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 induction chemotherapy with the "7+3" regimen, consisting of 7 days of cytarabine and 3 days of an anthracycline (typically daunorubicin), with additional targeted agents based on specific molecular and cytogenetic profiles. 1, 2

Risk Assessment Before Treatment

Before initiating treatment, comprehensive evaluation is essential:

• Morphological examination, cytochemistry, immunophenotyping, and cytogenetic analysis of peripheral blood and bone marrow 1
• Molecular testing for established prognostic markers (FLT3, NPM1, CEBPA, etc.) 2
• HLA typing for patients who may be candidates for allogeneic stem cell transplantation 1
• Cardiac evaluation including echocardiography for patients with cardiac risk factors 1, 2
• Coagulation screening prior to central venous line insertion 1

Induction Therapy Based on Patient Subgroups

Standard-Risk Patients Eligible for Intensive Chemotherapy

• Standard "7+3" regimen:
  • Cytarabine 100-200 mg/m² continuous IV infusion for 7 days
  • Anthracycline (daunorubicin or idarubicin) for 3 days 1, 2, 3

Specific AML Subtypes with Targeted Approaches

1. Core Binding Factor (CBF) AML (with t(8;21) or inv(16)/t(16;16)):

   • 7+3+GO: Standard 7+3 plus gemtuzumab ozogamicin (GO) for CD33+ patients 1, 2

2. FLT3-mutated AML:

   • 7+3+midostaurin: Standard 7+3 plus midostaurin 50 mg twice daily on days 8-21 2, 4

3. Therapy-related AML (t-AML) or AML with myelodysplasia-related changes (MRC-AML) in patients ≥60 years:

   • CPX-351 (liposomal formulation of daunorubicin and cytarabine) 1, 2

4. Acute Promyelocytic Leukemia (APL):

   • ATRA-based regimens with anthracyclines, with or without cytarabine 1, 2
   • Immediate ATRA should be initiated when APL is suspected, even before confirmatory results 1

Patients Not Eligible for Intensive Chemotherapy

• Hypomethylating agents (azacitidine or decitabine) with venetoclax 2, 5
• Low-dose cytarabine with or without venetoclax 1
• Best supportive care for those with poor performance status and significant comorbidities 1

Response Evaluation and Consolidation Therapy

• Bone marrow evaluation 14-21 days after induction therapy 1, 2
• For patients achieving complete remission (CR), consolidation therapy options include:
  1. High-dose cytarabine for favorable-risk patients 1
  2. Allogeneic stem cell transplantation for intermediate/high-risk patients 1, 2
  3. Autologous stem cell transplantation in specific cases 1

Special Considerations

• Hyperleukocytosis: Consider cytoreduction with hydroxycarbamide, cytarabine, or anthracycline; leukapheresis is generally not recommended except in specific circumstances 1
• CNS involvement: Intrathecal cytarabine twice weekly until clearance of blasts from CSF 1
• APL-specific management: Avoid leukapheresis due to risk of exacerbating coagulopathy 1

Common Pitfalls to Avoid

1. Delaying treatment unnecessarily, particularly in patients with hyperleukocytosis or symptoms of leukostasis 2
2. Failing to identify specific genetic subtypes that require targeted therapy (FLT3, CBF, APL) 1, 2
3. Overlooking cardiac toxicity risk with anthracyclines, especially at cumulative doses >300 mg/m² 2
4. Delaying allogeneic transplantation in eligible high-risk patients who achieve remission 2
5. Using midostaurin as single-agent induction therapy for FLT3-mutated AML (not indicated) 4

The treatment landscape for AML has evolved significantly in recent years, with molecular profiling driving more personalized approaches that have improved outcomes. The standard "7+3" regimen remains the backbone of therapy for most patients, but is increasingly augmented with targeted agents based on specific molecular and cytogenetic profiles 6, 5.