Acute Leukemia

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Acute Leukemia

• David Lee, MD, FRCPC

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Overview

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

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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)
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Myeloid maturation
MATURATION
Adapted and modified from U Va website
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Acute Leukemia

• accumulation of blasts in the marrow

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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

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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

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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

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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

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Causes of acute leukemias

• idiopathic (most)
• underlying hematologic disorders
• chemicals, drugs
• ionizing radiation
• viruses (HTLV I)
• hereditary/genetic conditions

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Clincal manifestations

• symptoms due to
• marrow failure
• tissue infiltration
• leukostasis
• constitutional symptoms
• other (DIC)
• usually short duration of symptoms

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Marrow failure

• neutropenia infections, sepsis
• anemia fatigue, pallor
• thrombocytopenia bleeding

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Infiltration of tissues/organs

• enlargement of liver, spleen, lymph nodes
• gum hypertrophy
• bone pain
• other organs CNS, skin, testis, any organ

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Gum hypertrophy
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Chloromas
NEJM 1998
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Leukostasis

• accumulation of blasts in microcirculation with
  impaired perfusion
• lungs hypoxemia, pulmonary infiltrates
• CNS stroke
• only seen with WBC gtgt 50 x 109/L

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Constitutional symptoms

• fever and sweats common
• weight loss less common

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Laboratory features

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

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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)

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Distinguishing AML from ALL

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

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AML
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AML
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Auer rods in AML
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ALL
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Treatment of acute leukemias

• Choice of Rx is influenced by
• type (AML vs ALL)
• age
• curative vs palliative intent

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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

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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
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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

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Prognosis
Adult AML
Adult ALL
similar to or worse than AML
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Overview

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