Acute myeloid leukaemia

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

AML is a genetically diverse group of clonal myeloid neoplasms with marrow failure and variable tissue infiltration. Presentation ranges from incidental pancytopenia to fulminant sepsis, haemorrhage, leucostasis or tumour lysis. Examine for pallor, infection, bruising, hepatosplenomegaly, gingival hypertrophy, skin lesions, retinal changes and neurological or respiratory compromise. Obtain an urgent expert film, but do not diagnose from Auer rods alone. APL morphology—abnormal heavily granulated promyelocytes, bundles of Auer rods or a bilobed microgranular pattern—changes immediate care.

Diagnosis integrates morphology, flow immunophenotype, cytogenetics and molecular genetics. Bone-marrow aspirate provides morphology, flow and molecular material; trephine defines cellularity, fibrosis and infiltrative pattern. Blood can be used urgently when circulating blasts are abundant. Send rapid PML::RARA whenever APL is possible and test FLT3 promptly where an induction inhibitor decision depends on it. Document NPM1, CEBPA, TP53 and myelodysplasia-related lesions, karyotype and other defining fusions. Preserve material for measurable residual disease and consider germline assessment when age, phenotype or family history suggests predisposition.

Stabilisation runs beside diagnostics. Neutropenic sepsis receives immediate local empiric antibiotics after cultures without waiting for marrow results. Major bleeding receives component support and source control. Hyperleukocytic symptomatic disease requires hydration balanced against respiratory status, allopurinol or rasburicase according to lysis risk and urgent hydroxycarbamide or protocol treatment. Avoid routine red-cell transfusion before cytoreduction in severe leucostasis unless oxygen delivery demands it, because increased viscosity can worsen microvascular flow. Platelet and fibrinogen thresholds are higher for active bleeding, CNS disease and suspected APL.

The MDT selects intensive therapy using performance status, frailty, cardiac, renal and hepatic reserve, cytogenetic and molecular risk and patient goals. UK induction schedules and trial allocation vary; typical backbones combine cytarabine with an anthracycline, with FLT3 or other targeted additions when indicated. Response assessment after induction determines further therapy. Consolidation may use additional chemotherapy or allogeneic stem-cell transplantation. Favourable genetics with deep MRD response may avoid transplant in first remission, while adverse-risk or persistent MRD commonly strengthens the transplant indication when fitness and donor options permit.

For adults unsuitable for intensive therapy, supportive care alone, low-intensity therapy or azacitidine with venetoclax are considered. A licensed cycle uses azacitidine 75 mg/m² SC on days 1–7 of each 28-day cycle and venetoclax ramped to 400 mg daily; CYP3A inhibitors require major venetoclax reduction, and marrow assessment guides interruptions for prolonged cytopenia. Antimicrobial prophylaxis must be coordinated with interactions. Early cycles often require frequent transfusion, lysis chemistry and infection review. Treatment continues while benefit and tolerability persist rather than for an arbitrary fixed count of cycles.

Supportive care is disease treatment. Use irradiated or CMV-appropriate components according to transplant and local policy, antifungal and antiviral prophylaxis according to regimen, dental review and fertility preservation before treatment when safe. Discuss contraception and avoid pregnancy during teratogenic therapy; urgent cancer care and reproductive planning require a specialist team. Monitor nutrition, mucositis and psychosocial burden. At remission, record the molecular marker used for MRD, planned schedule, relapse warning symptoms, vaccination and late-effect follow-up.

Key points

Suspect AML with unexplained cytopenias, circulating blasts, recurrent infection, bleeding, bone pain or gingival and skin infiltration; a normal total white-cell count does not exclude it.
First-line tests are urgent FBC and expert blood film, coagulation and fibrinogen, renal, liver, urate, LDH, calcium, phosphate, cultures and group samples.
Confirm with bone-marrow aspirate and trephine, flow cytometry, karyotype or FISH and a rapid molecular panel; some defining genetic AML diagnoses do not require 20% blasts.
Always create an emergency APL branch: send rapid PML::RARA testing and begin oral tretinoin immediately if morphology suggests APL.
Intensive versus non-intensive treatment is based on physiological fitness, frailty, organ function, genetics and patient goals—not chronological age alone.
Fit adults receive a current UK protocol using induction and consolidation with genotype-directed additions; exact cytarabine and anthracycline schedules are centre and trial specific.
Adults unsuitable for intensive chemotherapy may receive azacitidine plus venetoclax when commissioned and appropriate, with mandatory tumour-lysis, CYP3A and prolonged-cytopenia management.
FLT3, NPM1, CEBPA, TP53 and other lesions influence prognosis, targeted treatment and transplant decisions; obtain adequate diagnostic material before non-essential steroids or chemotherapy.
Measurable residual disease after induction and consolidation refines relapse risk and transplant strategy; morphological remission alone is not the whole response.
Leukapheresis is not routine AML treatment and must never delay hydroxycarbamide or definitive therapy; use it only for selected symptomatic leucostasis through apheresis expertise.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Acquired driver lesions

