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Testing for SARS-CoV-2 is central to COVID-19 management. Rapid antigen test from self-collected anterior nasal swabs (SCANS-RAT) are often used in children but their performance have not been assessed in real-life. We aimed to compare this testing method to the two methods usually used: reverse transcription polymerase chain reaction from nasopharyngeal swabs collected by healthcare workers (HCW-PCR) and rapid antigen test from nasopharyngeal swabs collected by healthcare workers (HCW-RAT), estimating the accuracy and acceptance, in a pediatric real-life study. From September 2021 to January 2022, we performed a manufacturer-independent cross-sectional, prospective, multicenter study involving 74 pediatric ambulatory centers and 5 emergency units throughout France. Children ≥6 months to 15 years old with suggestive symptoms of COVID-19 or children in contact with a COVID-19-positive patient were prospectively enrolled. We included 836 children (median 4 years), 774 (92.6%) were symptomatic. The comparators were HCW-PCR for 267 children, and HCW-RAT for 593 children. The sensitivity of the SCANS-RAT test compared to HCW-RAT was 91.3% (95%CI 82.8; 96.4). Sensitivity was 70.4% (95%CI 59.2; 80.0) compared to all HCW-PCR and 84.6% (95%CI 71.9; 93.1) when considering cycle threshold <33. The specificity was always >97%. Among children aged ≥6 years, 90.9% of SCANS-RAT were self-collected without adult intervention. On appreciation rating (from 1, very pleasant, to 10, very unpleasant), 77.9% of children chose a score ≤3. SCANS-RAT have good sensitivity and specificity and are well accepted by children. A repeated screening strategy using these tests can play a major role in controlling the pandemic.
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Importance: An association between pneumococcal nasopharyngeal carriage and invasive pneumococcal disease (IPD) has been previously established. However, it is unclear whether the decrease in IPD incidence observed after implementation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic was associated with concomitant changes in pneumococcal carriage and respiratory viral infections. Objective: To assess changes in IPD incidence after the implementation of NPIs during the COVID-19 pandemic and examine their temporal association with changes in pneumococcal carriage rate and respiratory viral infections (specifically respiratory syncytial virus [RSV] and influenza cases) among children in France. Design, Setting, and Participants: This cohort study used interrupted time series analysis of data from ambulatory and hospital-based national continuous surveillance systems of pneumococcal carriage, RSV and influenza-related diseases, and IPD between January 1, 2007, and March 31, 2021. Participants included 11 944 children younger than 15 years in France. Exposures: Implementation of NPIs during the COVID-19 pandemic. Main Outcomes and Measures: The estimated fraction of IPD change after implementation of NPIs and the association of this change with concomitant changes in pneumococcal carriage rate and RSV and influenza cases among children younger than 15 years. The estimated fraction of change was analyzed using a quasi-Poisson regression model. Results: During the study period, 5113 children (median [IQR] age, 1.0 [0.6-4.0] years; 2959 boys [57.9%]) had IPD, and 6831 healthy children (median [IQR] age, 1.5 [0.9-3.9] years; 3534 boys [51.7%]) received a swab test. Data on race and ethnicity were not collected. After NPI implementation, IPD incidence decreased by 63% (95% CI, -82% to -43%; P < .001) and was similar for non-13-valent pneumococcal conjugate vaccine serotypes with both high disease potential (-63%; 95% CI, -77% to -48%; P < .001) and low disease potential (-53%; 95% CI, -70% to -35%; P < .001). The overall pneumococcal carriage rate did not significantly change after NPI implementation (-12%; 95% CI, -37% to 12%; P = .32), nor did the carriage rate for non-PCV13 serotypes with high disease potential (-26%; 95% CI, -100% to 52%; P = .50) or low disease potential (-7%; 95% CI, -34% to 20%; P = .61). After NPI implementation, the estimated number of influenza cases decreased by 91% (95% CI, -74% to -97%; P < .001), and the estimated number of RSV cases decreased by 74% (95% CI, -55% to -85%; P < .001). Overall, the decrease in influenza and RSV cases accounted for 53% (95% CI, -28% to -78%; P < .001) and 40% (95% CI, -15% to -65%; P = .002) of the decrease in IPD incidence during the NPI period, respectively. The decrease in IPD incidence was not associated with pneumococcal carriage, with carriage accounting for only 4% (95% CI, -7% to 15%; P = .49) of the decrease. Conclusions and Relevance: In this cohort study of data from multiple national continuous surveillance systems, a decrease in pediatric IPD incidence occurred after the implementation of NPIs in France; this decrease was associated with a decrease in viral infection cases rather than pneumococcal carriage rate. The association between pneumococcal carriage and IPD was potentially modified by changes in the number of RSV and influenza cases, suggesting that interventions targeting respiratory viruses, such as immunoprophylaxis or vaccines for RSV and influenza, may be able to prevent a large proportion of pediatric IPD cases.
