acute leukaemia

when to suspect

• unexplained cytopenias — any combination of anaemia, thrombocytopenia, neutropaenia
• new fatigue, pallor, easy bruising/bleeding, recurrent or unusual infections, fevers
• bone/joint pain — especially younger patients (ALL)
• gingival hyperplasia, leukaemia cutis (purpuric nodules) — AML with monocytic differentiation
• hepatosplenomegaly, lymphadenopathy
• mediastinal mass — T-cell ALL
• spontaneous DIC with bleeding — APL until proven otherwise

initial workup

Order before haematology arrives:

• FBC with manual differential — do not rely on automated differential alone
• blood film — request urgent review
• coagulation: PT, PTT, fibrinogen → identify DIC early
• biochemistry: LDH, uric acid, phosphate, calcium, potassium, creatinine (TLS screen)
• blood cultures if febrile
• CXR — infection, mediastinal mass, pulmonary infiltrates
• type and screen
• G6PD status if rasburicase may be needed
• ECG — baseline QTc assessment before arsenic trioxide initiation

blood film clues

AML

• myeloblasts: large cells, fine chromatin, prominent nucleoli, moderate cytoplasm
• Auer rods — pathognomonic for myeloid lineage; needle-like crystalline inclusions
• myeloperoxidase (MPO) positivity confirms myeloid lineage

APL (M3)

variant	morphology	key feature
hypergranular	promyelocytes packed with coarse azurophilic granules	”faggot cells” — bundles of Auer rods
microgranular (M3v)	fine/absent granulation, bilobed/folded nuclei	easily mistaken for AMML or monocytes

• flow cytometry: CD34⁻, HLA-DR⁻, strongly MPO⁺, CD33⁺

acute monocytic / myelomonocytic (M4/M5)

• monoblasts and promonocytes: folded/lobulated nuclei, abundant grey-blue cytoplasm, vacuolated
• nonspecific esterase (NSE) positive
• gingival infiltration and skin involvement more common
• can cause pulmonary infiltration mimicking pneumonia → steroid-responsive (dexamethasone)

ALL

• lymphoblasts: smaller cells, scant cytoplasm, no granules, no Auer rods
• L3/Burkitt morphology: deeply basophilic vacuolated cytoplasm with nuclear clefting

leukostasis

Clinical diagnosis of microvascular obstruction by leukaemic cells → end-organ damage. It is a clinical syndrome, not simply a WBC number.

thresholds of concern

scenario	WBC threshold	notes
AML blasts	>100 × 10⁹/L	highest risk — large sticky blasts; most common in AMML
AML monocytic (M4/M5)	>50–100 × 10⁹/L	higher risk at lower counts due to blast adhesion
ALL blasts	>200 × 10⁹/L	lower risk — lymphoblasts smaller and less adhesive
ALL (symptomatic)	>400 × 10⁹/L	emergent treatment required
CML (mature neutrophils)	~200 × 10⁹/L	approximate — mature cells more deformable; leukostasis less common
CLL (mature lymphocytes)	~300–400 × 10⁹/L	approximate — very rare; small deformable cells

clinical features

• pulmonary: dyspnoea, hypoxia, diffuse CXR infiltrates
• CNS: headache, confusion, visual changes, focal deficits, obtundation
• other: renal failure, priapism, limb ischaemia

management

1. IV hydration — aggressive, no potassium
2. hydroxyurea 50–100 mg/kg/day — first-line cytoreduction
3. dexamethasone 10 mg IV BID — especially for pulmonary leukostasis/infiltrates
4. avoid RBC transfusion until WBC <100 × 10⁹/L — ↑ viscosity worsens leukostasis
5. platelet transfusion — give freely to reduce ICH risk
6. leukapheresis — consider if symptomatic and unresponsive to above; mortality benefit not established
7. cytarabine 0.5–2 g single dose if hydroxyurea insufficient
8. definitive chemotherapy ASAP — most important intervention

APL — the “don’t miss” diagnosis

Cure rate >90% with timely treatment. Early mortality 12–30% depending on setting (pooled 12% in meta-analysis; up to 30% in population-based registries), primarily from haemorrhage. Academic-community partnerships with standardised supportive care have reduced 1-month mortality to ~3% — ECOG-ACRIN EA9131, JAMA Oncol. 2025.

