What is the management approach for a case of acute myeloid leukemia (AML)?

Management of Acute Myeloid Leukemia

The management of acute myeloid leukemia (AML) requires intensive induction chemotherapy with cytarabine and anthracycline ("7+3" regimen) followed by consolidation therapy and consideration for allogeneic stem cell transplantation, with treatment modifications based on molecular markers and risk stratification. 1

Diagnosis and Risk Assessment

• Essential diagnostic workup includes:

  • Flow cytometry of bone marrow blasts
  • Standard cytogenetics on bone marrow cells
  • Molecular analysis for prognostic markers (FLT3, NPM1, CEBPA, RUNX1)
  • HLA typing for potential transplant candidates 1

• Risk stratification based on:

  • Cytogenetic profile
  • Molecular markers
  • Age
  • Performance status
  • Comorbidities 1

Treatment Approach by Risk Category

Induction Therapy

1. Standard "7+3" regimen:

   • Cytarabine 100-200 mg/m² continuous IV infusion for 7 days
   • Anthracycline (daunorubicin, idarubicin, or mitoxantrone) for 3 days 1

2. For FLT3-mutated AML:

   • Add midostaurin 50 mg twice daily on days 8-21 to standard "7+3" regimen 2
   • Midostaurin is FDA-approved in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation for newly diagnosed FLT3-positive AML 2

3. For CD33+ AML:

   • Consider adding gemtuzumab ozogamicin (GO) 1

4. For patients ≥60 years with secondary AML:

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

5. For patients unfit for intensive chemotherapy:

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

Management of Hyperleukocytosis

For patients presenting with hyperleukocytosis (WBC >100 × 10⁹/L):

• Initiate emergency measures to reduce leukemia-related complications
• Consider leukapheresis for symptomatic leukostasis
• Administer rasburicase for tumor lysis syndrome prevention
• Do not delay chemotherapy initiation 4

Consolidation Therapy

1. For favorable-risk patients:

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

2. For intermediate/high-risk patients:

   • Allogeneic stem cell transplantation in first complete remission 4, 1

3. For FLT3-mutated patients:

   • Consider maintenance therapy with FLT3 inhibitors post-transplant 1

4. For APL (acute promyelocytic leukemia):

   • ATRA-based regimens with anthracyclines, with or without cytarabine 4
   • For high-risk APL (WBC >10,000/μL), combine ATRA with chemotherapy to decrease APL differentiation syndrome 4

Response Assessment

• Complete remission (CR) defined as:

  • Neutrophils >1,000/μL
  • Platelets >100,000/μL
  • <5% blasts in bone marrow
  • No extramedullary disease
  • Transfusion independence 1

• Bone marrow evaluation 14-21 days after induction therapy 1

Management of Relapsed/Refractory AML

1. For all relapsed patients who can tolerate intensive treatment:

   • Reinduction chemotherapy with antimetabolite (cytarabine, fludarabine) and anthracycline-based approaches 4

2. For FLT3-mutated relapsed/refractory AML:

   • Gilteritinib (FLT3 inhibitor) 1
   • Consider combination approaches (venetoclax plus hypomethylating agent with FLT3 inhibitor) 1

3. For patients achieving second CR:

   • Allogeneic stem cell transplantation is recommended 4

Supportive Care

• CNS-directed therapy with intrathecal triple chemotherapy for patients at high risk of CNS involvement 4
• Prophylaxis for tumor lysis syndrome 1
• Infection prophylaxis and management 1
• Monitoring for anthracycline-induced cardiotoxicity (especially with cumulative doses >300 mg/m²) 1

Common Pitfalls to Avoid

• Delaying treatment in patients with hyperleukocytosis or symptoms of leukostasis
• Undertreatment of fit elderly patients or overtreatment of unfit patients
• Neglecting molecular testing, which is crucial for treatment decisions
• Delaying transplant evaluation in eligible patients who achieve remission
• Failing to monitor for FLT3 inhibitor-related toxicities, including QT prolongation, myelosuppression, and gastrointestinal issues 1

The management of AML has evolved significantly with the incorporation of targeted therapies based on molecular markers, but the backbone of treatment remains intensive chemotherapy for fit patients, with allogeneic stem cell transplantation offering the best chance for long-term survival in intermediate and high-risk disease.