Acute Myeloid Leukaemia

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Acute Myeloid Leukaemia

• Dr. Soheir Adam, MRCPath
• Assistant Professor
• Department of Haematology, KAUH

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Acute Myeloid Leukaemia

• Definition
• - It is a clonal malignant disease, in which
  there is maturation arrest of the haemopoietic
  precursors at an early stage of development
• - It is characterized by the presence of gt 20
  blasts in the bone marrow

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Acute Myeloid Leukaemia

• Pathophysiology
• - The activation of abnormal genes through
  chromosomal translocations and other
  abnormalities
• - Exposure to radiation e.g. high incidence of
  leukaemia among survivors of the atomic bomb in
  Japan
• - Past exposure to chemotherapy
• Alkylating agents
• Topoisomerase II inhibitors
• - Antecedent haematological disorders
• myelodysplastic syndrome
• myeloproliferative disease e.g. CML

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Myelodysplastic Syndrome

• A group of clonal disorders that are
  characterized by progressive cytopenias and
  dysplasia
• Occurs mainly in elderly patients
• The more severer forms ultimately progress to
  acute leukaemia
• Usuaaly associated with chromosomal abnormalities
  in a large proportion of cases

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Acute Myeloid Leukaemia

• FAB classification
• MO AML with minimal differentiation
• M1 AML without maturation
• M2 AML with maturation
• M3 Acute promyelocytic leukaemia
• M4 Acute myelomonocytic leukaemia
• M5a Acute monoblastic leukaemia
• b
• M6 Erythroleukaemia
• M7 Acute megacaryoblastic leukaemia

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Acute Myeloid Leukaemia

• Presentation
• - Anaemia, bleeding and/or repeated infections
• - Organ/skin infiltration specially in M5
• - DIC specially in AML, M3
• - Hyperleukostasis (headache, dizziness,
  blurring of vision)

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Acute Myeloid Leukaemia

• Lab work up
• - CBC and peripheral smear examination
• - P.T., APTT, fibrinogen D-dimers
• - LDH, uric acid
• - Urea and electrolytes
• - LFT
• - Blood cultures

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Acute Myeloid Leukaemia

• Lab work up
• Bone marrow aspiration and trephine biopsy for
• - Morphology
• - Cytochemical stains
• - Immunophenotyping
• - Cytogenetic analysis

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Acute Myeloid Leukaemia

• Other investigations
• - Chest X-ray
• - ECG
• - MGA scan (cardiac toxicity of anthracycline
  chemotherapeutics)

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Acute Myeloid Leukaemia

• Prognostic criteria
• Cytogenetic abnormalities are the single most
  important prognostic factors in AML.
• - Good prognostic abnormalities
• M3 t(15, 17)
• M2 t(8,21)
• M3 inv(16)
• - Poor prognostic abnormalities
• Monosomy 7
• Monosomy 5

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Acute Myeloid Leukaemia

• Management
• Induction and consolidation
• - Combination of Anthracycline Ara-C
• - A total of 3 to 5 courses
• Late intensification
• - High dose Ara-C in young good risk group
• - Matched All-BMT in fit, bad risk fit
• - Mini-allo BMT or autologus BMT in older
  patients

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Acute Myeloid Leukaemia

• Management
• - About 50 of patients achieve CR after first
  course
• - Another 10 enter remission after 2nd course

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Acute Promyelocytic Leukaemia

• Clinical presentation
• - Younger age on presentation as compared to
  other AML subtypes
• - Often patients have low counts on
  presentation
• - Bone marrow has gt30 promyelocytes
• - It is commonly associated with DIC which is
  the main reason for early deaths
• - Aggressive replacement with platelets and
  cryoprecipitate is the mainstay of early
  management

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Acute Promyelocytic Leukaemia

• T(15,17) is a good prognostic indicator and is
  present in 95 of cases
• This translocation involves the retinoic acid
  receptor gene rendering the tumor cells
  susceptible to all-trans retinoic acid (ATRA)
• CR achieved in gt90 of cases with ATRA and
  chemotherapy