Acute Myeloid Leukaemia

Name: Acute Myeloid Leukaemia: Mini Review for Clinicians, Algorithms & Cases
Creator: Dr. Haritha Chiramana
License: https://creativecommons.org/licenses/by-nc-nd/4.0/

Haematological cancers, part 7 · AML in fit and unfit adults · Genetics and ELN risk · Induction, transplant and maintenance · Targeted therapy at relapse · Acute promyelocytic leukaemia · Leukaemia emergencies · Key points for clinicians · Last updated 17 October 2026

For health professionals. This section uses clinical terms and is general education for doctors, nurses and students, not advice for an individual patient. Patients and families: please read our patient guides instead, Cancer Myth Busters · Understanding your cancer report · Living through cancer treatment, or speak with your own doctor.

Who this page is for, and where to start

Printable PDFs for this moduleMini reviews, slides, algorithms, quick references and the MCQ booklet are on the Printable Teaching Resources page. No PDF downloads are kept on this page.

Printable Teaching Resources →

For your patientsPlain-language Telugu–English answers for patients and families: the Leukaemia Myth Busters (20 myths), symptoms and warning signs and the Telugu handouts.

Open the leukaemia myths →

SurgeonsScreening and workup (03), local therapy with surgery types (05), algorithms (07), cases (11)

Physicians & oncologistsBiomarkers (04), systemic therapy (06), algorithms (07), survivorship (08), cases (11)

Postgraduate residentsOncology and other specialities: case vignettes (11), landmark trials (09) and 0 cited trials (12) for exams and journal clubs

Medical studentsAt a glance (01), presentation and common traps (02), the figures, and follow-up (08)

Prepared and reviewed by Dr. Haritha Chiramana, MD, DM, Senior Medical Oncologist & Hemato-Oncologist, C.R. Reddy Cancer Center, Nellore, Andhra Pradesh, India. She teaches oncology to postgraduates and medical students; colleges and departments may write to info@drharitha.co.in for teaching sessions. Printable Teaching Resources and how to cite → Phone 0861 232 5344 · WhatsApp +91 79896 42272.

01 At a glance

AML is the commonest acute leukaemia of adults (about 80% of adult acute leukaemias); median age at diagnosis 65–68 years in Western registries. It is a group of diseases defined by genetics, not one disease.
Suspect it from a blood count: blasts on the smear, unexplained cytopenias, fever, bleeding or a very high white count. Fatigue and pallor often precede the diagnosis by months.
Stabilise before you classify: in the first hours look for APL (bleeding, low fibrinogen: start ATRA on suspicion), leukostasis, tumour lysis and neutropenic infection (antibiotics within 60 minutes).
Classify by genetics (WHO 5th edition or ICC 2022): marrow morphology and flow, karyotype, FISH and a rapid FLT3/NPM1/IDH panel plus a myeloid NGS panel. ELN 2022 sorts patients into favourable, intermediate and adverse risk (ELN 2022^[1]).
Fit adults: 7+3 induction, with midostaurin or quizartinib for FLT3 mutations, gemtuzumab for CD33-positive core-binding-factor AML, and CPX-351 for therapy-related or myelodysplasia-related AML; then consolidation or allogeneic transplant by risk and MRD.
Unfit adults: venetoclax with azacitidine improves survival over azacitidine alone (VIALE-A^[2]); IDH1-mutated AML: ivosidenib with azacitidine (AGILE^[3]).
APL is an emergency and one of the most curable leukaemias: ATRA plus arsenic trioxide gives 72-month event-free survival of about 97% in low/intermediate-risk disease (APL0406^[4]).
Relapse: repeat the genetics; targeted drugs (gilteritinib, IDH inhibitors, menin inhibitors) or salvage chemotherapy bridge to allogeneic HCT, the only cure.
India: patients are younger (median 40 years in Vellore) and arrive after weeks of symptoms from far away; cost decides who is treated, multidrug-resistant infections drive induction deaths, and APL early deaths remain high (Philip 2015^[5]; Mamlekar 2025^[6]).

Figure 1. The four steps (UpToDate AML overview, diagnosis and induction reviews; Philip 2015 for India).

02 Clinical presentation, common traps & causes

Figure 2. Presenting findings (UpToDate AML diagnosis review; extramedullary disease on PET in 3,522 patients). Leukaemia cutis is mostly monocytic AML.

Who gets it, and why

Age: incidence rises with age; about 4 per 100,000 adults a year in the USA. AML is under 10% of acute leukaemias in children under 10 (where ALL dominates) but about 80% in adults.
Causes: unknown in most. Known risks: previous chemotherapy (alkylating agents, topoisomerase II inhibitors) or radiotherapy (therapy-related AML), an earlier MDS or MPN, benzene, smoking (greatest risk above 60), and obesity (especially APL). Most AML arises from clonal haematopoiesis that has gathered further mutations.
Inherited predisposition: familial disorders may underlie 5–10% of AML/MDS in older adults and 10–20% in young adults. Clues: relatives with blood cancers, long-standing cytopenias, a germline-type variant (DDX41, RUNX1, GATA2, biallelic CEBPA) on NGS. This matters when a sibling is the planned donor (Klco 2021^[7]).
APL: 5–20% of AML depending on region; peaks in young adults (median age 40–50 years in Western series; 33 years in Lucknow).
India: in a 2-year prospective Vellore series of 380 adults and children with non-APL AML, median age was 40, symptoms had lasted a median of 4 weeks, patients travelled a median of 580 km, and only 29% started standard treatment, 81% of the rest for lack of money (Philip 2015^[5]). At AIIMS, 480 patients aged 8–60 treated with 3+7 and high-dose cytarabine had 18.4% induction mortality (Bahl 2015^[8]).

Common traps

"Viral fever" treated for weeks. Fever with pallor, bruises or gum bleeding needs a CBC with a smear the same day.
A normal or low white count read as "not leukaemia". A quarter to two-fifths of patients have fewer than 5,000 white cells; the smear, not the count, makes the diagnosis.
Gum swelling sent to the dentist. Gingival hypertrophy and violaceous skin nodules suggest monocytic AML.
Bleeding treated with plasma alone while the diagnosis waits. Bleeding with low fibrinogen and granular cells is APL until proved otherwise: ATRA the same day.
A red cell transfusion in a breathless patient with 200,000 white cells. It raises blood viscosity and can precipitate leukostasis: cytoreduce first, transfuse slowly if essential.
"Hyperkalaemia" treated in a patient with a huge white count. Potassium leaks from cells in a clotted sample; check a heparinised (plasma) sample.
A mass biopsied and called "small round cell tumour" or lymphoma. Myeloid sarcoma needs myeloid immunostains; it is AML whatever the marrow shows.

03 Diagnosis, workup & staging essentials

Figure 3. Emergencies at presentation (UpToDate AML diagnosis, complications, hyperleukocytosis, TLS and neutropenic fever reviews).

Making the diagnosis

Blood: CBC with differential and smear review; PT, aPTT and fibrinogen; metabolic panel with LDH, urate and phosphate. When many blasts circulate, flow cytometry and genetics can be done on blood.
Marrow: unilateral aspirate (500-cell count) and biopsy from the posterior iliac crest; the sternum is acceptable for aspiration only. Warn the laboratory: fresh samples are needed for flow, karyotype, FISH and molecular tests. Bleeding or infection at the site is unusual even with low counts.
Lineage: myeloblasts are large with prominent nucleoli; Auer rods are pathognomonic. Flow cytometry (CD13, CD33, CD117, MPO; CD34 often) confirms myeloid lineage and sets the baseline for MRD.
Genetics: banding karyotype (FISH does not replace it), rapid FLT3 (ITD and TKD), NPM1 and IDH1/2, and a myeloid NGS panel including TP53, CEBPA, RUNX1, ASXL1 and splicing genes; PML::RARA by PCR or FISH when APL is possible.
Diagnosis: ≥10% myeloid blasts with a defining genetic lesion (APL, CBF fusions, KMT2A, DEK::NUP214, MECOM, CEBPA), any blast count with mutated NPM1 (WHO), ≥20% for BCR::ABL1 and for most AML without a defining lesion; myeloid sarcoma counts as AML at any marrow blast count (WHO 2022^[9]; ICC 2022^[10]).
CNS and imaging: brain CT for suspected bleeding, MRI and lumbar puncture only for neurological symptoms (CNS involvement is found in about 1–3% at diagnosis and does not by itself worsen outcome) (Ganzel 2021^[11]); PET-CT for suspected myeloid sarcoma.

