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Acute Leukemia

Acute Leukemia. David Lee, MD, FRCPC. Overview. Concepts, biology Epidemiology Clinical and laboratory manifestations Diagnosis Management and prognosis. Classification of leukemias. Acute. Chronic. Myeloid origin. Acute Myeloid Leukemia (AML). Chronic Myeloid Leukemia (CML).

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Acute Leukemia

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  1. Acute Leukemia David Lee, MD, FRCPC

  2. Overview • Concepts, biology • Epidemiology • Clinical and laboratory manifestations • Diagnosis • Management and prognosis

  3. 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)

  4. 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

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

  6. Acute Leukemia • accumulation of blasts in the marrow

  7. How to distinguish AML vs CMLfrom looking at peripheral blood Myeloid cell CML AML normal blasts qq promyelocytes q myelocytes q metamyelocytes q bands q neutrophils q # q

  8. 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

  9. 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 Classification of acute leukemias

  10. 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 +

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

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

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

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

  15. 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 • only seen with WBC >> 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 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)

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

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

  28. 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

  29. 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

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

  31. Overview • Concepts, biology • Epidemiology • Clinical and laboratory manifestations • Diagnosis • Management and prognosis

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