohistiocytosis

Author: Eric Jeziorski, Bénédicte Neven, Pierre-Simon Rohrlich, Isabelle Pellier, Vincent Barlogis, Caroline Elie, Stéphanie Chhun, Yves Bertrand, Geneviève de Saint Basile, Laurent Dupic, Caroline Thomas, Mathieu Fusaro, Wadih Abou Chahla, Bénédicte Bruno, Guillaume Morelle, Alain Fischer, Martin Castelle, Jean Louis Stephan, Despina Moshous, Catherine Paillard, Capucine Picard, Aude Marie-Cardine, Stéphane Blanche, and Coralie Briand
Subjects: medicine.medical_specialty, Hemophagocytic lymphohistiocytosis, education.field_of_study, business.industry, medicine.medical_treatment, Immunology, Population, Cell Biology, Hematology, Hematopoietic stem cell transplantation, medicine.disease, Biochemistry, Tolerability, Intensive care, Internal medicine, Clinical endpoint, medicine, Alemtuzumab, education, Prospective cohort study, business, medicine.drug
Abstract: Background Hemophagocytic lymphohistiocytosis (HLH) is an inflammatory condition caused by uncontrolled proliferation of activated lymphocytes and macrophages secreting an excess of inflammatory cytokines. When untreated, primary HLH is invariably fatal. Treatment requires the achievement of remission of HLH prior to allogeneic hematopoietic stem cell transplantation. Despite significant treatment progress, pre-HSCT mortality remains a challenge. In the Etoposide-based HLH-94 and HLH-2004 studies pre-HSCT mortality was 27% and 19%, respectively. A better understanding of the pathophysiology of primary HLH has opened new avenues for targeted immunotherapy. Based on our previous observation concerning the use of Antithymoglobulin in HLH, we propose a new therapeutic strategy with Alemtuzumab in association with steroids and cyclosporine A (CSA) as first line treatment in primary HLH. In contrast to ATG, Alemtuzumab does not activate T lymphocytes while killing them. Therefore, we expect a better tolerance and efficacy of Alemtuzumab. This may have a positive impact not only on survival until HSCT, but also on overall survival and quality of life, especially with regard to long-term neurological sequelae. Methods 24 consecutive treatment naïve patients with genetically confirmed primary HLH had received first line Alemtuzumab in association to steroids and CSA from 01/2009 to 06/2015 in the Unit for Pediatric Immunology in Necker Hospital Paris, as well as two additional patients in 10/2016 and 10/2018 respectively, who could not be included in the prospective trial. From 06/2015 to 06/2019, 29 patients have been enrolled in a multicenter, open, phase I/II, non-comparative, non randomized study (NCT02472054). Patients with lymphohistiocytic activation syndrome who had not received any specific treatment prior to enrollment except steroids and CSA were included. Treatment consisted in intravenous administration of Alemtuzumab in association to Methylprednisolone and CSA. The primary outcome measures is the number of surviving patients until HSCT, secondary outcome measures the number of complete remissions following treatment at Day (D)14, D21, D28. To assess the efficacy of the Alemtuzumab, the time of delay between the first administration of Alemtuzumab and complete remission will be determined. Alemtuzumab Pharmacokinetics will be done. All adverse events are reported. Results Retrospective analysis of 26 patients (pilot study): The median age of patients was 1.9 months (birth - 7 years), 6 patients were neonates. When Alemtuzumab was started, out of 26 patients 12 (46.1%) required intensive care, 8 (30.7%) mechanical ventilation, 13 (50%) had neurological involvement, 9 (34.6%) hepatocellular insufficiency. One 2-month-old Munc13-4 patient died at H+48 after two administrations of Alemtuzumab (total dose 1.5mg/kg) for hepatic failure and acute renal failure. A second patient with Perforin deficiency did not respond neither to three courses of Alemtuzumab (cumulative dose 6.5mg/kg) nor repeated Etoposid, 40mg/kg ATG, or Ruxulotinib. He died at D+65. The 24 remaining patients survived until HSCT (survival 92.3%). As shown in the figure, two patients required additional treatment. Overall 22 patients achieved CR, 2 PR at the time of HSCT. The prospective study enrolled 29 patients from 06/2015 to 06/2019. Median age at onset of HLH was 0.5 years (range 0.02 to 17.2 years), one patient withdrawed consent. 12 patients received one course, 13 two, 2 three and one patient 4 courses of Alemtuzumab. 24 patients with a genetic confirmed HLH predisposition reached the primary endpoint with 22 surviving until HSCT (91,6%). One patient is still awaiting HSCT. The three remaining patients are one CA-EBV patient and a newborn with secondary HLH due to fulminant HSV hepatitis, who both died, as well as a patient with predominant neurological HLH without genetic diagnosis who is in sustained remission without any specific treatment. Detailed results from the completed study will be presented. Conclusions This is the first report on Alemtuzumab as first line approach in the treatment of primary HLH. Our results in more than 50 pediatric patients treated in a pilot study and prospective trial indicate that Alemtuzumab allows controlling HLH activity with a favorable safety and tolerability profile in a very fragile population. 92.3% and 91.6% of patients respectively survived to HSCT. Figure Disclosures No relevant conflicts of interest to declare. Off Label Disclosure: Alemtuzumab (Campath) has been used in a prospective trial to evaluate its efficacy as first line treatment in Familial Lymphohistiocytosis.
Published: 2019
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26. Cryopréservation du tissu testiculaire chez l’enfant

Author: Agnès Liard-Zmuda, Aude Marie-Cardine, Brahim Arkoun, A. Bironneau, Albanne Travers, Bertrand Macé, J.-P. Milazzo, Jean-Pierre Vannier, Nathalie Rives, Louis Sibert, and Pascale Schneider
Subjects: Infertility, endocrine system, urogenital system, business.industry, General Medicine, medicine.disease, Cryopreservation, In vitro maturation, Transplantation, Andrology, In vivo, Toxicity, medicine, Ovarian tissue cryopreservation, business, Spermatogenesis
Abstract: The toxicity of cancer therapies can affect all organs and tissues. Some treatments damage spermatogonial stem cells (SSCs), with a risk of infertility. Storage and reimplantation of frozen testicular tissue is a recent approach tofertilitypreservationfor young boys. However, thawed frozen prepubertal testicular tissue must undergo a maturation process to restore sperm production. This process, currently being studied in animal models, can be achieved by in vivo transplantation of SSCs into seminiferous tubules or by testicular grafting, possibly following in vitro maturation.
Published: 2013
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27. Benefits of rituximab as a second-line treatment for autoimmune haemolytic anaemia in children: a prospective French cohort study

