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TextbookHaematologyAcute Myeloid Leukaemia

Acute Myeloid Leukaemia

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Malignant proliferation of myeloid blast cells in bone marrow. Most common acute leukaemia in adults (median age 68 years). Characterised by Auer rods on blood film and ≥20% myeloid blasts in marrow.

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Key Facts

  • Most common acute leukaemia in adults: median age 68 years; incidence increases with age
  • ≥20% myeloid blasts in bone marrow (WHO); Auer rods (fused azurophilic granules) pathognomonic
  • DIC: associated with acute promyelocytic leukaemia (APL; t(15;17) PML-RARA) - haematological emergency
  • APL treatment: all-trans retinoic acid (ATRA) + arsenic trioxide (ATO) - highly curable (~90% in low/intermediate risk)
  • Intensive chemotherapy: daunorubicin + cytarabine ('3+7' induction); allogeneic SCT for intermediate/poor risk in CR1
  • FLT3 mutation: ~30% of AML; add midostaurin (NICE TA823) during induction/consolidation
  • Tumour lysis syndrome: major risk; allopurinol/rasburicase prophylaxis
  • Prognosis: 5-year survival ~30% overall; highly variable by cytogenetics/molecular (5–80%)

Overview

Key Facts

Acute myeloid leukaemia (AML) is a heterogeneous group of haematological malignancies characterised by clonal proliferation of myeloid blasts in the bone marrow and blood.

Epidemiology

  • Most common acute leukaemia in adults: ~3,000 new cases/year in UK
  • Median age at diagnosis: 68 years
  • Incidence increases with age

Aetiology

  • De novo: most cases
  • Secondary: prior MDS, myeloproliferative neoplasm, previous chemotherapy/radiation (therapy-related AML)
  • Risk factors: benzene, smoking, Down syndrome (10–20× risk), Fanconi anaemia

Pathophysiology

  • Two-hit model: (1) class I mutations promoting proliferation (FLT3, RAS) + (2) class II mutations blocking differentiation (PML-RARA, CBF)
  • Clonal expansion of myeloid blasts → marrow failure
  • Infiltration of organs (liver, spleen, gums, skin, CNS)

Clinical Presentation

Bone Marrow Failure

  • Anaemia: fatigue, pallor, dyspnoea
  • Neutropenia: recurrent/severe infections
  • Thrombocytopenia: bleeding, bruising, petechiae

Tissue Infiltration

  • Hepatosplenomegaly
  • Gingival hypertrophy (monocytic subtypes - M4/M5)
  • Skin infiltration (leukaemia cutis)
  • CNS involvement (more common in monocytic)

Specific

  • DIC: especially APL t(15;17) - bleeding and thrombosis
  • Leucostasis: WCC >100 × 10⁹/L → respiratory distress, neurological symptoms
  • Tumour lysis syndrome

Red Flags

  • Bleeding with DIC (APL - start ATRA immediately if suspected)
  • Leucostasis (WCC >100)
  • Febrile neutropenia

Differential Diagnosis

DiagnosisKey FeaturesInvestigation
ALLLymphoid blasts, TdT+, younger patientsFlow cytometry, cytogenetics
MDS<20% blasts, dysplasia, elderlyBone marrow
CML blast crisisPrior CML, BCR-ABL1 positiveBCR-ABL1, history
Reactive leucocytosisInfection, no blastsBlood film, clinical
Aplastic anaemiaPancytopenia, hypocellular marrow, no blastsBone marrow

Diagnosis / Investigation

Bloods

  • FBC: anaemia, thrombocytopenia, WCC variable (low/normal/very high); circulating blasts
  • Blood film: myeloid blasts, Auer rods (pathognomonic), cytoplasmic granules
  • Coagulation: DIC screen (prolonged PT/APTT, low fibrinogen, high D-dimer) - especially APL
  • LDH, urate: raised
  • U&Es, Ca, PO4, LFTs: baseline + TLS risk

Bone Marrow

  • Aspirate + trephine: ≥20% myeloid blasts
  • Flow cytometry: CD13, CD33, CD34, MPO (myeloid markers)
  • Cytogenetics: t(15;17) PML-RARA (APL), t(8;21), inv(16) (CBF - good risk), complex karyotype (poor)
  • Molecular: FLT3-ITD (~30%), NPM1 (~30%), CEBPA, TP53, IDH1/2, RUNX1

Classification

  • WHO 2022: based on genetic abnormalities (not morphology alone)

Management

APL (t(15;17)) - EMERGENCY

  • ATRA (all-trans retinoic acid) 45mg/m²/day: start IMMEDIATELY if APL suspected (do NOT wait for cytogenetics)
  • ATRA + arsenic trioxide (ATO): standard for low/intermediate risk APL (~90% cure)
  • Differentiation syndrome: ATRA/ATO can cause fever, oedema, respiratory distress → dexamethasone 10mg BD

Non-APL AML

Fit for intensive therapy:

  • Induction ('3+7'): daunorubicin 60mg/m² × 3 days + cytarabine 100–200mg/m² × 7 days
  • FLT3+: add midostaurin 50mg BD (NICE TA823; RATIFY trial)
  • CR achieved in ~60–80%
  • Consolidation: high-dose cytarabine (HiDAC) or allogeneic SCT (intermediate/poor risk)

Unfit (elderly/comorbid):

  • Azacitidine 75mg/m² × 7 days/28 days ± venetoclax (NICE TA957; VIALE-A trial)
  • Low-dose cytarabine: alternative
  • Best supportive care: transfusions, antibiotics, palliative

Supportive

  • TLS prevention: allopurinol (rasburicase if high risk - contraindicated in G6PD deficiency)
  • Febrile neutropenia: piperacillin-tazobactam, antifungals
  • Blood products, G-CSF

Referral Criteria

  • Haematology: URGENT same-day referral for suspected acute leukaemia
  • Specialist centre: SCT assessment

Prognosis

  • Highly variable by genetics:
    • APL: ~90% cure with ATRA + ATO
    • CBF AML (t(8;21), inv(16)): ~65–75% 5-year survival
    • NPM1+/FLT3-: ~60% 5-year survival
    • FLT3-ITD: ~30–40% (improved with midostaurin)
    • Complex karyotype/TP53: <10% 5-year survival
  • Overall 5-year survival: ~30% (all ages); ~50% in <60 years
  • Elderly (>70): median survival ~6–12 months with treatment
  • Venetoclax + azacitidine: improved median survival from 10 to 15 months in elderly

Other Relevant Information

ELN 2022 Risk Stratification

RiskGenetic
Favourablet(15;17), t(8;21), inv(16), NPM1 without FLT3-ITD, CEBPA biallelic
IntermediateNPM1 with FLT3-ITD, normal karyotype without other markers
AdverseComplex karyotype, TP53, RUNX1, ASXL1, del(7q), t(6;9)
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