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TextbookHaematologyAcute Myeloid Leukaemia

Acute Myeloid Leukaemia

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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