Author: Patrick Lutz, Guy Leverger, Isabelle Pellier, Eric Jeziorski, Aude Marie-Cardine, Marlène Pasquet, Corinne Armari-Alla, Nathalie Aladjidi, Brigitte Nelken, Christophe Piguet, Stéphane Ducassou, Hervé Chambost, Fanny Fouissac, Y Perel, Sophie Bayart, Alain Fisher, Helder Fernandes, Yves Bertrand, Marc Michel, Odile Lejars, Thierry Leblanc, Corinne Guitton, Philippe Vic, Fabrice Monpoux, CHU de Bordeaux Pellegrin [Bordeaux], 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), CHU Bordeaux [Bordeaux], Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital de la Tronche, Service pédiatrique d'hématologie-oncologie, Hôpital Jeanne de Flandre [Lille], Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Service d'hématologie, immunologie biologiques et cytogénétique, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de pédiatrie, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Hématogoie pédiatrique, hôpital Sud, Hôpital Charles Nicolle [Rouen], Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), 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), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and CHU Rouen
Subjects: Male, medicine.medical_specialty, Evans syndrome, Adolescent, [SDV]Life Sciences [q-bio], Steroid withdrawal, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Humans, Blood Transfusion, Prospective Studies, Child, Complete response, ComputingMilieux_MISCELLANEOUS, Second line treatment, business.industry, Drug Substitution, Hematology, medicine.disease, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Child, Preschool, Immunology, National study, Hematinics, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, Female, Steroids, Anemia, Hemolytic, Autoimmune, France, business, 030215 immunology, Cohort study, medicine.drug
Abstract: Summary Childhood autoimmune haemolytic anaemia (AIHA) requires second-line immunosuppressive therapy in 30–50% of cases. It appears that rituximab is indicated in such circumstances. This prospective national study reports the practice, efficacy and tolerance of rituximab in children with isolated AIHA and AIHA in the setting of Evans syndrome (ES). Sixty-one children were given rituximab between 2000 and 2014. The median interval from diagnosis to rituximab was 9·9 [interquartile range (IQR) 1·6–28·5] months. Forty-six patients responded (75%) and the 6-year relapse-free survival (RFS) was 48%. Twenty patients relapsed at a median interval of 10·8 (IQR 3·9–18·7) months, rituximab allowed steroid withdrawal in 44/61 (72%) of children. In isolated AIHA, complete response and 6-year RFS were significantly higher than in ES (P
Published: 2016
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28. Possible Pathogenic Role of the Transmembrane Isoform of CD160 NK Lymphocyte Receptor in Paroxysmal Nocturnal Hemoglobinuria

Author: Martine Bagot, Armand Bensussan, Jérôme Giustiniani, Aude Marie-Cardine, S. Sabour-Alaoui, A. Razafindratsita, Gérard Socié, C. Bos, J. Bernard, Anna D. Petropoulou, R.P. de Latour, P. Le Bouteiller, and Daniel Olive
Subjects: Adult, Male, Gene isoform, Lymphocyte, Hemoglobinuria, Paroxysmal, Gene Expression, Biology, GPI-Linked Proteins, Biochemistry, Cell Line, Interferon-gamma, Antigens, CD, hemic and lymphatic diseases, HLA-A2 Antigen, MHC class I, medicine, Humans, Protein Isoforms, Receptors, Immunologic, Receptor, Molecular Biology, Aged, Effector, Antibodies, Monoclonal, General Medicine, Middle Aged, medicine.disease, Transmembrane protein, Killer Cells, Natural, medicine.anatomical_structure, Membrane protein, Child, Preschool, Immunology, Paroxysmal nocturnal hemoglobinuria, biology.protein, Molecular Medicine, Female, Protein Binding
Abstract: PIGA mutations in paroxysmal nocturnal hemoglobinuria (PNH) patients lead to a glycosylphosphatidylinositol (GPI)-linked membrane proteins expression deficiency. Herein, we report the constitutive expression of the transmembrane CD160 (CD160-TM) activating receptor on non PIGA-mutated PNH patients circulating NK cells. In healthy individuals, only the GPI-anchored isoform of CD160 receptors is expressed on the circulating NK lymphocytes, while the transmembrane isoform appears after ex vivo activation. Similarly to CD160-GPI, we identified CD160-TM as a receptor for the MHC class I molecules. We demonstrate that PNH patients NK lymphocytes spontaneously produce significant amounts of IFN-γ that is inhibited by anti-CD160-TM or anti-MHC class I mAbs. These results indicate that circulating NK cells from PNH patients exhibit a self-MHC class I molecule reactive effector function, which could be mediated through the recruitment of CD160-TM receptor. Our data provide new insights regarding the possible role of CD160-TM on PNH patients NK lymphocytes and in the pathogenesis of the disease.
Published: 2012
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29. Tumeurs myofibroblastiques inflammatoires localisées de l’enfant : recommandations diagnostiques et thérapeutiques

Author: Aude Marie-Cardine, Daniel Orbach, and Dominique Berrebi
Subjects: Gynecology, Cancer Research, Inflammatory pseudotumour, medicine.medical_specialty, business.industry, Inflammatory myofibroblastic tumour, Hematology, General Medicine, medicine.disease, Oncology, medicine, Inflammatory pseudotumor, Radiology, Nuclear Medicine and imaging, Head and neck, business
Abstract: Resume Objectifs A partir d’une revue de la litterature internationale, le groupe des « Tumeurs rares pediatriques » de la Societe francaise des cancers de l’enfant propose des recommandations diagnostiques et therapeutiques des tumeurs myofibroblastiques inflammatoires de localisation unique de l’enfant. Commentaires principaux Ces tumeurs surviennent a tous les âges et concernent l’ensemble des organes, preferentiellement les voies aeriennes superieures et basses. L’analyse histologique retrouve une proliferation de cellules fusiformes de nature myofibroblastique associee a une composante inflammatoire. Le diagnostic de tumeur myofibroblastique inflammatoire est un diagnostic d’elimination et doit ecarter celui des sarcomes. Conclusions principales La distinction entre une tumeur myofibroblastique inflammatoire et un sarcome est essentielle compte-tenu des differences de prise en charge. Le traitement curatif de ces tumeurs est principalement chirurgical encadre avant ou apres le geste operatoire par une corticotherapie. En cas d’inoperabilite, un traitement par chimiotherapie peut se discuter afin d’eviter une chirurgie mutilante.
Published: 2011
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30. Collaborateurs

