Leukaemia (AML, ALL, CML, CLL)

📋 Key Information Summary

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Leukaemia classification: Acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), and chronic lymphocytic leukaemia (CLL) — each with distinct biology, prognosis, and treatment paradigms.
Molecular markers drive therapy: BCR-ABL (CML — TKI therapy), FLT3-ITD/TKD (AML — midostaurin/gilteritinib), NPM1, CEBPA, TP53, and Philadelphia chromosome (Ph+ ALL — dasatinib/ponatinib) are essential for risk stratification and treatment selection.
CML outcomes transformed by TKIs: Imatinib, dasatinib, nilotinib, and bosutinib achieve >90% 10-year survival; ponatinib for T315I mutation. All TKIs are PBS-listed in Australia.
AML remission induction: 7+3 (cytarabine continuous infusion ×7 days + anthracycline ×3 days) remains the standard for fit patients <60 years; venetoclax + azacitidine is the preferred lower-intensity regimen for older/unfit patients.
ALL induction: Multi-agent vincristine, corticosteroid, L-asparaginase, and anthracycline-based regimens; Ph+ ALL requires concurrent TKI (dasatinib preferred per Australian protocols).
CLL watch-and-wait: Asymptomatic early-stage CLL (Rai 0–I, Binet A) requires observation only; treatment indicated for symptomatic, progressive, or high-risk disease.
CLL targeted agents: BTK inhibitors (ibrutinib, zanubrutinib) and BCL-2 inhibitor (venetoclax + obinutuzumab) have replaced chemoimmunotherapy as first-line for most patients; both PBS-subsidised.
Allogeneic stem cell transplant (allo-SCT): Curative for intermediate/high-risk AML in first remission, relapsed/refractory ALL, and selected CML patients failing ≥2 TKIs. Australian Bone Marrow Donor Registry and international cord blood banks available.
Tumour lysis syndrome (TLS): Medical emergency requiring aggressive IV hydration + rasburicase (or allopurinol) prophylaxis before and during cytoreductive therapy, especially in ALL and high-WBC AML.
Minimal residual disease (MRD): Increasingly used to guide therapy intensity — MRD negativity at end of induction predicts favourable outcome in ALL and AML.
Supportive care: Broad-spectrum antimicrobials for neutropaenic sepsis, blood product support, G-CSF post-induction (selected AML subtypes), and fertility counselling for all patients of reproductive age.
Aboriginal and Torres Strait Islander considerations: Higher age-standardised incidence, later presentation, reduced access to specialist centres and allo-SCT in remote areas, and poorer survival — culturally safe, multidisciplinary care essential.
Pregnancy: Acute leukaemia in pregnancy requires urgent multidisciplinary haematology/obstetric planning; TKIs are teratogenic (category D) and must be discontinued.

Introduction & Australian Epidemiology

Leukaemia encompasses a heterogeneous group of malignant clonal proliferations of haematopoietic cells that originate in the bone marrow and may involve the peripheral blood, lymph nodes, spleen, and extramedullary sites. Broadly classified as acute or chronic, and myeloid or lymphoid, the four major subtypes — acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), and chronic lymphocytic leukaemia (CLL) — each carry distinct molecular pathogenesis, clinical behaviour, and therapeutic paradigms.

The advent of targeted tyrosine kinase inhibitor (TKI) therapy has transformed CML from a disease with a median survival of 3–5 years to one with near-normal life expectancy. Similarly, BTK inhibitors and venetoclax-based regimens have revolutionised CLL management, while advances in molecular profiling continue to refine risk stratification and treatment intensity in AML and ALL.

Australian Epidemiology

AML: Approximately 1,100–1,200 new diagnoses per year in Australia; median age at diagnosis ~68 years; age-standardised incidence ~4.5 per 100,000.
ALL: Most common childhood cancer (~450 cases/year across all ages); bimodal peak at 2–5 years and >60 years; 5-year survival >90% in paediatric patients.
CML: ~330–380 new diagnoses per year; median age ~55 years; 10-year overall survival >80–85% with TKI therapy.
CLL: Most common adult leukaemia in Western countries (~1,500 new cases/year in Australia); median age at diagnosis ~72 years; often incidental lymphocytosis on routine blood count.
Aboriginal and Torres Strait Islander peoples experience higher incidence and poorer outcomes for several leukaemia subtypes, compounded by geographic isolation, delayed diagnosis, and barriers to specialist care access.

Classification of Leukaemias

Accurate classification is essential for prognosis, treatment selection, and clinical trial eligibility. The current WHO Classification (5th edition, 2022) and ICC (2022) integrate morphology, immunophenotype, cytogenetics, and molecular genetics.

