Asunto(s)
Leucemia Bifenotípica Aguda/diagnóstico , Monocitos/patología , Biomarcadores , Biopsia , Médula Ósea/patología , Niño , Preescolar , Terapia Combinada , Susceptibilidad a Enfermedades , Femenino , Humanos , Inmunofenotipificación , Leucemia Bifenotípica Aguda/etiología , Leucemia Bifenotípica Aguda/metabolismo , Leucemia Bifenotípica Aguda/terapia , Linfocitos/metabolismo , Linfocitos/patología , Masculino , Monocitos/metabolismo , Neoplasia Residual/diagnósticoAsunto(s)
Anemia/diagnóstico , Betacoronavirus , Infecciones por Coronavirus/diagnóstico , Hemoglobinopatías/diagnóstico , Neumonía Viral/diagnóstico , Encuestas y Cuestionarios , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia/epidemiología , COVID-19 , Niño , Preescolar , Infecciones por Coronavirus/epidemiología , Femenino , Hemoglobinopatías/epidemiología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología , SARS-CoV-2 , Adulto JovenRESUMEN
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.
Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Busulfano/análogos & derivados , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Acondicionamiento Pretrasplante/métodos , Antineoplásicos Alquilantes/efectos adversos , Busulfano/efectos adversos , Busulfano/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Humanos , Lactante , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Trasplante HomólogoAsunto(s)
Trasplante de Células Madre Hematopoyéticas , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Niño , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Inducción de Remisión , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante HomólogoRESUMEN
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.