Author: Grégoire, Benoist, Antoine, Bourrillon, Christophe, Delacourt, Christèle, Gras-Le Guen, Benoit, Billy (de), Agnès, Liard-Zmuda, Patrick, Tounian, François, Angoulvant, Jean-Baptiste, Arnoux, Frédéric, Auber, Guillaume, Aubertin, Georges, Audry, Stéphane, Auvin, Justine, Bacchetta, Martine, Balençon, Pascal, Barat, Marc, Bellaïche, Jacques, Beltrand, Etienne, Bidat, Arnaud, Bonnard, Claire, Bouvattier, Dominique, Bremond-Gignac, Frédéric, Brioude, Olivier, Brissaud, Jean-Claude, Carel, Ania, Carsin, Mireille, Castanet, Brigitte, Chabrol, Gérard, Chéron, Bertrand, Chevallier, Jacques, Cheymol, Pierre, Corre, Régis, Coutant, Laurianne, Coutier, Pierrick, Cros, Jean-Christophe, Cuvellier, Jean-Hugues, Dalle, Stéphane, Dauger, Céline, Delestrain, Amandine, Divaret-Chauveau, François, Doz, David, Drummond, Béatrice, Dubern, Sophie, Dugue, Thomas, Édouard, Brigitte, Fauroux, Albert, Faye, Pierre, Fayoux, Cyril, Flamant, Elisabeth, Fournier-Charrière, Virginie, Gandemer, Alexandra, Gauthier, Olivia, Gillion-Boyer, Lisa, Giovannini-Chami, Emmanuel, Grimprel, Alice, Hadchouel-Duvergé, Sébastien, Héritier, Christina, Ioan Iulia, Pierre-Henri, Jarreau, Etienne, Javouhey, Eric, Jeziorski, Elsa, Kermorvant, Béatrice, Kugener, François, Labarthe, André, Labbé, Géraldine, Labouret, Elise, Launay, Rémi, Laporte, Nicolas, Leboulanger, Joël, Lechevallier, Juliane, Léger, Stéphanie, Lejeune, Stéphanie, Leroux, Guillaume, Lezmi, Anne, Lienhardt-Roussie, Agnès, Linglart, Mathie, Lorrot, Natalie, Loundon, Jehanne, Malek, Christophe, Marguet, Aude, Marie Cardine, Laetitia, Martinerie, Emmanuel, Mas, Thierry, Merrot, Matthieu, Milh, Despina, Moshous, Pierre-Yves, Mure, Javotte, Nancy, Nadia, Nathan, Irene, Netchine, Marc, Nicolino, Richard, Nicollas, Sylvie, Odent, Caroline, Ovaert, Françoise, Paris, Laurent, Pasquier, Aurélie, Phulpin, Capucine, Picard, Georges, Picherot, Guillaume, Podevin, Michel, Polak, Philippe, Ravasse, Rachel, Reynaud, Sylvie, Rossignol, Sébastien, Rouget, Jean-Christophe, Rozé, Philippe, Sachs, Frédérique, Sauvat, Cyril, Schweitzer, Isabelle, Sermet-Gaudelus, Chantal, Stheneur, Isabelle, Talon, Aline, Tamalet, Maïté, Tauber, Jessica, Taytard, Jean-Benoît, Thambo, Caroline, Thumerelle, Renaud, Tournemire (de), Barbara, Tourniaire, Michel, Tsimaratos, François, Varlet, Alain, Verloes, Ariane, Zaloszyc, Catherine, Cyteval, Philippe, Petit, Damien, Bonnard, and Emmanuel, Lescanne
Published: 2020
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31. Transitional B cells in humans: Characterization and insight from B lymphocyte reconstitution after hematopoietic stem cell transplantation

Author: Olivier Boyer, Anne Perdrix, Ingrid Dutot, Jean-Pierre Vannier, Aude Marie-Cardine, François Tron, Florence Divay, Alexa S. Green, Serge Jacquot, Nathalie Contentin, and Hervé Tilly
Subjects: Adult, Male, medicine.medical_treatment, Lymphocyte, Immunology, Naive B cell, B-Lymphocyte Subsets, Hematopoietic stem cell transplantation, Biology, CD38, CD19, Antigens, CD, medicine, Humans, Immunology and Allergy, B cell, B-Lymphocytes, CD24, Precursor Cells, B-Lymphoid, Hematopoietic Stem Cell Transplantation, Cell Differentiation, Middle Aged, Flow Cytometry, medicine.anatomical_structure, Cord blood, biology.protein, Female
Abstract: Transitional B cells have been recently identified in human peripheral blood. However, their precise role in human B cell differentiation has not been established. Therefore, besides characterizing them further in the blood of healthy adults and children and cord blood, we used the immune reconstitution after hematopoietic stem cell transplantation (HSCT) model to define their role in human B cell development. Human transitional B cells are reliably identified as CD19(+) CD24(high) CD38(high) lymphocytes and represent approximately 4% of B cells in healthy adult peripheral blood. In contrast, they are abundant in cord blood (near 50% of B cells) and their percentage progressively decreases during infancy. Similarly, after HSCT, all B cells first appearing in peripheral blood are transitional B cells; afterwards, the transitional B cell percentage progressively decreases while the mature naïve B cell proportion rises. Our results now formally demonstrate that transitional B cells are necessary developmental intermediates for human mature B cell generation.
Published: 2008
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32. Single- vs double-unit cord blood transplantation for children and young adults with acute leukemia or myelodysplastic syndrome

Author: Mohamad Mohty, Fanny Rialland, Patrick Lutz, Karine Baumstarck, Anderson Loundou, Sophie Esmiol, Charlotte Jubert, Claire Galambrun, Ibrahim Yakoub-Agha, Mauricette Michallet, Didier Blaise, Cécile Pochon, Anne Sirvent, Jean-Hugues Dalle, Gérard Michel, Claire Oudin, Bénédicte Bruno, Virginie Gandemer, Aude Marie-Cardine, Vanderson Rocha, Mylène Seux, Noel Milpied, Cecile Renard, Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Gustave Roussy (IGR), Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, 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 Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de pédiatrie, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, 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 ), CHU Pontchaillou [Rennes], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hématologie Clinique [Nantes], Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Stress Cellulaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Chimie Provence (LCP), Université de Provence - Aix-Marseille 1-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), France Monacord, Centre Scientifique de Monaco (CSM), Hôpital Robert Debré Paris, Hôpital Robert Debré, 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 ), 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)-Université de Provence - Aix-Marseille 1-Institut de Chimie du CNRS (INC)
Subjects: Male, Transplantation Conditioning, [SHS.PSY]Humanities and Social Sciences/Psychology, Graft vs Host Disease, Biochemistry, Gastroenterology, 0302 clinical medicine, Child, Acute leukemia, Leukemia, Hematology, Total body irradiation, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Quality, 3. Good health, Survival Rate, surgical procedures, operative, 030220 oncology & carcinogenesis, Child, Preschool, Acute Disease, Female, Cord Blood Stem Cell Transplantation, Whole-Body Irradiation, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Immunology, Disease-Free Survival, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Survival rate, Antilymphocyte Serum, business.industry, Myelodysplastic syndromes, Cell Biology, medicine.disease, Surgery, Transplantation, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Myelodysplastic Syndromes, Chronic Disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Busulfan, 030215 immunology
Abstract: Transplantation of 2 unrelated cord blood (UCB) units instead of 1 has a been proposed to increase the cell dose. We report a prospective a randomized study, designed to compare single-vs double-UCB a transplantation in children and young adults with acute leukemia in a remission or myelodysplasia. Eligible patients had at least two 4-6 a HLA-identical UCBs with >3x10(7) nucleated cells/kg for the first and a >1.5x10(7) for the second. The primary end point was the 2-year a cumulative incidence of transplantation strategy failure, a composite a end point including transplant-related mortality (TRM), engraftment a failure, and autologous recovery. Randomized patients who did not a proceed to transplantation due to refractory disease were considered a transplantation failures. A total of 151 patients were randomized and a included in the intent-to-treat analysis; 137 were transplanted. a Double-UCB transplantation did not decrease transplantation strategy a failure (23.4% 6 4.9% vs 14.9% +/- 4.2%). Two-year posttransplant a survival, disease-free survival, and TRM were 68.8% +/- 6.0%, 67.6% a +/- 6.0%, and 5.9% +/- 2.9% after single-unit transplantation a compared with 74.8% +/- 5.5%, 68.1% +/- 6.0%, and 11.6% +/- 3.9% a after double-unit transplantation. The final relapse risk did not a significantly differ, but relapses were delayed after double-unit a transplantation. Overall incidences of graft-versus-host disease (GVHD) a were similar, but chronic GVHD was more frequently extensive after a double-UCB transplantation (31.9% +/- 5.7% vs 14.7% +/- 4.3%, a P=.02). In an exploratory subgroup analysis, we found a significantly a lower relapse risk after double-unit transplantation in patients a receiving total body irradiation without antithymocyte globulin (ATG), a whereas the relapse risk was similar in the group treated with busulfan, a cyclophosphamide, and ATG. Single-UCB transplantation with adequate cell a dose remains the standard of care and leads to low TRM. Double-unit a transplantation should be reserved for patients who lack such units. a This trial was registered at www. clinicaltrials. gov as #NCT01067300.
Published: 2016
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33. Unrelated stem cell transplantation for severe acquired aplastic anemia: improved outcome in the era of high-resolution HLA matching between donor and recipient