Feature	AML	ALL	CML	CLL
Cell of origin	Myeloid precursors	B- or T-lymphoid precursors	Myeloid stem cell	Mature B-lymphocytes
Key cytogenetics	t(8;21), inv(16), t(15;17), complex karyotype	t(9;22) [Ph+], t(12;21) [ETV6-RUNX1], KMT2A rearrangements	t(9;22) BCR-ABL1 — hallmark	del(13q), trisomy 12, del(11q), del(17p)
Key molecular	FLT3-ITD, NPM1, CEBPA, IDH1/2, TP53	IKZF1, Ph-like, CRLF2, JAK2	BCR-ABL1 p210; T315I gatekeeper mutation	TP53 mutation, IGHV mutational status, NOTCH1, SF3B1
Median age	~68 years	Bimodal (2–5 yr, >60 yr)	~55 years	~72 years
Peripheral blood	Blasts ≥20% (WHO 2022: some entities at <20%)	Lymphoblasts	CML chronic phase — basophilia, left-shifted myeloid series	CLL cells ≥5 × 10⁹/L for ≥3 months

WHO 5th Edition Key Entities (2022)

AML with defining genetic abnormalities: AML with t(8;21), inv(16)/t(16;16), t(9;11), t(6;9), inv(3), t(15;17), NPM1 mutation, biallelic CEBPA, RUNX1, and MECOM rearrangements.
AML with myelodysplasia-related changes: Now redefined by specific cytogenetic/molecular features rather than morphologic dysplasia alone.
ALL subtypes: B-ALL with BCR-ABL1 (Ph+ ALL), B-ALL with KMT2A rearrangement, T-ALL, and early T-cell precursor (ETP) ALL.
CLL/SLL: Unified entity; CLL defined by peripheral blood monoclonal B-cells ≥5 × 10⁹/L; small lymphocytic lymphoma (SLL) if tissue-based without significant blood involvement.

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Critical classification step: All leukaemias require bone marrow aspirate, trephine biopsy, flow cytometry, karyotyping, and targeted molecular panel (NGS). FISH for BCR-ABL1 must be performed within 24 hours if CML or Ph+ ALL is suspected — TKI therapy should commence without delay.

Pathogenesis & Molecular Markers

Leukaemogenesis requires a sequence of cooperating genetic events — class I mutations providing proliferation/survival advantage (e.g., FLT3, KIT, RAS, BCR-ABL) and class II mutations impairing differentiation (e.g., NPM1, CEBPA, RUNX1, PML-RARA). Epigenetic dysregulation (DNMT3A, TET2, IDH1/2) increasingly recognised as initiating events.

Key Molecular Markers

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BCR-ABL1 (Philadelphia Chromosome)

t(9;22)(q34;q11) · CML & Ph+ ALL

Role Constitutively active tyrosine kinase driving proliferation; present in >95% CML and ~25% adult ALL, ~3–5% paediatric ALL

Targeted therapy Imatinib (1st-gen TKI), dasatinib, nilotinib, bosutinib (2nd-gen), ponatinib (3rd-gen — T315I mutation)

Monitoring Quantitative RT-PCR (qPCR) for BCR-ABL1 IS (International Scale); 3-month BCR-ABL1 >10% IS = warning; major molecular response (MMR) ≤0.1% IS target

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FLT3 Mutations

FLT3-ITD & FLT3-TKD · AML

Incidence FLT3-ITD in ~25–30% of AML; FLT3-TKD in ~5–10%

Prognosis FLT3-ITD with high allelic ratio (>0.5) confers adverse prognosis; FLT3-TKD more indeterminate

Targeted therapy Midostaurin (Rydapt®) — add to 7+3 induction for newly diagnosed FLT3-mutated AML; Gilteritinib (Xospata®) — relapsed/refractory FLT3-mutated AML

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NPM1 Mutation

Nucleophosmin-1 · AML

Incidence ~30% of adult AML; ~60% of cytogenetically normal AML

Prognosis Favourable when NPM1-mutated/FLT3-ITD-negative without adverse karyotype; adverse if co-occurring FLT3-ITD high allelic ratio

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TP53 Mutation / del(17p)

Tumour suppressor · AML & CLL

AML Associated with complex karyotype, therapy-related AML; adverse prognosis; poor response to standard chemotherapy; consider allo-SCT early

CLL del(17p)/TP53 mutation — worst prognosis; chemoimmunotherapy ineffective; BTK inhibitor (zanubrutinib/ibrutinib) or venetoclax-based therapy preferred first-line