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COVID-19 , Vacinas contra Influenza , Influenza Humana , Infecções Pneumocócicas , Vírus , COVID-19/epidemiologia , Criança , Estudos de Coortes , Humanos , Lactente , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Masculino , Pandemias , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Streptococcus pneumoniaeRESUMO
The Parents and Caregivers group in the face of ethics in pediatrics of the Île-de-France Ethics Area wondered about the association of the words Disability and Cancer by focusing on the study of the course of children with intellectual disability, treated for cancer. These situations are exceptional, the number of cases in France must not be more than fifty per year. We gathered the testimony of five families of children using a semi-directive survey taking up the journey from birth, announcement of the handicap, the diagnosis of cancer and its treatment. The verbatim show that each story is unique and rich in lessons, despite the feeling of "double penalty": "He did not deserve this, a handicap plus cancer is a lot for one person", "the shot moreover." A healthcare team was also interviewed and raised an additional question: "First, the double penalty then, what's the point?" Through these testimonies, we sought to question the ethical principles of care, which can be shaken up in these extraordinary supported.
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Temas Bioéticos , Tomada de Decisão Clínica/ética , Crianças com Deficiência , Deficiência Intelectual , Neoplasias/terapia , Agenesia do Corpo Caloso/diagnóstico , Agenesia do Corpo Caloso/psicologia , Cuidadores , Criança , Pré-Escolar , Crianças com Deficiência/estatística & dados numéricos , Síndrome de Down/diagnóstico , Síndrome de Down/psicologia , Família/psicologia , Relações Familiares , Feminino , Síndrome do Cromossomo X Frágil/diagnóstico , Síndrome do Cromossomo X Frágil/psicologia , França/epidemiologia , Humanos , Lactente , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/psicologia , Masculino , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/psicologia , Pais/psicologia , Autonomia Pessoal , Pesquisa Qualitativa , Revelação da VerdadeRESUMO
AIM: The aim was to describe and to analyze the ethics of decision-making in situations involving children with intellectual disability and cancer, from the referent-doctor's point-of-view, in pediatric oncology units in France. METHODS: Pediatricians working in pediatric oncology units were interviewed through an online questionnaire and a semi-directive interview was systematically proposed. We analyzed the ethical issues that arose during the process of decision-making and we made suggestions in order to address them. RESULTS: Sixteen doctors reported twenty-one clinical cases. Of these cases, one third of the children had a change in their oncologic treatment, with a risk of pejorative outcome on the prognosis. Despite the fact that ethical issues appeared in 80 % of the cases, there were few consultations with ethical committees. Decision-making process showed no difference compared to children without intellectual disability, thus raising ethical issues in the medical team. Our study showed discrepancy between frequently reported ethical issues, high consensus rate regarding treatment decision and lack of consultation with ethical committees. DISCUSSION: We propose three steps to guide the decision-making process in situations involving children with intellectual disability and cancer: 1/deeper understanding of the child through reinforced interactions with their caregivers, 2/better cross-boundary discussions, to improve the effectiveness of the multidisciplinary staff, and 3/more systematic ethical committees consultation.