Author: Zina Chir, N. Maillard, Noel Milpied, Claire Galambrun, Jean-Michel Boiron, Sébastien Maury, Pierre Bordigoni, Aude Marie-Cardine, Judith Kanold, Gérard Socié, Marie-Lorraine Balère-Appert, and Karima Yakouben
Subjects: Male, Time Factors, Transplantation Conditioning, T-Lymphocytes, medicine.medical_treatment, Hemoglobinuria, Paroxysmal, Graft vs Host Disease, Kaplan-Meier Estimate, Hematopoietic stem cell transplantation, Hepatitis, Cohort Studies, HLA Antigens, Cause of Death, Living Donors, Child, Histocompatibility Testing, Graft Survival, Hematopoietic Stem Cell Transplantation, Anemia, Aplastic, Hematology, Middle Aged, Combined Modality Therapy, Survival Rate, Treatment Outcome, Child, Preschool, Female, Immunosuppressive Agents, Vidarabine, Adult, Reoperation, medicine.medical_specialty, Adolescent, Anemia, Lymphocyte Depletion, Statistics, Nonparametric, Internal medicine, medicine, Humans, Transplantation, Homologous, Aplastic anemia, Survival rate, Survival analysis, Antilymphocyte Serum, Proportional Hazards Models, Retrospective Studies, Chi-Square Distribution, business.industry, Infant, Newborn, Bone marrow failure, Infant, medicine.disease, Survival Analysis, Surgery, Histocompatibility, Transplantation, business
Abstract: Background and Objectives Severe acquired aplastic anemia (SAA) is a potentially fatal bone marrow failure syndrome occurring mainly in children and young adults. Immunosuppressive regimens and hematopoietic stem cell transplantation (HSCT) are the only two available curative treatments. Patients who lack an HLA-identical sibling donor may receive HSCT from an unrelated donor, a strategy historically associated with high mortality rates. Thus, for patients refractory to immunosuppressive regimens, the decision to transplant stem cells from unrelated donors is weighed against supportive care and often represents a dilemma for physicians. We aimed to determine whether outcome after unrelated HSCT has improved in recent years and, if so, to determine the factors responsible for the improvement. Design and Methods We analyzed the outcome of 89 patients (median age 17 years, range 0–52) with acquired SAA undergoing HSCT from an unrelated donor between 1989 and 2004. Cases were consecutively reported to the French Registry (SFGM-TC) by 25 centers. Results Patients transplanted during two successive time-periods (1989–1998 and 1999–2004) had different 5-year survival probabilities (±95% confidence interval): 29±7% and 50±7%, respectively ( p
Published: 2007
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34. Association céfépime-amikacine chez les enfants neutropéniques fébriles atteints d’hémopathies ou de tumeurs malignes

Author: P Schneider, J.P. Vannier, Blot N, P Tron, and Aude Marie-Cardine
Subjects: Gynecology, medicine.medical_specialty, business.industry, Cefepime, Pediatrics, Perinatology and Child Health, β lactams, Medicine, business, medicine.drug
Abstract: Resume Objectif . – Notre objectif a ete d’evaluer a posteriori l’efficacite d’un traitement associant cefepime et amikacine en premiere intention chez les enfants neutropeniques febriles traites par chimiotherapie. Patients et methodes . – Soixante-cinq episodes febriles survenant chez 43 enfants neutropeniques, traites par cefepime-amikacine, ont ete evalues selon l’etat clinique, la profondeur et la duree de la neutropenie, la pathologie maligne et les traitements initialement recus. Resultats . – Trente-neuf des 65 (60 %) episodes ont ete traites avec succes par l’association cefepime-amikacine. Parmi les 26 autres, l’adjonction de vancomycine et d’amphotericine B a ete efficace dans 11 et 5 cas (respectivement 76 et 84 % de succes). La longueur et la profondeur de la neutropenie n’ont pas ete retrouvees associees a une difference d’efficacite. Les episodes febriles survenus au decours des chimiotherapies pour tumeurs solides ont ete rapidement controles par la double, voire la triple, antibiotherapie preconisee. En revanche, les enfants traites pour hemopathies ont eu un taux de reponse moins bon ( p = 0,03). Conclusion. – Chez les enfants neutropeniques febriles, l’association cefepime-amikacine s’est averee etre un traitement empirique efficace. Plus que la duree d’aplasie, c’est l’etat immunitaire de l’enfant et eventuellement l’etat general de celui-ci qui sont les elements preponderants du pronostic infectieux.
Published: 2003
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35. Rhabdomyosarcomas in children with neurofibromatosis type I: A national historical cohort

