28 results on '"Valteau-Couanet, D."'
Search Results
2. [What place for an Ethics committee in a comprehensive cancer centre? For an ethics embodied in real life].
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Blot F, Vigouret-Viant L, Valteau-Couanet D, Verotte N, Ponzio A, Massard C, Marsico G, Lacaze-Guillet M, Hubert N, Dumont S, de Jesus A, Nicotra L, Chardonnet F, and Billaud V
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- Bioethical Issues, Cancer Care Facilities organization & administration, Clinical Decision-Making ethics, Congresses as Topic organization & administration, Decision Support Systems, Clinical, France, Humans, Cancer Care Facilities ethics, Ethics Committees
- Abstract
The Ethics committee of Gustave Roussy cancer center is devoted to both reflection and action. The group has 40 members, professionals, patients and outside experts. These meet in plenary meetings or in specific working sessions and intervene at the request of any professional faced with ethical questions in the care. This Ethics Committee has voluntarily a double vocation: on one hand, a reflective group on major issues of ethics in health and its involvement in hospital life; on the other hand, a working group embedded in the daily lives of the care. The themes addressed at the meetings (plenary sessions, annual meetings) include shared-decision making, advance directives, refusal of care, religious aspects, or biomedical research… Daily activity centered on the care revolves around several times a week meetings, in various services, "Supportive Collegial Meetings" such as proposed in the 3rd French Cancer Plan; these include nursing staff members, oncologists, intensive and palliative care specialists, psychologist, around difficult medical and/or ethical situations. In case of situation requiring an urgent discussion, a referral to the Ethics Committee brings together within 24hours four to five members of the Committee and the care team. Moreover, the Ethics Committee helped develop Aid to Decision making Form upon care gradation for hospitalized cancer patients. Through these interventions on a daily basis, assistance of professionals, reflexive vocation or even delivery of training, the Ethics Committee contributes to an acculturation around anticipation and collegiality in the care. Its double polarity aims to reconcile "philosophical time' for the ethics process, and the connection with the routine issues raised by patients, their families and caregivers., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
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- 2019
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3. Nouvelles perspectives dans l’immunothérapie des cancers pédiatriques.
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Pasqualini C, Rialland F, Valteau-Couanet D, Michon J, and Minard-Colin V
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- Adolescent, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Agents, Immunological therapeutic use, Child, Combined Modality Therapy, Humans, Ipilimumab therapeutic use, Neoplasms immunology, Nivolumab therapeutic use, Tumor Microenvironment, CTLA-4 Antigen antagonists & inhibitors, Immunotherapy, Neoplasms therapy, Programmed Cell Death 1 Receptor antagonists & inhibitors
- Abstract
New Perspectives in Immunotherapies for Pediatric Malignancies: New therapeutic paradigms are needed to improve the survival of children and adolescents with high-risk malignancies, and to reduce the sequelae associated with treatment. Immunotherapies, targeting tumor cells and/or the immune system to enhance existing anti-tumor immunity or induce novel anti-tumor immune responses, are becoming increasingly successful in adult oncology. Based on the results obtained with anti-ganglioside2 antibodies in neuroblastoma, rituximab in mature B malignancies, immune checkpoint inhibitors in lymphoma and especially in Hodgkin lymphoma, blinatumomab and CAR-T CD19 cells for B-cell acute lymphoblastic leukemia, immunotherapy has demonstrated irrefutable benefits in pediatric patients. However, these results are currently limited to a minority of patients and histologies. Current and ongoing trials tend to focus on a single type of immunotherapy, but it is likely that combinations of immunotherapies with different mechanisms of action or combination with other classes of anti-cancer treatments will be additives or even synergistic. The development of this new class of drugs in the treatment of pediatric cancers has multiple challenges: to better evaluate the response to treatment, to define the optimal doses and schedules, to manage immuno-mediated toxicities, to identify its specific sequelae, and, finally, to better understand the strategies of immune evasion of pediatric cancers in order to develop efficient immunotherapies., (© 2018 Société Française du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés.)
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- 2018
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4. [High-risk neuroblastoma treatment strategy: The experience of the SIOPEN group].
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Valteau-Couanet D, Schleiermacher G, Sarnacki S, and Pasqualini C
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- Combined Modality Therapy methods, Consolidation Chemotherapy methods, Hematopoietic Stem Cell Transplantation, Humans, Immunotherapy, Induction Chemotherapy methods, Neoplasm, Residual, Neuroblastoma genetics, Radiotherapy, Adjuvant, Risk, Neuroblastoma therapy
- Abstract
High-risk neuroblastoma comprises nearly half of cases of neuroblastoma and the long-term survival is less than 50% despite complex and intensive treatments. Studies conducted in Europe and in North America in the last two decades have identified a strategy based on four therapeutic phases: an intensive induction therapy, a local control by surgery and radiation, a consolidation phase with single or tandem high dose chemotherapy and autologous transplant, and immunotherapy to eliminate residual disease. Future treatment improvements are based on progress at each of these therapeutic steps and ultimately a better stratification of the strategy adapted to the type of risk. A more extensive tumor molecular profiling at diagnosis and relapse will help to develop new therapeutics and to guide risk-based strategies. Earlier use of immunotherapy and identification of more effective combinations in induction or in maintenance treatment, identification of indications of more intense consolidations using high-dose chemotherapy combined or not with metabolic irradiation by 131I-MIBG and the introduction of other targeted treatments are tracks being explored., (Copyright © 2018. Published by Elsevier Masson SAS.)
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- 2018
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5. [Treatment-related cardiotoxicity in childhood cancer survivors: Risk factors and follow-up].
