骨髓衰竭综合征.ppt

Bone Marrow Failure Blanche P Alter, MD, MPH Clinical Genetics Branch Division of Cancer Epidemiology and Genetics Bethesda, MD Case Presentation 16 year old male Seen by family doctor because tennis instructor noticed that he was tiring easily History of trip outside the USA 5 months earlier Noted to have pallor and a large bruise on arm (where hit by tennis ball) CBC: Hb 8.5 g/dL, platelets 40,000/mL, WBC 2000/mL (20% neutrophils) Next Step Look at blood smear R/o circulating blasts Do a bone marrow Aspirate Cell types Cytogenetics Biopsy Cellularity Pancytopenia with Hypocellular Marrow Acquired aplastic anemia Inherited bone marrow failure syndrome Hypocellular Myelodysplastic Syndrome Aleukemic leukemia Marrow lymphoma Pancytopenia with Cellular Marrow Primary marrow disease Leukemia Myelodysplastic syndrome Paroxysmal nocturnal hemoglobinuria Systemic disease Lupus Hypersplenism Infection, e.g. brucellosis, sarcoidosis, tuberculosis Bone Marrow (BM) Biopsy Aplastic Anemia: Signs and Symptoms Anemia fatigue, lassitude, dyspnea Thrombocytopenia bruises, petechiae serious bleeding Neutropenia infections Severity of Aplastic Anemia Severe 2 of the following 3: neutrophils 500/mL, platelets 20,000/mL, reticulocytes 20,000/mL BM cellularity 25% with 30% hematopoietic cells Very severe Neutrophils 200/mL Non-severe (moderate) Better than severe Nosology of Aplastic Anemia Genetics Acquired Inherited Cell biology Stem cell Immune Acquired Aplastic Anemia Radiation Drugs (cytotoxics, chloramphenicol, nonsteroidals, anticonvulsants, gold) Chemicals (benzene, insecticides, pesticides, fertilizer) Viruses (Epstein-Barr, hepatitis [non-A,B,C], human immunodeficiency) Genetic polymorphisms in detoxifying enzymes Paroxysmal nocturnal hemoglobinuria (PNH) Pregnancy Immune diseases (eosinophilic fasciitis, hypoimmunoglobulinemia, thymoma) IDIOPATHIC Evidence for Immune Disease Autologous recovery after immunosuppression for transplant Even syngeneic transplants require condit