Author: Anne, Crucis, Wilfrid, Richer, Laurence, Brugières, Christophe, Bergeron, Aude, Marie-Cardine, Jean-Louis, Stephan, Pauline, Girard, Nadege, Corradini, Martine, Munzer, Brigitte, Lacour, Veronique, Minard-Colin, Sabine, Sarnacki, Dominique, Ranchere-Vince, Daniel, Orbach, and Franck, Bourdeaut
Subjects: Cohort Studies, Male, Neurofibromatosis 1, Reverse Transcriptase Polymerase Chain Reaction, Child, Preschool, Rhabdomyosarcoma, Humans, Infant, Female, Kaplan-Meier Estimate, Disease-Free Survival, Retrospective Studies
Abstract: Rhabdomyosarcoma (RMS) occasionally occurs in a context of a predisposition syndrome. The most common predisposition syndromes include germline TP53 mutations and constitutive alterations in RAS pathway activation, such as Costello syndrome, Noonan syndrome and neurofibromatosis type 1. We report a national retrospective series of 16 RMS occurring in neurofibromatosis type 1 (NF1) patients during childhood, within a 20-year period.The mean age at diagnosis of the cancer was 2.5 years. All were embryonal subtype. Most tumours developed in the pelvis. One was metastatic. Chemotherapy and radiotherapy were normally scheduled without any specific toxicity. The 5-year event-free survival and overall survival were 67% and 87%, respectively. Long-term sequel related to chemotherapy consisted in two chronic tubulopathies, hence not obviously different from non-NF1 patients. No second cancer was reported so far with a median follow-up of 9.7 years. The genomic analysis performed on six samples revealed the abnormalities commonly observed in sporadic RMS: gain of chromosome 2 (5/6), 8 (6/6) and chromosome 11p loss of heterozygosity (5/6). Interestingly, we identified small deletions in tumour suppressor genes that may synergize with NF1 inactivation.Patients with neurofibromatosis are prone to develop embryonal-type RMS that require the same treatment as sporadic cases.
Published: 2015

36. Epidemiology of Acute Viral Gastroenteritis in Children Hospitalized in Rouen, France

Author: Karine Gourlain, Mallet E, Aude Marie-Cardine, O. Mouterde, Claudine Buffet-Janvresse, Marie-France Hellot, and Nathalie Castignolles
Subjects: Rotavirus, Microbiology (medical), medicine.medical_specialty, viruses, medicine.disease_cause, Rotavirus Infections, Virus, Astrovirus, fluids and secretions, Epidemiology, medicine, Humans, Dehydration, biology, business.industry, Infant, Newborn, Calicivirus, Infant, virus diseases, biology.organism_classification, Virology, Caliciviridae, Gastroenteritis, Hospitalization, Infectious Diseases, Child, Preschool, Acute Disease, Enterovirus, France, Viral disease, business
Abstract: This study assessed the epidemiologic characteristics of acute viral gastroenteritis in hospitalized children. A stool sample obtained from each child was analyzed for the presence of astrovirus, calicivirus, rotavirus, adenovirus, enterovirus, and digestive bacteria. Of the 438 stool samples obtained, 138 tested positive foror =1 pathogen during the winters of 1997-1998 and 1998-1999 (P.001). Virologic tests revealed rotavirus in 17.3% of samples, calicivirus in 7.3%, astrovirus in 6.8%, adenovirus in 0.7%, andor =1 virus in 5.4%. Median age was higher for patients with rotavirus gastroenteritis than it was for those with astrovirus or calicivirus gastroenteritis (P=.014). Mean duration of hospitalization was statistically significantly lower for children with rotavirus gastroenteritis (P=.022), despite the more-frequent dehydration observed among children with rotavirus versus those with astrovirus or calicivirus gastroenteritis (P=.007). In contrast, enteral rehydration was more rapidly achieved in patients with gastroenteritis due to rotavirus.
Published: 2002
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37. Salivary Transmission in an Intrafamilial Cluster of Hepatitis B

Author: O. Mouterde, Mallet E, Claudine Buffet-Janvresse, Sabine Dubuisson, and Aude Marie-Cardine
Subjects: Adult, Male, Saliva, Disease cluster, Feeding behavior, Disease Transmission, Infectious, medicine, Humans, Transmission (medicine), business.industry, Infant, Newborn, Gastroenterology, Viral hepatitis b, Feeding Behavior, Hepatitis B, medicine.disease, Virology, Chronic disease, Child, Preschool, Acute Disease, Carrier State, Chronic Disease, Pediatrics, Perinatology and Child Health, Immunology, Female, Viral disease, business
Published: 2002
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38. 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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39. [Cryopreservation of testicular tissue in children]

Author: Nathalie, Rives, Jean-Pierre, Milazzo, Albanne, Travers, Brahim, Arkoun, Amandine, Bironneau, Louis, Sibert, Agnès, Liard-Zmuda, Aude, Marie-Cardine, Pascale, Schneider, Jean-Pierre, Vannier, and Bertrand, Macé
Subjects: Cryopreservation, Male, Transplantation, Heterotopic, Adolescent, Radiotherapy, Fertility Preservation, Infant, Antineoplastic Agents, Seminiferous Tubules, Transplantation, Autologous, Spermatogonia, Child, Preschool, Neoplasms, Replantation, Testis, Animals, Humans, Child, Infertility, Male
Abstract: The toxicity of cancer therapies can affect all organs and tissues. Some treatments damage spermatogonial stem cells (SSCs), with a risk of infertility. Storage and reimplantation of frozen testicular tissue is a recent approach tofertilitypreservationfor young boys. However, thawed frozen prepubertal testicular tissue must undergo a maturation process to restore sperm production. This process, currently being studied in animal models, can be achieved by in vivo transplantation of SSCs into seminiferous tubules or by testicular grafting, possibly following in vitro maturation.
Published: 2014

40. Une découverte fortuite et tardive de maladie de Bruton

Author: Pauline Treguier, Aude Marie-Cardine, and Pascale Schneider
Subjects: Oncology, Pediatrics, Perinatology and Child Health, Hematology
Abstract: Introduction Un jeune homme de 17 ans est adresse en consultation d’immunologie pediatrique pour une decouverte fortuite d’hypogammaglobulinemie. Il est issu de parents caucasiens non consanguins, sans antecedents familiaux de dys-immunite. Il a presente, durant l’enfance, de nombreux episodes febriles, des otites frequentes et une ethmoidite sans sequelle, et des verrues resistantes aux traitements topiques. Materiels et methodes Un bilan sanguin a ete effectue a ses 4 ans retrouvant une hypogammaglobulinemie severe, banalisee devant un bon etat general, predominante sur les IgM ( Haemophilus influenzae et anti-pneumococcique. Aucun foyer profond n’est retrouve. Resultats Devant une forte suspicion de deficit immunitaire hereditaire, une recherche genetique est faite et retrouve une mutation faux sens sur l’exon 2 du gene BTK entrainant la production d’une proteine de Bruton deletere. La maladie de Bruton ou agammaglobulinemie liee a l’X est un deficit de l’immunite hereditaire se manifestant dans les deux premieres annees de vie, chez les garcons, par des infections des voies aeriennes recidivantes a germes extracellulaires. Elle est due a un deficit en Bruton Proteine Kinase entrainant une hypogammaglobulinemie profonde avec une absence de lymphocyte B circulants, plusieurs mutations ont ete decrites. Discussion Plusieurs cas de diagnostic tardif, paucisymptomatique, ont ete decrits dans la litterature [1] , la penetrance variable de la maladie de Bruton est-elle fonction de la mutation causale ? Faut-il supplementer ses patients ? Faut-il proposer une enquete genetique familiale ?
Published: 2016
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41. Revisiting Splenectomy in Childhood Immune Thrombocytopenic Purpura in the Era of New Therapies: The French Experience

