What is the initial treatment for Acute Myeloid Leukemia (AML)?

Initial Treatment for Acute Myeloid Leukemia (AML)

The initial treatment for Acute Myeloid Leukemia (AML) should include induction chemotherapy with an anthracycline (typically daunorubicin) for 3 days and cytarabine for 7 days, commonly known as the "7+3" regimen, with additional targeted agents based on molecular profile. 1, 2

Patient Assessment Before Treatment

Before initiating treatment, several key assessments should be performed:

• Complete blood count, coagulation studies, and chemistry panel
• Bone marrow examination with cytogenetics and molecular testing
• Cardiac evaluation including echocardiography 1
• CT scans of chest and abdomen to identify potential infectious foci 1
• HLA typing for patients who may be candidates for allogeneic stem cell transplantation 1

Treatment Algorithm Based on Patient Factors

For Fit Patients Eligible for Intensive Chemotherapy:

1. Standard Induction Regimen: "7+3" regimen

   • Cytarabine 100-200 mg/m² continuous IV infusion for 7 days 3
   • Daunorubicin 60-90 mg/m² IV for 3 days 4

2. Molecular-Based Additions:

   • For CD33+ AML: Add gemtuzumab ozogamicin (GO) 1
   • For FLT3-mutated AML: Add midostaurin 50 mg twice daily on days 8-21 2
   • For core binding factor (CBF) AML: "7+3+GO" regimen 1
   • For therapy-related AML or AML with myelodysplasia-related changes: Consider CPX-351 (liposomal daunorubicin and cytarabine) 1, 2

For Elderly or Unfit Patients Not Eligible for Intensive Chemotherapy:

• Hypomethylating agents (azacitidine or decitabine) with or without venetoclax 1, 2
• Low-dose cytarabine with or without venetoclax 2
• Supportive care only for very frail patients with significant comorbidities 1

Response Evaluation

• Bone marrow examination should be performed 14-21 days after induction therapy 1, 2
• Complete remission is defined as:
  • Neutrophils >1,000/μL
  • Platelets >100,000/μL
  • <5% blasts in bone marrow
  • No extramedullary disease
  • Transfusion independence 2

Post-Remission (Consolidation) Therapy

After achieving remission, consolidation therapy is essential to prevent relapse 1:

1. For favorable-risk AML:

   • High-dose cytarabine for 3-4 cycles 1, 2

2. For intermediate/high-risk AML:

   • Allogeneic stem cell transplantation if an HLA-matched donor is available 1
   • High-dose cytarabine or autologous stem cell transplantation if transplant is not feasible 1

Special Considerations

• Acute Promyelocytic Leukemia (APL): Treatment differs significantly and should include all-trans retinoic acid (ATRA) plus chemotherapy 1
• Hyperleukocytosis: May require emergency leukapheresis before starting induction chemotherapy 1
• Elderly patients: More susceptible to treatment complications, particularly infections 1
• Central nervous system involvement: Requires additional intrathecal cytarabine 1

Potential Complications and Management

• Myelosuppression: Monitor for infections and provide appropriate antimicrobial prophylaxis
• Tumor lysis syndrome: Ensure adequate hydration and consider rasburicase for hyperuricemia 1
• Cardiotoxicity: Monitor cardiac function, especially with cumulative anthracycline doses >300 mg/m² 2

Key Pitfalls to Avoid

• Delaying treatment unnecessarily in patients with hyperleukocytosis or symptoms of leukostasis 2
• Undertreatment of fit elderly patients who could benefit from intensive therapy 2, 5
• Neglecting molecular testing, which is crucial for targeted therapy selection 2
• Overtreatment of unfit patients who may benefit more from less intensive approaches 2

Recent evidence suggests that standard "7+3" chemotherapy may represent undertreatment for many patients, and the addition of targeted agents based on molecular profiling can significantly improve outcomes 6, 7. However, the backbone of AML treatment remains induction chemotherapy with an anthracycline and cytarabine, with modifications based on patient and disease characteristics.