Figure 4. Work-up (ELN 2022 recommendations, Döhner 2022; UpToDate AML diagnosis and induction reviews).

Figure 5. Classification (Khoury 2022; Arber 2022; UpToDate AML classification and diagnosis reviews). Simplified.

Not AML: the differentials to exclude

ALL, mixed phenotype acute leukaemia, blastic plasmacytoid dendritic cell neoplasm and CML in blast phase: flow cytometry and BCR::ABL1 testing separate them (ALL and CML are parts 8 and 9).
MDS: blasts below the AML threshold with dysplasia; ICC calls 10–19% blasts MDS/AML. MPNs can transform; ask about earlier high counts or a large spleen.
Megaloblastic anaemia (B12, folate, copper deficiency) can mimic AML with severe cytopenias: measure vitamin levels. Aplastic anaemia: hypocellular marrow without blasts.
Leukaemoid reaction in severe infection: few blasts, no maturation block, a clear cause. Inherited marrow failure (Fanconi anaemia, telomere disorders): somatic clues and germline testing.

04 Biology and biomarkers that change treatment

Biology in brief

A clonal disease of stem and progenitor cells: AML usually grows out of age-related clonal haematopoiesis (DNMT3A, TET2, ASXL1) after further mutations; on average 13 mutations per genome, about five in recurrently mutated AML genes (TCGA 2013^[12]).
Two kinds of hit: lesions that drive proliferation (FLT3, KIT, RAS) cooperate with lesions that block differentiation (CBF fusions, CEBPA, NPM1). Leukaemic cells suppress normal haematopoiesis rather than simply crowding it out.
Clones evolve: relapse may come from the dominant clone gaining mutations or from a minor clone that survived treatment, so genetics must be repeated at relapse.
IDH1/2 mutations (about 20%) make the oncometabolite 2-hydroxyglutarate and block differentiation: ivosidenib, olutasidenib and enasidenib release the block, which is why they can cause differentiation syndrome.

Figure 6. Mutation frequencies from The Cancer Genome Atlas (Ley 2013), as reported in the UpToDate molecular genetics review; drug list from the treatment reviews.

Figure 7. Genetic risk (Döhner 2022; Döhner 2024; UpToDate AML risk factors and prognosis review). Myelodysplasia-related mutations count as adverse.

Markers that change treatment

Marker	Frequency	What it changes
FLT3-ITD / TKD	~28% (all FLT3)	Midostaurin or quizartinib with induction; gilteritinib at relapse; ITD = intermediate risk
NPM1	~27%	Favourable without FLT3-ITD; PCR MRD guides transplant; menin inhibitors at relapse
CBF fusions (t(8;21), inv(16))	t(8;21): 1–7% of adults, median age 25–30	Gemtuzumab if CD33+; favourable; MRD by PCR
IDH1 / IDH2	~20%	Ivosidenib + azacitidine (unfit); IDH inhibitors at relapse
TP53	~8% (more in older and therapy-related)	Adverse in every model; poor response to all current therapy; trials
Myelodysplasia-related genes	Common in older adults	Adverse (ELN 2022); CPX-351 if fit; transplant in CR1
KMT2A rearrangement	Uncommon	Adverse (except t(9;11)); menin inhibitor at relapse
PML::RARA	APL: ≥95% of cases	ATRA + arsenic; PCR monitoring to molecular remission
CD33	Nearly all CBF AML	Gemtuzumab ozogamicin

MRD: after induction and consolidation, measurable residual disease by flow or PCR is a strong predictor: in a meta-analysis, MRD-negative patients had 5-year OS of 68% vs 34% (Short 2020^[13]). NPM1 transcripts measured by PCR predict relapse (Ivey 2016^[14]).
ELN 2024 for lower-intensity therapy: with venetoclax and azacitidine, median survival was 26.5 months (no FLT3-ITD, RAS or TP53 mutation), 12.1 months (FLT3-ITD or RAS) and 5.5 months (TP53) (ELN 2024^[15]).

05 Local therapy: radiotherapy, surgery & procedures

Radiotherapy

Myeloid sarcoma compressing a vital structure, or persisting after recovery from induction: add RT (about 20 Gy is generally enough) to systemic treatment, which remains the main therapy.
CNS disease: leptomeningeal AML without deficits is treated with intrathecal methotrexate, cytarabine or triple therapy; cranial nerve palsies or other deficits need RT (for example 18–25 Gy to the brain, field down to C2), started as soon as CNS involvement is suspected because nerve recovery falls with delay. Cranial rather than craniospinal RT spares the marrow; avoid high-dose systemic chemotherapy for two weeks before, during and after cranial RT.
Spinal cord compression by a chloroma: dexamethasone, urgent MRI and RT and/or decompression with surgical and radiation oncology input.

Procedures and their pitfalls

Lumbar puncture: only for neurological symptoms in adults (no routine CNS prophylaxis); image first if there are focal signs or altered mentation; correct platelets and clotting; the most experienced operator; many centres give one dose of intrathecal chemotherapy at the diagnostic tap. In APL, defer the LP until the coagulopathy is corrected.
Leukapheresis: no proven benefit on its own; used with hydroxyurea only for symptomatic leukostasis when induction cannot start at once (Oberoi 2014^[16]).
Central venous catheters: needed for induction, but avoid insertion in APL until the coagulopathy is controlled; most AML-related clots are line-related.
Allogeneic HCT: the main "procedure" of curative AML care. Type HLA of the patient and siblings at diagnosis in fit patients; eligibility depends on performance status and heart, lung, liver and kidney function, not age alone.

06 Systemic therapy: indications & options

Fit adults: induction

Figure 8. Fitness (Ferrara 2013; UpToDate medically unfit adults and older adults pretreatment evaluation reviews).

Figure 9. Induction (Stone 2017; Erba 2023; Hills 2014; Lancet 2018; Fathi 2026; UpToDate induction and therapy-related neoplasm reviews). Regimen names only, no doses.

7+3 (seven days of cytarabine with daunorubicin or idarubicin on days 1–3) gives complete remission in about three-quarters of fit younger adults; higher daunorubicin exposure improved outcomes in younger adults (Fernandez 2009^[17]).
FLT3-mutated: add midostaurin (ITD or TKD; RATIFY: median OS 75 vs 26 months, 4-year OS 51% vs 44%) or quizartinib (ITD; QuANTUM-First: median OS 32 vs 15 months), and continue the inhibitor in consolidation and maintenance (RATIFY^[18]; QuANTUM-First^[19]).
CD33-positive CBF AML: add gemtuzumab ozogamicin: fewer relapses and better 5-year survival in favourable and intermediate cytogenetics, largest in CBF AML (Hills 2014^[20]).
Therapy-related or myelodysplasia-related AML (favourable or intermediate genetics): CPX-351, a liposomal daunorubicin-cytarabine, rather than 7+3: 5-year OS 18% vs 8% in patients aged 60–75, with more patients reaching transplant (Lancet 2018^[21]; Lancet 2021^[22]). TP53-mutated therapy-related AML: CPX-351, other intensive regimens or lower-intensity therapy, ideally in a trial.
Azacitidine-venetoclax for fit adults: in the PARADIGM trial it gave more composite remissions (78% vs 53%) and more transplants than 7+3, with similar overall survival (Fathi 2026^[23]): acceptable for selected intermediate- or adverse-risk patients; most experts await longer follow-up.
Special cases: limited heart function → non-anthracycline induction; myeloid sarcoma → add RT; first-trimester pregnancy → termination, then treatment; later pregnancy → discuss urgent induction against temporary measures such as leukapheresis.
Response: marrow at the nadir (day 14–21; <20% cellularity and <5% blasts) and at count recovery (~day 28): CR needs <5% marrow blasts, no circulating blasts and no extramedullary disease; record MRD.

Fit adults: after remission

Figure 10. Post-remission choices (Koreth 2009; Wei 2020 QUAZAR; Short 2020; Ivey 2016; UpToDate post-remission review).

