What is the initial treatment for acute myeloid leukemia (AML)?

Initial Treatment for Acute Myeloid Leukemia (AML)

The standard initial treatment for newly diagnosed AML is the "7+3" regimen consisting of 7 days of cytarabine (100-200 mg/m² continuous IV infusion) plus 3 days of an anthracycline (typically daunorubicin 60-90 mg/m²). 1, 2

Treatment Approach Based on AML Subtype and Patient Factors

Standard Induction Therapy (Fit Patients)

• Core "7+3" regimen:
  • Cytarabine 100-200 mg/m² by continuous IV infusion for 7 days
  • Daunorubicin 60-90 mg/m² IV for 3 days or idarubicin 12 mg/m² for 3 days 1

Treatment Modifications Based on AML Subtype

1. Core Binding Factor (CBF) AML:

   • 7+3+GO: Standard 7+3 plus gemtuzumab ozogamicin (GO) for CD33+ patients
   • GO significantly improves 6-year overall survival by 20.7% in CBF-AML 1

2. Therapy-related AML (tAML) or AML with myelodysplasia-related changes (MRC-AML):

   • CPX-351 (liposomal daunorubicin and cytarabine) for patients ≥60 years
   • Improves 2-year overall survival by 18.8% compared to standard 7+3 1

3. FLT3-mutated AML:

   • 7+3+midostaurin: Standard 7+3 plus midostaurin 50 mg twice daily on days 8-21 2

4. Acute Promyelocytic Leukemia (APL):

   • Low/intermediate risk (WBC ≤10,000/mcL):
     • All-trans retinoic acid (ATRA) 45 mg/m² in 2 divided doses daily plus arsenic trioxide
   • High risk (WBC >10,000/mcL):
     • ATRA 45 mg/m² in 2 divided doses daily plus anthracycline 1
   • Important: Start ATRA immediately upon suspicion of APL without waiting for genetic confirmation to prevent lethal bleeding complications 1

Treatment for Older/Unfit Patients

For patients who cannot tolerate intensive chemotherapy:

• Venetoclax plus hypomethylating agent (azacitidine or decitabine)
• Glasdegib plus low-dose cytarabine
• Hypomethylating agents alone 2

Post-Induction Assessment and Consolidation

1. Response Assessment:

   • Bone marrow evaluation 14-21 days after induction therapy 2
   • Note: For APL, premature assessment (day 10-14) can be misleading; first molecular remission assessment should be made after consolidation 1

2. Consolidation Options:

   • High-dose cytarabine (3 g/m² q12h on days 1,3, and 5) for 3-4 cycles 2
   • Allogeneic stem cell transplantation for intermediate/high-risk patients 1, 2
   • For FLT3-mutated AML: Consider allogeneic transplant in first complete remission 2

Important Considerations and Pitfalls

Critical Pitfalls to Avoid

1. Delaying treatment in APL: Start ATRA immediately upon suspicion of APL to prevent fatal hemorrhage 1
2. Inappropriate cytoreduction: Avoid leukapheresis in APL as it may exacerbate coagulopathy 1
3. Mixing regimens: Use the same regimen consistently through all treatment components (induction and consolidation) 1
4. Premature response assessment: Avoid nadir marrow assessment in APL patients 1

Monitoring and Supportive Care

• Monitor for differentiation syndrome and coagulopathy in APL patients 1
• Assess for anthracycline-related cardiotoxicity, especially with cumulative doses >300 mg/m² 2
• Provide prophylaxis for tumor lysis syndrome and management of infections 2

Special Considerations for Elderly Patients

Older patients (>60 years) may benefit from:

• CPX-351 for tAML or MRC-AML 1
• Lower-intensity regimens if unfit for standard induction 1, 3
• Careful dose adjustment based on performance status and comorbidities 3

The choice of initial therapy should be guided by cytogenetic and molecular features, age, performance status, and comorbidities to maximize survival outcomes while minimizing treatment-related mortality.