Additional Key Markers

Marker	Disease	Significance
CEBPA (biallelic)	AML	Favourable risk entity in WHO 2022; standalone favourable marker
IDH1 / IDH2	AML	Targetable with ivosidenib/enasidenib; ~15–20% AML
ETV6-RUNX1	Paediatric ALL	Favourable prognosis; ~25% B-ALL in children
KMT2A (MLL) rearrangement	ALL / AML	Adverse in most contexts; t(4;11) infant ALL — very poor prognosis
IGHV mutational status	CLL	Mutated IGHV — favourable (median OS >20 yr); unmutated — inferior prognosis
ZAP-70 / CD38	CLL	Surrogates for IGHV status when molecular testing unavailable; high expression = adverse

Clinical Features & Diagnosis

Acute Leukaemia (AML & ALL)

Presentation reflects marrow failure (cytopenias) and organ infiltration by leukaemic blasts.

Bone marrow failure: Fatigue and pallor (anaemia), spontaneous bleeding, petechiae, gum hypertrophy (thrombocytopaenia), recurrent or severe infections (neutropaenia).
Organ infiltration: Hepatosplenomegaly, lymphadenopathy (more prominent in ALL), bone pain (especially paediatric ALL), CNS involvement (headache, cranial nerve palsies — more common in ALL).
Leukostasis: Medical emergency with WBC >100 × 10⁹/L — pulmonary infiltrates, hypoxia, visual disturbance, priapism, stroke. Requires urgent cytoreduction (leukapheresis or hydroxycarbamide).
Disseminated intravascular coagulation (DIC): Especially in acute promyelocytic leukaemia (APL) — t(15;17) PML-RARA; immediate all-trans retinoic acid (ATRA) essential.

Chronic Myeloid Leukaemia (CML)

Chronic phase (most common at diagnosis): Often asymptomatic — incidental finding of elevated WBC on routine FBC. Symptoms may include fatigue, weight loss, splenic fullness/pain (massive splenomegaly), night sweats, gout.
Accelerated phase: Increasing blast count (10–19%), basophilia ≥20%, persistent thrombocytopaenia unresponsive to therapy, clonal evolution.
Blast crisis: Blasts ≥30% (WHO) or ≥20% (ELN); behaves as acute leukaemia (AML or ALL phenotype); poor prognosis.

Chronic Lymphocytic Leukaemia (CLL)

Asymptomatic: >70% diagnosed incidentally from persistent monoclonal lymphocytosis ≥5 × 10⁹/L on routine FBC.
Symptomatic: Painless lymphadenopathy (cervical, axillary, inguinal), hepatosplenomegaly, fatigue, B-symptoms (fever, drenching night sweats, >10% unintentional weight loss over 6 months).
Complications: Autoimmune haemolytic anaemia (AIHA, ~10%), immune thrombocytopaenia (ITP), hypogammaglobulinaemia with recurrent infections, transformation to Richter syndrome (aggressive DLBCL, ~5–10% lifetime).

Diagnostic Workup

Essential

Full blood count with differential & peripheral blood film

MBS Item 65070 — morphological assessment of blasts, smudge cells (CLL), basophilia (CML)

Essential

Bone marrow aspirate & trephine biopsy

Morphology, blast percentage, dysplasia assessment, cellularity

Essential

Multiparameter flow cytometry

Immunophenotyping — myeloid vs lymphoid lineage assignment; CLL score (CD5+, CD23+, CD200+, dim CD20, dim CD79b)

Essential

Conventional karyotyping (G-banding)

Requires viable cells; identifies complex karyotype, deletions, translocations

Essential

FISH panel

BCR-ABL1 (CML, Ph+ ALL), PML-RARA (APL), TP53 deletion (CLL), KMT2A rearrangement

Available

NGS molecular panel

FLT3-ITD/TKD, NPM1, CEBPA, IDH1/2, DNMT3A, TP53, ASXL1, RUNX1, KIT; available at major Australian centres (Royal Adelaide, Peter Mac, Westmead)

Available

BCR-ABL1 quantitative PCR (International Scale)

CML monitoring — standardised to WHO International Scale; send to reference laboratory if local IS calibration unavailable

Referral

Cerebrospinal fluid analysis

ALL (mandatory) — lumbar puncture with intrathecal cytology and flow cytometry if CNS symptoms or T-ALL/high-risk B-ALL

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Acute promyelocytic leukaemia (APL) — medical emergency: If peripheral blood film or bone marrow morphology suggests APL (hypergranular promyelocytes, Auer rods, Faggot cells), commence ATRA (all-trans retinoic acid) 45 mg/m²/day immediately while awaiting PML-RARA confirmation. Do NOT give platelet transfusions prophylactically until APL excluded or ATRA commenced, as this may worsen DIC.