Without post-remission therapy almost everyone relapses. Choice depends on ELN risk, MRD, age and fitness.
Favourable risk: consolidation chemotherapy (intermediate-dose cytarabine is suggested over high-dose for most); transplant only for persistent or rising MRD. Intermediate risk: consolidation or allogeneic HCT, decided on MRD, donor and transplant risk. Adverse risk: allogeneic HCT in first CR (Koreth 2009^[24]).
Maintenance: oral azacitidine for patients ≥55 years with intermediate- or adverse-risk AML after consolidation (QUAZAR: median OS 25 vs 15 months) (QUAZAR^[25]); an FLT3 inhibitor after chemotherapy or after HCT for FLT3-mutated AML.
Transplant conditioning: myeloablative regimens give fewer relapses but more transplant deaths than reduced-intensity regimens, with similar long-term survival; the choice follows age and comorbidity.

Unfit adults

Figure 11. Lower-intensity therapy (DiNardo 2020 VIALE-A; Montesinos 2022 AGILE; UpToDate medically unfit adults review). Compare within a trial, not across trials.

Unfit but not frail: venetoclax with azacitidine or decitabine (VIALE-A: OS 15 vs 10 months; CR 37% vs 18%) (VIALE-A^[2]). IDH1-mutated: ivosidenib with azacitidine (AGILE: OS 24 vs 8 months) (AGILE^[3]). Without venetoclax: azacitidine or decitabine alone (AZA-AML-001^[26]; Kantarjian 2012^[27]).
Not suitable for an HMA (earlier HMA for MDS, severe organ dysfunction): low-dose cytarabine (with venetoclax in VIALE-C) or a targeted drug by mutation (VIALE-C^[28]).
Monitoring: with venetoclax or ivosidenib combinations, check the marrow early in cycle 1 (day 14–21) because responses are fast and counts may need time off venetoclax; then every three cycles. Venetoclax doses are adjusted when azole antifungals are given.
Frail: supportive care (transfusions, antimicrobials, symptom control) is the mainstay; gentle therapy if the patient chooses it. Discuss resuscitation and intensive care early.

Relapsed or refractory AML

Figure 12. Relapsed disease (Perl 2019; DiNardo 2018; Stein 2017; FDA notices 2025; UpToDate relapsed AML review).

20–50% fail to reach CR with intensive induction, and many who do will relapse. Repeat the marrow with flow and NGS, type HLA and involve the transplant team at once.
FLT3: gilteritinib beat salvage chemotherapy (median OS 9.3 vs 5.6 months; CR/CRh 34% vs 15%) (ADMIRAL^[29]). IDH1: ivosidenib or olutasidenib (CR in about a third) (DiNardo 2018^[30]). IDH2: enasidenib (CR 19%, median OS 9 months) (Stein 2017^[31]).
NPM1-mutated or KMT2A-rearranged: menin inhibitors. Revumenib (KMT2A-rearranged acute leukaemia, and NPM1-mutated AML from October 2025) and ziftomenib (NPM1, 13 November 2025; CR+CRh 21% in 112 adults) are FDA-approved (FDA 2025^[32]); they cause differentiation syndrome and QT prolongation. Not covered by the supplied UpToDate relapse topic (updated before these approvals): web-verified; Indian availability to be confirmed.
No target: salvage chemotherapy (FLAG-IDA, MEC, cladribine-based) for the fit, venetoclax with an HMA for others, and clinical trials. Transplant in CR2 (myeloablative if fit); after a transplant relapse, a second HCT or donor lymphocytes are the only curative options.

Acute promyelocytic leukaemia

Figure 13. APL (Lo-Coco 2013; Cicconi 2020; Park 2011; Mamlekar 2025; UpToDate APL diagnosis and initial treatment reviews). No doses.

Diagnosis: abnormal promyelocytes with dense granules and Auer rod bundles (hypergranular), or bilobed nuclei with few visible granules (microgranular, about a quarter); CD13/CD33 positive, CD34 and HLA-DR usually negative; t(15;17) PML::RARA in ≥95%. Start ATRA when APL is suspected; confirmation comes later.
Coagulopathy: transfuse platelets and cryoprecipitate to keep platelets ≥30,000–50,000/µL and fibrinogen >150 mg/dL; no heparin; antifibrinolytics only in selected patients; avoid central lines, lumbar puncture and bronchoscopy before and during induction.
Low/intermediate risk (WBC ≤10,000/µL): ATRA plus arsenic trioxide (APL0406: 72-month EFS 97% vs 77%; fewer relapses and no induction deaths) (APL0406^[4]; Cicconi 2020^[33]). AML17 tested ATRA-ATO in all risk groups (AML17^[34]). Where ATO is not available: ATRA with an anthracycline.
High risk (WBC >10,000/µL): ATRA with an anthracycline, or ATRA plus ATO with hydroxyurea or an anthracycline for a rising white count (Sanz 2000^[35]).
After induction: ATO-based consolidation; after an ATO-containing regimen and a molecular remission, no maintenance; without ATO, intermittent ATRA maintenance. Relapse occurs in 5–10% overall and 20–30% of high-risk patients: ATRA plus ATO, then autologous HCT if PCR-negative; gemtuzumab for molecular relapse where available.
India: CMC Vellore showed durable remissions with single-agent arsenic trioxide in newly diagnosed APL (Mathews 2006^[36]; Mathews 2010^[37]). In 102 patients at SGPGIMS Lucknow (2014–2024; median age 33; 47% high risk; median 18 days from symptoms to diagnosis), induction mortality was 24.5%, mostly from bleeding and infection, and 34% received less platelet or cryoprecipitate support than planned because of shortages (Mamlekar 2025^[6]).

Figure 14. Differentiation syndrome (De Botton 1998; Montesinos 2009; UpToDate differentiation syndrome review). Percentages are approximate incidences.

Differentiation syndrome affects about a quarter of patients with APL on ATRA and/or ATO, up to a fifth on IDH or menin inhibitors, and about 3% on gilteritinib or quizartinib (De Botton 1998^[38]; Montesinos 2009^[39]). Give dexamethasone as soon as it is suspected; continue the drug unless the syndrome is severe or does not respond in 24–48 hours.

Emergencies and supportive care (shared by acute leukaemias)

Figure 15. Hyperleukocytosis and TLS (Oberoi 2014; Cairo 2004; Coiffier 2008; UpToDate hyperleukocytosis and TLS reviews). No doses.

Hyperleukocytosis (WBC >100,000/µL) occurs in 10–20% of new AML; leukostasis (brain, lungs) can occur below that threshold when blasts dominate. Fit: start induction at once. Induction delayed: hydroxyurea (plus leukapheresis only if symptomatic). Hold or slow red cell transfusion; give platelets as needed.
Tumour lysis: high risk in AML with WBC ≥100,000/µL; intermediate with 25,000–100,000 or LDH ≥2× normal (Montesinos 2008^[40]). High risk: IV fluids plus rasburicase (not in G6PD deficiency); intermediate: fluids plus allopurinol (Cairo 2004^[41]; Coiffier 2008^[42]).
DIC is common in APL and in monocytic AML with a high count: measure PT, aPTT, fibrinogen and D-dimer at diagnosis and support with platelets and cryoprecipitate (ISTH score^[43]).

Figure 16. Infections (Freifeld 2011; Taplitz 2018; Bucaneve 2005; Cornely 2007; Jain 2020; UpToDate neutropenic fever and prophylaxis reviews).

Prophylaxis for expected ANC <500/µL for more than 7 days: a fluoroquinolone (Bucaneve 2005^[44]; Taplitz 2018^[45]); antifungal prophylaxis from the start of induction (fluconazole, switching to a mould-active azole for a second induction or refractory disease) (Cornely 2007^[46]); aciclovir for HSV-seropositive patients.
Neutropenic fever is an emergency: cultures, then an antipseudomonal beta-lactam within 60 minutes; vancomycin only for line, skin or soft-tissue infection, pneumonia or instability; do not change antibiotics for fever alone in a stable patient; add an antifungal after 4–7 days of unexplained fever (IDSA 2011^[47]).
India: multidrug-resistant organisms grew in 55% and fungal pneumonia was diagnosed in 55% of patients during induction at an Indian tertiary cancer centre, despite prophylaxis (Jain 2020^[48]). Local resistance data should drive empirical choices.
Blood products: leukocyte-depleted (and in many centres irradiated) products; red cells for haemoglobin ≤8 g/dL in most; platelets below 10,000/µL or higher with bleeding, fever, sepsis or coagulopathy. No erythropoiesis-stimulating agents during induction.