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Fresneau B, Fayech C, Butel T, Haddy N, Valteau-Couanet D, and Ou P
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- Adult, Age of Onset, Antibiotics, Antineoplastic adverse effects, Cardiomyopathies epidemiology, Cardiomyopathies therapy, Cardiotoxicity, Child, Follow-Up Studies, Heart Diseases epidemiology, Heart Diseases therapy, Humans, Neoplasms epidemiology, Radiation Injuries epidemiology, Radiation Injuries etiology, Radiation Injuries therapy, Risk Factors, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cardiomyopathies etiology, Heart Diseases etiology, Neoplasms drug therapy, Radiotherapy adverse effects, Survivors statistics & numerical data
- Abstract
Anthracycline-induced cardiotoxicity (ACT) is a severe complication in children and young adults that may lead to congestive heart failure. Some risk factors have been identified: high anthracycline cumulative dose, high radiation dose delivered on the cardiac area, or young age during the treatment. Primary prevention is not clearly defined in children. The dexrazoxane iron chelator seems to be interesting based on its short-term cardioprotective property in patients receiving doxorubicin-containing regimens. However, its long-term benefits remain to be determined, as well as the risk of secondary cancer. Childhood cancer survivors treated with anthracyclines are annually followed in the long-term. Trans-thoracic echocardiography is classically performed every 2 to 5 years for assessing the ventricular hemodynamics and function. Recent modern techniques including echocardiography with strain assessment and cardiac MRI seems to be promising for an early detection of myocardial impairment. Further studies are mandatory for validating their usefulness in the setting of anthracycline-induced cardiomyopathy. Recently, ACT predisposing variants in genes involved in oxydative stress and in metabolism and transport of anthracyclines have been identified. Their use in clinical practice could improve ACT risk stratification of children treated with anthracyclines-containing regimens. Predictive models combining replicated genetic variants and clinical factors need to be validated with the challenge to identify patients at high risk of cardiomyopathy. The objective is to personalize treatment strategy according to individual genetic background., (Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)
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- 2017
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6. Mutation-Independent Activation of the Anaplastic Lymphoma Kinase in Neuroblastoma.
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Regairaz M, Munier F, Sartelet H, Castaing M, Marty V, Renauleaud C, Doux C, Delbé J, Courty J, Fabre M, Ohta S, Vielh P, Michiels S, Valteau-Couanet D, and Vassal G
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- Adolescent, Anaplastic Lymphoma Kinase, Cell Line, Tumor, Cell Transformation, Neoplastic metabolism, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Mutation genetics, Phosphorylation genetics, Protein Kinase Inhibitors pharmacology, Pyridines pharmacology, Receptor Protein-Tyrosine Kinases genetics, Signal Transduction drug effects, Cell Proliferation genetics, Cell Transformation, Neoplastic drug effects, Neuroblastoma metabolism, Receptor Protein-Tyrosine Kinases metabolism
- Abstract
Activating mutations of anaplastic lymphoma kinase (ALK) have been identified as important players in neuroblastoma development. Our goal was to evaluate the significance of overall ALK activation in neuroblastoma. Expression of phosphorylated ALK, ALK, and its putative ligands, pleiotrophin and midkine, was screened in 289 neuroblastomas and 56 paired normal tissues. ALK was expressed in 99% of tumors and phosphorylated in 48% of cases. Pleiotrophin and midkine were expressed in 58% and 79% of tumors, respectively. ALK activation was significantly higher in tumors than in paired normal tissues, together with ALK and midkine expression. ALK activation was largely independent of mutations and correlated with midkine expression in tumors. ALK activation in tumors was associated with favorable features, including a younger age at diagnosis, hyperdiploidy, and detection by mass screening. Antitumor activity of the ALK inhibitor TAE684 was evaluated in wild-type or mutated ALK neuroblastoma cell lines and xenografts. TAE684 was cytotoxic in vitro in all cell lines, especially those harboring an ALK mutation. TAE684 efficiently inhibited ALK phosphorylation in vivo in both F1174I and R1275Q xenografts but demonstrated antitumor activity only against the R1275Q xenograft. In conclusion, ALK activation occurs frequently during neuroblastoma oncogenesis, mainly through mutation-independent mechanisms. However, ALK activation is not associated with a poor outcome and is not always a driver of cell proliferation and/or survival in neuroblastoma., (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2016
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7. [Multidisciplinarity, education, and training in pediatric oncology-hematology].
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Vassal G, Landman-Parker J, Baruchel A, Bergeron C, Rubie H, Coze C, Chastagner P, Leverger G, Bertrand Y, Valteau-Couanet D, Michon J, Couanet D, Rivière AM, Avenell D, Pérel Y, and Doz F
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- Adolescent, Child, France, Humans, Interdisciplinary Communication, Neoplasms therapy, Surveys and Questionnaires, Hematology education, Medical Oncology education, Pediatrics education
- Abstract
Introduction: According to the European Society of Pediatric Oncology (SIOPE) standard of care guidelines, high-quality care of children and adolescents with cancer needs to be delivered by well-trained multidisciplinary teams in specialist centers working with designated shared-care local centers in a so-called hub-and-spoke model. The Diplôme Inter-Universitaire d'Oncologie Pédiatrique (DIUOP) is the only European training program in pediatric oncology in French for all physicians involved in care of patients with pediatric malignancies. In agreement with the SIOPE syllabus, the DIUOP is composed of training courses (120h), on-site practical training in a specialist center, and a research project to be defended before an examining board., Method: All graduates received a questionnaire to describe their current professional position. A comprehensive PubMed analysis retrieved all papers published form DIUOP research projects., Results: From 2000 to 2011, 290 physicians were trained: 242 pediatricians, 21 surgeons, and 19 radiation therapists. Eight had another specialty including imaging, hematology, and pathology. Ninety-two were initially trained outside of France: 50% in Europe (mainly in Italy, Belgium, and Switzerland), 42% in Africa and the Middle East, and 8% in South America. Of the 266 graduates, 74% answered the questionnaire, and 90% of them take care of children and adolescents with cancer. Sixty-nine articles, i.e., one out of four research projects, were published in 34 journals with a median impact factor of 3.5 (0-22.6), 85% in English., Conclusion: DIUOP is the only French-speaking European education program providing a high-quality, professionalizing, and comprehensive multidisciplinary training program for French and international specialists taking care of children and adolescents with cancer., (Copyright © 2015. Published by Elsevier SAS.)