when to suspect

• pancytopaenia with few circulating blasts — APL often has low WBC
• DIC/bleeding disproportionate to platelet count
• hypergranular promyelocytes or faggot cells on film
• microgranular variant: bilobed nuclei, may look monocytic
• flow: CD34⁻, HLA-DR⁻, strong MPO⁺, CD33⁺

APL coagulopathy management

• maintain platelets ≥50 × 10⁹/L — aggressive transfusion
• maintain fibrinogen >1.5 g/L — cryoprecipitate/FFP
• keep PT and PTT near normal
• monitor coagulation studies daily until coagulopathy resolves
• avoid central line placement during active coagulopathy

risk stratification

risk	WBC	treatment implications
low	≤10 × 10⁹/L	ATRA + ATO — Lo-Coco, NEJM. 2013 established ATRA + ATO as standard for low/intermediate-risk APL
high	>10 × 10⁹/L	ATRA + idarubicin + ATO (idarubicin is part of preferred regimen); higher DS risk

differentiation syndrome

Previously “retinoic acid syndrome.” Occurs with ATRA, arsenic trioxide, IDH inhibitors, menin inhibitors, and FLT3 inhibitors. Incidence 2–37% in APL.

clinical features

• unexplained fever
• dyspnoea, hypoxia, pulmonary infiltrates (can mimic pneumonia)
• pleural and/or pericardial effusions
• weight gain, peripheral oedema
• hypotension
• acute renal failure
• often associated with rising WBC >10 × 10⁹/L

management

1. dexamethasone 10 mg IV BID for 3–5 days, then taper over 2 weeks — start at first suspicion
2. prophylaxis: high-risk patients (WBC >10 × 10⁹/L) or ATRA/ATO regimens → prednisone 0.5 mg/kg/day from day 1; switch to dexamethasone if DS develops
3. hydroxyurea for associated leukocytosis
4. interrupt ATRA/ATO if significant hypoxia develops — consider resuming once hypoxia resolves; also interrupt for renal failure or haemodynamic instability
5. refractory → anthracycline (idarubicin/daunorubicin) or gemtuzumab ozogamicin

tumour lysis syndrome

Acute leukaemia (especially ALL and AML with WBC >100 × 10⁹/L) is high-risk for TLS. Key points for the leukaemia context:

• screen G6PD before starting rasburicase
• high-risk patients → rasburicase prophylaxis before chemotherapy; intermediate → allopurinol
• aggressive IV hydration (no K⁺, no bicarbonate) — start before chemo
• monitor K⁺, PO₄, Ca²⁺, uric acid, creatinine every 4–6 hours during induction
• spontaneous TLS can occur before treatment — check TLS labs on all new presentations

See tumour lysis syndrome for full Cairo-Bishop criteria, risk stratification, rasburicase dosing/contraindications, and electrolyte management.

what NOT to do

• dismiss leukaemia because WBC is low — APL often presents with neutropaenia
• rely on automated differential — misclassifies monocytes ↔ blasts; always get manual diff + film
• wait for cytogenetics to start ATRA — APL coagulopathy kills in hours
• transfuse RBCs in hyperleukocytosis with WBC >100 × 10⁹/L — ↑ viscosity → worse leukostasis
• skip DIC screen — PT, PTT, fibrinogen on ALL new leukaemia presentations
• place central lines during active APL coagulopathy
• trust lab values in hyperleukocytosis without question — blast fragility → spurious results in chemistry and coagulation panels; consider point-of-care testing

key trials summary

trial	year	finding
Lo-Coco, NEJM. 2013	2013	ATRA + ATO non-inferior to ATRA + chemo in low/intermediate-risk APL; better OS, fewer relapses
Montesinos, Blood. 2009	2009	defined DS incidence and risk factors; early dexamethasone ↓ severity
ECOG-ACRIN EA9131, JAMA Oncol. 2025	2025	academic-community partnership with standardised supportive care reduced APL 1-month mortality to 3.0%