India: check availability and cost before planning

Availability and cost in India change often and were not verified for this page. Before planning treatment, check current access and cost of venetoclax, azacitidine (injectable and oral), midostaurin, quizartinib, gilteritinib, ivosidenib, enasidenib, gemtuzumab ozogamicin, CPX-351, revumenib and ziftomenib, rasburicase and mould-active azoles.
Check local access to rapid FLT3/NPM1 testing, NGS panels, flow MRD and PML::RARA PCR, HLA typing and allogeneic transplant (sibling, unrelated and haploidentical) early, so that results and donor searches do not delay treatment.

Quick reference (also as a printable PDF on the Printable Teaching Resources page)

Table A. Diagnosis and work-up tests and what they change

Test	When	What it changes	Pitfalls
CBC + smear review	Every suspected case	Blasts, Auer rods, abnormal promyelocytes (APL)	A normal or low white count does not exclude AML
PT, aPTT, fibrinogen, D-dimer	Every case, at once	DIC; APL suspicion; transfusion targets	Recheck often in APL
Potassium, phosphate, calcium, urate, creatinine, LDH	Before and during induction	Tumour lysis risk and prevention	Pseudohyperkalaemia and false low glucose/oxygen with very high counts
Marrow aspirate + biopsy; flow cytometry	All (blood alone may do if many blasts)	Myeloid lineage; blast %; baseline for MRD	Tell the laboratory first; sternum for aspirate only
Karyotype ± FISH	All	CBF, KMT2A, MECOM, complex/monosomal: ELN risk	FISH does not replace banding
FLT3, NPM1, IDH1/2 (rapid); NGS myeloid panel	All	Midostaurin/quizartinib; ELN risk; targeted drugs	Repeat at relapse; germline variants may show up
PML::RARA by PCR or FISH	Suspected APL	Confirms APL; baseline for molecular remission	Do not wait for it to start ATRA
HLA typing (patient and siblings)	Fit patients; intermediate/adverse risk	Donor search early	Exclude a familial disorder before using a sibling donor
Echo; HBV, HCV, HIV; pregnancy test	Before induction	Anthracycline choice; antiviral prophylaxis	Weak heart: non-anthracycline induction
Brain imaging + lumbar puncture	Neurological symptoms only	CNS disease → intrathecal therapy ± RT	Correct platelets and clotting first; defer in APL

Table B. Treatment by setting

Setting	Usual approach	Alternatives	Key points
Fit, FLT3 wild type	7+3 (cytarabine + daunorubicin or idarubicin)	Venetoclax + HMA in selected intermediate/adverse risk	Day 14–21 nadir marrow; remission marrow ~day 28
Fit, FLT3 mutated	7+3 + midostaurin (ITD or TKD) or quizartinib (ITD)	—	Continue the inhibitor in consolidation and maintenance
Fit, CBF AML (CD33+)	7+3 + gemtuzumab ozogamicin	—	Follow fusion transcripts (MRD) by PCR
Therapy-related or MDS-related AML	CPX-351, then allogeneic HCT	Venetoclax + HMA if less fit	Five-year OS 18% vs 8% with 7+3
In CR: favourable risk	Intermediate-dose cytarabine consolidation	HCT if MRD persists	MRD guides
In CR: intermediate risk	Consolidation or allogeneic HCT	Oral azacitidine maintenance (≥55)	MRD-positive → transplant
In CR: adverse risk	Allogeneic HCT in first CR	Consolidation if no donor	Start donor search at diagnosis
Unfit, not frail	Venetoclax + azacitidine (or decitabine)	IDH1: ivosidenib + azacitidine; HMA alone; low-dose cytarabine	Marrow day 14–21 of cycle 1; adjust venetoclax with azoles
Frail	Supportive care	Gentle therapy if the patient wishes	Transfusions, antimicrobials, symptom control at home
APL, WBC ≤10,000	ATRA + arsenic trioxide	ATRA + anthracycline if no ATO	ATRA on suspicion; no maintenance after ATO-based CR
APL, WBC >10,000	ATRA + anthracycline, or ATRA + ATO with cytoreduction	—	Highest risk of bleeding and differentiation syndrome
Relapsed or refractory	Targeted drug by mutation, or salvage chemotherapy	Venetoclax + HMA; trial	Allogeneic HCT is the only cure

Table C. Treatment options: evidence and best fit

Option	Best fit	Evidence	Watch for
Midostaurin + 7+3	FLT3-ITD or TKD, fit	RATIFY^[18]: 4-year OS 51% vs 44%	Nausea, mucositis
Quizartinib + 7+3	FLT3-ITD, fit	QuANTUM-First^[19]: median OS 32 vs 15 months	QT prolongation, neutropenia
Gemtuzumab ozogamicin	CD33+ CBF AML	Hills 2014^[20]: fewer relapses, better OS (fav/int)	Liver sinusoidal obstruction
CPX-351	t-AML, AML-MR, 60–75 years	Lancet 2021^[22]: 5-year OS 18% vs 8%	Long cytopenias
Oral azacitidine maintenance	≥55 years, intermediate/adverse, in CR	QUAZAR^[25]: OS 25 vs 15 months	Cytopenias, nausea
Venetoclax + azacitidine	Unfit adults	VIALE-A^[2]: OS 15 vs 10 months; CR+CRi 65% vs 23%	Febrile neutropenia, TLS at start
Ivosidenib + azacitidine	IDH1-mutated, unfit	AGILE^[3]: OS 24 vs 8 months	Differentiation syndrome, QT prolongation
Gilteritinib	Relapsed FLT3-mutated	ADMIRAL^[29]: OS 9.3 vs 5.6 months	Differentiation syndrome, liver tests
Ivosidenib / olutasidenib; enasidenib	Relapsed IDH1; IDH2	DiNardo 2018^[30]; Stein 2017^[31]	Differentiation syndrome
Revumenib; ziftomenib	Relapsed NPM1 (revumenib also KMT2A)	FDA 2025^[32]: CR+CRh 21% (ziftomenib)	Differentiation syndrome, QT; India availability to confirm
ATRA + arsenic trioxide	APL, low/intermediate risk	APL0406^[4]: 72-month EFS 97% vs 77%	Differentiation syndrome, QT, liver
Allogeneic HCT	Adverse risk, MRD-positive, relapse	Koreth 2009^[24]: benefit in intermediate/adverse risk	GVHD, infection, transplant mortality

Table D. Managing problems during treatment

Problem	Prevent	Recognise	Act
Neutropenic fever	Fluoroquinolone; azole; hand hygiene	Temperature ≥38 °C with ANC <500	Cultures; antipseudomonal beta-lactam within 60 minutes
Invasive mould infection	Mould-active azole if second induction	Fever after 4–7 days of antibiotics; lung nodules	Antifungal therapy; look for the source
Tumour lysis	Fluids; allopurinol or rasburicase by risk	Rising K, PO4, urate, creatinine; low Ca	Fluids, K-lowering, dialysis; no Ca for asymptomatic low Ca
Leukostasis	Start cytoreduction early	Breathless, hypoxic, confused, visual change	Induction or hydroxyurea; leukapheresis if symptomatic
DIC / APL bleeding	ATRA early; platelets and cryoprecipitate	Low fibrinogen, oozing, headache	Keep platelets ≥30–50,000 and fibrinogen >150; no heparin
Differentiation syndrome	Watch weight, oxygen, creatinine daily	Fever, dyspnoea, oedema, effusions, hypotension	Dexamethasone at once; pause drug only if severe
Typhlitis	Early imaging if abdominal pain	Right-sided pain, distension, diarrhoea at nadir	Supportive care, broad antibiotics; surgery if perforation
Anthracycline heart damage	Baseline echo and ECG	Breathlessness, oedema	Echo; cardiology; non-anthracycline options
CNS disease	Not routine prophylaxis in adults	Headache, cranial nerve palsy	Intrathecal therapy; RT for deficits or masses
QT prolongation	ECG; correct K and Mg	Prolonged QTc on ECG	Hold arsenic, quizartinib, ivosidenib or menin inhibitor; correct electrolytes

07 Management algorithms

Six decision paths pull together sections 02–06.