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- 2015
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8. [Evaluation of a program for teenagers going back to high-school].
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Dugas K, Rollin Z, Brugières L, Valteau-Couanet D, and Gaspar N
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- Adolescent, Child, Family, Female, Humans, Interpersonal Relations, Male, Surveys and Questionnaires, Faculty, Program Evaluation, Schools, Social Support, Students
- Abstract
Objective: Education of adolescent with cancer has become an imperative but is often difficult even after treatments. A special support program focusing on teacher teams and pupils was designed to limit these difficulties. After a 4-years experience, this support program was evaluated., Methods: Questionnaires (one after the intervention, another few months after) were sent to the participating families who were also proposed to be interviewed with a semi-structured list of open-ended questions. A questionnaire was also sent to the teaching staff and to the pupils., Results: On 23 interventions prepared, 15 interventions were performed: eight for pupils and seven in teacher teams. Eleven patients who benefited from these interventions responded to the first questionnaires, and seven to the second part of the study and 142 high schools pupils have responded to the questionnaires. In the comparative study, 21 patients were analysed. The interventions give useful information to teacher team, helping them understanding "invisible crippling". The program avoids bullying and questions for the patient-pupil.
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- 2014
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9. Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial.
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Corbacioglu S, Cesaro S, Faraci M, Valteau-Couanet D, Gruhn B, Rovelli A, Boelens JJ, Hewitt A, Schrum J, Schulz AS, Müller I, Stein J, Wynn R, Greil J, Sykora KW, Matthes-Martin S, Führer M, O'Meara A, Toporski J, Sedlacek P, Schlegel PG, Ehlert K, Fasth A, Winiarski J, Arvidson J, Mauz-Körholz C, Ozsahin H, Schrauder A, Bader P, Massaro J, D'Agostino R, Hoyle M, Iacobelli M, Debatin KM, Peters C, and Dini G
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- Adolescent, Bilirubin blood, Child, Child, Preschool, Female, Graft vs Host Disease epidemiology, Hepatic Veno-Occlusive Disease drug therapy, Hepatic Veno-Occlusive Disease epidemiology, Humans, Incidence, Infant, Infusions, Intravenous, Male, Multiple Organ Failure epidemiology, Renal Insufficiency epidemiology, Fibrinolytic Agents therapeutic use, Hematopoietic Stem Cell Transplantation adverse effects, Hepatic Veno-Occlusive Disease prevention & control, Polydeoxyribonucleotides therapeutic use
- Abstract
Background: Hepatic veno-occlusive disease is a leading cause of morbidity and mortality after haemopoietic stem-cell transplantation (HSCT). We aimed to assess whether defibrotide can reduce the incidence of veno-occlusive disease in this setting., Methods: In our phase 3 open-label, randomised controlled trial, we enrolled patients at 28 European university hospitals or academic medical centres. Eligible patients were younger than 18 years, had undergone myeloablative conditioning before allogeneic or autologous HSCT, and had one or more risk factor for veno-occlusive disease based on modified Seattle criteria. We centrally assigned eligible participants on the basis of a computer-generated randomisation sequence (1:1), stratified by centre and presence of osteopetrosis, to receive intravenous defibrotide prophylaxis (treatment group) or not (control group). The primary endpoint was incidence of veno-occlusive disease by 30 days after HSCT, adjudicated by a masked, independent review committee, in eligible patients who consented to randomisation (intention-to-treat population), and was assessed with a competing risk approach. Patients in either group who developed veno-occlusive disease received defibrotide for treatment. We assessed adverse events to 180 days after HSCT in all patients who received allocated prophylaxis. This trial is registered with ClinicalTrials.gov, number NCT00272948., Findings: Between Jan 25, 2006, and Jan 29, 2009, we enrolled 356 eligible patients to the intention-to-treat population. 22 (12%) of 180 patients randomly allocated to the defibrotide group had veno-occlusive disease by 30 days after HSCT compared with 35 (20%) of 176 controls (risk difference -7·7%, 95% CI -15·3 to -0·1; Z test for competing risk analysis p=0·0488; log-rank test p=0·0507). 154 (87%) of 177 patients in the defibrotide group had adverse events by day 180 compared with 155 (88%) of 176 controls., Interpretation: Defibrotide prophylaxis seems to reduce incidence of veno-occlusive disease and is well tolerated. Thus, such prophylaxis could present a useful clinical option for this serious complication of HSCT., Funding: Gentium SpA, European Group for Blood and Marrow Transplantation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
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- 2012
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10. [Malignant primary cardiac tumors in childhood and adolescence].