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Tomada de Decisão Clínica/ética , Crianças com Deficiência , Pesquisas sobre Atenção à Saúde , Deficiência Intelectual , Neoplasias/terapia , Adolescente , Adulto , Temas Bioéticos , Criança , Pré-Escolar , Tomada de Decisão Clínica/métodos , Consenso , Técnicas de Apoio para a Decisão , Comitês de Ética Clínica/estatística & dados numéricos , Feminino , França , Humanos , Lactente , Deficiência Intelectual/complicações , Masculino , Neoplasias/complicações , Neoplasias/patologia , Cuidados Paliativos , Equipe de Assistência ao Paciente , Medição de Risco , Revelação da Verdade , Adulto JovemRESUMO
OBJECTIVE: To analyse parents' and children's understanding of consent information and assess their decision-making process in paediatric oncology. DESIGN: Prospective observational study. SETTINGS: Eleven French paediatric oncology units. PATIENTS: Parents and children who have been asked to give consent for participation in an early phase trial. INTERVENTIONS: Thirty-seven children and 119 parents were questioned using an audio-recorded semistructured interview. MAIN OUTCOME MEASURES: The participants' understanding of nine elements of the informed consent was assessed by comparing their answers with the informed consent leaflet. Their decision-making process was also evaluated. RESULTS: Most parents and children had an excellent understanding regarding their participation in a clinical trial (respectively 88.2% and 48.6%), the right to withdraw (76.5% and 43.2%) and the prospects of collective benefits (74.8% and 48.6%). By contrast, less than half of the parents and few of the children correctly understood the alternatives (respectively 47.5% and 27%), the risks related to participation (44.5% and 10.8%), the prospects of individual benefits (33.6% and 10.8%) and the purpose of the clinical trial (12.6% and 2.7%). Twenty-six (70.3%) children participated in the decision-making process. Most parents and children felt they had no choice but to participate in the trial to have access to a new anticancer treatment. CONCLUSIONS: What might appear to be a poor understanding of the research protocol may actually correspond to the families' interpretation of the situation as a coping mechanism. All children (except infants) should get age-tailored information in order for them to have a meaningful involvement in research.
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Ensaios Clínicos Fase I como Assunto , Compreensão , Tomada de Decisões , Consentimento Livre e Esclarecido , Pais , Participação do Paciente , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Neoplasias/terapia , Estudos ProspectivosRESUMO
Central nervous system (CNS) involvement at diagnosis of pediatric acute myeloid leukemia (AML) is not considered as an independent prognostic factor. This study describes the prognostic value of pediatric AML with CNS involvement at diagnosis. Pediatric patients were treated for de novo AML in the French multicenter trial ELAM02. Lumbar puncture was carried out in the first week, and the treatment was adapted to the CNS status. No patient received CNS radiotherapy. The patients were classified into 2 groups: CNS+ and CNS-. Of the 438 patients, 16% (n=70) had CNS involvement at diagnosis, and 29% showed clinical signs. The patients with CNS disease were younger (40% were below 2 y old), had a higher white blood cell count (median of 45 vs. 13 G/L), and had M4 and M5 morphologies. The complete remission rate was similar at 92.8% for CNS+ and 88.5% for CNS-. There was no significant difference between the CNS+ and the CNS- group in overall survival (76% and 71%, respectively) and event-free survival (57% and 52%, respectively). Regarding the occurrence of first relapse, the CNS+ group had a higher combined relapse rate of 26.1% compared with 10% for the CNS- group. The results indicate that CNS involvement at diagnosis of pediatric AML is not an independent prognostic factor. Triple intrathecal chemotherapy combined with high-dose intravenous cytarabine should be the first-line treatment for CNS disease.
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Neoplasias do Sistema Nervoso Central/diagnóstico , Leucemia Mieloide Aguda/diagnóstico , Prognóstico , Adolescente , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Casos e Controles , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/mortalidade , Criança , Pré-Escolar , Citarabina/administração & dosagem , França , Humanos , Lactente , Leucemia Monocítica Aguda , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mielomonocítica Aguda , Contagem de Leucócitos , Recidiva , Análise de SobrevidaRESUMO
Despite significant progress in the treatment of pediatric acute myeloblastic leukemia (AML), relapse remains the commonest cause of death. Randomized ELAM02 trial questioned if maintenance therapy with interleukin-2 (IL2), for 1 year, improves disease-free survival (DFS). Patients aged 0 to 18 years, with newly diagnosed AML (excluding patients with acute promyelocytic leukemia or down syndrome AML) were enrolled. They received 1 course of induction treatment (cytarabine and mitoxantrone) and 3 courses of consolidation treatment (high-dose cytarabine in courses 1 and 3). According to the cytogenetics risk, patients not undergoing hematopoietic stem cell transplantation, still in complete remission (CR) after the third course of consolidation treatment, were eligible for randomization to 1 year of maintenance therapy with monthly courses of IL2 or no maintenance treatment. There were 438 evaluable patients, 154 of whom were randomized to the IL2/no maintenance groups. Relapse occurred in 28 patients from the IL2+ group and 29 patients in the IL2- group. Survival was similar in the 2 groups, with a 4-year DFS of 62% without IL2 and 66% with IL2 (Pâ=â0.75). In the CBF population, 4-year DFS was 55% without IL2 and 78% with IL2 (Pâ=â0.07). No deaths from toxicity or excess of serious adverse events related to IL2 treatment were recorded. Prolonged IL2 for maintenance therapy after intensive chemotherapy is feasible and safe in pediatric AML patients in their first CR. Such treatment did not improve DFS in this study, but a positive trend was observed in favor of IL2 maintenance therapy among core binding factor acute myeloblastic leukemia.
