18. HEMATOLIGIC MALIGNANCY MULE.pptx - LEUKEMIAS Mulugeta E Normal Hematopoiesis CD34 CD38 Hematopoietic Stem Cell c-kit Thy1 CD71 HLA-DR IL3R

18. HEMATOLIGIC MALIGNANCY MULE.pptx - LEUKEMIAS Mulugeta E...

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LEUKEMIAS Mulugeta E.
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Normal Hematopoiesis Modified from Dick: ASH Education Program Book, 2001 CD34+, CD38- ( ) SCID-Repopulating Cell c-kit+, Thy1+, CD71+, HLA-DR+, IL3R - ( ) Hematopoietic Stem Cell
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Most common of child hood malignancies accounts for 41% of all malignancies in < 15 yrs Clonal proliferation of malignant stem cells in the bone marrow Genetic abnormalities in the hematopoietic cells give rise to colonial proliferation of cells. Results in disruption of normal marrow function and, ultimately marrow failure.
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Types Acute: Rapid proliferation Acute lymphoblastic leukemia (ALL) -77% Acute myelogenous Leukemia ( AML )-11% Chronic : slow proliferation Chronic myelogenous leukemia ( CML) 2-3% Juvenile chronic myelogenous leukemia (JCML) – 1-2% CLL
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ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)
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EPIDEMIOLOGY Peak incidence 2-6 yrs M>F More common in children with Down syndrome Ataxia – telangiectasia Fanconi syndrome
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ETIOLOGY In most cases no known reason Possible causes identified Environmental Ionizing radiation Toxins Infectious (eg, HTLV-I, EBV) Immunodeficiency Syndromes (eg, AT, SD) Genetic Familial (eg, twin concordance, Li-Fraumeni) Congenital chromosomal (eg, Trisomy 21, instability syndromes) Acquired chromosomal anomalies
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PATHOGENESIS Precise molecular events that cause leukemic transformation are unknown. Abnormal proliferation of immature hematopoietic cells that have lost their capacity to differentiate Monoclonal-final leukemic event occurs in a single cell Malignant clone expands
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Hyper cellular marrow Interfere normal hematopoiesis Pancytopenia
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CLASSIFICATION I. ALL- cell origin Progenitor B cells – 85% T-Cells -15% B-Cells Common cell ALL II. Morphology FAB classification
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L1 Cells are small, uniform blasts Nucleoli are small Scanty cytoplasm L2 Cells are large, Variable in size Large nucleoli Abundant cytoplasm L3 large cells, regular in size Oval/ round in shape Prominent nucleolus Abundant cytoplasm
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Clinical Manifestations Commonly presents with Anemia Bleeding diathesis Infections Pallor Weakness and irritability Low ulcerations Gum bleeding, epistaxis Petechia, purpura or echymosis
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Lymphadenopathy Hilar LAP and Mediastinal mass Hepatosplenomegally Bone pain / joint swelling Leukemic meningitis Headache Nausea / vomiting Focal deficit Seizure
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Deposition of leukemic cells in organs manifests with specific organ dysfunction Mediastinal mass- SVC obstruction Pleural effusion / Ascites Cardiac tamponed Hepatic /splenic infiltration Testicular mass Septicemia – Neutropenia/ Pancytopenia
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DX CBC Anemia Thrombocytopenia Leukocytosis Peripheral blood smear – blast cells BM – replaced by leukemic lymphoblast _ More than 25% Blast cells in the BM
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Bone marrow biopsy CSF – CNS leukemia- WBC > 5(blast cells) CXR- Mediastinal involvement Organ function tests Serum uric acid
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