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Fresneau B, Oberlin O, Brugières L, Valteau-Couanet D, and Patte C
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- Adolescent, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Burkitt Lymphoma drug therapy, Burkitt Lymphoma pathology, Burkitt Lymphoma surgery, Chemotherapy, Adjuvant, Combined Modality Therapy, Cough etiology, Diagnosis, Differential, Dyspnea etiology, Echocardiography, Fatal Outcome, Female, Heart Atria pathology, Heart Atria surgery, Heart Neoplasms drug therapy, Heart Neoplasms pathology, Heart Neoplasms surgery, Hemangiosarcoma drug therapy, Hemangiosarcoma pathology, Hemangiosarcoma surgery, Humans, Male, Neoplasm Recurrence, Local diagnosis, Neoplasm Recurrence, Local pathology, Neoplasm, Residual diagnosis, Neoplasm, Residual pathology, Pulmonary Heart Disease diagnosis, Pulmonary Heart Disease etiology, Sarcoma, Synovial drug therapy, Sarcoma, Synovial pathology, Sarcoma, Synovial surgery, Superior Vena Cava Syndrome diagnosis, Superior Vena Cava Syndrome etiology, Tomography, X-Ray Computed, Burkitt Lymphoma diagnosis, Heart Neoplasms diagnosis, Hemangiosarcoma diagnosis, Sarcoma, Synovial diagnosis
- Abstract
Primary heart tumors are uncommon in children. The majority of them are benign, with only 10% malignant. Among malignant cardiac tumors, sarcoma (rhabdomyosarcoma, angiosarcoma, synovial sarcoma) and lymphoma (Burkitt's lymphoma, large B-cell lymphoma, lymphoblastic lymphoma) predominate. There are few published pediatric series on malignant primary cardiac tumors. We report here 3 observations of primary malignant cardiac tumors, 2 cases of sarcoma (angiosarcoma and synovial sarcoma) and 1 case of Burkitt's lymphoma. A precise pathological diagnosis is necessary for the proper management of these patients. For sarcoma, treatment associates surgery and chemotherapy. Surgery should be as complete as possible because of the lack of chemotherapy sensitivity of some sarcomas, mainly angiosarcoma and synovial sarcoma. Therefore, the prognosis of cardiac sarcoma remains poor. For primary cardiac lymphoma, management should not be different from lymphoma in other locations. Chemotherapy is the main treatment, and surgery has to be used only when complications occur. Prognosis depends on histology and not lymphoma location, and so is better than the prognosis for sarcoma., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)
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- 2010
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11. [Homage to Olivier Hartmann (1944-2009)].
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Rubie H and Valteau-Couanet D
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- France, History, 20th Century, History, 21st Century, Hematopoietic Stem Cell Transplantation history, Medical Oncology history, Pediatrics history
- Published
- 2009
12. [Retroperitonal fibrosis and lymphoma in a 15-year-old boy].
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Milcent K, Franchi-Abella S, Larrar S, Guitton C, Valteau-Couanet D, Koné-Paut I, and Bader-Meunier B
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- Adolescent, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biopsy, Humans, Lymph Nodes pathology, Magnetic Resonance Imaging, Male, Treatment Outcome, Lymphoma, Large-Cell, Anaplastic drug therapy, Lymphoma, Large-Cell, Anaplastic pathology, Retroperitoneal Fibrosis diagnosis, Retroperitoneal Fibrosis etiology
- Abstract
Retroperitoneal fibrosis (RF) is a rare disease in children. We report the case of a 15-year-old boy who presented with a 2-month history of dorsal pain and a 2-week history of fever. The erythrocyte sedimentation rate and serum C-reactive protein value were high. Magnetic resonance imaging revealed a large heterogeneous retroperitoneal mass, suggestive of RF. Percutaneous biopsy of inguinal lymph node provided the diagnosis of anaplastic large cell lymphoma. This is the first report of RF revealing malignancy in childhood. It emphasizes that malignancy must be carefully searched for in children with unexplained RF.
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- 2008
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13. [Malignant ovarian tumors in childhood].
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Valteau-Couanet D, Dubrel M, Dufour C, Couanet D, Hartmann O, and Patte C
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- Child, Endocrine Gland Neoplasms epidemiology, Female, Humans, Male, Neoplasm Staging, Ovarian Neoplasms pathology, Testicular Neoplasms epidemiology, Ovarian Neoplasms epidemiology
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- 2008
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14. [Prognosis of neuroblastoma in childhood. Methods of assessment and clinical use].
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Pérel Y, Valteau-Couanet D, Michon J, Lavrand F, Coze C, Bergeron C, Notz A, Plantaz D, Chastagner P, Bernard F, Thomas C, and Rubie H
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- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Child, Preschool, Humans, Infant, Infant, Newborn, Neuroblastoma genetics, Neuroblastoma therapy, Patient Selection, Prognosis, Risk Factors, Stem Cell Transplantation, Genetic Markers, Neoplasm Staging, Neuroblastoma pathology
- Abstract
Neuroblastoma and its benign counterpart, ganglioneuroma, are pediatric neuroblastic tumors arising in the sympathetic nervous system from neural-crest cells. Neuroblastoma, the most common extra-cranial solid tumour during childhood, is unique for its broad spectrum of clinical virulence from spontaneous remission to rapid and fatal progression despite intensive multimodality therapy. To a large extent, outcome could be predicted by the stage of disease and the age at diagnosis. However, a number of molecular events in neuroblastoma tumors, accounting for the variability of outcome and response to therapy, have been identified over the past decades. Among these, MYCN amplification is the most relevant prognostic factor and was the first genetic marker, in paediatric oncology, to be included in clinical strategies as a guide for therapeutic decision. This has allowed the most suitable intensity of therapy to be delivered according to a risk-stratified strategy, from observation to megadose chemotherapy with stem cell transplantation. Recent advances in understanding the biology and genetics of neuroblastoma will ultimately allow to select poor-risk patients for appropriate future biologically based therapies.
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- 2004
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15. [Neonatal localized neuroblastoma: 52 cases treated from 1990 to 1999].