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OBJECTIVE: To assess quality of life and satisfaction regarding immunoglobulin-replacement therapy (IgRT) treatment according to the route (intravenous Ig [IVIg] or subcutaneous Ig [SCIg]) and place of administration (home-based IgRT or hospital-based IgRT). SUBJECTS AND METHODS: Children 5-15 years old treated for primary immunodeficiency disease (PIDD) with IgRT for ≥3 months were included in a prospective, noninterventional cohort study and followed over 12 months. Quality of life was assessed with the Child Health Questionnaire - parent form (CHQ-PF)-50 questionnaire. Satisfaction with IgRT was measured with a three-dimensional scale (Life Quality Index [LQI] with three components: factor I [FI], treatment interference; FII, therapy-related problems; FIII, therapy settings). RESULTS: A total of 44 children (9.7±3.2 years old) receiving IgRT for a mean of 5.6±4.5 years (median 4.1 years) entered the study: 18 (40.9%) were receiving hospital-based IVIg, two (4.6%) were receiving home-based IVIg, and 24 (54.6%) were treated by home-based SCIg. LQI FIII was higher for home-based SCIg than for hospital-based IVIg (P=0.0003), but there was no difference for LQI FI or LQI FII. LQI FIII significantly improved in five patients who switched from IVIg to SCIg during the follow-up when compared to patients who pursued the same regimen (either IVIg or SCIg). No difference was found on CHQ-PF50 subscales, LQI FI, or LQI FII. CONCLUSION: Home-based SCIg gave higher satisfaction regarding therapy settings than hospital-based IVIg. No difference was found on other subscales of the LQI or CHQ-PF50 between hospital-based IVIG and home-based SCIG.
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Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/patologia , Polipose Intestinal/diagnóstico , Polipose Intestinal/patologia , Dor Abdominal , Adolescente , Linfoma de Burkitt/terapia , Tratamento Farmacológico , Humanos , Polipose Intestinal/terapia , Masculino , Resultado do TratamentoAssuntos
Doenças do Sistema Nervoso Autônomo/etiologia , Rubor/etiologia , Hipo-Hidrose/etiologia , Neuroblastoma/cirurgia , Complicações Pós-Operatórias/etiologia , Gânglio Estrelado/patologia , Doenças do Sistema Nervoso Autônomo/diagnóstico , Feminino , Rubor/diagnóstico , Humanos , Hipo-Hidrose/diagnóstico , Lactente , Gânglio Estrelado/cirurgia , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: This retrospective cohort study aimed to determine the predictive relevance of clinical characteristics, additional cytogenetic aberrations, and cKIT and RAS mutations, as well as to evaluate whether specific treatment elements were associated with outcomes in pediatric t(8;21)-positive patients with acute myeloid leukemia (AML). PATIENTS AND METHODS: Karyotypes of 916 pediatric patients with t(8;21)-AML were reviewed for the presence of additional cytogenetic aberrations, and 228 samples were screened for presence of cKIT and RAS mutations. Multivariable regression models were used to assess the relevance of anthracyclines, cytarabine, and etoposide during induction and overall treatment. End points were the probability of achieving complete remission, cumulative incidence of relapse (CIR), probability of event-free survival, and probability of overall survival. RESULTS: Of 838 patients included in final analyses, 92% achieved complete remission. The 5-year overall survival, event-free survival, and CIR were 74%, 58%, and 26%, respectively. cKIT mutations and RAS mutations were not significantly associated with outcome. Patients with deletions of chromosome arm 9q [del(9q); n = 104] had a lower probability of complete remission (P = .01). Gain of chromosome 4 (+4; n = 21) was associated with inferior CIR and survival (P < .01). Anthracycline doses greater than 150 mg/m(2) and etoposide doses greater than 500 mg/m(2) in the first induction course and high-dose cytarabine 3 g/m(2) during induction were associated with better outcomes on various end points. Cumulative doses of cytarabine greater than 30 g/m(2) and etoposide greater than 1,500 mg/m(2) were associated with lower CIR rates and better probability of event-free survival. CONCLUSION: Pediatric patients with t(8;21)-AML and additional del(9q) or additional +4 might not be considered at good risk. Patients with t(8;21)-AML likely benefit from protocols that have high doses of anthracyclines, etoposide, and cytarabine during induction, as well as from protocols comprising cumulative high doses of cytarabine and etoposide.