Algorithm 1Suspected acute leukaemia: the first 24 hours

Blasts on the smear, unexplained cytopenias, bleeding with low fibrinogen, very high white count → CBC and smear, PT/aPTT/fibrinogen, chemistry with urate, phosphate and LDH; cultures if febrile

Emergencies now

APL suspected (abnormal promyelocytes, DIC) → ATRA today + platelets and cryoprecipitate

WBC >100,000 or symptoms → cytoreduce

Fever with neutropenia → antibiotics within 60 min

APL: no heparin, no lines or LP until clotting is corrected

Confirm and classify

Marrow: morphology, flow, karyotype, FISH

Rapid → FLT3, NPM1, IDH1/2, PML::RARA

Full → myeloid NGS panel

WHO 5 / ICC name; ELN risk

Myeloid sarcoma = AML

Plan

Fitness: ECOG, comorbidity, wishes

Fit → Algorithms 2 and 3

Unfit → Algorithm 4

APL → Algorithm 6

HLA-type patient and siblings

All: TLS prevention by risk · leukocyte-depleted blood products · echo, viral serology, pregnancy test · early referral to a leukaemia centre.

Algorithm 2Fit adults: induction by genetic subgroup

Fit for intensive therapy (ECOG 0–2, no severe organ disease) → rapid genetics back within days

FLT3 mutated

7+3 + midostaurin (ITD/TKD) or quizartinib (ITD)

Same drug in consolidation

Then maintenance

RATIFY · QuANTUM-First

CBF or other

CBF, CD33+ → 7+3 + gemtuzumab

Other → 7+3

Nadir marrow day 14–21

Weak heart → non-anthracycline

t-AML or AML-MR

CPX-351

Early donor search

Allogeneic HCT in first CR

TP53: CPX-351, other intensive or HMA-based

All: fluoroquinolone + fluconazole prophylaxis · aciclovir if HSV-positive · remission marrow with MRD at ~day 28.

Algorithm 3In first complete remission: consolidate, transplant, maintain

CR after induction → ELN 2022 risk, MRD (PCR for NPM1 and CBF; flow for others), donor availability, fitness

Favourable

Intermediate-dose cytarabine

MRD by PCR (NPM1, CBF)

MRD persists or rises → HCT

Most avoid transplant

Intermediate

MRD-negative → consolidation or HCT

MRD-positive → HCT

≥55 after consolidation → oral azacitidine

FLT3: inhibitor maintenance

Adverse

Allogeneic HCT in first CR

No donor → consolidation

MRD-negativity does not downgrade risk

All: HLA typing at diagnosis · MRD-negative 5-year OS 68% vs 34% · CBC at intervals; marrow if counts fall or MRD rises.

Algorithm 4Unfit adults

Not fit for intensive induction → frailty, comorbidity, goals; IDH1, FLT3, NPM1, TP53 status

Unfit, not frail

IDH1 → ivosidenib + azacitidine

Others → venetoclax + azacitidine or decitabine

Marrow day 14–21 of cycle 1

VIALE-A · AGILE

Venetoclax or HMA not possible

No venetoclax → HMA alone

No HMA → low-dose cytarabine or targeted drug

Response after 3 cycles

Prior HMA for MDS: targeted drug or trial

Frail

Supportive care: transfusions, antimicrobials

Hydroxyurea if the count climbs

Gentle therapy if wished

Home care and palliative team

All: TLS prevention at venetoclax start · adjust venetoclax with azoles · continue while responding · revisit goals each cycle.

Algorithm 5Relapsed or refractory AML

Relapse, or no CR after induction → repeat marrow with flow and NGS; HLA typing; transplant consultation now

Targetable

FLT3 → gilteritinib

IDH1 / IDH2 → ivosidenib or olutasidenib / enasidenib

NPM1 or KMT2A → menin inhibitor (FDA; India to confirm)

ADMIRAL

Not targetable

Fit → FLAG-IDA, MEC or similar

Less fit → venetoclax + HMA

Clinical trial

Primary refractory: 20–50%

Consolidate the response

Allogeneic HCT in CR2 (myeloablative if fit)

Relapse after HCT: second HCT or donor lymphocytes

Otherwise palliative goals

All: differentiation syndrome with IDH, FLT3 and menin drugs · antifungal cover with salvage · honest discussion of prognosis.

Algorithm 6Acute promyelocytic leukaemia

Suspected APL (bleeding, DIC, abnormal promyelocytes) → ATRA today; platelets ≥30,000–50,000/µL and fibrinogen >150 mg/dL; PCR or FISH for PML::RARA

WBC ≤10,000

ATRA + arsenic trioxide

Consolidation: ATO-based

PCR-negative → observe (no maintenance)

APL0406 · AML17

WBC >10,000

ATRA + anthracycline

ATRA + ATO + hydroxyurea or anthracycline

Highest bleeding and DS risk

No ATO in the plan → ATRA maintenance

Relapse

ATRA + ATO

PCR-negative CR2 → autologous HCT

Relapse 5–10% (high risk 20–30%) · molecular relapse: gemtuzumab where available

All: daily weight, oxygen and creatinine (differentiation syndrome → dexamethasone at once) · ECG for QT on arsenic · no heparin · no central lines or LP during induction.

08 Survivorship, follow-up & late effects

Figure 17. Response and follow-up (ELN 2022; Shah 2013 for survival by age; UpToDate induction, post-remission and prognosis reviews).

Response: CR (<5% marrow blasts, no circulating blasts, no extramedullary disease), CR with partial (CRh) or incomplete (CRi) count recovery, and MRD status by flow or PCR (ELN 2022^[1]).
Monitoring: clinical review and CBC at regular intervals; some experts follow MRD in blood (NPM1, CBF fusions). A falling count or a rising MRD level needs a marrow examination.
Outcomes: five-year survival falls with age: about 50% under 40, 33% at 40–59, 13% at 60–69 and 3% at 70–79 in England (2001–2006) (Shah 2013^[49]); results are better in younger adults with favourable genetics and with modern targeted and transplant care.
Late effects: anthracycline heart damage, infertility (offer fertility advice before treatment), chronic graft-versus-host disease and infections after transplant, second cancers, fatigue and the financial toll of treatment.
Living after AML: encourage activity and normal contact with people (with sensible infection precautions while counts are low); follow the transplant team's vaccination schedule after HCT; report fever, bleeding and new tiredness promptly.

09 Landmark trials

Figure 18. How to read a survival curve (illustrative). Use the absolute gap at a fixed time and overall survival, not the median or PFS alone, when weighing benefit against toxicity and cost.

Figure 19. Landmark results as reported in the UpToDate induction, post-remission, unfit, relapsed, therapy-related and APL reviews.

RATIFY^[18] and QuANTUM-First^[19]: an FLT3 inhibitor with 7+3 → better survival → every fit FLT3-mutated patient gets one.
Hills 2014^[20]: gemtuzumab with induction → fewer relapses → standard in CD33-positive CBF AML.
CPX-351 phase 3^[21]: CPX-351 vs 7+3 in older patients with secondary AML → better 5-year survival and more transplants.
QUAZAR^[25]: oral azacitidine maintenance in CR (≥55 years) → longer survival.
VIALE-A^[2] and AGILE^[3]: combinations with azacitidine → longer survival for unfit adults.
ADMIRAL^[29]: gilteritinib vs salvage chemotherapy for relapsed FLT3-mutated AML → longer survival.
APL0406^[4]: ATRA + arsenic trioxide vs ATRA + chemotherapy → higher cure with less toxicity.
MRD meta-analysis^[13]: MRD negativity roughly doubles 5-year survival across ages, subtypes and methods.

10 Practice pearls & pitfalls

Fever, pallor and bleeding: a CBC with a smear today, not another course of antibiotics for "viral fever".
A normal white count does not exclude AML; the smear makes the diagnosis.
Bleeding with low fibrinogen and granular cells: start ATRA the same day, before genetic confirmation.
In APL keep platelets ≥30,000–50,000/µL and fibrinogen >150 mg/dL; no heparin; no lines or LP during induction.
WBC >100,000 with breathlessness or confusion: cytoreduce now; avoid red cell transfusion if you can.
Neutropenic fever: cultures, then an antipseudomonal beta-lactam within 60 minutes; know your hospital's resistance pattern.
Send FLT3, NPM1 and the karyotype on day 1: they change induction.
Fitness, not age, decides intensive versus lower-intensity therapy.
Type HLA of the patient and siblings at diagnosis in fit patients; check for a familial disorder before using a sibling donor.
Repeat the genetics at relapse: the target may have changed.
Differentiation syndrome with ATRA, ATO, IDH or menin inhibitors: dexamethasone first, questions later.

11 Case vignettes: lines of management

Nine cases from the clinic.

