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Acute Myeloid Leukaemia (AML)

Table of Contents

  • Introduction
  • Aetiology
  • Risk Factors
  • Clinical Features
  • Differential Diagnosis
  • Investigations
  • Classification
  • Management
  • Complications
  • Prognosis
  • References
  • Related Notes
  • Test Yourself

Introduction

  • AML is a malignant neoplastic disease of the myeloid cell line in the bone marrow, also called acute myelogenous or myelocytic leukaemia.
  • Constitutes ~25% of childhood leukaemias (often infancy) but most common acute leukaemia in adults (median age ~68 years).
  • Proliferation of immature, non-functional blast cells disrupts normal haematopoiesis causing pancytopenia.

Aetiology

  • Uncontrolled growth of myeloid precursors leads to accumulation of blasts.
  • Blasts impair formation of RBCs, WBCs, and platelets causing anemia, thrombocytopenia, and immunosuppression.
  • Blasts may infiltrate blood and tissues, including skin (leukaemia cutis).

Risk Factors

  • Pre-existing haematological disorders: myelodysplastic syndrome (MDS), myeloproliferative disorders, aplastic anaemia, paroxysmal nocturnal haemoglobinuria (PNH).
  • Congenital disorders: Down syndrome, Bloom syndrome.
  • Environmental exposures: prior chemotherapy, radiation, tobacco smoke, benzene.
  • Most cases are de novo in previously healthy individuals.

Clinical Features

History

  • Symptoms develop over days to weeks, or may be asymptomatic with lab abnormalities.
  • Symptoms due to marrow failure:
  • Anaemia: fatigue, pallor, dyspnoea, tachycardia.
  • Thrombocytopenia: mucosal bleeding, bruising, petechiae, epistaxis, menorrhagia, spontaneous hemorrhage.
  • Neutropenia: recurrent/severe infections, persistent fevers.
  • Leukemic infiltration: respiratory distress, altered mental status (leukostasis emergency).

Examination

  • Pallor, cardiac murmurs from anaemia.
  • Fever, signs of infection.
  • Petechiae, purpura, ecchymoses.
  • Leukemia cutis (skin infiltrates).
  • Signs of leukostasis: neurological or respiratory compromise.

Differential Diagnosis

  • Other causes of pancytopenia: aplastic anaemia, MDS, lymphoma, viral infections (EBV, CMV, HIV, Parvovirus B19), autoimmune diseases (SLE), drug-induced cytopenias.

Investigations

Laboratory

  • Full blood count: variable WBC (normal, high, or low), anemia (normocytic/normochromic), thrombocytopenia.
  • Peripheral blood smear: myeloblasts with large nuclei, prominent nucleoli, Auer rods (pathognomonic).
  • Elevated LDH and uric acid from cell turnover.
  • Coagulation profile to assess bleeding risk.

Bone Marrow Biopsy

  • Required to confirm diagnosis: ≥20% blasts in marrow or blood.
  • Typically hypercellular marrow with blast infiltration.
  • Immunophenotyping, cytogenetics, FISH, molecular studies for subtype classification.

Flow Cytometry

  • Identifies surface antigen expression (e.g., CD34, HLA-DR, CD117, CD13, CD33).
  • Differentiates AML subtypes.

Classification

WHO 2016 Classification

  • AML with recurrent genetic abnormalities
  • AML with myelodysplasia-related changes
  • Therapy-related myeloid neoplasms
  • AML not otherwise specified
  • Myeloid sarcoma
  • Myeloid proliferations related to Down syndrome

FAB Classification

  • M0 to M7 based on differentiation and lineage (e.g., M3 = acute promyelocytic leukaemia)

Management

Chemotherapy

  • Main treatment with induction (2-6 weeks) to reduce blasts, followed by consolidation cycles.
  • Maintenance therapy (months to years) to maintain remission.
  • Common agents: Cytarabine (ara-C), Daunorubicin, Idarubicin, ATRA and arsenic for APML.

Bone Marrow Transplant

  • Allogeneic transplant indicated for high-risk cytogenetics, refractory disease, or high leukocyte count.

Supportive Care

  • Blood transfusions for anemia and thrombocytopenia.
  • Infection prophylaxis (antibacterial, antifungal, antiviral).
  • Oral care for mucositis.
  • Allopurinol to prevent tumor lysis syndrome.
  • Antiemetics for chemotherapy side effects.

Complications

  • Leukostasis (high blast counts causing respiratory/neuro distress).
  • Tumor lysis syndrome (hyperuricemia, hyperkalemia, hyperphosphatemia).
  • Disseminated intravascular coagulation (especially in APML).
  • Infection due to immunosuppression.

Prognosis

  • 5-year survival ~25% in adults, higher (~67%) in patients <20 years.
  • Poor prognosis linked to age, cytogenetic abnormalities, response to therapy.

References

  • De Kouchkovsky I, Abdul-Hay M. Blood Cancer J. 2016;6(7):e441.
  • Vakiti A, Mewawalla P. StatPearls. 2020.
  • Angelescu S et al. Maedica (Bucur). 2012;7(3):254-60.
  • Jonathon E, Kolitz M. UpToDate Topic 94786. 2020.
  • Percival ME et al. Blood Rev. 2017;31(4):185-92.
  • Rose-Inman H, Kuehl D. Emerg Med Clin North Am. 2014;32(3):579-96.
  • Arber DA et al. WHO Classification. 2016.

Test Yourself

  • [Link to AML quizzes and flashcards]

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