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Antineoplásicos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Terapia de Alvo Molecular , Mutação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-kit/genética , Translocação Genética/efeitos dos fármacos , Proteínas ras/genética , Adolescente , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Criança , Pré-Escolar , Aberrações Cromossômicas/efeitos dos fármacos , Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Citarabina/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Alemanha , Transplante de Células-Tronco Hematopoéticas , Humanos , Incidência , Quimioterapia de Indução , Cooperação Internacional , Estimativa de Kaplan-Meier , Cariótipo , Leucemia Mieloide Aguda/mortalidade , Masculino , Terapia de Alvo Molecular/métodos , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas c-kit/efeitos dos fármacos , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento , Proteínas ras/efeitos dos fármacosRESUMO
This study investigates invasive fungal infections (IFIs) in patients with acute myelogenous leukemia who were included in the Enfant Leucemie Aigue 02 protocol between 2005 and 2011. Among 387 patients, 15 had aspergillosis, 9 had candidiasis, and 2 had mucormycosis. The most frequent localization of IFIs was in the lungs. It was found that after a median of 34 months, 2 deaths were attributable to IFI without any difference in survival between the groups with and without IFI.
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Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/epidemiologia , Micoses/epidemiologia , Micoses/etiologia , Adolescente , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Micoses/tratamento farmacológico , Estudos Retrospectivos , Falha de TratamentoRESUMO
Comprehensive clinical studies of patients with acute megakaryoblastic leukemia (AMKL) are lacking. We performed an international retrospective study on 490 patients (age ≤18 years) with non-Down syndrome de novo AMKL diagnosed from 1989 to 2009. Patients with AMKL (median age 1.53 years) comprised 7.8% of pediatric AML. Five-year event-free (EFS) and overall survival (OS) were 43.7% ± 2.7% and 49.0% ± 2.7%, respectively. Patients diagnosed in 2000 to 2009 were treated with higher cytarabine doses and had better EFS (P = .037) and OS (P = .003) than those diagnosed in 1989 to 1999. Transplantation in first remission did not improve survival. Cytogenetic data were available for 372 (75.9%) patients: hypodiploid (n = 18, 4.8%), normal karyotype (n = 49, 13.2%), pseudodiploid (n = 119, 32.0%), 47 to 50 chromosomes (n = 142, 38.2%), and >50 chromosomes (n = 44, 11.8%). Chromosome gain occurred in 195 of 372 (52.4%) patients: +21 (n = 106, 28.5%), +19 (n = 93, 25.0%), +8 (n = 77, 20.7%). Losses occurred in 65 patients (17.5%): -7 (n = 13, 3.5%). Common structural chromosomal aberrations were t(1;22)(p13;q13) (n = 51, 13.7%) and 11q23 rearrangements (n = 38, 10.2%); t(9;11)(p22;q23) occurred in 21 patients. On the basis of frequency and prognosis, AMKL can be classified to 3 risk groups: good risk-7p abnormalities; poor risk-normal karyotypes, -7, 9p abnormalities including t(9;11)(p22;q23)/MLL-MLLT3, -13/13q-, and -15; and intermediate risk-others including t(1;22)(p13;q13)/OTT-MAL (RBM15-MKL1) and 11q23/MLL except t(9;11). Risk-based innovative therapy is needed to improve patient outcomes.
