Assuntos
Leucemia Aguda Bifenotípica/diagnóstico , Monócitos/patologia , Biomarcadores , Biópsia , Medula Óssea/patologia , Criança , Pré-Escolar , Terapia Combinada , Suscetibilidade a Doenças , Feminino , Humanos , Imunofenotipagem , Leucemia Aguda Bifenotípica/etiologia , Leucemia Aguda Bifenotípica/metabolismo , Leucemia Aguda Bifenotípica/terapia , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Monócitos/metabolismo , Neoplasia Residual/diagnósticoAssuntos
Anemia/diagnóstico , Betacoronavirus , Infecções por Coronavirus/diagnóstico , Hemoglobinopatias/diagnóstico , Pneumonia Viral/diagnóstico , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/epidemiologia , COVID-19 , Criança , Pré-Escolar , Infecções por Coronavirus/epidemiologia , Feminino , Hemoglobinopatias/epidemiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Adulto JovemRESUMO
BACKGROUND: Inherited thrombocytopenias (ITs) are a heterogeneous group of disorders characterized by low platelet counts and often disproportionate bleeding with over 30 genes currently implicated. Previously the UK-GAPP study using whole exome sequencing (WES) identified a pathogenic variant in 19 of 47 (40%) patients of which 71% had variants in genes known to cause IT. AIMS: To employ a targeted next-generation sequencing platform to improve efficiency of diagnostic testing and reduce overall costs. METHODS: We have developed an IT-specific gene panel as a pre-screen for patients prior to WES using the Agilent SureSelectQXT transposon-based enrichment system. RESULTS: Thirty-one patients were analyzed using the panel-based sequencing, of which; 10% (3/31) were identified with a classified pathogenic variant, 16% (5/31) were identified with a likely pathogenic variant, 51% (16/31) were identified with variants of unknown significance, and 23% (7/31) were identified with either no variant or a benign variant. DISCUSSION AND CONCLUSION: Although requiring further clarification of the impact of the genetic variations, the application of an IT-specific next generation sequencing panel is an viable method of pre-screening patients for variants in known IT-causing genes prior to WES. With an added benefit of distinguishing IT from idiopathic thrombocytopenic purpura (ITP) and the potential to identify variants in genes known to have a predisposition to hematological malignancies, it could become a critical step in improving patient clinical management.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Bussulfano/análogos & derivados , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Condicionamento Pré-Transplante/métodos , Antineoplásicos Alquilantes/efeitos adversos , Bussulfano/efeitos adversos , Bussulfano/uso terapêutico , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Transplante HomólogoAssuntos
Transplante de Células-Tronco Hematopoéticas , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Criança , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Transplante HomólogoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Eritroblastos/patologia , Eritropoese , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Transplante de Medula Óssea , Criança , Terapia Combinada , Dexametasona/administração & dosagem , Feminino , Humanos , Mercaptopurina/administração & dosagem , Metotrexato/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Resultado do TratamentoRESUMO
Bleeding and thrombosis are not infrequent problems in children receiving treatment for acute lymphoblastic leukaemia (ALL). The exact frequency varies with age, co-morbidity and treatment schedule, but the risk is highest in the first few weeks of treatment when disease and treatment-related haemostatic abnormalities prevail. Recommendations for prevention and management are lacking due to a weak evidence base, resulting in considerable variation in practice. This article describes our personal practice in this area with reference to the available literature on the subject.
