What is the recommended induction chemotherapy regimen for Acute Myeloid Leukemia (AML)?

Standard Induction Chemotherapy for Acute Myeloid Leukemia (AML)

The standard induction chemotherapy regimen for AML is "7+3" consisting of 7 days of cytarabine (100-200 mg/m² continuous infusion) plus 3 days of an anthracycline (typically daunorubicin 60-90 mg/m² or idarubicin 12 mg/m²), with modifications based on disease and patient characteristics. 1

Core Induction Regimens by Patient Population

For Younger Patients (<60 years) with Standard Risk AML:

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

For Patients with Specific Genetic Mutations:

• FLT3-mutated AML:
  • Standard "7+3" plus midostaurin 50 mg orally twice daily on days 8-21 1
• CD33-positive Core Binding Factor (CBF) AML:
  • Standard "7+3" plus gemtuzumab ozogamicin (GO) 1, 2

For Therapy-related AML or AML with Myelodysplasia-Related Changes:

• CPX-351 (liposomal daunorubicin 44 mg/m² and cytarabine 100 mg/m²) as IV infusion over 90 minutes on days 1,3, and 5 1

For Older Patients (≥60 years) or Those Unfit for Intensive Therapy:

• Lower-intensity options:
  • Hypomethylating agents (azacitidine, decitabine) with or without venetoclax 1
  • Low-dose cytarabine 1

Response Assessment and Post-Induction Management

A bone marrow aspirate and biopsy should be performed 14-21 days after starting induction therapy to assess response 1, 2:

For Patients with Significant Residual Disease Without Hypoplasia:

• Additional therapy with standard-dose cytarabine and anthracycline or
• Escalation to high-dose cytarabine (1.5-3 g/m² every 12 hours for 6 days) 1

For Patients Achieving Complete Remission:

• Consolidation therapy with intermediate-dose cytarabine for favorable-risk patients
• Consider allogeneic stem cell transplantation for intermediate or high-risk patients 1

Evidence Quality and Considerations

The "7+3" regimen has been the backbone of AML induction therapy for decades, with strong evidence supporting its efficacy. Multiple randomized trials have shown complete remission rates of approximately 65% in younger patients 1.

Higher doses of daunorubicin (90 mg/m² vs. 45 mg/m²) have shown improved outcomes in some studies, particularly in younger patients 1. The ALFA-9801 study demonstrated that idarubicin induction yielded significantly higher complete remission rates compared to high-dose daunorubicin in patients aged 50-70 years (80% vs. 70%, p=0.03) 1.

Important Caveats and Pitfalls

1. Cytogenetic and molecular testing should be performed before starting therapy, as results guide treatment selection and prognosis 1

2. Age alone should not determine treatment intensity - functional status, comorbidities, and disease characteristics are more important than chronological age 1

3. Patients with hyperleukocytosis (WBC >100×10⁹/L) may require cytoreduction with hydroxyurea before starting induction therapy 1

4. Tumor lysis syndrome prevention is essential, particularly in patients with high white blood cell counts 1

5. Supportive care including prophylactic antibiotics, antifungals, and transfusion support is critical during the period of bone marrow aplasia 1

6. Early mortality during induction is primarily due to infections and hemorrhage, with rates of 5-10% in younger patients and up to 20% in older patients 1

The choice of induction regimen should be guided by patient-specific factors (age, performance status, comorbidities) and disease-specific factors (cytogenetics, molecular mutations), with the goal of achieving complete remission while minimizing treatment-related mortality.