Somatic mutations and chromosomal rearrangements in a haematopoietic progenitor disturb differentiation, self-renewal and survival, producing a clonally expanding myeloid blast population.

Antecedent myeloid disease

Myelodysplastic syndrome, myeloproliferative neoplasm and clonal haematopoiesis can evolve into AML through additional lesions and often confer adverse-risk biology.

Therapy-related disease

Previous cytotoxic chemotherapy or radiotherapy can select damaged clones; latency, cytogenetics and prior exposure influence classification, prognosis and transplant planning.

Germline predisposition

Inherited RUNX1, CEBPA, DDX41, GATA2 and marrow-failure syndromes are uncommon but affect family counselling, related-donor selection and surveillance.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Differentiation arrest
Leukaemic progenitors fail to mature and accumulate as blasts, replacing normal marrow and releasing dysfunctional cells into blood and tissues.
2
Marrow failure
Suppression of erythropoiesis, granulopoiesis and megakaryopoiesis causes anaemia, infection and bleeding even when the total white-cell count is high.
3
Tissue and microvascular injury
Blasts can infiltrate skin, gingiva, spleen or CNS and, at high burden, impair microcirculation through adhesion and viscosity-dependent leucostasis.
4
Rapid cell breakdown
Spontaneous or treatment-driven lysis releases potassium, phosphate and nucleic acids, producing arrhythmia, hypocalcaemia, urate nephropathy and acute kidney injury.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Marrow failure

Fatigue, dyspnoea, infection, oral ulceration, petechiae, bruising or bleeding reflect anaemia, neutropenia and thrombocytopenia.

Circulating blasts

An abnormal film may show myeloblasts, Auer rods or monocytic differentiation, but lineage and subtype require integrated laboratory confirmation.

Tissue infiltration

Gingival enlargement, violaceous skin lesions, nodes, splenomegaly or focal neurological signs occur more often in selected monocytic or genetic subtypes.

Hyperleukocytic emergencyRed flag

Hypoxaemia, confusion, headache, focal deficit, priapism or retinal haemorrhage with high blasts suggests leucostasis rather than a harmless laboratory count.

APL warningRed flag

Bleeding, low fibrinogen and abnormal promyelocytes demand immediate tretinoin and PML::RARA testing before final classification.

Red flags requiring action

Fever, rigors, hypotension, hypoxia or confusion with neutropenia is a haematological emergency requiring empiric broad-spectrum antibiotics within the local sepsis pathway.
Dyspnoea, hypoxaemia, headache, confusion, focal deficit, priapism or retinal change with a very high myeloid count suggests leucostasis and requires immediate cytoreduction planning.
Bleeding, bruising, low fibrinogen or prolonged coagulation with abnormal promyelocytes suggests APL; tretinoin and aggressive blood support must begin on morphological suspicion.
Hyperkalaemia, hyperphosphataemia, hypocalcaemia, rising urate or creatinine before or after therapy indicates tumour lysis and requires continuous cardiac and metabolic escalation.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line: FBC and expert blood filmFirst stepFirst line
Why
Identify blasts, cytopenias and morphology that changes emergency care.
Interpretation and limitations
A normal or low WBC does not exclude AML. Auer rods support myeloid differentiation; suspicious promyelocytes trigger immediate APL treatment and rapid molecular confirmation.
02
Reference-standard integrated marrow assessment
Why
Confirm lineage, disease-defining category and baseline burden.
Interpretation and limitations
Combine aspirate morphology and flow with trephine histology, karyotype or FISH and molecular testing; dry tap or fibrosis increases reliance on trephine and blood material.
03
Rapid genetics
Why
Identify emergencies, targeted therapy and prognostic groups in time for induction decisions.
Interpretation and limitations
Prioritise PML::RARA when suspected and urgent FLT3 where treatment depends on it; complete NPM1, CEBPA, TP53 and the accredited myeloid panel.
04
Emergency and treatment baseline
Why
Detect DIC, lysis, infection and organ limits before cytoreduction.
Interpretation and limitations
Check PT, APTT, fibrinogen, D-dimer, urate, LDH, electrolytes, calcium, phosphate, creatinine, liver tests, cultures, ECG and echocardiogram where anthracycline is considered.
05
Measurable residual disease
Why
Quantify response below morphology and refine relapse and transplant planning.
Interpretation and limitations
Use a validated molecular marker such as NPM1 or multiparameter flow at protocol-defined times; interpret regeneration and assay sensitivity with the specialist laboratory.
06
Transplant and infection preparation
Why
Avoid delay if allogeneic transplant becomes the consolidation strategy.
Interpretation and limitations
Perform HLA typing, CMV and viral screening, comorbidity assessment and early donor search; assess fertility and pregnancy before gonadotoxic or teratogenic treatment.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Acute lymphoblastic leukaemia