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Aberrações Cromossômicas , Leucemia Megacarioblástica Aguda/genética , Leucemia Megacarioblástica Aguda/terapia , Adolescente , Antimetabólitos Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Citarabina/uso terapêutico , Intervalo Livre de Doença , Feminino , Rearranjo Gênico , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Estimativa de Kaplan-Meier , Cariotipagem , Leucemia Megacarioblástica Aguda/diagnóstico , Leucemia Megacarioblástica Aguda/epidemiologia , Masculino , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: In neuroblastoma, activating ALK receptor tyrosine kinase point mutations play a major role in oncogenesis. We explored the potential occurrence of ALK mutations at a subclonal level using targeted deep sequencing. EXPERIMENTAL DESIGN: In a clinically representative series of 276 diagnostic neuroblastoma samples, exons 23 and 25 of the ALK gene, containing the F1174 and R1275 mutation hotspots, respectively, were resequenced with an extremely high depth of coverage. RESULTS: At the F1174 hotspot (exon 23), mutations were observed in 15 of 277 samples (range of fraction of mutated allele per sample: 0.562%-40.409%). At the R1275 hotspot (exon 25), ALK mutations were detected in 12 of 276 samples (range of fraction of mutated allele: 0.811%-73.001%). Altogether, subclonal events with a mutated allele fraction below 20% were observed in 15/27 ALK-mutated samples. The presence of an ALK mutation was associated with poorer 5-year overall survival (OS: 75% vs. 57%, P = 0.0212 log-rank test), with a strong correlation between F1174 ALK mutations and MYCN amplification being observed. CONCLUSIONS: In this series, deep sequencing allows the detection of F1174 and R1275 ALK mutational events at diagnosis in 10% of cases, with subclonal events in more than half of these, which would have gone undetected by Sanger sequencing. These findings are of clinical importance given the potential role of ALK mutations in clonal evolution and relapse. These findings also demonstrate the importance of deep sequencing techniques for the identification of patients especially when considering targeted therapy.
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Evolução Clonal/genética , Mutação , Neuroblastoma/genética , Receptores Proteína Tirosina Quinases/genética , Adolescente , Adulto , Alelos , Quinase do Linfoma Anaplásico , Criança , Pré-Escolar , Análise Mutacional de DNA , Éxons , Feminino , Amplificação de Genes , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neuroblastoma/diagnóstico , Neuroblastoma/mortalidade , Prognóstico , Adulto JovemRESUMO
Acute myeloid leukemia with t(6;9)(p22;q34) is listed as a distinct entity in the 2008 World Health Organization classification, but little is known about the clinical implications of t(6;9)-positive myeloid leukemia in children. This international multicenter study presents the clinical and genetic characteristics of 62 pediatric patients with t(6;9)/DEK-NUP214-rearranged myeloid leukemia; 54 diagnosed as having acute myeloid leukemia, representing <1% of all childhood acute myeloid leukemia, and eight as having myelodysplastic syndrome. The t(6;9)/DEK-NUP214 was associated with relatively late onset (median age 10.4 years), male predominance (sex ratio 1.7), French-American-British M2 classification (54%), myelodysplasia (100%), and FLT3-ITD (42%). Outcome was substantially better than previously reported with a 5-year event-free survival of 32%, 5-year overall survival of 53%, and a 5-year cumulative incidence of relapse of 57%. Hematopoietic stem cell transplantation in first complete remission improved the 5-year event-free survival compared with chemotherapy alone (68% versus 18%; P<0.01) but not the overall survival (68% versus 54%; P=0.48). The presence of FLT3-ITD had a non-significant negative effect on 5-year overall survival compared with non-mutated cases (22% versus 62%; P=0.13). Gene expression profiling showed a unique signature characterized by significantly higher expression of EYA3, SESN1, PRDM2/RIZ, and HIST2H4 genes. In conclusion, t(6;9)/DEK-NUP214 represents a unique subtype of acute myeloid leukemia with a high risk of relapse, high frequency of FLT3-ITD, and a specific gene expression signature.