Author: Corinne Guitton, Patrick Boutard, Marlène Pasquet, Dominique Plantaz, Nathalie Aladjidi, Thierry Leblanc, Aude Marie-Cardine, Guy Leverger, Patrick Lutz, Raoul Santiago, Jean-Louis Stephan, Sophie Bayart, Claire Godard Sebillotte, Anne Lambilliotte, Vincent Barlogis, Corinne Pondarré, Pierre Rohrlich, Karine de Bosredon, Y Perel, and Martine Munzer
Subjects: Cytopenia, Pediatrics, medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Gold standard, Splenectomy, Retrospective cohort study, medicine.disease, Thrombocytopenic purpura, hemic and lymphatic diseases, Relative risk, medicine, business, Laparoscopy, Rare disease
Abstract: Objective: While splenectomy is the gold standard treatment for refractory primary immune thrombocytopenia (ITP) in adult, its place remains debated in children. The French Rare Disease Plan provided us the opportunity to conduct a collaborative study of the efficiency and tolerance of this procedure in childhood ITP. Patients and methods: A retrospective study was conducted in France in order to identify children with ITP treated with splenectomy during a 9-year period. A total of 78 children were included. Data from the ongoing CEREVANCE national cohort of childhood auto-immune cytopenia in 30 units were reviewed and completed by a direct contact with the referent physicians. International terminology for response definition was used. Relapsefree survival was assessed by the Kaplan-Meier method. Results: The median ages at ITP diagnosis and splenectomy were 9.6 and 12.4 years respectively. The median duration of ITP before splenectomy was 24 months (1-162); 62 children had chronic ITP. The median number of treatment lines before splenectomy was 2 (1-7). Laparoscopy was used in 81% of cases. Four children underwent immediate surgical complications. With a median follow-up of 41 months, complete remission (CR) was maintained at the latest news in 84% of children. CR was obtained in 77% of cases with intra-splenic platelets destruction, and in no case with non-splenic destruction (p=0.11). Using a very strict definition for relapse, the 5-year relapse-free survival was 51% [IC95% 37-64]. No death or overwhelming sepsis was reported. Conclusions: In this national study with a long term follow up, the excellent benefit/risk ratio of splenectomy for refractory ITP confirms that in skilled and concerted teams, the procedure is still at the forefront of curative treatments. Isotopic evaluation is of value but other prognostic factors for CR are to be determined. Lifelong survey of potential infectious and thrombotic risk at adult age has to be coordinated by the referring physician. The place for other therapeutic options, in order to postpone as late as possible the splenectomy in childhood ITP is now to be determined.
Published: 2012
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42. [Guidelines for management of localized inflammatory myofibroblastic tumours in children]

Author: Aude, Marie-Cardine, Dominique, Berrebi, and Daniel, Orbach
Subjects: Humans, France, Child, Granuloma, Plasma Cell
Abstract: The paediatric rare tumours group from the Société française des cancers de l'enfant makes syntheses and guidelines for diagnosis and treatment for localized paediatric inflammatory myofibroblastic tumours according to international articles.All ages are concerning. Localizations are ubiquitous, more frequently in the superior and inferior airway. Histology showed a majority of fusiform cells, corresponding to myofibroblastic cells and an inflammatory infiltrate. Inflammatory myofibroblastic tumour diagnosis should only be confirmed in the absence of sarcoma molecular markers.Distinction between inflammatory myofibroblastic tumour and sarcoma is essential due to the different care. The curative treatment of inflammatory myofibroblastic tumour consists on surgery with before or after corticotherapy. In case of unresectability, chemotherapy may be helpful to avoid mutilating surgery.
Published: 2011

43. Decreased activity of soluble thrombomodulin and plasma procoagulant phospholipids in childhood bone marrow transplantation with severe complications

Author: Patrick Van Dreden, Aude Marie-Cardine, Jean-Pierre Vannier, Aurélie Rousseau, Marc Vasse, Pascale Schneider, and Estelle Houivet
Subjects: Blood Platelets, Male, Bone marrow transplantation, Endothelium, Adolescent, Thrombomodulin, Proinflammatory cytokine, medicine, Humans, Secretion, Favorable outcome, Child, Phospholipids, Bone Marrow Transplantation, business.industry, Hematology, Soluble thrombomodulin, Blood Coagulation Factors, medicine.anatomical_structure, Child, Preschool, Immunology, Allogeneic BMT, Female, business, Biomarkers
Abstract: Complications of bone marrow transplantation (BMT) are usually considered to be related to the secretion of inflammatory cytokines, which generate membrane microparticles rich in procoagulant phospholipids (PPL) from different cellular origins and release of endothelial proteins such as thrombomodulin (TM). The use of soluble TM quantified by ELISA (TM:Ag) as a marker of endothelial injury is complex in children since it is age-dependent.Using a functional assay which quantifies the activity of sTM activity (TMa), we performed a pilot study to analyze the ratio TMa/TM:Ag in a control group of 25 healthy children, 8 children with autologous and 16 children with allogeneic BMT. In this last group, 8 experienced BMT complications. In addition, we used a functional assay which quantifies PPL.In healthy children the ratio TMa/TM:Ag was independent of age and stable in children with a favorable outcome but significantly (p0.05) reduced by the use of antithymocyte globulin during the conditioning regimen, and regularly decreased in children with BMT complications. Surprisingly, low plasma PPL levels were associated with a poor outcome.The ratio TMa/TM:Ag could constitute a marker of endothelium injury, and its follow-up could be of interest for an early discrimination of children with high risk of complications during allogeneic BMT. The decrease of PPL could be also another marker of a poor evolution and deserves further investigations.
Published: 2010