Management — Chemotherapy, TKI & Bone Marrow Transplant

Acute Myeloid Leukaemia (AML)

Remission Induction — Fit Patients (<60–65 years)

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Cytarabine

Ara-C · Cytosar® · Antimetabolite

Adult dose (7+3) 100–200 mg/m²/day IV continuous infusion × 7 days

Paediatric dose 100 mg/m² IV q12h or continuous infusion; protocol-dependent

Renal adjustment Caution if CrCl <60 mL/min; no standard dose reduction but monitor closely

PBS status ✔ PBS General Benefit

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Idarubicin

Zavedos® · Anthracycline

Adult dose (7+3) 12 mg/m² IV bolus × 3 days (days 1, 2, 3)

Key caution Cumulative cardiotoxicity — pre-treatment echocardiogram/MUGA essential; avoid if LVEF <45%

PBS status ✔ PBS General Benefit

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Midostaurin

Rydapt® · FLT3 inhibitor

Indication Newly diagnosed FLT3-mutated AML — add to 7+3 induction and consolidation

Adult dose 50 mg PO BD with food on days 8–21 of each induction/consolidation cycle

PBS status ✔ Authority Required (FLT3-mutated AML)

Lower-Intensity / Unfit Older Patients

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Venetoclax + Azacitidine

Venclexta® + Vidaza® · BCL-2 inhibitor + hypomethylating agent

Indication Newly diagnosed AML unfit for intensive chemotherapy; also AML with IDH1/2, NPM1, FLT3 co-mutations

Venetoclax dose Ramp-up: 100 mg day 1, 200 mg day 2, 400 mg day 3 onwards (PO daily); reduce to 100 mg with posaconazole, 70 mg with voriconazole

Azacitidine dose 75 mg/m² SC/IV daily × 7 days per 28-day cycle

PBS status ✔ Authority Required (AML, unfit for intensive chemo)

Acute Promyelocytic Leukaemia (APL)

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Highly curable (>90%): ATRA + arsenic trioxide (ATO) is the preferred treatment for standard-risk APL (WBC <10 × 10⁹/L), replacing ATRA + chemotherapy. High-risk APL (WBC ≥10 × 10⁹/L) adds idarubicin or gemtuzumab ozogamicin. Intrathecal prophylaxis recommended.

Acute Lymphoblastic Leukaemia (ALL)

Adult ALL — Induction (Australian ALLG Protocol)

Phase 1 (4 weeks): Vincristine 1.4 mg/m² IV weekly (max 2 mg), dexamethasone 10 mg/m²/day PO/IV (or prednisolone 60 mg/m²), daunorubicin 45 mg/m² IV (days 1–3), L-asparaginase 6,000 IU/m² IM/IV (days 4, 6, 8, 10, 12, 14).
Phase 2 (consolidation): High-dose methotrexate (1–3 g/m² IV with folinic acid rescue), cyclophosphamide, cytarabine, 6-mercaptopurine — protocol-dependent.
Maintenance (2–3 years): Daily 6-mercaptopurine + weekly methotrexate with dose titration to target WBC 2–3 × 10⁹/L.

Ph+ ALL — TKI Integration

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Dasatinib

Sprycel® · 2nd-gen TKI

Indication Ph+ ALL — preferred TKI in combination with ALL chemotherapy (per ALLG and EWALL studies)

Adult dose 100 mg PO daily (reduced from CML dose of 100 mg OD to 140 mg OD depending on protocol; 100 mg common in ALL)

Key toxicity Pleural effusion (~20–30%), pulmonary arterial hypertension, QTc prolongation

PBS status ✔ Authority Required (Ph+ ALL)

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Ponatinib

Iclusig® · 3rd-gen TKI (pan-BCR-ABL)

Indication Ph+ ALL with T315I mutation, or failure/intolerance of ≥2 prior TKIs

Adult dose 45 mg PO daily (starting dose); reduce to 30 mg or 15 mg based on response/toxicity

Key toxicity Arterial thrombotic events (MI, stroke, PAD) — requires cardiovascular risk assessment and monitoring

PBS status ✔ Authority Required

Chronic Myeloid Leukaemia (CML) — TKI Therapy

TKI therapy has transformed CML into a chronic manageable condition. Treatment selection depends on disease risk (Sokal/ELTS score), comorbidities, and patient preference. All TKIs are PBS-subsidised for CML in Australia.

