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Acute Leukemias

Acute Leukemias. 4 th Year Medical Student KAU. Acute Leukemia. Is a type of cancer characterized by the production of large numbers of immature, abnormal blood cells ( Blasts )that look and act differently from normal blood cells. Acute Leukemia. accumulation of blasts in the marrow.

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Acute Leukemias

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  1. Acute Leukemias 4th Year Medical Student KAU

  2. Acute Leukemia • Is a type of cancer characterized by the production of large numbers of immature, abnormal blood cells ( Blasts )that look and act differently from normal blood cells

  3. Acute Leukemia accumulation of blasts in the marrow

  4. Leukemias • Subdivided into acute and chronic subsets • Also subdivided into myeloid (primarily granulocytes) or lymphoid • Acute: represent arrested stages of differentiation • Chronic: increased production and lack of apoptosis

  5. Significance of adult acute leukemia a hematologic urgency usually fatal within weeks to months without chemotherapy with treatment, high mortality due to disease or treatment-related complications (unlike childhood acute leukemia) notify Hematologist promptly if acute leukemia is suspected

  6. Hematopoiesis BFU-E/CFU-E CFU-GM CFU-Baso CFU-Eos PLURIPOTENT STEM CELL MIXED PROGENITOR CELL COMMITTED PROGENITOR CELL RECOGNIZABLE BONE MARROW PRECURSOR CELL MATURE BLOOD CELL pronormoblast red cell myeloblast monoblast neutrophil monocyte eosinophil myeloid progenitor cell basophil CFU-Meg megakaryocyte platelet pluripotent stem cell pre-T lymphoblast T-cell pre-B lymphoblast B-cell lymphoid progenitor cell & plasma cell

  7. Classification of Acue leukemias Acute Myeloid origin Acute Myeloid Leukemia (AML) Lymphoid origin Acute Lymphoblastic Leukemia (ALL)

  8. Classification of acute leukemias ALL mainly children M > F curable in 70% of children curable in minority of adults AML mainly adults M > F curable in minority of adults

  9. Incidence Acute Leukemias

  10. Causes of acute leukemias idiopathic (most) underlying hematologic disorders chemicals, drugs ionizing radiation viruses (HTLV I) hereditary/genetic conditions

  11. Acute Lymphoblastic Leukemia (ALL) • L1: high nuclear:cytoplasmic ratio; rare nucleoli; 50% adult ALL • L2: lower nuclear:cytoplasmic ratio; 44% adult ALL • L3: vacuolated, basophilic cytoplasm; 6% adult ALL

  12. Myeloid maturation myeloblast promyelocyte myelocyte metamyelocyte band neutrophil MATURATION Adapted and modified from U Va website

  13. FAB Classification: AML M0: undifferentiated; 2-3% AML M1: >3% MPO; 20% AML M2: inc gran; Auer rods; 30% AML M3: inc promyelocytes; 10% AML M4: myelomono; 25% AML M5: monoblastic; 5% AML M6: erythroleukemia; 4% AML M7: megakaryocytic; 1% AML

  14. Clincal manifestations symptoms due to: marrow failure tissue infiltration leukostasis constitutional symptoms other (DIC) usually short duration of symptoms

  15. Marrow failure neutropenia: infections, sepsis anemia: fatigue, pallor thrombocytopenia: bleeding

  16. Infiltration of tissues/organs enlargement of liver, spleen, lymph nodes gum hypertrophy bone pain other organs: CNS, skin, testis, any organ

  17. Gum hypertrophy

  18. Chloromas A B C NEJM 1998

  19. Leukostasis accumulation of blasts in microcirculation with impaired perfusion lungs: hypoxemia, pulmonary infiltrates CNS: stroke only seen with WBC >> 50 x 109/L

  20. Constitutional symptoms fever and sweats common weight loss less common

  21. Laboratory features WBC usually elevated, but can be normal or low blasts in peripheral blood normocytic anemia thrombocytopenia DIC

  22. Bone marrow in acute leukemia necessary for diagnosis useful for determining type useful for prognosis Acute leukemias are defined by the presence of > 20% blasts in bone marrow (% of nucleated marrow cells)

  23. Distinguishing AML from ALL light microscopy AML: Auer rods, cytoplasmic granules ALL: no Auer rods or granules. special stains (cytochemistry) flow cytometry

  24. AML

  25. ALL

  26. Auer rods in AML

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