Recognise acute myeloid leukaemia, confirm lineage and defining genetics urgently, stabilise cytopenic and hyperleukocytic emergencies and select biology- and fitness-led treatment with measurable residual disease follow-up.
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.
Somatic mutations and chromosomal rearrangements in a haematopoietic progenitor disturb differentiation, self-renewal and survival, producing a clonally expanding myeloid blast population.
Myelodysplastic syndrome, myeloproliferative neoplasm and clonal haematopoiesis can evolve into AML through additional lesions and often confer adverse-risk biology.
Previous cytotoxic chemotherapy or radiotherapy can select damaged clones; latency, cytogenetics and prior exposure influence classification, prognosis and transplant planning.
Inherited RUNX1, CEBPA, DDX41, GATA2 and marrow-failure syndromes are uncommon but affect family counselling, related-donor selection and surveillance.
Leukaemic progenitors fail to mature and accumulate as blasts, replacing normal marrow and releasing dysfunctional cells into blood and tissues.
Suppression of erythropoiesis, granulopoiesis and megakaryopoiesis causes anaemia, infection and bleeding even when the total white-cell count is high.
Blasts can infiltrate skin, gingiva, spleen or CNS and, at high burden, impair microcirculation through adhesion and viscosity-dependent leucostasis.
Spontaneous or treatment-driven lysis releases potassium, phosphate and nucleic acids, producing arrhythmia, hypocalcaemia, urate nephropathy and acute kidney injury.
Fatigue, dyspnoea, infection, oral ulceration, petechiae, bruising or bleeding reflect anaemia, neutropenia and thrombocytopenia.
An abnormal film may show myeloblasts, Auer rods or monocytic differentiation, but lineage and subtype require integrated laboratory confirmation.
Gingival enlargement, violaceous skin lesions, nodes, splenomegaly or focal neurological signs occur more often in selected monocytic or genetic subtypes.
Hypoxaemia, confusion, headache, focal deficit, priapism or retinal haemorrhage with high blasts suggests leucostasis rather than a harmless laboratory count.
Bleeding, low fibrinogen and abnormal promyelocytes demand immediate tretinoin and PML::RARA testing before final classification.
ALL can present identically with blasts and cytopenias; flow cytometry and defining molecular lesions establish lineage and mixed-phenotype cases.
MDS with excess blasts overlaps biologically, but current classification uses blast percentage and AML-defining genetics to assign the disease category.
Severe infection or inflammation produces mature neutrophilia with left shift rather than a clonal blast phenotype; film, flow and molecular testing distinguish them.
APL is an AML subtype requiring an immediate separate emergency branch because coagulopathy and differentiation therapy alter the first hours of care.
Disease and chemotherapy cause prolonged neutropenia and thrombocytopenia, leading to bacterial or fungal sepsis and mucosal, pulmonary or intracranial bleeding.
High blast burden can cause respiratory or neurological microvascular failure, and rapid cytoreduction can precipitate fatal electrolyte and renal complications.
Mucositis, cardiotoxicity, organ injury, infertility, secondary malignancy and graft-versus-host disease vary with chemotherapy, targeted therapy and transplantation.
Residual resistant clones detected molecularly or phenotypically can expand after remission, requiring salvage, clinical trial or allogeneic transplant assessment.
AML classification now includes genetic entities that can establish disease below a conventional blast threshold. Integrated laboratory reporting prevents mislabelling as MDS.
Tretinoin is low-cost and rapidly addresses the driver; delaying it for definitive genetics risks early haemorrhagic death in a highly curable disease.
Age correlates with frailty and adverse genetics but cannot substitute for performance, cognition, organ reserve, social support and the patient's informed priorities.
Two morphologically complete remissions can carry very different relapse risks. Marker kinetics help decide chemotherapy, transplant and pre-emptive investigation.
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.
Do not wait for marrow histology before giving antibiotics for neutropenic sepsis or tretinoin for morphologically suspected APL.
Do not assume a high white count means adequate neutrophils; circulating blasts do not provide normal antibacterial function.
Do not transfuse red cells reflexively before cytoreduction in severe symptomatic hyperleukocytosis without senior assessment of viscosity and oxygen delivery.
Do not select intensive or non-intensive care from age alone or equate lower intensity with low toxicity.
Do not start venetoclax without lysis stratification and CYP3A review, especially when azole antifungal prophylaxis is planned.
Do not call morphological remission cure or omit a validated MRD plan when a trackable marker exists.
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A patient presents with bruising, fibrinogen 0.8 g/L and circulating abnormal promyelocytes with bundles of Auer rods. PML::RARA testing will take several hours. What is the best immediate disease-specific action?
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.
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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.
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.
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.
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.
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.