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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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