ALL can present identically with blasts and cytopenias; flow cytometry and defining molecular lesions establish lineage and mixed-phenotype cases.

High-grade MDS

MDS with excess blasts overlaps biologically, but current classification uses blast percentage and AML-defining genetics to assign the disease category.

Leukaemoid reaction

Severe infection or inflammation produces mature neutrophilia with left shift rather than a clonal blast phenotype; film, flow and molecular testing distinguish them.

Acute promyelocytic leukaemia

APL is an AML subtype requiring an immediate separate emergency branch because coagulopathy and differentiation therapy alter the first hours of care.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Suspected AMLStabilise while preserving diagnosisFirst stepBlasts, unexplained cytopenias or an AML emergency is identified.

1Send FBC, film, coagulation, fibrinogen, lysis, infection and group tests and obtain urgent blood or marrow diagnostic material.
2Treat sepsis, bleeding and lysis immediately; start tretinoin on APL suspicion and cytoreduce symptomatic hyperleukocytosis with haematology.
3DefinitiveComplete integrated morphology, flow, cytogenetic and molecular classification before the definitive MDT regimen.

02Fit for intensive therapyUse risk-adapted induction and consolidationPhysiological fitness and patient goals support curative-intent intensive treatment.

1Review cardiac and organ reserve, fertility, infection and HLA status and classify cytogenetic and molecular risk.
2Start the current UK intensive protocol with genotype-directed additions and protocol lysis, antimicrobial and transfusion support.
3Assess morphology and MRD, then choose further chemotherapy or allogeneic transplant using response and relapse risk.

03Not fit for intensive therapyDeliver active low-intensity care safelyFrailty, comorbidity or informed preference makes intensive induction unsuitable.

1Define goals, genetics, lysis risk, infection burden, transfusion needs and the feasibility of repeated outpatient and inpatient monitoring.
2Consider commissioned azacitidine plus venetoclax or another evidence-based low-intensity option with interaction-adjusted dosing.
3Use early marrow response to manage cytopenic intervals and continue only while clinical benefit and tolerability justify treatment.

04Relapsed or refractory AMLRe-biopsy and target the current cloneMorphological, molecular or clinical relapse occurs or induction fails.

1Repeat marrow, flow and molecular testing because actionable clones and phenotype can change.
2Control sepsis, bleeding, lysis and counts, then consider trial, mutation-directed or salvage therapy through the AML MDT.
3Assess whether response can bridge to allogeneic transplant and align treatment intensity with prognosis and patient goals.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Commissioned first-line low-intensity treatment for untreated AML when intensive chemotherapy is unsuitable and the patient can complete lysis and cytopenia monitoring.

Azacitidine with venetoclax

Give azacitidine 75 mg/m² subcutaneously on days 1–7 of each 28-day cycle and venetoclax orally 100 mg day 1, 200 mg day 2 and 400 mg from day 3 when no interacting inhibitor requires reduction.

Classify tumour-lysis risk, hydrate and lower urate; strong CYP3A inhibitors require major venetoclax dose reduction and are contraindicated during some ramp contexts. Perform early marrow assessment to distinguish aplasia from persistent AML and adjust post-remission duration through protocol. Avoid pregnancy and breastfeeding.

Rapid temporary reduction of a dangerous blast count while molecular classification and definitive systemic therapy are organised.

Hydroxycarbamide

For urgent AML cytoreduction give a specialist protocol dose commonly 50–100 mg/kg/day orally in two or three divided doses, adjusted frequently to count, renal function and definitive-treatment timing.