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Michalowski MB, Rubie H, Michon J, Montamat S, Bergeron C, Coze C, Perel Y, Valteau-Couanet D, Guitard J, Guys JM, Piolat C, Munzer C, and Plantaz D
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- Female, Humans, Infant, Newborn, Infant, Newborn, Diseases, Male, Neuroblastoma pathology, Prognosis, Retrospective Studies, Survival Analysis, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neuroblastoma drug therapy, Neuroblastoma surgery
- Abstract
Unlabelled: Neuroblastoma is the most frequent tumor observed in the newborn. The aim of this study was to review clinical features, treatment and outcome of newborns diagnosed with a localized neuroblastoma., Population and Methods: Data from 52 cases treated according to the NBL 90 and 94 protocols between 1990 and 1999 in 18 French centers of pediatric oncology were analyzed., Results: The median age at diagnosis was 12 days (range 0-28) with antenatal detection in 14 patients (27%). Tumor location was abdominal in 40 patients (adrenal in 20 of the 40), thoracic in eight, pelvic in three, and cervical in one. N-myc amplification was observed in one out of 40 evaluable cases. The size of the primary tumor was less than 5 cm in 25 cases, between 5 and 10 cm in 25 and more than 10 cm in two. Dumbbell tumor was observed in seven, of whom five had neurological deficit. One child died from hemorrhage after fine needle biopsy during diagnostic procedure. Primary surgical resection was attempted in 37 infants, of whom two died of surgery related complications and three had nephrectomy. Tumor was deemed as unresectable in 14 patients, and primary chemotherapy was given followed by surgical excision in 12. One of them died a few days after the beginning of chemotherapy. As a whole, continuous complete remission was achieved in 48 children, four of them after relapse. Overall survival was 92% with a median follow-up of 46 months (0-113 months)., Conclusion: The excellent prognosis of localized NB in neonates needs very restrictive surgical indications, with well-established anatomic and imaging criteria. Indeed, chemotherapy based on weight and managed by expert teams should allow to perform surgical excision in safer conditions for unresectable tumors.
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- 2004
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16. [Pseudotumoral diseases: ten years of experience in a pediatric oncology department].
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Raimondo G, Ridola V, Brugières L, Couanet D, Valteau-Couanet D, Grill J, Pein F, and Hartmann O
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- Child, Diagnosis, Differential, False Positive Reactions, Female, Humans, Male, Medical Oncology, Pediatrics, Referral and Consultation, Retrospective Studies, Abdominal Neoplasms diagnosis, Bone Neoplasms diagnosis, Diagnostic Errors, Soft Tissue Neoplasms diagnosis
- Abstract
Purpose: Among the 350 new patients per year treated in the pediatric oncology department of the Gustave-Roussy Institute, about 2% have no tumor. This study analyzes these children presenting a pseudotumoral disease., Patients and Methods: Ten-year-retrospective study. Patients for which no follow up in oncology was necessary after one consultation or hospitalization were selected., Outcome: Between 1990 and 2000, 64 patients were seen in the pediatric department for pseudotumoral disease. The reasons of orientation were mainly a soft tissue mass (15 cases), an abdominal mass (14 cases), or a bone lesion (13 cases). Diagnosis was most often infectious diseases (33 cases), or post-traumatic lesions (10 cases). Diagnosis was established following several consultations or an hospitalization for 29 of 64 patients. In 75% of the cases new investigations were necessary to determine the diagnosis. A biopsy was performed in 19. For two children, diagnosis was corrected after the beginning of chemotherapy., Conclusion: Pseudotumoral diseases leading to a consultation in pediatric oncology are rare and represent two per cent of the patients. For these difficult cases, only a pluridisciplinary discussion may lead to diagnosis.
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- 2002
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17. [Difficulties in coping with treatment: causes, solutions].
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Oppenheim D, Corradini N, Valteau-Couanet D, and Hartmann O
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- Attitude of Health Personnel, Cerebellar Neoplasms therapy, Child, Dissent and Disputes, Female, Humans, Male, Medulloblastoma therapy, Patient Satisfaction, Cerebellar Neoplasms psychology, Maternal Behavior, Medulloblastoma psychology, Paternal Behavior, Professional-Family Relations
- Abstract
We present a case of parents who had difficulties accepting their child's treatment (HD chemotherapy and stem cell transplantation) and coping with it. The conversation between the paediatrician and the mother revealed that she feared being dispossessed of her maternal role by the nurses, that constraints would interfere with her relationship with her son, that the medical team would make her feel intellectually, culturally and socially inferior, that the conflict the couple was facing would be exacerbated in this setting. Collaboration between the paediatrician, the nursing staff and the psycho-oncologist allowed these conscious and unconscious elements to be understood. Talking, not conflict nor constraints, served to allay their fears, to avoid inappropriate reactions of the medical team, to preserve the therapeutic alliance. The child accepted this trying treatment because he saw that his parents were reassured about its quality and about preserving their sense of identity and their value. Coping difficulties may stem from fear of treatment (too trying physically and psychologically), from its consequences (destabilisation of the family, the individual's social and professional status, his/her sense of identity), from rekindled old problems that were not adequately solved (jealousy, revolt, trauma, bereavement). Dialogue and team work are necessary to solve them.