44. Reduced frequency of regulatory T cells in peripheral blood stem cell compared to bone marrow transplantations

Author: Ingrid Dedreux, Nathalie Contentin, Olivier Boyer, Celine A. Blache, Dominique Bastit, Stéphanie François, Pascal Pommier, Aude Marie-Cardine, Joe-Marc Chauvin, and Serge Jacquot
Subjects: Bone marrow transplantation, T cell, Graft vs Host Disease, chemical and pharmacologic phenomena, Apoptosis, T-Lymphocytes, Regulatory, Immunophenotyping, Interleukin-7 Receptor alpha Subunit, Bone Marrow, Risk Factors, T-Lymphocyte Subsets, Granulocyte Colony-Stimulating Factor, Medicine, Humans, IL-2 receptor, Leukapheresis, Lymphocyte Count, L-Selectin, Bone Marrow Transplantation, Transplantation, Peripheral Blood Stem Cell Transplantation, business.industry, hemic and immune systems, Forkhead Transcription Factors, Regulatory T cells, Hematology, Peripheral blood, Tissue Donors, medicine.anatomical_structure, surgical procedures, operative, Immunology, Leukocyte Common Antigens, Hematopoietic stem cell transplant, Stem cell, business, Human
Abstract: Peripheral blood stem cell transplantation (PBSCT) is an alternative to bone marrow transplantation (BMT). Although CD4(+)CD25(+)CD127(lo) regulatory T cells (Tregs) have been shown to play important roles in the control of T cell reactivity, the Treg contents of both graft types have not been analyzed comparatively to date. We report herein that Treg frequencies are significantly reduced in PBSC compared to BM transplants. Furthermore, most Tregs from PBSC transplants are CD62L(lo), a phenotype reported to have poor suppressor activity. Both granulocyte-colony stimulating factor (G-CSF) administration and leukapheresis were found to contribute to the loss of CD62L(+) Tregs. Although higher T cell numbers are infused in PBSCT than in BMT, it is possible that the reduced Treg content of PBSC transplants may represent 1 factor contributing to the higher risk of GVHD reported after PBSCT.
Published: 2009

45. Endostatin variations in childhood acute lymphoblastic leukaemia--comparison with basic fibroblast growth factor and vascular endothelial growth factor

Author: Cécile Corbière, Lionel Cazin, Vannier Jp, Pascale Schneider, Marc Vasse, C. Boquet, E. Legrand, Aude Marie-Cardine, Université de Caen Normandie (UNICAEN), Normandie Université (NU), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Microenvironnement et régulation cellulaire intégrés (MERCI), Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)
Subjects: Vascular Endothelial Growth Factor A, Cancer Research, MESH: Remission Induction, Angiogenesis, [SDV]Life Sciences [q-bio], Basic fibroblast growth factor, MESH: Hepatomegaly, Immunoenzyme Techniques, chemistry.chemical_compound, 0302 clinical medicine, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Child, Lymphocytes, RNA, Neoplasm, Child, 0303 health sciences, Neovascularization, Pathologic, Reverse Transcriptase Polymerase Chain Reaction, Lymphoblast, Remission Induction, MESH: Enzyme-Linked Immunosorbent Assay, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Infant, MESH: Case-Control Studies, 3. Good health, Endostatins, Vascular endothelial growth factor, Oncology, 030220 oncology & carcinogenesis, Child, Preschool, [SDE]Environmental Sciences, cardiovascular system, Fibroblast Growth Factor 2, Endostatin, MESH: Neoplasm Recurrence, Local, Hepatomegaly, medicine.medical_specialty, Stromal cell, MESH: Immunophenotyping, Adolescent, Blotting, Western, Enzyme-Linked Immunosorbent Assay, macromolecular substances, Biology, Immunophenotyping, 03 medical and health sciences, Internal medicine, MESH: Cell Proliferation, MESH: Endostatins, medicine, MESH: Blotting, Western, Humans, Secretion, RNA, Messenger, MESH: Immunoenzyme Techniques, 030304 developmental biology, MESH: RNA, Messenger, Cell Proliferation, MESH: Adolescent, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Humans, MESH: Fibroblast Growth Factor 2, MESH: Vascular Endothelial Growth Factor A, MESH: Child, Preschool, Infant, MESH: RNA, Neoplasm, Secretory protein, Endocrinology, chemistry, Case-Control Studies, MESH: Lymphocytes, Neoplasm Recurrence, Local, MESH: Neovascularization, Pathologic
Abstract: International audience; Angiogenic factors such as basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) were previously studied in childhood acute lymphoblastic leukaemia (ALL) but little is known concerning the anti-angiogenic response in ALL. At diagnosis, the plasma levels of the anti-angiogenic factor endostatin were significantly higher in 33 children with ALL than in controls (median values 17.7 and 7.6 ng/ml, respectively, p=0.0192) but no relationship was observed with plasma bFGF or VEGF levels. The highest levels were observed in patients with an hyperdiploïd karyotype. Expression of mRNA for collagen XVIII/endostatin in lymphoblasts was detected in 19/24 cases but protein secretion was found only in 14/28 supernatants of cultured lymphoblasts. No direct relationship appeared between secretion of endostatin by lymphoblasts and plasma levels. In addition, endostatin levels remained elevated in remission, suggesting that endostatin could have a stromal origin as well. No prognostic value of plasma endostatin could be assessed. In conclusion, the present data indicate that an anti-angiogenic response is observed in some ALL children, but its physiopathological importance remains to be established.
Published: 2006
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46. Inolimomab in steroid-refractory acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: retrospective analysis and comparison with other interleukin-2 receptor antibodies

Author: Fabrice Kwiatkovski, Gomez Nunez, Frédéric Garban, Claire Galambrun, Nathalie Dhedin, Ibrahim Yakoub-Agha, Alain Fischer, Isabelle Darlavoix, Reza Tabrizi, Rocio Parody, Aude Marie-Cardine, Aspasia Stamatoullas, Jose-Luis Diez-Martin, Jean-Paul Vernant, Mauricette Michallet, Jean-Pierre Jouet, Catherine Faucher, Martin Goerner, Jacques-Olivier Bay, Amina Zinai, Noel Milpied, Jean-Pierre Vannier, and Helene Esperou
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Graft vs Host Disease, Hematopoietic stem cell transplantation, Gastroenterology, Adrenal Cortex Hormones, Internal medicine, Inolimomab, medicine, Humans, Transplantation, Homologous, Child, Survival rate, Retrospective Studies, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Antibodies, Monoclonal, Infant, Receptors, Interleukin-2, Immunotherapy, Middle Aged, Survival Rate, Regimen, surgical procedures, operative, medicine.anatomical_structure, Cord blood, Child, Preschool, Immunology, Acute Disease, Female, Bone marrow, business, medicine.drug
Abstract: Background The use of monoclonal antibodies against interleukin-2 receptor (IL-2R)-alpha chains could be an effective treatment of acute graft-versus-host disease (GvHD). Experimental model and clinical studies have reported various results. Methods Inolimomab is a murine anti-IL-2R. Eighty-five patients were evaluated retrospectively for the safety and efficacy of inolimomab given for the treatment of steroid-resistant acute GvHD (aGvHD) following allogeneic hematopoietic stem cell transplantation (HSCT). Diseases were immune deficiency, hematological malignancies, or solid tumors. Seventy-six percent of the patients received a myeloablative regimen. The source of HSCT was bone marrow for 45 patients, peripheral blood for 36 patients, and cord blood for 4 patients. Donors were 49 siblings and 36 unrelated. Acute GvHD was diagnosed within a median of 28 days after transplantation (grade II, 26 patients; grade III, 26 patients; grade IV, 33 patients). Inolimomab was administered in the event of steroid-resistant aGvHD with a median dose of 0.468 mg per kg (median period of treatment: 18 days). Results Twenty-five complete responses and 29 partial responses (total response rate: 63%) were observed with no side effects. There was no correlation between aGvHD grading and quality of response. Better responses were observed in cutaneous aGvHD. The overall survival probability was 26% (median follow-up: 20 months). Fifty-seven percent of patients died of toxicity related mortality, mostly aGvHD. Response to inolimomab seemed sustained (11% relapse in responders). Conclusion Inolimomab is well-tolerated and effective for severe steroid-resistant aGvHD. The optimum regimen remains to be defined.
Published: 2005