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Imatinib

Glivec® · 1st-gen TKI · Standard first-line

Adult dose 400 mg PO daily with food and a large glass of water

Paediatric dose 260–340 mg/m²/day PO (max 400 mg for BSA ≥1.2 m²; 600 mg for BSA ≥1.6 m² with resistant disease)

Key toxicities Oedema, nausea, myalgias, rash, cytopenias; monitor LFTs, TSH

Renal adjustment No dose reduction required in mild–moderate impairment; 400 mg alternate days if CrCl 20–40 mL/min; avoid if CrCl <20 mL/min

PBS status ✔ Authority Required (CML)

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Dasatinib

Sprycel® · 2nd-gen TKI

Adult dose 100 mg PO daily (chronic phase); 140 mg PO daily (advanced phase)

Key toxicity Pleural effusion, pulmonary arterial hypertension (PAH) — baseline and monitoring ECG, CXR

PBS status ✔ Authority Required (2nd-line CML)

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Nilotinib

Tasigna® · 2nd-gen TKI

Adult dose 300 mg PO BD (empty stomach — 1 hour before or 2 hours after food)

Key toxicity QTc prolongation, peripheral arterial disease, hyperglycaemia, pancreatitis

PBS status ✔ Authority Required (2nd-line CML)

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Bosutinib

Bosulif® · 2nd-gen TKI

Adult dose 400–500 mg PO daily with food

Key toxicity Diarrhoea (common), hepatotoxicity — monitor LFTs closely

PBS status ✔ Authority Required (2nd-line CML)

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Ponatinib

Iclusig® · 3rd-gen TKI

Indication T315I gatekeeper mutation — resistant to all 1st/2nd-gen TKIs; or failure of ≥2 prior TKIs

Adult dose 45 mg PO daily; target dose reduction to 15 mg once CCyR achieved

PBS status ✔ Authority Required (T315I / ≥2 TKI failures)

CML Monitoring Milestones (European LeukaemiaNet 2022)

Baseline

Sokal/ELTS risk score; quantitative RT-PCR (BCR-ABL1 IS); bone marrow cytogenetics if PCR unavailable

3 months

BCR-ABL1 IS ≤10% = optimal; >10% = warning; assess compliance, drug interactions

6 months

BCR-ABL1 IS ≤1% = optimal; >1% = warning

12 months

BCR-ABL1 IS ≤0.1% (MMR) = optimal; >1% = failure — consider TKI switch

Then q3–6 months

Sustained MMR (≤0.1% IS) or deeper molecular response (MR4, MR4.5) — eligible for treatment-free remission (TFR) trial after ≥3 years deep response

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Treatment-free remission (TFR): Eligible CML patients in sustained MR4.5 (BCR-ABL1 ≤0.0032% IS) for ≥3 years on TKI may attempt TKI cessation under close molecular monitoring (q4 weeks × 6 months, then q8–12 weeks indefinitely). ~40–60% maintain molecular remission. Mandatory PCR monitoring — molecular relapse (loss of MMR) requires TKI resumption.

Chronic Lymphocytic Leukaemia (CLL)

Staging & Treatment Indications

Rai stage 0 / Binet A (low risk): Observation only — no treatment benefit shown; monitor FBC, clinical review q3–6 months.
Treatment indicated (iwCLL criteria): Progressive marrow failure, massive/symptomatic splenomegaly, massive/symptomatic lymphadenopathy, progressive lymphocytosis (increase >50% over 2 months or doubling time <6 months), autoimmune cytopenia unresponsive to steroids, B-symptoms.

First-Line Therapy

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Zanubrutinib

Brukinsa® · BTK inhibitor · 2nd-gen (preferred)

Adult dose 160 mg PO BD (or 320 mg PO daily — per product label)

Advantage Superior PFS vs ibrutinib (ALPINE trial); fewer cardiac events, atrial fibrillation; preferred per Australian expert consensus

Key toxicity Bruising, infection, neutropaenia; atrial fibrillation (lower than ibrutinib)

PBS status ✔ Authority Required (CLL)

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Venetoclax + Obinutuzumab

Venclexta® + Gazyva® · Time-limited (12 months)

Venetoclax dose Ramp-up: 20 mg × 1 week → 50 mg × 1 week → 100 mg × 1 week → 200 mg × 1 week → 400 mg daily thereafter