Case 1APL · bleeding · ATRA on suspicion

Gum bleeding and a "low" white count

32 years, womanWBC 2,800/µLFibrinogen 90 mg/dL

A 32-year-old teacher from Nellore has had gum bleeding and bruises for 5 days. Haemoglobin 8.1 g/dL, white count 2,800/µL, platelets 18,000/µL; PT prolonged, fibrinogen 90 mg/dL, D-dimer high. The smear shows a few large cells with dense granules and bundles of Auer rods.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Suspect
Bleeding with DIC, a low count and granular cells: APL until proved otherwise. Early bleeding death is the main threat.
Act today
ATRA started within hours, before PCR results; platelets and cryoprecipitate to keep platelets ≥30,000–50,000/µL and fibrinogen >150 mg/dL; no heparin; no central line or lumbar puncture.
Confirm
PML::RARA positive by RT-PCR. White count ≤10,000/µL: low/intermediate risk.
Treat
ATRA plus arsenic trioxide; daily weight, oxygen and creatinine; ECG for QT. ATO-based consolidation; PCR-negative remission → observation, no maintenance.

Teaching points

Start ATRA on suspicion; do not wait for genetics.
In APL a low white count is usual, and bleeding kills early.
ATRA plus arsenic cures most low-risk APL.

See: Sections 03 and 06, Algorithm 6.

Case 2APL · differentiation syndrome

Breathless on day 9

24 years, manHigh-risk APLATRA + ATO + anthracycline

A 24-year-old with high-risk APL (white count 38,000/µL at diagnosis) on ATRA, arsenic trioxide and an anthracycline develops fever of 38.6 °C, breathlessness, a 4 kg weight gain and bilateral lung opacities with small effusions on day 9. His creatinine is rising.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Recognise
Three or more features (fever, dyspnoea, weight gain, opacities, effusions, kidney injury): differentiation syndrome. Infection and fluid overload are the mimics.
Act
Dexamethasone at once, without waiting for tests; cultures and broad-spectrum antibiotics; oxygen; diuretic.
The drugs
Severe (needing intensive care) or no response in 24–48 hours: pause ATRA and arsenic, and restart when it resolves. Otherwise continue them.
Then
Most patients recover. Keep watching weight, oxygen and creatinine daily through induction.

Teaching points

Differentiation syndrome is a clinical diagnosis: treat first.
Steroids at once; stop the drug only if severe.
The same syndrome occurs with IDH and menin inhibitors.

See: Section 06 (APL), Algorithm 6.

Case 3AML · NPM1 with FLT3-ITD · fit

Fever and 62,000 white cells

45 years, manNPM1 + FLT3-ITDELN intermediate

A 45-year-old electrician has 2 weeks of fever and tiredness. White count 62,000/µL with 70% blasts, haemoglobin 7.9 g/dL, platelets 31,000/µL, LDH 2.5 times normal. Karyotype normal; NPM1 mutated; FLT3-ITD present. ECOG 1.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

First 24 hours
Fever: cultures, then antibiotics within the hour. White count 25,000–100,000: intermediate TLS risk → IV fluids and allopurinol. No leukostasis symptoms.
Classify
NPM1 with FLT3-ITD: ELN 2022 intermediate risk (FLT3-ITD removes NPM1 from the favourable group).
Induce
7+3 with quizartinib (or midostaurin); nadir marrow on day 14–21; remission marrow with NPM1 MRD by PCR.
After CR
Consolidation with the FLT3 inhibitor; NPM1 MRD-positive → allogeneic HCT; FLT3 inhibitor maintenance. Siblings HLA-typed at diagnosis.

Teaching points

Send FLT3 and NPM1 on day 1: they change induction.
FLT3-ITD makes NPM1-mutated AML intermediate risk.
PCR MRD guides transplant.

See: Sections 04 and 06, Algorithms 2 and 3.

Case 4AML · core binding factor · favourable

Tiredness and bruises at 28

28 years, womant(8;21)CD33 positive

A 28-year-old has 3 weeks of tiredness and bruising. White count 9,000/µL with 40% blasts containing Auer rods; platelets 42,000/µL. Karyotype t(8;21) with RUNX1::RUNX1T1; blasts CD33 positive.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Classify
RUNX1::RUNX1T1: AML by definition (≥10% blasts is enough); ELN favourable.
Before treatment
Fertility counselling and pregnancy test; echo; HBV, HCV and HIV tests.
Induce
7+3 with gemtuzumab ozogamicin (CD33-positive CBF AML).
After CR
Intermediate-dose cytarabine consolidation; follow RUNX1::RUNX1T1 transcripts by PCR; allogeneic HCT only if MRD persists or rises.

Teaching points

CBF AML: gemtuzumab adds benefit.
Favourable risk usually means no transplant in first CR.
A rising transcript predicts relapse: act early.

See: Sections 04 and 06, Algorithms 2 and 3.

Case 5Hyperleukocytosis · leukostasis

Confused and breathless with 210,000 white cells

52 years, manWBC 210,000/µLMonocytic AML

A 52-year-old from Gudur has 2 days of headache, blurred vision and breathlessness; oxygen saturation 88%. White count 210,000/µL, mostly monoblasts; gum hypertrophy. Serum potassium 6.4 mmol/L, creatinine 1.6 mg/dL, urate 11 mg/dL.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Recognise
Leukostasis (brain, lungs) with high TLS risk. Recheck potassium on a heparinised sample (pseudohyperkalaemia) and send the blood gas on ice.
Cytoreduce
Fit: start induction now. If induction cannot start at once: hydroxyurea plus leukapheresis (he is symptomatic). Leukapheresis alone has no proven benefit.
Protect
IV fluids; rasburicase after a G6PD check; avoid red cell transfusion unless essential; platelets as needed; watch for DIC; brain CT for focal signs.
Then
Induction chosen by genetics; with monocytic AML, look for skin and CNS involvement if symptoms suggest it.

Teaching points

WBC >100,000 with symptoms is an emergency.
Treat the leukaemia (chemotherapy or hydroxyurea), not just the number.
Red cell transfusion raises viscosity: avoid or go slowly.

See: Sections 03 and 06, Algorithm 1.

Case 6Induction · neutropenic fever

Fever on day 10 of induction

38 years, womanANC 100/µLDay 10 of 7+3

A 38-year-old on day 10 of 7+3 develops a temperature of 38.8 °C; blood pressure 100/60 mmHg; a central line is in place. She is on levofloxacin and fluconazole prophylaxis.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Hour 1
Blood cultures (line and peripheral), then an antipseudomonal beta-lactam (cefepime, meropenem or piperacillin-tazobactam) within 60 minutes, chosen with local resistance data.
Add
Vancomycin only for line or skin infection, pneumonia or haemodynamic instability.
Day 4–7
Still febrile but stable: do not change antibiotics for fever alone; search for fungal infection; add an antifungal (mould-active if a second induction follows).
Watch
Right-sided abdominal pain → CT for neutropenic enterocolitis (typhlitis); diarrhoea → test for C. difficile.

Teaching points

Neutropenic fever: antibiotics within the hour.
Know your hospital's resistance pattern.
Persistent fever: think fungus.

See: Section 06 (emergencies and supportive care).

Case 7Therapy-related AML

Pancytopenia 5 years after breast cancer

61 years, womanPrior chemotherapy and RT−7, del(5q)

A 61-year-old treated 5 years ago with anthracycline-cyclophosphamide chemotherapy and radiotherapy for breast cancer now has pancytopenia with 24% marrow blasts. Karyotype: −7 and del(5q); TP53 not mutated. ECOG 1, normal heart function.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Classify
Therapy-related myeloid neoplasm (AML after cytotoxic therapy) with adverse cytogenetics.
Induce
Fit: CPX-351 rather than 7+3 (5-year OS 18% vs 8% in older adults with secondary AML).
After CR
Allogeneic HCT in first remission; start the donor search now.
If less fit
Venetoclax with an HMA, as for de novo AML.

Teaching points

Ask about previous chemotherapy and radiotherapy.
Therapy-related AML: CPX-351 and transplant.
The prognosis is worse than for de novo AML.

See: Sections 02 and 06, Algorithm 2.