47. Les techniques de préservation de la fertilité chez le garçon

Author: A. Bironneau, Brahim Arkoun, Nathalie Rives, A. Liard-Zmuda, Ludovic Dumont, J.-P. Milazzo, P Schneider, Louis Sibert, J.P. Vannier, Bertrand Macé, and Aude Marie-Cardine
Subjects: business.industry, Pediatrics, Perinatology and Child Health, Medicine, business
Published: 2013
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48. Erythrocytosis in a child with a hepatic adenoma

Author: Valérie Greene, Josette Metayer, Aude Marie-Cardine, Bruno Bachy, Pascale Schneider, and Jean-Pierre Vannier
Subjects: Cancer Research, medicine.medical_specialty, Pathology, Adenoma, medicine.medical_treatment, Childhood cancer, Polycythemia, Gastroenterology, Adenoma, Liver Cell, Text mining, Internal medicine, medicine, Humans, Child, Erythropoietin, business.industry, Liver Neoplasms, medicine.disease, Cytokine, Oncology, Pediatrics, Perinatology and Child Health, Hepatic tumor, Female, Complication, business, medicine.drug
Published: 2001

49. Outcomes After Reduced-Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) In 163 Pediatric Patients (<18 years old): A Retrospective Study On Behalf Of The SFGM-TC

Author: Patrick Lutz, Catherine Paillard, Marion Strullu, Myriam Labopin, Nicole Raus, Gaelle Guillerm, Charlotte Jubert, Regis Peffaut De La Tour, Nathalie Fegueux, Aude-Marie Cardine, Gérard Michel, Jean-Hugues Dalle, Jean-Henri Bourhis, Yves Bertrand, Fanny Rialland, Patrice Chevallier, Mohamad Mohty, Pierre Rohrlich, Alexandra Salmon, and Yves Beguin
Subjects: medicine.medical_specialty, Univariate analysis, Myeloid, business.industry, Immunology, Retrospective cohort study, Cell Biology, Hematology, Biochemistry, Gastroenterology, Transplantation, medicine.anatomical_structure, Internal medicine, Cord blood, medicine, Cumulative incidence, Bone marrow, business, Prospective cohort study
Abstract: Introduction Outcomes after RIC allo-SCT in children are rarely reported. The largest series published thus far included 47 children with hematologic malignancies (Pulsipher et al, Blood, 2009). There is thus currently no large series describing the results of RIC allo-SCT in children. Patients and Methods 163 pediatric patients ( Results Engraftment was observed in 85.5% of cases with a median time for neutrophils recovery of 20 days (range: 1-79). With a median follow-up of 23 months (range: 1-169), 2-year (2-y) OS, DFS, RI and NRM were 46+-5%, 37.5+-4%, 40+-3% and 22+-3%, respectively. Cumulative incidence (CI) of acute GVHD at day+100 was 36+-4% while 2-y CI of chronic GVHD was 24.5+-3%. In univariate analysis, factors such as disease status (CR vs active), donor type, source of stem cells, TBI or ATG administration were not associated with outcomes. There were a trend for better 2-y DFS in patients allotransplanted after 15.5 months from the diagnosis (42+-6% vs 33+-6%, p=0.09), for higher 2-y RI but a lower 2-y NRM in patients allografted before 10 years old (52+-7% vs 35+-5%, p=0.07; 12+-5% vs 35+-5%, p=0.06, respectively) and finally a trend for better 2-y OS in patients with lymphoid malignancies (54+-7 vs 41+-6%, p=0.09). Patients allografted after 2004 (n=122; median age: 13.2 years (range: 1-17.9); male 60%; myeloid malignancies 59%, CR: 63%) showed significantly higher 2-y OS (52+-5% vs 31+-7%, p=0.006) and DFS (45+-5% vs 18+-6%) due in part to a significantly lower 2-y NRM (17+-4% vs 36+-8%, p=0.01) reflecting probably a better patient’s selection before transplant. In patients allografted since 2004 multivariate analysis revealed that lymphoid malignancy was the only favourable and independent factor for LFS and OS (HR: 0.55, 95%CI: 0.32-0.97, p=0,04; HR: 0.47, 95%CI: 0.25-0.88, p=0.02). Conclusion This large series shows that RIC allo-SCT is feasible with acceptable toxicity in pediatric patients, especially in cases of lymphoid malignancy. Prospective studies are needed to confirm the potential role of RIC allo-SCT in the pediatric setting, with a special focus on long-term side effects, which are a matter of concern in children. Disclosures: Mohty: Novartis: Honoraria, Research Support Other.
Published: 2013
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50. CL032 - Purpura thrombopénique immunologique de l’enfant : la place de la splénectomie

Author: Raoul Santiago, Guy Leverger, S. Claeyssens, C. Godard Sebillotte, Nathalie Aladjidi, Hervé Chambost, Sophie Bayart, Thierry Leblanc, Y. Perel, Corinne Pondarré, Pierre Rohrlich, F. Lavrand, Aude Marie-Cardine, and Anne Lambilliotte
Subjects: Pediatrics, Perinatology and Child Health
Abstract: Objectif Decrire l’efficacite, la tolerance, et les facteurs predictifs de reussite de la splenectomie dans le purpura thrombopenique immunologique (PTI) de l’enfant. Patients et Methodes Etude retrospective nationale des enfants de moins de 18 ans, traites par splenectomie pour un PTI du 1 er janvier 2000 au 31 aout 2009, conduite par le CEREVANCE, incluant 74 enfants. Resultats L’âge median au diagnostic etait 9,4 ans (0,8-16,5), l’âge median a la splenectomie de 12,5 ans (3,5-17,4), la duree mediane d’evolution du PTI avant splenectomie de 26 mois (1-162). L’intervention a ete realisee par cœlioscopie dans 79% des cas, convertie en laparotomie dans 19% des cas, 9 complications post-operatoires ont ete notees. A 1 mois de la splenectomie, 81% des enfants etaient en remission complete (RC). Avec un suivi median apres splenectomie de 38 mois (0,3-109), 85% des enfants etaient en RC, et 70% sans traitement ni poussee depuis plus d’un an (RCD). Aucune infection severe n’a ete observee. Les enfants en RCD etaient significativement plus âges au diagnostic initial (âge median 11,1 vs 8,2, p = 0,019). Conclusion Cette etude confirme l’excellent rapport benefice-risque de la splenectomie dans le PTI du grand enfant. L’observance des mesures antiinfectieuses est a poursuivre toute la vie.
Published: 2010
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53 results on '"Aude Marie‐Cardine"'

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