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Acute Myeloid Leukaemia. Dr. Soheir Adam, MRCPath Assistant Professor Department of Haematology, KAUH. 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

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Acute myeloid leukaemia

Acute Myeloid Leukaemia

Dr. Soheir Adam, MRCPath

Assistant Professor

Department of Haematology, KAUH


Acute myeloid leukaemia1
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 > 20% blasts in the bone marrow


Acute myeloid leukaemia2
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


Myelodysplastic syndrome
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


Acute myeloid leukaemia3
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


Acute myeloid leukaemia4
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)


Acute myeloid leukaemia5
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


Acute myeloid leukaemia6
Acute Myeloid Leukaemia

  • Lab work up

    Bone marrow aspiration and trephine biopsy for:

    - Morphology

    - Cytochemical stains

    - Immunophenotyping

    - Cytogenetic analysis


Acute myeloid leukaemia7
Acute Myeloid Leukaemia

  • Other investigations

    - Chest X-ray

    - ECG

    - MGA scan (cardiac toxicity of anthracycline chemotherapeutics)


Acute myeloid leukaemia8
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


Acute myeloid leukaemia9
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


Acute myeloid leukaemia10
Acute Myeloid Leukaemia

  • Management

    - About 50% of patients achieve CR after first course

    - Another 10% enter remission after 2nd course


Acute promyelocytic leukaemia
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 >30% 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


Acute promyelocytic leukaemia1
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 >90% of cases with ATRA and chemotherapy


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