Obinutuzumab 1,000 mg IV on days 1, 8, 15 of cycle 1; day 1 of cycles 2–6

Duration 12 months fixed duration (6 cycles combination + 6 cycles venetoclax monotherapy)

TLS management Hospital-based TLS prophylaxis for ramp-up; IV hydration + rasburicase if TLS risk high

PBS status ✔ Authority Required (CLL)

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Ibrutinib

Imbruvica® · 1st-gen BTK inhibitor

Adult dose 420 mg PO daily until progression or intolerance

PBS status ✔ Authority Required (CLL)

Allogeneic Stem Cell Transplant (Allo-SCT)

Allo-SCT remains the only curative option for high-risk/relapsed haematological malignancies and is performed at Australian transplant centres (Royal Adelaide Hospital, Westmead Hospital, Peter MacCallum Cancer Centre, Royal Brisbane and Women's Hospital, Alfred Hospital, Royal Perth Hospital).

Disease	Allo-SCT Indication	Timing
AML	Intermediate/high-risk in CR1; relapsed/refractory in CR2; TP53-mutated	CR1 for adverse-risk; CR2 for favourable-risk relapse
ALL (adult)	Ph+ ALL (consider post-induction); high-risk B-ALL (KMT2A, hypodiploid); relapsed/refractory	CR1 for high-risk; CR2 mandatory
CML	Failure of ≥2 TKIs; T315I mutation (if ponatinib unsuitable); blast crisis in second chronic phase	After TKI failure
CLL	Young, fit patients with TP53 dysfunction who relapse after BTK inhibitor and venetoclax	After targeted therapy failure

Australian Bone Marrow Donor Registry (ABMDR)

Matched unrelated donor (MUD) search initiated via ABMDR; typical turnaround 2–4 months for 10/10 HLA-matched donor.
Haploidentical transplant increasingly used (post-transplant cyclophosphamide platform) when MUD unavailable.
Umbilical cord blood from international banks also available.

Supportive Care

1

Tumour Lysis Syndrome Prophylaxis

IV hydration ≥2–3 L/m²/day; allopurinol 300 mg PO daily (or rasburicase 0.2 mg/kg IV if high risk / uric acid elevated); monitor U&E, phosphate, calcium, uric acid q6–8h during induction.

2

Neutropaenic Sepsis Management

Commence empirical piperacillin-tazobactam 4.5 g IV q6h (or meropenem 1 g IV q8h if septic shock) within 60 minutes of fever onset. MBS-rebated cultures (blood × 2, urine). G-CSF (filgrastim) post-induction for selected AML subtypes and allo-SCT.

3

Blood Product Support

Irradiated, CMV-safe blood products for all patients receiving purine analogues, allo-SCT, or anti-thymocyte globulin. Transfusion thresholds: Hb <70 g/L (symptomatic); platelets <10 × 10⁹/L (or <20 with fever/active bleeding).

4

Antimicrobial Prophylaxis

Aciclovir 400 mg PO BD (HSV/VZV prophylaxis); fluconazole 200 mg PO daily (or posaconazole 300 mg PO daily if high-risk AML induction); trimethoprim-sulfamethoxazole (PJP prophylaxis) during ALL maintenance.

5

Fertility Preservation

Discuss with all patients of reproductive age before commencing chemotherapy. Sperm banking (males), oocyte/embryo cryopreservation (females) — refer to fertility specialist. GnRH agonist (goserelin) may be considered for females during chemotherapy.

Risk Stratification & Prognosis

AML — European LeukaemiaNet (ELN) 2022 Risk Classification

Favourable

Favourable Risk AML

t(8;21), inv(16)/t(16;16), NPM1-mutated without FLT3-ITD high AR, biallelic CEBPA mutation

4-yr OS: 50–70% · Consolidation: HD-AC (non-APL) · Allo-SCT: not in CR1

Intermediate

Intermediate Risk AML

Normal karyotype with NPM1-mutated + FLT3-ITD low AR; t(9;11); cytogenetic abnormalities not classified as favourable or adverse

4-yr OS: 30–50% · Allo-SCT: consider in CR1 based on MRD and patient factors

Adverse

Adverse Risk AML

Complex karyotype, monosomal karyotype, TP53 mutation, FLT3-ITD high AR, KMT2A rearrangements (non-t(9;11)), del(17p), ASXL1, RUNX1 (in some contexts)