It is not curative and must not delay APL-specific tretinoin or induction. Monitor FBC and lysis chemistry at least daily, use renal adjustment and safe handling, and avoid in pregnancy unless life-saving specialist benefit clearly outweighs fetal risk.

Rapidly degrades existing uric acid during high-burden AML and urgent cytoreduction.

Rasburicase

Give 0.2 mg/kg intravenously once daily for up to 7 days for high-risk or established tumour lysis, with number of doses individualised to urate production and response under the BSH protocol.

Contraindicated in G6PD deficiency because of haemolysis and methaemoglobinaemia; test at-risk ancestry if urgency permits. Send post-dose urate samples on ice for immediate analysis to prevent falsely low ex-vivo results.

Curative-intent remission induction for physiologically fit adults followed by response-adapted consolidation or allogeneic transplantation.

Intensive AML induction

Use the exact current UK centre or trial protocol, which commonly combines weight- or surface-area-calculated cytarabine and an anthracycline with genotype-directed additions; independent reconstitution of a generic schedule is unsafe.

Verify protocol, body surface area, cumulative anthracycline exposure, cardiac function, liver and renal adjustments, antimicrobial prophylaxis, fertility preservation and pregnancy prevention. Expect prolonged aplasia and provide accredited specialist supportive care.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Infection and haemorrhage

Disease and chemotherapy cause prolonged neutropenia and thrombocytopenia, leading to bacterial or fungal sepsis and mucosal, pulmonary or intracranial bleeding.

Leucostasis and lysis

High blast burden can cause respiratory or neurological microvascular failure, and rapid cytoreduction can precipitate fatal electrolyte and renal complications.

Treatment toxicity

Mucositis, cardiotoxicity, organ injury, infertility, secondary malignancy and graft-versus-host disease vary with chemotherapy, targeted therapy and transplantation.

Relapse or refractory disease

Residual resistant clones detected molecularly or phenotypically can expand after remission, requiring salvage, clinical trial or allogeneic transplant assessment.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

During emergency stabilisation repeat FBC, coagulation and fibrinogen, potassium, phosphate, calcium, urate, LDH, creatinine, fluid balance and clinical respiratory or neurological status at a frequency matched to instability.
During induction monitor infection, cultures, mucositis, transfusion need, organ toxicity and drug-specific cardiac or hepatic effects daily within the inpatient protocol.
With venetoclax use protocol-timed lysis chemistry during ramp and early treatment, full interaction review and marrow assessment to guide interruptions and subsequent cycle duration.
After remission measure MRD with the same validated molecular or flow method at protocol time points and act on a confirmed trajectory rather than a single ambiguous result.
Before and after transplant monitor donor, infection, graft function, graft-versus-host disease, relapse markers, fertility, endocrine and psychosocial late effects.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Twenty percent has exceptions

AML classification now includes genetic entities that can establish disease below a conventional blast threshold. Integrated laboratory reporting prevents mislabelling as MDS.

APL is a first-hour branch

Tretinoin is low-cost and rapidly addresses the driver; delaying it for definitive genetics risks early haemorrhagic death in a highly curable disease.

Fitness is multidimensional

Age correlates with frailty and adverse genetics but cannot substitute for performance, cognition, organ reserve, social support and the patient's informed priorities.

MRD changes consolidation

Two morphologically complete remissions can carry very different relapse risks. Marker kinetics help decide chemotherapy, transplant and pre-emptive investigation.

Cytopenia has two meanings

During low-intensity therapy persistent low counts can represent active AML or treatment-induced remission marrow; marrow assessment prevents both premature abandonment and unsafe continuation.

11Common pitfallsFrequent interpretation and management errors.

01
Do not wait for marrow histology before giving antibiotics for neutropenic sepsis or tretinoin for morphologically suspected APL.
02
Do not assume a high white count means adequate neutrophils; circulating blasts do not provide normal antibacterial function.
03
Do not transfuse red cells reflexively before cytoreduction in severe symptomatic hyperleukocytosis without senior assessment of viscosity and oxygen delivery.
04
Do not select intensive or non-intensive care from age alone or equate lower intensity with low toxicity.
05
Do not start venetoclax without lysis stratification and CYP3A review, especially when azole antifungal prophylaxis is planned.
06
Do not call morphological remission cure or omit a validated MRD plan when a trackable marker exists.