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Proteínas Cromossômicas não Histona/genética , Cromossomos Humanos Par 6 , Cromossomos Humanos Par 9 , Leucemia Mieloide/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Oncogênicas/genética , Translocação Genética , Adolescente , Medula Óssea/patologia , Criança , Pré-Escolar , Feminino , Perfilação da Expressão Gênica , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/mortalidade , Leucemia Mieloide/terapia , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Proteínas de Ligação a Poli-ADP-Ribose , Recidiva , Resultado do TratamentoRESUMO
A minority of children with chronic immune thrombocytopenia (ITP) require therapeutic intervention to prevent haemorrhagic risk. This retrospective national study evaluated romiplostim in childhood non-responsive or refractory chronic ITP. Between 2009 and 2012, 10 patients whose Buchanan score was 3-4 were treated with romiplostim. The median duration of thrombocytopenia was 1·9 years (0·8-15). The median duration of romiplostim treatment was 9 months (3-36). A response was observed in 5/10 patients (one complete, four partial). No serious adverse effect was noticed. The long-term benefit/risk balance of this innovative treatment is currently recorded by Centre de Référence National des Cytopénies Auto-immunes de l'Enfant.
Assuntos
Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Trombopoetina/uso terapêutico , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , França , Humanos , Lactente , Masculino , Receptores Fc/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Estudos Retrospectivos , Trombopoetina/administração & dosagem , Trombopoetina/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Apheresis is a major challenge in peripheral stem cell collection from low-weight children with cancer. Comparisons between the new apheresis device Optia (TerumoBCT) and the earlier COBE Spectra (CaridianBCT) have been performed in adults but not in low-weight children. The objective was to compare the performance of these two devices in small children. STUDY DESIGN AND METHODS: In this retrospective study, all patients were reviewed weighing less than 15 kg undergoing stem cell collection using the Optia device between April 2011 and April 2012. They were paired on weight in a 3:1 ratio with patients whose cells had been collected with the COBE Spectra since 2006. RESULTS: Six patients were treated with the Optia and were matched with 18 patients treated with the Spectra. No side effects occurred. Collection efficiency (CE) was similar between the two groups (50% vs. 47%), but CD34 cell blood clearance was lower with the Optia (0.4 mL/min/kg vs. 0.6 mL/min/kg, p < 0.01). Platelet (PLT) loss and hemoglobin (Hb) loss were significantly reduced with the Optia (respectively, 32% vs. 54%, p < 0.01; and 1.4 g/dL vs. 2.9 g/dL, p < 0.01). Apheresis duration was increased with the Optia (159 min vs. 134 min, p < 0.05). The cell product harvested with the Optia had a lower volume and lower hematocrit, but similar white blood cell and PLT content. CONCLUSION: Compared with the Spectra, the Optia allows similar CE with a reduced PLT and Hb loss but with a longer duration.
Assuntos
Remoção de Componentes Sanguíneos/instrumentação , Células-Tronco Hematopoéticas/citologia , Antígenos CD34/análise , Peso Corporal , Criança , Pré-Escolar , Feminino , Hemoglobinas/análise , Humanos , Lactente , Masculino , Contagem de Plaquetas , Estudos RetrospectivosAssuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide/genética , Síndromes Mielodisplásicas/genética , Proteínas Nucleares/genética , Trombocitopenia/genética , Regiões 5' não Traduzidas/genética , Doença Aguda , Saúde da Família , Predisposição Genética para Doença/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , MutaçãoRESUMO
In pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong indicators of prognosis. Some recurrent cytogenetic abnormalities, such as t(8;16)(p11;p13), are so rare that collaborative studies are required to define their prognostic impact. We collected the clinical characteristics, morphology, and immunophenotypes of 62 pediatric AML patients with t(8;16)(p11;p13) from 18 countries participating in the International Berlin-Frankfurt-Münster (I-BFM) AML study group. We used the AML-BFM cohort diagnosed from 1995-2005 (n = 543) as a reference cohort. Median age of the pediatric t(8;16)(p11;p13) AML patients was significantly lower (1.2 years). The majority (97%) had M4-M5 French-American-British type, significantly different from the reference cohort. Erythrophagocytosis (70%), leukemia cutis (58%), and disseminated intravascular coagulation (39%) occurred frequently. Strikingly, spontaneous remissions occurred in 7 neonates with t(8;16)(p11;p13), of whom 3 remain in continuous remission. The 5-year overall survival of patients diagnosed after 1993 was 59%, similar to the reference cohort (P = .14). Gene expression profiles of t(8;16)(p11;p13) pediatric AML cases clustered close to, but distinct from, MLL-rearranged AML. Highly expressed genes included HOXA11, HOXA10, RET, PERP, and GGA2. In conclusion, pediatric t(8;16)(p11;p13) AML is a rare entity defined by a unique gene expression signature and distinct clinical features in whom spontaneous remissions occur in a subset of neonatal cases.