4-yr OS: 10–20% · Allo-SCT: recommended in CR1 · Consider clinical trial

CLL — Modified Rai Staging

Stage	Criteria	Risk	Median Survival
Rai 0	Lymphocytosis only (blood + marrow)	Low	>10 years
Rai I	Lymphocytosis + lymphadenopathy	Intermediate	~7 years
Rai II	Lymphocytosis + hepatomegaly/splenomegaly	Intermediate	~7 years
Rai III	Lymphocytosis + anaemia (Hb <110 g/L)	High	~2–3 years
Rai IV	Lymphocytosis + thrombocytopaenia (<100 × 10⁹/L)	High	~2–3 years

Special Populations

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Pregnancy

TKIs (all classes)

Category D — teratogenic (craniosynostosis, skeletal anomalies with imatinib). Discontinue immediately upon confirmed pregnancy. If CML diagnosed in pregnancy, monitor closely; consider interferon-alpha (IFN-α) as bridging therapy.

Acute leukaemia in pregnancy

1st trimester: discuss termination vs treatment (delay increases maternal mortality). 2nd/3rd trimester: standard chemotherapy can be administered with obstetric co-management. ATRA may be used in APL (limited safety data).

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Paediatrics

Paediatric ALL

Excellent outcomes (>90% 5-yr ESR) with risk-stratified multi-agent chemotherapy. Asparaginase (PEG-asparaginase preferred) essential. Ph+ ALL in children: dasatinib or imatinib added to chemotherapy. Cranial irradiation now reserved for CNS-positive disease only.

Paediatric AML

Intensive ADE (cytarabine/daunorubicin/etoposide) or similar protocols; Gemtuzumab ozogamicin (Mylotarg®) for CD33+ favourable-risk AML. Allo-SCT in CR1 for high-risk disease.

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Elderly (≥65–70 years)

AML in elderly

Venetoclax + azacitidine (preferred lower-intensity regimen) — superior OS vs azacitidine alone (VIALE-A trial). Consider comorbidity burden (HCT-CI score), performance status, and patient goals of care. Intensive 7+3 only if physiologically fit with favourable disease biology.

CLL in elderly

Most CLL patients are elderly; zanubrutinib or venetoclax + obinutuzumab well tolerated in fit elderly. Avoid FCR (fludarabine-based) in patients >65 years due to toxicity.

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Renal Impairment

Cytarabine

No formal dose reduction; however, high-dose cytarabine (HD-AC) toxicity (cerebellar, conjunctival) increased in renal impairment — avoid HD-AC or reduce to 1 g/m² q12h if CrCl <60 mL/min.

Imatinib

400 mg alternate days if CrCl 20–40 mL/min; avoid if CrCl <20 mL/min.

Venetoclax

No dose adjustment for mild–severe renal impairment (CrCl ≥15 mL/min). Not studied in dialysis.

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Hepatic Impairment

Imatinib / Dasatinib

Reduce dose by 25–50% in moderate hepatic impairment (Child-Pugh B). Avoid in severe impairment (Child-Pugh C).

Nilotinib

Not recommended in moderate or severe hepatic impairment.

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Immunocompromised

HIV-positive patients

Leukaemia treatment should proceed as per standard protocols; consult infectious disease for ART optimisation. Drug interactions with TKIs and antiretrovirals require careful review (CYP3A4 interactions).

Post-transplant immunosuppression

Allo-SCT patients require prolonged antiviral, antifungal, and PJP prophylaxis; monitor CMV/EBV reactivation with quantitative PCR.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Epidemiology

Aboriginal and Torres Strait Islander peoples have higher age-standardised incidence and mortality for AML and ALL compared with non-Indigenous Australians. CML incidence is similar, but survival disparities exist. CLL is underreported due to diagnostic access barriers.

Diagnostic delay

Later stage at presentation due to reduced access to primary care, pathology services, and specialist haematology review in remote and very remote communities. High index of suspicion for unexplained cytopenias, lymphadenopathy, or splenomegaly in Aboriginal and Torres Strait Islander patients is essential.

Treatment access

Allo-SCT is only available at major metropolitan centres, requiring relocation away from community — significant cultural, financial, and psychosocial burden. Telehealth haematology reviews (MBS-rebated) and outreach services should be maximised.

Pharmacogenomics

Thiopurine metabolism TPMT genotyping before 6-mercaptopurine (ALL maintenance); Aboriginal and Torres Strait Islander peoples may carry different TPMT/NUDT15 variant frequencies — screen to avoid severe myelosuppression.

Cultural safety

Engage Aboriginal and Torres Strait Islander Health Workers and Liaison Officers. Respect Sorry Business and cultural obligations. Provide culturally appropriate information in language where possible. Ensure Yarning spaces available in oncology wards. Partner with Aboriginal Community Controlled Health Organisations (ACCHOs) for follow-up care.

