What is the management of Acute Myeloid Leukemia (AML)?

Management of Acute Myeloid Leukemia (AML)

The standard treatment for AML consists of induction chemotherapy with a "7+3" regimen (7 days of cytarabine plus 3 days of an anthracycline), followed by risk-stratified consolidation therapy that may include high-dose cytarabine and/or hematopoietic stem cell transplantation. 1

Diagnosis and Pre-Treatment Evaluation

Before initiating treatment, the following assessments are essential:

• Flow cytometry characterization of bone marrow blasts
• Standard cytogenetics on bone marrow cells
• Molecular analysis for established prognostic subgroups
• HLA typing for patients under 55 years without severe comorbidities 2

Risk stratification is crucial and should be based on:

• Cytogenetic profile
• Molecular markers (FLT3, NPM1, CEBPA, etc.)
• Age and performance status
• Comorbidities 2

Induction Therapy

Standard Approach

• 7+3 regimen:
  • Cytarabine 100-200 mg/m² continuous IV infusion for 7 days
  • Anthracycline for 3 days:
    • Daunorubicin (60-90 mg/m²) or
    • Idarubicin (10-12 mg/m²) or
    • Mitoxantrone (10-12 mg/m²) 2, 1

Modified Approaches Based on Patient Characteristics

• For CD33+ AML: Consider adding gemtuzumab ozogamicin ("7+3+GO") 1
• For FLT3-mutated AML: Consider adding midostaurin ("7+3+midostaurin") 1
• For older patients (≥60 years): Consider CPX-351 (liposomal formulation of daunorubicin and cytarabine) 1

For Unfit or Elderly Patients

• Venetoclax plus hypomethylating agent (azacitidine or decitabine)
• Venetoclax plus low-dose cytarabine
• Hypomethylating agents alone (azacitidine or decitabine)
• Glasdegib plus low-dose cytarabine 1, 3

Response Assessment

Bone marrow evaluation should be performed:

• 14-21 days after starting induction therapy
• After 4-6 weeks for patients receiving intensive therapy
• After 8-12 weeks for patients receiving lower-intensity therapy 1

Complete remission (CR) is defined as:

• Neutrophils >1,000/μL
• Platelets >100,000/μL (>80,000/μL in pediatric patients)
• <5% blasts in bone marrow
• No extramedullary disease
• Transfusion independence 2

Consolidation Therapy

For Favorable-Risk Patients

• High-dose cytarabine (3 g/m² q12h on days 1,3, and 5) for 3-4 cycles 2

For Intermediate-Risk Patients

• Age <40 years: Allogeneic stem cell transplantation from HLA-compatible sibling
• Age ≥40 years: High-dose cytarabine or autologous stem cell transplantation if no donor available 2

For High-Risk Patients

• Age <55 years: Allogeneic stem cell transplantation from HLA-compatible sibling
• If no sibling donor: Consider unrelated donor transplantation (especially for patients ≤30 years) 2

Special Considerations

Pediatric AML

• Treatment requires intensive anthracycline and cytarabine-based therapy using at least 4-5 courses
• Cumulative anthracycline doses >300 mg/m² have been associated with significant cardiac toxicity 2

Relapsed/Refractory AML

• No standard of care exists, but options include:
  • Salvage chemotherapy regimens
  • Clinical trials with novel agents
  • Allogeneic stem cell transplantation if not previously performed 4

Common Pitfalls to Avoid

• Delaying treatment unnecessarily, particularly in patients with hyperleukocytosis
• Undertreatment of fit elderly patients based solely on age
• Overtreatment of unfit patients with intensive chemotherapy
• Neglecting molecular testing, which is crucial for treatment decisions 1
• Failing to monitor for anthracycline-induced cardiotoxicity, especially with cumulative doses >300 mg/m² 2

Emerging Therapies

Several targeted therapies are showing promise:

• IDH1/2 inhibitors (ivosidenib, enasidenib) for patients with respective mutations
• Multikinase inhibitors like nilotinib for KIT-expressing AML 1, 5
• Novel approaches targeting chemotherapy resistance mechanisms 6

Clinical trials should always be considered and are strongly encouraged for all AML patients, particularly those with high-risk disease or relapsed/refractory status 1.