Subject(s)
Leukemia, Biphenotypic, Acute/diagnosis , Monocytes/pathology , Biomarkers , Biopsy , Bone Marrow/pathology , Child , Child, Preschool , Combined Modality Therapy , Disease Susceptibility , Female , Humans , Immunophenotyping , Leukemia, Biphenotypic, Acute/etiology , Leukemia, Biphenotypic, Acute/metabolism , Leukemia, Biphenotypic, Acute/therapy , Lymphocytes/metabolism , Lymphocytes/pathology , Male , Monocytes/metabolism , Neoplasm, Residual/diagnosisSubject(s)
Anemia/diagnosis , Betacoronavirus , Coronavirus Infections/diagnosis , Hemoglobinopathies/diagnosis , Pneumonia, Viral/diagnosis , Surveys and Questionnaires , Adolescent , Adult , Aged , Aged, 80 and over , Anemia/epidemiology , COVID-19 , Child , Child, Preschool , Coronavirus Infections/epidemiology , Female , Hemoglobinopathies/epidemiology , Humans , Infant , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Young AdultABSTRACT
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.
Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Busulfan/analogs & derivatives , Hematopoietic Stem Cell Transplantation/methods , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Transplantation Conditioning/methods , Antineoplastic Agents, Alkylating/adverse effects , Busulfan/adverse effects , Busulfan/therapeutic use , Disease-Free Survival , Female , Graft vs Host Disease/etiology , Humans , Infant , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/surgery , Transplantation, HomologousSubject(s)
Hematopoietic Stem Cell Transplantation , Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Adult , Child , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Remission Induction , Retrospective Studies , Survival Rate , Transplantation, HomologousSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Erythroblasts/pathology , Erythropoiesis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Bone Marrow Transplantation , Child , Combined Modality Therapy , Dexamethasone/administration & dosage , Female , Humans , Mercaptopurine/administration & dosage , Methotrexate/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/surgery , Treatment OutcomeABSTRACT
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.