Social determinants

Address housing insecurity, transport barriers to treatment centres, financial toxicity of treatment (even with PBS subsidy, out-of-pocket costs for supportive medications and travel are significant). Link with Closing the Gap PBS co-payment relief and Patient Assistance Transport Schemes (PATS).

Monitoring & Follow-Up

AML post-induction: Repeat bone marrow at day 14 (if persistent blasts — consider re-induction) and day 28 (assess remission status). MRD by multiparameter flow cytometry or molecular (NPM1, FLT3) — guides consolidation intensity and transplant decision.
ALL MRD: End of induction (day 28–35) and end of consolidation MRD by PCR/NGS (immunoglobulin/T-cell receptor gene rearrangements). MRD ≥10⁻⁴ at end of induction = high risk — consider allo-SCT.
CML on TKI: BCR-ABL1 IS q3 months until MCR achieved; then q3–6 months indefinitely. Peripheral blood FBC + LFTs q2 weeks initially, then monthly. Echocardiogram at baseline and annually for dasatinib (PAH risk). ECG at baseline and q3 months for nilotinib (QTc).
CLL: Watch-and-wait patients — FBC, clinical review q3–6 months. On BTK inhibitors — monitor for atrial fibrillation (ECG at baseline, then annually), bleeding risk, infection prophylaxis. On venetoclax — monitor for TLS during ramp-up, cytopenias.
Late effects: Anthracycline cardiotoxicity monitoring (echocardiogram annually for 5 years post-treatment, then as indicated). Secondary malignancy screening (MDS/AML after alkylating agents). Bone health assessment post-allo-SCT.

Quick Reference — First-Line Regimens

AML (fit, <65 yr)

Cytarabine + Idarubicin (7+3) ± Midostaurin (FLT3+)

Induction × 1 cycle; Consolidation × 3–4 cycles HD-AC ± allo-SCT

Consider allo-SCT in CR1 for intermediate/adverse risk

AML (unfit, ≥65 yr)

Venetoclax + Azacitidine

28-day cycles until progression

Ramp-up venetoclax; TLS prophylaxis

APL

ATRA + Arsenic trioxide (ATO) ± Idarubicin (high WBC)

Induction → consolidation → maintenance

Emergency ATRA on clinical suspicion; >90% cure

ALL (adult)

Vincristine + Dexamethasone + Daunorubicin + L-Asparaginase

Induction → consolidation → maintenance (2–3 yr)

Add dasatinib for Ph+ ALL; intrathecal chemo for all

CML (first-line)

Imatinib 400 mg PO daily

Continuous (consider TFR after ≥3 yr MR4.5)

qPCR monitoring; switch if suboptimal response

CLL (first-line)

Zanubrutinib 160 mg PO BD OR Venetoclax + Obinutuzumab

BTKi: continuous; V+O: 12 months fixed

del(17p)/TP53: BTKi preferred; chemoimmunotherapy inferior

📚 References

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3. Hochhaus A, Baccarani M, Silver RT, et al. European LeukaemiaNet 2020 recommendations for treating chronic myeloid leukaemia. Leukemia. 2020;34(4):966–984.
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6. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617–629. (VIALE-A trial)
7. Tam CS, Brown JR, Kahl BS, et al. Zanubrutinib versus ibrutinib in relapsed/refractory chronic lymphocytic leukaemia and small lymphocytic lymphoma: interim analysis of a randomised, open-label, phase 3 trial (ALPINE). Lancet Oncol. 2023;24(3):294–306.
8. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225–2236. (CLL14 trial)
9. 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(5):454–464. (RATIFY trial)
10. Australian Institute of Health and Welfare (AIHW). Cancer data in Australia: Leukaemia. Canberra: AIHW; 2024. Available from: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia
11. Conyers R, Trahair T, Lock RB, et al. Childhood acute lymphoblastic leukaemia in Australia: a contemporary analysis from the ANZCHOG ALL8 trial. Med J Aust. 2023;218(4):177–183.
12. Cancer Council Australia. Clinical practice guidelines for the management of acute leukaemia. Sydney: Cancer Council Australia; 2023. Available from: https://wiki.cancer.org.au/australiawiki
13. Australian Bone Marrow Donor Registry (ABMDR). Annual Report 2023. Sydney: ABMDR; 2023. Available from: https://www.abmdr.org.au
14. Royal Australasian College of Physicians (RACP). Position statement on the health of Aboriginal and Torres Strait Islander peoples. Sydney: RACP; 2023.