- Published
- 2002
18. Dendritic cells for NK/LAK activation: rationale for multicellular immunotherapy in neuroblastoma patients.
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Valteau-Couanet D, Leboulaire C, Maincent K, Tournier M, Hartmann O, Bénard J, Beaujean F, Boccaccio C, Zitvogel L, and Angevin E
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- Cell Survival immunology, Child, Child, Preschool, Humans, Immunophenotyping, Monocytes immunology, Neuroblastoma immunology, Dendritic Cells immunology, Immunotherapy methods, Killer Cells, Lymphokine-Activated immunology, Killer Cells, Natural immunology, Lymphocyte Activation immunology, Neuroblastoma therapy
- Abstract
Natural killer (NK)/lymphokine-activated killer (LAK) cell-based immunotherapy could be beneficial against major histocompatibility complex class I-negative tumor residual disease such as neuroblastoma (NB), provided that interleukin 2 (IL-2) or surrogate nontoxic NK cell stimulatory factors could sustain NK cell activation and survival in vivo. Here we show that human monocyte-derived dendritic cells (MD-DCs) promote potent NK/LAK effector functions and long-term survival, circumventing the need for IL-2. This study demonstrates (1) the feasibility of differentiating granulocyte colony-stimulating factor-mobilized hematopoietic peripheral blood stem cells (PBSCs) into high numbers of functional MD-DCs and NK/LAK cells in a series of 12 children with stage 4 neuroblastoma (NB); (2) potent DC-mediated NK cell activation in autologous settings; (3) the reciprocal capacity of NK/LAK cells to turn immature DCs into maturing cells electively capable of triggering NK cell functions; and (4) the unique capacity of maturing DCs to sustain NK cell survival, superior to that achieved in IL-2. These data show a reciprocal interaction between DCs and NK/LAK cells, leading to the amplification of NK cell effector functions, and support the implementation of DC/NK cell-based immunotherapy for purging the graft and/or controlling minimal residual disease after autologous stem cell transplantation.
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- 2002
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19. In vivo elimination of acentric double minutes containing amplified MYCN from neuroblastoma tumor cells through the formation of micronuclei.
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Valent A, Bénard J, Clausse B, Barrois M, Valteau-Couanet D, Terrier-Lacombe MJ, Spengler B, and Bernheim A
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- Child, Preschool, DNA, Neoplasm genetics, Gene Amplification, Humans, In Situ Hybridization, Fluorescence, Infant, Micronuclei, Chromosome-Defective genetics, Micronucleus Tests, Neuroblastoma pathology, Polymerase Chain Reaction, Genes, myc genetics, Micronuclei, Chromosome-Defective metabolism, Neuroblastoma genetics
- Abstract
Neuroblastoma, the most common solid extracranial neoplasm in children, shows an appreciable variability in clinical evolution. Amplification of the MYCN oncogene in this tumor is detected in 25 to 30% of cases and is associated with poor clinical outcome. In this study, quantitative polymerase chain reaction and fluorescence in situ hybridization were used to determine MYCN amplification status in 46 neuroblastoma tumors. MYCN amplification was detected in tumors from 11 patients. Fluorescence in situ hybridization revealed the presence of micronuclei containing amplified MYCN sequences in 8 of the 11 tumors. Micronuclei are indicative of spontaneous elimination or loss of amplified sequences by tumor cells. Because the elimination of amplified sequences can be enhanced in vitro by specific drugs such as hydroxyurea, our observations suggest a new therapeutic strategy specifically targeted to cells with amplified genes.
- Published
- 2001
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20. [A functional gene map is required to adapt therapy of metastatic neuroblastoma].
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Raguénez G, Douc-Rasy S, Blanc E, Goldschneider D, Barrois M, Valteau-Couanet D, and Bénard J
- Subjects
- Age Factors, Animals, Child, Child, Preschool, Gene Amplification, Humans, Infant, Mice, Models, Animal, Neoplasm Proteins metabolism, Nerve Growth Factors metabolism, Neuroblastoma drug therapy, Neuroblastoma secondary, Prognosis, Genes, myc genetics, Neuroblastoma genetics
- Abstract
Neuroblastoma is a very common solid tumor which arises in childhood and shows an extreme heterogeneity at the clinical, histological and genetic levels. Besides age and stage, N-myc amplification and 1p deletion are prognostic factors of the disease: in Europe, these genetic markers are used to conduct therapy. In France, N-myc amplification is a factor of bad prognosis which leads, in all forms of the disease including localised forms and metastatic forms of children aged of less than 1 year, to a myeloablative treatment with autologous hematopoietic stem cells transplantation. By contrast, N-myc amplification has no impact on the survival of children aged of more than 1 year with a poor prognosis (30% overall survival, 5 years) but this genetic abnormality is taken into account to treat primary tumor of these patients. In an attempt to find out prognostic factors of these aggressive forms of the disease, various pathways (apoptosis, differentiation angiogenesis, detoxication, immune response) have been recently surveyed, but studies have been carried out on a limited number of genes. Moreover, experimental models of human metastatic neuroblastoma have been obtained in which variations of genes transcript levels involved in these pathways, are observed. The current break-through of cDNA microarrays allows to develop a dynamic transcriptomic scanning of these models as well as of tumors and bone marrows from patients upon conventional chemotherapy. This technology will enable: i) to define molecular entities of the metastatic disease; ii) to apply adapted treatment; iii) to develop new therapeutic strategies.
- Published
- 2001
21. [What is new in pediatric oncology?].
- Author
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Oberlin O, Brugières L, Patte C, Kalifa C, Vassal G, Valteau-Couanet D, and Hartmann O
- Subjects
- Brain Neoplasms therapy, Burkitt Lymphoma drug therapy, Child, Genetic Predisposition to Disease, Humans, Oncogenes, Quality of Life, Medical Oncology trends, Pediatrics trends
- Abstract
The significant progress made in pediatric oncology during recent years has been due to a major breakthrough in the field of molecular biology and the introduction of new therapeutic strategies that take into account both the quality and the duration of life. Molecular biology has already been instrumental in more fully categorizing the 'small round-cell tumor' group, and in reclassifying the 'Ewing family' tumors. It also provides a valuable tool for the prognostic evaluation of neuroblastomas through the analysis of the N-myc oncogene. In addition, it has permitted the identification of the Li-Fraumeni syndrome of predisposition to cancer in the child, thereby raising the problematical ethical issue of communicating relevant information to subjects at risk. Two examples illustrate innovative strategic concepts: 1) Burkitt's lymphoma, or an example of the successful de-intensification of treatment; and 2) brain tumors in young children, regarding which the desire to improve the quality of life has led to innovative attempts to replace radiotherapy by chemotherapy. Considerable progress has been made in the field of neuropsychology, thereby permitting an improved assessment of disorders and a better management of rehabilitation programs. New anti-cancer agents and also chemo- and radiotherapy that spare healthy tissue are also being developed. Gene therapy and molecular biology will play a major role in future therapeutic strategies; and are now at the preclinical trial stage. This significant overall progress leads to a reconsideration of the organizational approach toward treatment of the pediatric patient population suffering from cancer, and a critical assessment of disease management, which should take into account not only the technical aspects of the disease but also familial and social considerations.
