Acute Myeloid Leukemia.ppt

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					Acute Leukemia

David Lee, MD, FRCPC
                  Overview
•   Concepts, biology
•   Epidemiology
•   Clinical and laboratory manifestations
•   Diagnosis
•   Management and prognosis
    Classification of leukemias

               Acute                  Chronic

Myeloid    Acute Myeloid         Chronic Myeloid Leukemia
           Leukemia (AML)        (CML)
origin

Lymphoid   Acute Lymphoblastic   Chronic Lymphocytic Leukemia
           Leukemia (ALL)        (CLL)
origin
                        ALL
                              naïve


                               B-lymphocytes

                                                       Plasma
                Lymphoid                                cells
                progenitor             T-lymphocytes


                       AML
Hematopoietic   Myeloid               Neutrophils
stem cell       progenitor

                                      Eosinophils


                                      Basophils


                                      Monocytes


                                      Platelets


                                      Red cells
               Myeloid maturation

myeloblast promyelocyte   myelocyte   metamyelocyte   band            neutrophil




                          MATURATION

                                                        Adapted and modified from U Va website
           Acute Leukemia
• accumulation of blasts in the marrow
How to distinguish AML vs CML
from looking at peripheral blood
Myeloid cell     CML   AML   normal
blasts            q     q
promyelocytes     q
myelocytes        q
metamyelocytes    q
bands             q
neutrophils       q    #        q
    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
        Classification of acute
             leukemias
ALL                        AML
• mainly children          • mainly adults
• M>F                      • M>F
• curable in 70% of
  children
• curable in minority of   • curable in minority of
  adults                     adults
                 Two-hit model of
                 leukemogenesis
Loss of function of          Gain of function mutations of
transcription factors        tyrosine kinases
needed for differentiation
                             eg. FLT3, c-KIT mutations
eg. AML1-ETO                     N- and K-RAS mutations
    CBFb-SMMHC                   BCR-ABL
    PML-RARa                     TEL-PDGFbR




differentiation                enhanced                      Acute
     block              +     proliferation                  Leukemia
     Causes of acute leukemias
•   idiopathic (most)
•   underlying hematologic disorders
•   chemicals, drugs
•   ionizing radiation
•   viruses (HTLV I)
•   hereditary/genetic conditions
       Clincal manifestations
• symptoms due to:
  – marrow failure
  – tissue infiltration
  – leukostasis
  – constitutional symptoms
  – other (DIC)
• usually short duration of symptoms
           Marrow failure
• neutropenia:        infections, sepsis
• anemia:             fatigue, pallor
• thrombocytopenia:   bleeding
     Infiltration of tissues/organs
•   enlargement of liver, spleen, lymph nodes
•   gum hypertrophy
•   bone pain
•   other organs: CNS, skin, testis, any organ
Gum hypertrophy
Chloromas


    A

    B

    C
            NEJM 1998
              Leukostasis
• accumulation of blasts in microcirculation
  with impaired perfusion
• lungs: hypoxemia, pulmonary infiltrates
• CNS: stroke
• only seen with WBC >> 50 x 109/L
    Constitutional symptoms
• fever and sweats common
• weight loss less common
        Laboratory features
• WBC usually elevated, but can be normal
  or low
• blasts in peripheral blood
• normocytic anemia
• thrombocytopenia
• neutropenia
• DIC
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)
  Distinguishing AML from ALL
• light microscopy
  – AML: Auer rods, cytoplasmic granules
  – ALL: no Auer rods or granules.
• flow cytometry
• special stains (cytochemistry)
AML
AML
Auer rods in AML
ALL
 Treatment of acute leukemias
Choice of Rx is influenced by:
• type (AML vs ALL)
• age
• curative vs palliative intent
       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
     Chemotherapy for acute
          leukemias
• Phases of ALL treatment
  – induction
  – intensification
  – CNS prophylaxis     post-remission therapy

  – maintenance
• Phases of AML treatment
  – induction
  – consolidation (post-remission therapy)
      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
            Prognosis
Adult AML
    Age          CR          DFS
   < 60         75%         ~ 30%
   > 60         50%         5-15%
Adult ALL
  similar to or worse than AML
                  Overview
•   Concepts, biology
•   Epidemiology
•   Clinical and laboratory manifestations
•   Diagnosis
•   Management and prognosis

				
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posted:5/16/2012
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