Standard Treatment for Acute Myeloid Leukemia (AML)
The standard treatment for Acute Myeloid Leukemia (AML) is a risk-stratified approach with induction chemotherapy consisting of cytarabine for 7 days plus an anthracycline for 3 days (7+3 regimen), with specific modifications based on molecular and cytogenetic risk factors. 1, 2
Patient Risk Stratification
Treatment decisions should be based on:
Cytogenetic and molecular risk classification 1:
- Favorable risk: Core binding factor (CBF) AML, NPM1+/FLT3-, CEBPA+
- Intermediate risk: Normal karyotype without favorable mutations
- Adverse risk: Complex karyotype, -5/5q-, -7/7q-, MLL rearrangements, FLT3+
Patient factors 1:
- Age (≥60 years vs <60 years)
- Performance status
- Comorbidities
Standard Induction Therapy for Eligible Patients
Core Binding Factor (CBF) AML
- 7+3+GO regimen: 7 days of cytarabine (100-200 mg/m²/day continuous infusion), 3 days of daunorubicin (60-90 mg/m²), plus 1-3 days of gemtuzumab ozogamicin for CD33+ patients 1, 2
- This regimen has shown improved 6-year overall survival by 20.7% (to 75.5%) in CBF-AML patients 1
FLT3-Mutated AML
- 7+3+Midostaurin: Standard cytarabine and daunorubicin plus midostaurin 50 mg twice daily on days 8-21 2
Therapy-related AML (tAML) or AML with Myelodysplasia-Related Changes (MRC-AML)
- CPX-351 (liposomal daunorubicin and cytarabine) for patients ≥60 years 1, 2
- Improved 2-year overall survival by 18.8% (to 31.1%) in this population 1
Standard Risk AML (without specific mutations)
- 7+3 regimen: Cytarabine 100-200 mg/m²/day continuous infusion for 7 days with daunorubicin 60-90 mg/m² or idarubicin 10-12 mg/m²/day for 3 days 1, 2
Post-Induction Assessment and Consolidation
Bone marrow assessment 14-21 days after induction to evaluate response 2
Consolidation options based on risk stratification 1:
- Favorable risk: High-dose cytarabine (3-4 cycles)
- Intermediate risk: High-dose cytarabine or allogeneic hematopoietic cell transplantation (alloHCT)
- Adverse risk: AlloHCT if eligible
Number of consolidation cycles 1:
- 3-4 cycles for patients not undergoing transplantation
- 1-2 cycles for patients proceeding to transplantation
Treatment for Older or Unfit Patients
For patients ineligible for intensive chemotherapy:
- Hypomethylating agents (azacitidine, decitabine) 1, 3
- Low-dose cytarabine with or without targeted agents 1
- Venetoclax-based regimens (with azacitidine or low-dose cytarabine) 1
Common Pitfalls and Special Considerations
Hyperleukocytosis (WBC >100 × 10⁹/L): Consider cytoreduction with hydroxycarbamide, cytarabine, or daunorubicin before starting induction 1, 2
CNS involvement: Requires intrathecal cytarabine twice weekly until clearance of blasts from CSF 1
Gemtuzumab ozogamicin considerations: Maintain at least 2 months between last dose and allogeneic transplantation to reduce risk of sinusoidal obstruction syndrome 1, 2
Dose considerations: Higher doses of daunorubicin (90 mg/m²) may increase toxicity, particularly in younger patients (increased risk of invasive fungal disease, renal dysfunction, and neutropenic enterocolitis) 4
High-dose cytarabine toxicity: While potentially beneficial for remission duration, high-dose cytarabine in induction is associated with significantly more toxicity (leukopenia, thrombocytopenia, nausea, vomiting, and eye toxicity) 5
Monitoring for relapse: Bone marrow morphology every 3 months for 24 months and differential blood counts every 3 months for 5 years after treatment 1
Measurable residual disease (MRD) assessment: Recommended after 2 cycles of chemotherapy and at the end of treatment 1
The treatment landscape for AML is rapidly evolving, with newer targeted therapies being incorporated into standard regimens based on specific molecular markers, potentially moving away from the traditional 7+3 regimen toward more personalized approaches 6.