Treatment of Acute Leukaemia
Acute leukaemia treatment is fundamentally divided by subtype: for acute promyelocytic leukaemia (APL), start ATRA immediately upon clinical suspicion; for non-APL acute myeloid leukaemia (AML), use anthracycline plus cytarabine induction; and for acute lymphoblastic leukaemia (ALL), use pediatric-inspired multi-agent regimens with asparaginase regardless of age.
Acute Promyelocytic Leukaemia (APL)
Immediate Action Required
Start ATRA 45 mg/m² in 2 divided doses daily upon first clinical suspicion of APL—do not wait for genetic confirmation 1. Early ATRA initiation prevents the lethal complication of hemorrhagic death, which remains the primary cause of early mortality in APL despite its high curability 1.
Risk-Stratified Induction
Low/Intermediate Risk (WBC ≤10,000/mcL):
- ATRA 45 mg/m² daily + arsenic trioxide 0.15 mg/kg IV daily, OR
- ATRA + anthracycline (daunorubicin or idarubicin), OR
- ATRA + cytarabine (AIDA regimen) 1
High Risk (WBC >10,000/mcL):
- ATRA 45 mg/m² daily + anthracycline-based chemotherapy 1
- If unable to tolerate anthracyclines: arsenic trioxide 0.15 mg/kg IV daily until bone marrow remission 1
Critical Monitoring
Monitor aggressively for APL differentiation syndrome and coagulopathy throughout treatment 1. Do not perform premature marrow assessment at days 10-14—patients often remain molecularly positive at end of induction even with morphologic remission. First molecular assessment should occur after consolidation 1.
Consolidation
After achieving remission, proceed with consolidation using the same regimen backbone as induction. Use regimens consistently through all treatment phases—do not mix induction from one trial with consolidation from another 1. Arsenic trioxide consolidation: 0.15 mg/kg/day IV, 5 days/week for 4 weeks every 8 weeks 1.
Post-Consolidation
Maintenance chemotherapy and ATRA are beneficial in APL 2.
Non-APL Acute Myeloid Leukaemia
Induction Chemotherapy
Standard induction consists of anthracycline (daunorubicin, doxorubicin, or idarubicin) plus cytarabine ("7+3" regimen) 2, 3. Postpone chemotherapy only until diagnostic material is obtained. Patients with WBC >100,000/mcL require emergency leukapheresis before starting chemotherapy 2.
Risk-Stratified Consolidation
Favorable Risk (t(8;21), inv(16), t(15;17)):
- Chemotherapy only, preferably high-dose cytarabine
- Do not perform allogeneic stem cell transplant in first remission—relapse risk ≤35% does not justify transplant-related mortality 2, 3
Intermediate/Poor Risk:
- Allogeneic stem cell transplantation from HLA-identical sibling in first remission 2, 3
- Without family donor: matched unrelated donor (MUD) transplant 2, 3
- Complex aberrant karyotype or antecedent myelodysplastic syndrome are adverse prognostic factors requiring transplant consideration 2
Elderly Patients (>60-65 years) or Significant Comorbidities:
- Higher susceptibility to treatment complications 2, 3
- Consider venetoclax-based combinations over intensive chemotherapy 4
- Evaluate cardiac function with echocardiography before anthracycline exposure 2, 3
Targeted Therapies
Incorporate mutation-specific agents when applicable:
- FLT3 mutations: Add FLT3 inhibitors (midostaurin, gilteritinib, quizartinib) to induction and consolidation 4
- IDH1/2 mutations: Use ivosidenib, olutasidenib, or enasidenib 5, 4
Relapsed/Refractory Disease
For relapsed APL: arsenic trioxide induces remission even with ATRA resistance 2. For other AML: consider allogeneic transplantation in second remission 2.
Acute Lymphoblastic Leukaemia (ALL)
Induction Therapy
Use pediatric-inspired regimens containing asparaginase for all ages, including adolescents and young adults (AYAs)—these significantly outperform traditional adult protocols 6, 7.
Standard backbone includes:
- Vincristine
- Anthracycline (daunorubicin or doxorubicin)
- Corticosteroid (dexamethasone preferred over prednisone for superior CNS penetration) 6
- L-asparaginase 6
- Often cyclophosphamide 6
Philadelphia Chromosome Status
Ph-positive ALL (BCR-ABL+):
- Add tyrosine kinase inhibitor (dasatinib or ponatinib) to chemotherapy backbone 5
- This combination has transformed Ph+ ALL from incurable to 80%+ 5-year survival 5
Ph-negative ALL:
- Continue multi-agent pediatric-inspired regimen
- High-risk features: WBC ≥30×10⁹/L (B-cell) or ≥100×10⁹/L (T-cell), hypodiploidy, MLL rearrangements 6
CNS Prophylaxis
All ALL regimens must include CNS-directed therapy with intrathecal chemotherapy (methotrexate, cytarabine, and/or corticosteroids) 6.
Consolidation
Allogeneic hematopoietic stem cell transplantation is NOT routinely recommended in first remission 7. Consider only for:
- High-risk subsets
- Suboptimal response to initial therapy
- Minimal residual disease (MRD) positivity after induction 7
Relapsed/Refractory ALL
Use immunotherapy over chemotherapy for re-induction:
- Blinatumomab (anti-CD19) or inotuzumab ozogamicin (anti-CD22) 8, 9
- These agents have superior efficacy and tolerability compared to salvage chemotherapy 9
Essential Pre-Treatment Workup
All Acute Leukaemias
- Peripheral blood and bone marrow aspirate with morphology, cytochemistry, immunophenotyping, and cytogenetics 2
- Coagulation screening before central line insertion (especially critical in APL) 2, 3
- HLA typing of patient and first-degree relatives at diagnosis for transplant candidates 2, 3
Infection Screening
- Chest CT and abdominal imaging for suspected fungal infection 2, 3
- Dental and jaw imaging to identify infectious foci 3
Treatment Setting
Treat acute leukaemia only in experienced centers with:
- Multidisciplinary hematology/oncology services
- Bone marrow transplant unit access
- Infectious disease expertise
- Adequate transfusion services 2
Enroll patients in clinical trials whenever possible 2.