Case 8Unfit · venetoclax + azacitidine

A 74-year-old with heart failure

74 years, manHeart failure, diabetesNo IDH, FLT3 or TP53 change

A 74-year-old retired farmer with diabetes and heart failure (ejection fraction 40%) has tiredness and breathlessness. Haemoglobin 6.8 g/dL, white count 3,200/µL with 30% blasts, platelets 22,000/µL. NGS: no IDH1/2, FLT3 or TP53 mutation. He lives independently.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Assess
Unfit for intensive therapy (age, heart failure, diabetes) but not frail.
Treat
Venetoclax with azacitidine; TLS prevention at the start; venetoclax adjusted if an azole is used.
Monitor
Marrow on day 14–21 of cycle 1: a clear marrow with low counts → pause venetoclax to let counts recover; then marrow every 3 cycles.
Goals
Discuss quality of life, transfusion needs, travel for each cycle, and his wishes about resuscitation and intensive care.

Teaching points

Fitness, not age, decides.
VIALE-A: venetoclax with azacitidine improves survival.
Check the marrow early in cycle 1.

See: Section 06 (unfit adults), Algorithm 4.

Case 9Relapse · FLT3

Relapse 10 months after consolidation

50 years, manFLT3-ITD at relapseMatched sibling

A 50-year-old with NPM1-mutated AML (no FLT3 mutation at diagnosis) was MRD-negative after 7+3 and consolidation and did not have a transplant. Ten months later he has cytopenias and 35% marrow blasts; NGS now shows NPM1 and a new FLT3-ITD. His brother is a full HLA match.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Retest
Marrow with flow and NGS: FLT3-ITD has appeared; the clone has changed.
Treat
Gilteritinib (ADMIRAL) or salvage chemotherapy (FLAG-IDA); watch for differentiation syndrome. A menin inhibitor is another option for NPM1-mutated relapse where available.
Transplant
Second remission → allogeneic HCT from the matched brother.
After HCT
FLT3 inhibitor maintenance.

Teaching points

Always repeat the genetics at relapse.
Gilteritinib beats salvage chemotherapy for FLT3-mutated relapse.
Only a transplant can cure relapsed AML.

See: Section 06 (relapsed), Algorithm 5.

12 References & guidelines

European LeukemiaNet 2022 (intensive therapy) and 2024 (less-intensive therapy) recommendations; WHO Classification 5th edition and the International Consensus Classification (2022); NCCN Guidelines: Acute Myeloid Leukemia (current version); IDSA and ASCO/IDSA guidelines for neutropenic fever and antimicrobial prophylaxis; ISTH DIC criteria.
Cross-checked in October 2026 against 29 UpToDate topic reviews: acute myeloid leukemia in adults: overview; clinical manifestations, pathologic features, and diagnosis; classification; cytogenetic abnormalities; molecular genetics; pathogenesis; risk factors and prognosis; induction therapy in fit, younger adults; post-remission therapy in medically fit adults; management of medically unfit adults; treatment of relapsed or refractory AML; involvement of the central nervous system; overview of complications; AML in older adults: pretreatment evaluation and prognosis; therapy-related myeloid neoplasms: management and prognosis; familial disorders of acute leukemia and myelodysplastic syndromes; allogeneic HCT: indications, eligibility, and prognosis; clinical manifestations, pathologic features, and diagnosis of APL in adults; initial treatment of APL in adults; treatment of relapsed or refractory APL in adults; differentiation syndrome associated with treatment of acute leukemia; hyperleukocytosis and leukostasis in hematologic malignancies; tumor lysis syndrome (pathogenesis, clinical manifestations, definition, etiology and risk factors; prevention and treatment); overview of neutropenic fever syndromes; treatment of neutropenic fever syndromes in high-risk adults; prophylaxis of infection during chemotherapy-induced neutropenia in high-risk adults; prevention of invasive fungal infections in adults with hematologic malignancies and HCT recipients; evaluation and management of DIC in adults; and, for contrast only, AML in children and adolescents. All trial citations below come from the reference lists of these reviews, except the four Indian papers and the FDA menin-inhibitor notices, which were found and verified by web search on 17 October 2026.
Reviewed and approved by Dr. Haritha Chiramana, 17 October 2026.

Core trials and papers cited on this page (53)

Journal, year, volume and first page (or DOI); each links to PubMed.

