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Acute leukemia

Acute leukemia. Leukemia. Hematological malignancy in leukocyte cell lineage. Acute leukemia: outline. Concepts, biology Epidemiology Clinical and laboratory manifestations Diagnosis Management and prognosis. Classification of leukemias. Acute. Chronic. Myeloid origin.

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Acute leukemia

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  1. Acute leukemia

  2. Leukemia Hematological malignancy in leukocyte cell lineage

  3. Acute leukemia: outline • Concepts, biology • Epidemiology • Clinical and laboratory manifestations • Diagnosis • Management and prognosis

  4. Classification of leukemias Acute Chronic Myeloid origin Acute Myeloid Leukemia (AML) Chronic Myeloid Leukemia (CML) Lymphoid origin Acute Lymphoblastic Leukemia (ALL) Chronic Lymphocytic Leukemia (CLL)

  5. ALL naïve germinal center B-lymphocytes Plasma cells Lymphoid progenitor T-lymphocytes Neutrophils AML Myeloid progenitor Eosinophils Hematopoietic stem cell Basophils Monocytes Platelets Red cells

  6. myeloblast promyelocyte myelocyte metamyelocyte band neutrophil Myeloid maturation MATURATION

  7. Acute Leukemia accumulation of blasts in the marrow

  8. AML vs CML(dominant cells in the peripheral blood test) Myeloid cell CML AML normal blasts qq promyelocytesq myelocytesq metamyelocytesq bands q neutrophils q q

  9. Adult acute leukemia • Hematologic urgency • Usually fatal within weeks-months without chemotherapy • With treatment, high mortality due to disease or treatment-related complications (unlike childhood acute leukemia)

  10. ALL mainly children Male > Female curable in 70% of children curable in minority of adults AML mainly adults Male > Female curable in minority of adults Classification of acute leukemias

  11. Two-hit model of leukemogenesis Loss of function of transcription factors needed for differentiation eg. AML1-ETO CBFb-SMMHC PML-RARa Gain of function mutations of tyrosine kinases eg. FLT3, c-KIT mutations N- and K-RAS mutations BCR-ABL TEL-PDGFbR differentiation block enhanced proliferation Acute Leukemia +

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

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

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

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

  16. A B C Chloromas NEJM 1998

  17. Leukostasis • accumulation of blasts in microcirculation with impaired perfusion • lungs: hypoxemia, pulmonary infiltrates • CNS: stroke • Blast ≥ 50 x 109/L

  18. Constitutional symptoms • fever and sweats common • weight loss less common

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

  20. Bone marrow examination • determining type • prognosis • Acute leukemias: presence of > 20% blasts in bone marrow

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

  22. AML

  23. AML

  24. Auer rods in AML

  25. ALL

  26. FAB (1976) Classification for AML • M0 -- Undifferentiated AML • M1 -- AML without maturation • M2 -- AML with maturation • M3 -- Acute Promyelocytic Leukemia • M4 -- Acute Meylomonocytic Leukemia • M5 -- Acute Monocytic Leukemia • M6 -- Erythroleukemia (DiGuglielmo’s) • M7 -- Megakaryoblastic Leukemia

  27. FAB classificationfor ALL Subtype Morphology Occurrence (%) L1 Small round blasts 75 clumped chromatin L2 Pleomorphic larger blasts 20 clefted nuclei, fine chromatin L3 Large blasts, nucleoli,5 vacuolated cytoplasm

  28. FAB Classification of ALL • L1: mostly in children • L2: mostly in adults • L3: “Burkitt” large basophilic B-cell blasts with vacuoles

  29. Treatment of acute leukemias Choice of Regimen is influenced by: • type (AML vs ALL) • age • curative vs palliative intent

  30. Principles of treatment • combination chemotherapy • first goal: complete remission • further regimen to prevent relapse • supportive medical care • transfusions, antibiotics, nutrition • psychosocial support • patient and family

  31. Chemotherapy for acute leukemias • Phases of ALL treatment • induction • intensification • CNS prophylaxis • maintenance • Phases of AML treatment • induction • consolidation (post-remission therapy) post-remission therapy

  32. Hematopoietic stem cell transplantation • permits “rescue” from otherwise excessively toxic treatment • additional advantage of graft-vs-leukemia effect in allogeneic transplants • trade-off for allogeneic transplantation: greater anti-leukemic effect but more toxic

  33. Prognosis Adult AML Adult ALL similar to or worse than AML

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