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

Recommended Induction Regimen for Acute Myeloid Leukemia (AML)

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

Standard Induction Regimens by Patient Age and Risk Category

For Patients <60 Years:

• Favorable-risk cytogenetics (CBF-AML): 7+3 (cytarabine for 7 days + daunorubicin for 3 days) plus gemtuzumab ozogamicin (GO) for CD33-positive AML 1

• FLT3-mutated AML: Standard-dose cytarabine (200 mg/m² continuous infusion for 7 days) with daunorubicin (60 mg/m²) for 3 days and oral midostaurin 50 mg every 12 hours on days 8-21 1

• Therapy-related AML (t-AML), AML with myelodysplasia-related changes (AML-MRC): CPX-351 [liposomal daunorubicin (44 mg/m²) and cytarabine (100 mg/m²)] as intravenous infusion over 90 minutes on days 1,3, and 5 1

• Intermediate/poor-risk cytogenetics: Standard-dose cytarabine with daunorubicin or idarubicin 1

• Alternative regimen for intermediate/poor-risk: Standard-dose cytarabine (200 mg/m² continuous infusion for 7 days) with daunorubicin (60 mg/m² for 3 days) and cladribine (5 mg/m² for 5 days) 1

• High-dose cytarabine (HiDAC) option: HiDAC (2-3 g/m² every 12 hours for 4-6 days) with idarubicin or daunorubicin - category 1 recommendation for patients ≤45 years, category 2B for other age groups 1

For Patients ≥60 Years:

• Fit patients without unfavorable cytogenetics: Standard-dose cytarabine (100-200 mg/m² continuous infusion for 7 days) with idarubicin (12 mg/m²) or daunorubicin (60-90 mg/m²) for 3 days 1

• FLT3-mutated AML: Standard-dose cytarabine with daunorubicin and midostaurin 1

• t-AML or AML-MRC: CPX-351 (particularly for patients 60-75 years) 1

• Unfit patients or those declining intensive therapy: Lower-intensity therapy with hypomethylating agents (azacitidine, decitabine) or low-dose cytarabine 1

Dosing Specifics

• Cytarabine: 100-200 mg/m² continuous infusion for 7 days 2, 3

• Daunorubicin: 60-90 mg/m² for 3 days (higher dose of 90 mg/m² showed improved outcomes in patients <60 years) 1

• Idarubicin: 12 mg/m² daily for 3 days by slow (10-15 min) intravenous injection 2

• Midostaurin (for FLT3-mutated AML): 50 mg orally every 12 hours on days 8-21 1

Post-Induction Assessment

• Bone marrow aspirate and biopsy should be performed 14-21 days after start of therapy to assess response 1

• For patients with significant residual disease without hypoplasia after standard-dose cytarabine induction, options include:

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

• For FLT3-mutation-positive AML with residual disease: standard-dose cytarabine with anthracycline and midostaurin 1

Common Pitfalls and Caveats

• Cardiac toxicity: For patients with impaired cardiac function, consider cytarabine-based regimens with non-cardiotoxic agents 1

• Hyperleukocytosis: Patients with WBC >100 × 10⁹/L may require cytoreduction with hydroxycarbamide (50-60 mg/kg/day), IV/subcutaneous cytarabine, or IV daunorubicin before starting induction 1

• Dose adjustments: If daunorubicin (90 mg/m²) was used in induction, the recommended dose for reinduction prior to count recovery is 45 mg/m² for no more than 2 doses. Similarly, if idarubicin (12 mg/m²) was used, early reinduction dose should be limited to 10 mg/m² for 1-2 doses 1

• Baseline neutropenia: Patients with pre-treatment grade 4 neutropenia have higher risk of fever, documented infection, and bacteremia during induction 4

• GO administration: When using gemtuzumab ozogamicin, maintain at least 2 months between last dose and allogeneic stem cell transplantation to reduce risk of sinusoidal obstruction syndrome 1

Emerging Approaches

• Recent clinical trials have explored alternatives to the traditional 7+3 regimen, including:
  • Addition of targeted agents based on molecular profiling 5
  • Modified induction regimens with reduced toxicity profiles 6
  • Homoharringtonine-based regimens, which have shown promising results in some studies 7

The 7+3 regimen remains the backbone of AML induction therapy, with modifications based on cytogenetic/molecular risk factors, patient age, and comorbidities to optimize outcomes while minimizing treatment-related mortality 1, 5.