- Published
- 2000
- Full Text
- View/download PDF
22. [Opsoclonus-myoclonus syndrome associated with non-metastatic neuroblastoma. Long-term survival. Study of the French Society of Pediatric Oncologists].
- Author
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Plantaz D, Michon J, Valteau-Couanet D, Coze C, Chastagner P, Bergeron C, Nelken B, Martelli H, Peyroulet MC, Carpentier AF, Armari-Alla C, Pagnier A, and Rubie H
- Subjects
- Adolescent, Adrenal Cortex Hormones therapeutic use, Adult, Anticonvulsants therapeutic use, Child, Female, Humans, Immunization, Passive, Male, Paraneoplastic Syndromes, Nervous System pathology, Paraneoplastic Syndromes, Nervous System therapy, Prognosis, Prospective Studies, Retrospective Studies, Risk Factors, Survival Analysis, Treatment Outcome, Neuroblastoma complications, Paraneoplastic Syndromes, Nervous System etiology
- Abstract
Unlabelled: Opsoclonus-myoclonus is a rare syndrome characterized by multidirectional chaotic eye movements, myoclonus and ataxia. In children, it could be a paraneoplastic syndrome in association with neuroblastoma, usually with a high survival rate, but having a high frequency of neurologic and psychologic sequelae., Objectives: The aim of this study was to describe oncologic outcome (prospectively) and neurologic outcome (retrospectively) in children with non-metastatic neuroblastoma, and to determine its best treatment., Patients and Methods: Data were collected on 21 children diagnosed with localized neuroblastoma and opsoclonus-myoclonus between 1990-1999 from the French Society of Pediatric Oncology institutions., Results: Median age at diagnosis was 18 months. Location of the tumor was abdominal in 14 cases, thoracic in three cases, pelvic in three cases, and cervical in the last case. There was a majority of small tumors with a maximal diameter < 5 cm in 13 cases. Only four tumors were initially considered as unresectable tumors and received first-line chemotherapy. Complete macroscopic resection was performed in 20 cases (four after primary chemotherapy). Nine children received chemotherapy. Twenty children remained in first complete remission, and one relapsed and died (the unique NMYC amplified case). Treatment for opsoclonus-myoclonus varied widely. Only one child received no medical treatment for opsoclonus-myoclonus, because of complete resolution of neurologic symptoms after exclusive surgery. The following agents were used: corticosteroids in 18 cases, intravenously immune globulin in five cases, and antiepileptic drugs in seven cases. Ten patients experienced relapses of opsoclonus-myoclonus symptoms, mainly related to the decrease of steroid therapy (5/10). Ten of 16 assessable children had persistent neurologic deficits including speech delay or cognitive deficits (8/16), ataxia (6/16), motor delay (2/16), and behavioral problems (2/16). There is no correlation between neurologic outcome, and either age at diagnosis or duration of neurologic symptoms, or type of treatment of the tumor, particularly chemotherapy., Conclusion: Persistent neurologic deficits are characteristic for children with neuroblastoma and opsoclonus-myoclonus. Neurologic outcome seems unrelated to the treatment of neuroblastoma, which should exclusively be conducted according to oncological criteria. The treatment of opsoclonus-myoclonus should be standardized, mainly based on high-dose hydrocortisone, with a very low decreasing dosage, associated to intravenously immune globulin in severe cases. A biological immunologic work-up of the disease and cautious neurologic and psychologic standardized follow-up should be performed.
- Published
- 2000
- Full Text
- View/download PDF
23. [Carboxypeptidase-G2 rescue of methotrexate intoxication].
- Author
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Grill J, Amigo-Ferreiro ME, Schoepfer C, Bonnay M, Valteau-Couanet D, Hartmann O, and Vassal G
- Subjects
- Adolescent, Bone Neoplasms drug therapy, Humans, Male, Osteosarcoma drug therapy, Poisoning blood, Poisoning drug therapy, gamma-Glutamyl Hydrolase pharmacology, Antimetabolites, Antineoplastic poisoning, Methotrexate poisoning, gamma-Glutamyl Hydrolase therapeutic use
- Published
- 1998
24. [Research on bone marrow involvement in the diagnosis of solid tumors in children. Methods, results and interpretation].
- Author
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Pein F, Hartmann O, Sakiroglu C, Bayle C, Terrier-Lacombe MJ, Valteau-Couanet D, Lumbroso J, Oberlin O, Couanet D, and Patte C
- Subjects
- Bone Marrow Diseases pathology, Child, Humans, Methods, Bone Marrow Diseases diagnosis, Neoplasms diagnosis
- Abstract
The assessment of bone marrow involvement by tumor cells remains an essential problem at diagnosis in pediatric solid tumors. Besides the conventional cytological and histological methods, some modern cell density separation techniques have been described in order to improve the detection of minimal or scattered bone marrow involvement. Immunological or genetical (molecular biology) tools can be used for the recognition of separated cells. In terms of investigations, MRI and MIBG radionucleide scan, although giving no definite proof, have the ability to macroscopically study the scattering of bone marrow invasion in the particular case of neuroblastoma. In some pediatric tumors, especially neuroblastomas and non Hodgkin lymphomas, an extensive bone marrow investigation is mandatory at diagnosis. Such an investigation is only necessary in case of particular criteria at diagnosis of Hodgkin's disease, Ewing' sarcomas, rhabdomyosarcomas and retinoblastomas. All other pediatric solid tumors do not need to be investigated in terms of bone marrow involvement at diagnosis, with the exceptions of advanced disseminated disease or if an autologous bone marrow transplantation is planned.
