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Acute Leukemia

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usually fatal within weeks to months without chemotherapy ... curative vs palliative intent. Principles of treatment. combination chemotherapy ... – PowerPoint PPT presentation

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Title: Acute Leukemia


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
(No Transcript)
5
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 q q
  • 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
Classification of acute leukemias
  • ALL
  • mainly children
  • M gt F
  • curable in 70 of children
  • curable in minority of adults
  • AML
  • mainly adults
  • M gt F
  • curable in minority of adults

10
Two-hit model of leukemogenesis
Gain of function mutations of tyrosine
kinases eg. FLT3, c-KIT mutations N- and
K-RAS mutations BCR-ABL TEL-PDGFbR
Loss of function of transcription factors needed
for differentiation eg. AML1-ETO
CBFb-SMMHC PML-RARa
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
Chloromas
NEJM 1998
17
Leukostasis
  • accumulation of blasts in microcirculation with
    impaired perfusion
  • lungs hypoxemia, pulmonary infiltrates
  • CNS stroke
  • only seen with WBC gtgt 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 gt
    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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