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Acute Myeloid Leukaemia

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

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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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)

  7. 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

  8. Acute Myeloid Leukaemia • Lab work up Bone marrow aspiration and trephine biopsy for: - Morphology - Cytochemical stains - Immunophenotyping - Cytogenetic analysis

  9. Acute Myeloid Leukaemia • Other investigations - Chest X-ray - ECG - MGA scan (cardiac toxicity of anthracycline chemotherapeutics)

  10. 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

  11. 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

  12. Acute Myeloid Leukaemia • Management - About 50% of patients achieve CR after first course - Another 10% enter remission after 2nd course

  13. 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

  14. 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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