- Published
- 1995
- Full Text
- View/download PDF
25. [High dose chemotherapy followed by autologous bone marrow graft in solid tumors in children: arguments for].
- Author
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Hartmann O, Valteau-Couanet D, and Benhamou E
- Subjects
- Child, Child, Preschool, Combined Modality Therapy, Dose-Response Relationship, Drug, Follow-Up Studies, Humans, Neoplasm Metastasis, Neoplasms mortality, Neuroblastoma mortality, Remission Induction, Sarcoma, Ewing mortality, Survival Rate, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation, Neoplasms therapy, Neuroblastoma therapy, Sarcoma, Ewing therapy
- Abstract
Arguments for the use of high-dose chemotherapy followed by autologous bone marrow transplantation in pediatric solid tumors are discussed. The dose effect relationship in pediatric oncology conventional chemotherapy is emphasized. Results of high-dose chemotherapy followed by autologous bone marrow transplantation are encouraging in metastatic neuroblastoma and Ewing's sarcoma. The probability of event free survival is increased of about 30% as compared to that of conventional treatments. This therapeutic approach could be of value in other pediatric solid tumors, particularly in some poor prognosis forms of Wilm's tumors. However, until now, the results remain preliminary. On the other hand, the role of this strategy in chemoresistant tumors, such as malignant gliomas, remains under investigation.
- Published
- 1995
26. [Humoral immunity and infections during bone marrow transplantation in children: study of 127 transplanted patients successively in a same center].
- Author
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Grill J, Robert-Le Deley MC, Valteau-Couanet D, Brugières L, Kalifa C, and Hartmann O
- Subjects
- Adolescent, Adult, Antibody Formation, Child, Child, Preschool, Humans, Immunocompromised Host, Infant, Neoplasms drug therapy, Neoplasms therapy, Sepsis epidemiology, Sepsis etiology, Sepsis immunology, Transplantation, Autologous, Bone Marrow Transplantation immunology, Immunoglobulins analysis, Transplantation Immunology
- Abstract
Background: Children with malignant diseases are frequently given high dose chemotherapy plus autologous bone marrow transplants. Infectious complications can lead to morbidity and mortality in this type of treatment. This study was designed to determine whether immunoglobulin deficiency is an additional risk factor for infections., Patients and Methods: One hundred and twenty seven children with solid malignant tumors were treated between November 1987 and April 1992 in our Department by chemotherapy followed by autologous bone marrow transplantation. Their serum IgA, IgG and IgM concentrations were measured by nephelometry before chemotherapy, on the day of transplantation and every week thereafter. The frequency and severity of infectious episodes in all the children were recorded using a standard scale. The patients were divided into two subgroups, defined according to their serum IgG concentrations before the transplantation and 7 and 21 days later. RESULTS-Ig deficiency during transplantation was not associated with the occurrence of septicemia or focal infections. It was associated with the course of infection (P = 0.003) and with the occurrence of zoster virus infection during the first 6 months after transplantation (P = 0.003)., Conclusions: Immune replacement during bone marrow transplantation may be indicated in children at risk of Ig deficiency. Fifty percent of the children with solid tumors treated in our institution were at risk of this deficiency.
- Published
- 1994
27. [Place of CSF in pediatric oncology].
- Author
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Hartmann O and Valteau-Couanet D
- Subjects
- Adolescent, Antineoplastic Agents adverse effects, Antineoplastic Agents therapeutic use, Child, Child, Preschool, Drug Therapy, Combination, Humans, Infant, Infant, Newborn, Neutropenia chemically induced, Granulocyte Colony-Stimulating Factor therapeutic use, Granulocyte-Macrophage Colony-Stimulating Factor therapeutic use, Neoplasms drug therapy, Neutropenia drug therapy
- Published
- 1993
28. Is 600 mg/m2 the appropriate dosage of busulfan in children undergoing bone marrow transplantation?
- Author
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Vassal G, Deroussent A, Challine D, Hartmann O, Koscielny S, Valteau-Couanet D, Lemerle J, and Gouyette A
- Subjects
- Adolescent, Age Factors, Busulfan pharmacokinetics, Child, Child, Preschool, Drug Monitoring, Female, Humans, Infant, Male, Bone Marrow Transplantation, Busulfan administration & dosage
- Abstract
Recent studies have reported that the pharmacokinetics of high-dose busulfan in bone marrow transplantation (BMT) are age-dependent: with the usual dosage of 16 mg/kg over 4 days, systemic exposure is two to four times lower in children than in adults. Data suggested that the dose of busulfan should rather be calculated on the basis of the body surface area (BSA). We measured plasma pharmacokinetics of busulfan in 27 children (mean age, 5.4 years) who were administered a new dosage of 600 mg/m2 over 4 days, ie, 17.8 to 29.2 mg/kg (mean, 24.8 mg/kg), using a gas chromatography-mass spectrometry assay. Our results demonstrate that, with this new dosage, systemic exposure is significantly increased in children compared with that achieved with the usual dosage of 16 mg/kg (6,404 +/- 2,378 v 3,918 +/- 1,170 ng.h/mL; P = .003). Moreover, there is no longer a significant difference in systemic exposure between children treated with this new dosage and adults given a dose of 16 mg/kg of busulfan. However, despite the use of a dosage normalized to the BSA, there is still a wide interindividual variation in systemic exposure, ranging from 3,566 to 13,129 ng.h/mL, which may account for the high incidence of venoocclusive disease (VOD) of the liver that we have already reported. The optimal dosage and schedule of busulfan in children requires a more individual approach that could be based on dose adjustment and plasma level monitoring.
- Published
- 1992
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