Numbered in order of first citation in the text

ELN 2022 recommendations (Döhner 2022): Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 2022;140:1345. PubMed Diagnosis, classification, genetics, risk and MRD
VIALE-A (DiNardo 2020): DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med 2020;383:617. PubMed Unfit adults and relapsed disease
AGILE (Montesinos 2022): Montesinos P, Recher C, Vives S, et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia. N Engl J Med 2022;386:1519. PubMed Unfit adults and relapsed disease
APL0406 (Lo-Coco 2013): Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med 2013;369:111. PubMed Acute promyelocytic leukaemia and differentiation syndrome
AML in India: real-world data (Philip 2015): Philip C, George B, Ganapule A, et al. Acute myeloid leukaemia: challenges and real world data from India. Br J Haematol. Br J Haematol 2015;170:110. PubMed India
APL in North India (Mamlekar 2025): Mamlekar H, Gangadaran N, Yadav S, et al. Clinical profile and treatment outcomes in paediatric and adult acute promyelocytic leukemia: experience from a tertiary care centre in Northern India. Ann Hematol 104:4565. 2025. doi:10.1007/s00277-025-06646-x. PubMed India
Germline predisposition to myeloid neoplasms (Klco 2021): Klco JM, Mullighan CG. Advances in germline predisposition to acute leukaemias and myeloid neoplasms. Nat Rev Cancer 2021;21:122. PubMed Diagnosis, classification, genetics, risk and MRD
AML outcomes at AIIMS (Bahl 2015): Bahl A, Sharma A, Raina V, et al. Long-term outcomes for patients with acute myeloid leukemia: a single-center experience from AIIMS, India. Asia Pac J Clin Oncol. Asia Pac J Clin Oncol 2015;11:242. PubMed India
WHO 5th edition, myeloid (Khoury 2022): Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia 2022;36:1703. PubMed Diagnosis, classification, genetics, risk and MRD
ICC 2022 (Arber 2022): Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data. Blood 2022;140:1200. PubMed Diagnosis, classification, genetics, risk and MRD
CNS involvement in AML (Ganzel 2021): Ganzel C, Lee JW, Fernandez HF, et al. CNS involvement in AML at diagnosis is rare and does not affect response or survival: data from 11 ECOG-ACRIN trials. Blood Adv 2021;5:4560. PubMed Diagnosis, classification, genetics, risk and MRD
TCGA AML genomes (Ley 2013): Cancer Genome Atlas Research Network, Ley TJ, Miller C, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 2013;368:2059. PubMed Diagnosis, classification, genetics, risk and MRD
MRD meta-analysis (Short 2020): Short NJ, Zhou S, Fu C, et al. Association of measurable residual disease with survival outcomes in patients with acute myeloid leukemia: a systematic review and meta-analysis. JAMA Oncol 2020;6:1890. PubMed Diagnosis, classification, genetics, risk and MRD
NPM1 MRD (Ivey 2016): Ivey A, Hills RK, Simpson MA, et al. Assessment of minimal residual disease in standard-risk AML. N Engl J Med 2016;374:422. PubMed Diagnosis, classification, genetics, risk and MRD
ELN 2024 less-intensive risk (Döhner 2024): Döhner H, DiNardo CD, Appelbaum FR, et al. Genetic risk classification for adults with AML receiving less-intensive therapies: the 2024 ELN recommendations. Blood 2024;144:2169. PubMed Diagnosis, classification, genetics, risk and MRD
Leukapheresis meta-analysis (Oberoi 2014): Oberoi S, Lehrnbecher T, Phillips B, et al. Leukapheresis and low-dose chemotherapy do not reduce early mortality in acute myeloid leukemia hyperleukocytosis: a systematic review and meta-analysis. Leuk Res 2014;38:460. PubMed Emergencies and supportive care
Daunorubicin dose intensification (Fernandez 2009): Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med 2009;361:1249. PubMed Fit adults: induction and post-remission therapy
RATIFY (Stone 2017): Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med 2017;377:454. PubMed Fit adults: induction and post-remission therapy
QuANTUM-First (Erba 2023): Erba HP, Montesinos P, Kim HJ, et al. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First). Lancet 2023;401:1571. PubMed Fit adults: induction and post-remission therapy
Gemtuzumab meta-analysis (Hills 2014): Hills RK, Castaigne S, Appelbaum FR, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials. Lancet Oncol 2014;15:986. PubMed Fit adults: induction and post-remission therapy
CPX-351 phase 3 (Lancet 2018): Lancet JE, Uy GL, Cortes JE, et al. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol 2018;36:2684. PubMed Fit adults: induction and post-remission therapy
CPX-351 5-year (Lancet 2021): Lancet JE, Uy GL, Newell LF, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results. Lancet Haematol 2021;8:e481. PubMed Fit adults: induction and post-remission therapy
Azacitidine-venetoclax vs induction (Fathi 2026): Fathi AT, Perl AE, Fell GG, et al. Azacitidine-venetoclax or induction chemotherapy for acute myeloid leukemia (PARADIGM). N Engl J Med 2026;395:845. PubMed Fit adults: induction and post-remission therapy
Allogeneic HCT in first CR meta-analysis (Koreth 2009): Koreth J, Schlenk R, Kopecky KJ, et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA 2009;301:2349. PubMed Fit adults: induction and post-remission therapy
QUAZAR (Wei 2020): Wei AH, Döhner H, Pocock C, et al. Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission. N Engl J Med 2020;383:2526. PubMed Fit adults: induction and post-remission therapy
AZA-AML-001 (Dombret 2015): Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood 2015;126:291. PubMed Unfit adults and relapsed disease
Decitabine vs treatment choice (Kantarjian 2012): Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for older patients with newly diagnosed AML. J Clin Oncol 2012;30:2670. PubMed Unfit adults and relapsed disease
VIALE-C (Wei 2020): Wei AH, Montesinos P, Ivanov V, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood 2020;135:2137. PubMed Unfit adults and relapsed disease
ADMIRAL (Perl 2019): Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med 2019;381:1728. PubMed Unfit adults and relapsed disease
Ivosidenib in relapsed IDH1 AML (DiNardo 2018): DiNardo CD, Stein EM, de Botton S, et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med 2018;378:2386. PubMed Unfit adults and relapsed disease
Enasidenib in relapsed IDH2 AML (Stein 2017): Stein EM, DiNardo CD, Pollyea DA, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood 2017;130:722. PubMed Unfit adults and relapsed disease
Ziftomenib, KOMET-001 (FDA 2025): US Food and Drug Administration. FDA approves ziftomenib for relapsed or refractory acute myeloid leukemia with a NPM1 mutation (13 November 2025; KO-MEN-001 trial, 112 adults). Revumenib NPM1 approval, October 2025. Web-verified 17 October 2026. 2025. PubMed Unfit adults and relapsed disease
APL0406 long-term (Cicconi 2020): Cicconi L, Platzbecker U, Avvisati G, et al. Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial. Leukemia 2020;34:914. PubMed Acute promyelocytic leukaemia and differentiation syndrome
AML17 APL (Burnett 2015): Burnett AK, Russell NH, Hills RK, et al. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17). Lancet Oncol 2015;16:1295. PubMed Acute promyelocytic leukaemia and differentiation syndrome
APL relapse risk score (Sanz 2000): Sanz MA, Lo Coco F, Martín G, et al. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia. Blood 2000;96:1247. PubMed Acute promyelocytic leukaemia and differentiation syndrome
Single-agent arsenic, Vellore (Mathews 2006): Mathews V, George B, Lakshmi KM, et al. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood 2006;107:2627. PubMed India
Single-agent arsenic long-term, Vellore (Mathews 2010): Mathews V, George B, Chendamarai E, et al. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J Clin Oncol 2010;28:3866. PubMed India
Differentiation syndrome in APL (De Botton 1998): De Botton S, Dombret H, Sanz M, et al. Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in 413 cases of newly diagnosed acute promyelocytic leukemia. Blood 1998;92:2712. PubMed Acute promyelocytic leukaemia and differentiation syndrome
Differentiation syndrome with ATRA-idarubicin (Montesinos 2009): Montesinos P, Bergua JM, Vellenga E, et al. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy. Blood 2009;113:775. PubMed Acute promyelocytic leukaemia and differentiation syndrome
TLS risk in AML (Montesinos 2008): Montesinos P, Lorenzo I, Martín G, et al. Tumor lysis syndrome in patients with acute myeloid leukemia: identification of risk factors and development of a predictive model. Haematologica 2008;93:67. PubMed Emergencies and supportive care
TLS definition (Cairo 2004): Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol 2004;127:3. PubMed Emergencies and supportive care
Tumour lysis guidelines (Coiffier 2008): Coiffier B, Altman A, Pui CH, et al. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 2008;26:2767. PubMed Emergencies and supportive care
ISTH DIC score (Taylor 2001): Taylor FB Jr, Toh CH, Hoots WK, et al. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001;86:1327. PubMed Emergencies and supportive care
Levofloxacin prophylaxis (Bucaneve 2005): Bucaneve G, Micozzi A, Menichetti F, et al. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Engl J Med 2005;353:977. PubMed Emergencies and supportive care
ASCO/IDSA prophylaxis guideline (Taplitz 2018): Taplitz RA, Kennedy EB, Bow EJ, et al. Antimicrobial prophylaxis for adult patients with cancer-related immunosuppression: ASCO and IDSA clinical practice guideline update. J Clin Oncol 2018;36:3043. PubMed Emergencies and supportive care
Posaconazole prophylaxis (Cornely 2007): Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 2007;356:348. PubMed Emergencies and supportive care
IDSA neutropenic fever guideline (Freifeld 2011): Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2011;52:e56. PubMed Emergencies and supportive care
AML infections in an Indian centre (Jain 2020): Jain H, Rengaraj K, Sharma V, et al. Infection prevalence in adolescents and adults with acute myeloid leukemia treated in an Indian tertiary care center. JCO Glob Oncol. 2020. PubMed India
AML survival in England (Shah 2013): Shah A, Andersson TM, Rachet B, et al. Survival and cure of acute myeloid leukaemia in England, 1971-2006: a population-based study. Br J Haematol 2013;162:509. PubMed Diagnosis, classification, genetics, risk and MRD

Further reading (not cited in the text above)

Genomic classification of AML (Papaemmanuil 2016): Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med 2016;374:2209. PubMed Diagnosis, classification, genetics, risk and MRD
Unfitness criteria (Ferrara 2013): Ferrara F, Barosi G, Venditti A, et al. Consensus-based definition of unfitness to intensive and non-intensive chemotherapy in acute myeloid leukemia. Leukemia 2013;27:997. PubMed Diagnosis, classification, genetics, risk and MRD
Extramedullary AML in ECOG-ACRIN trials (Ganzel 2016): Ganzel C, Manola J, Douer D, et al. Extramedullary disease in adult acute myeloid leukemia is common but lacks independent significance: analysis of patients in ECOG-ACRIN Cancer Research Group trials, 1980-2008. J Clin Oncol 2016;34:3544. PubMed Diagnosis, classification, genetics, risk and MRD
APL early deaths in the population (Park 2011): Park JH, Qiao B, Panageas KS, et al. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood 2011;118:1248. PubMed Acute promyelocytic leukaemia and differentiation syndrome

How to cite this page

VancouverChiramana H. Acute Myeloid Leukaemia: a mini review for clinicians. Oncology Knowledge Hub [Internet]. Nellore (India): drharitha.co.in; 2026 [updated 2026 Oct 17; cited year month day]. Available from: https://drharitha.co.in/professionals/acute-myeloid-leukaemia

APA 7Chiramana, H. (2026, October 17). Acute Myeloid Leukaemia: A mini review for clinicians. Oncology Knowledge Hub. Retrieved Month Day, Year, from https://drharitha.co.in/professionals/acute-myeloid-leukaemia

Free to use and share for education with attribution; please do not alter or use commercially (CC BY-NC-ND 4.0). Replace the italic parts with the date you accessed the page.

Educational summary for health professionals, written in our own words from current guidelines and primary trials. No drug doses are given. Hodgkin, aggressive B-cell, indolent B-cell, T-cell and cutaneous lymphomas are parts 1–5 and multiple myeloma is part 6; acute lymphoblastic leukaemia and chronic myeloid leukaemia are parts 8 and 9; CLL is covered in the indolent B-cell module; MDS and myeloproliferative neoplasms are mentioned here only as differentials. Verify current guidelines, Indian regulatory approvals and individual patient factors before treatment decisions.

Written by Dr. Haritha ChiramanaSenior Medical Oncologist & Hemato-Oncologist · MD, DM (Medical Oncology) · C.R. Reddy Cancer Center, Nellore, Andhra Pradesh, India

Medically reviewed by Dr. Haritha Chiramana on 17 October 2026. This page is general education and cannot replace an individual consultation.