What is the long-term management and treatment for an adult with Acute Myeloid Leukemia (AML)?

Long-Term Management and Treatment for Adults with AML

The long-term management of adult AML should include risk-stratified consolidation therapy with allogeneic hematopoietic stem cell transplantation (HSCT) for intermediate and adverse-risk patients, while favorable-risk patients should receive high-dose cytarabine consolidation. 1

Risk Stratification for Treatment Planning

• Treatment decisions should be based on comprehensive risk assessment including cytogenetics, molecular markers, patient age, and performance status 2
• Favorable risk features include core binding factor (CBF) leukemias with t(8;21), inv(16), or t(16;16), and mutations in NPM1 and C/EBPa genes 2
• Adverse risk features include complex karyotype, therapy-related AML, and certain molecular mutations like FLT3 2
• Response to initial therapy and measurable residual disease (MRD) status should guide consolidation decisions 3

Consolidation Therapy Options

For Favorable-Risk Patients:

• High-dose cytarabine (HiDAC) is recommended as consolidation therapy (typically 3 cycles) 1
• Standard dosing is cytarabine 1.5-3 g/m² every 12 hours on days 1,3, and 5 1
• For patients aged 60-65 years, dose reduction to 1 g/m² is recommended 1
• Addition of gemtuzumab ozogamicin (GO) in consolidation cycles 1 and 2 is optional for CBF-AML 1

For Intermediate and Adverse-Risk Patients:

• Allogeneic HSCT is strongly recommended if the patient is eligible and a suitable donor is available 1, 2
• Donor selection hierarchy: HLA-identical sibling, matched unrelated donor, cord blood unit, or haploidentical donor 1, 2
• For patients without a suitable donor or with contraindications to allogeneic HSCT, options include:
  • Autologous HSCT (particularly for intermediate-risk patients) 1, 4
  • Multiple cycles of intensive chemotherapy consolidation 1

For FLT3-Mutated Patients:

• Midostaurin should be added to standard chemotherapy during both induction and consolidation 1, 5
• Up to 3 consolidation cycles should be applied in patients not undergoing allogeneic HSCT 1

Management of Relapsed/Refractory Disease

• Salvage therapy should be directed at achieving a new remission followed by allogeneic HSCT 1
• Salvage regimens typically include high-dose cytarabine (2-3 g/m²) combined with an anthracycline or other agents 1
• For patients ≥60 years, lower doses of cytarabine should be used due to toxicity concerns 1
• Prognostic factors affecting outcome after relapse include:
  • Duration of first remission (better if >6 months)
  • Cytogenetics at initial diagnosis
  • Prior HSCT status
  • Age at relapse 1
• Allogeneic HSCT is the preferred consolidation after achieving second remission 1
• For patients who relapse after allogeneic HSCT:
  • Consider discontinuation of immunoprophylaxis
  • Donor lymphocyte infusions may be beneficial if no active GVHD
  • Second transplant may be considered for late relapses (>1 year after first HSCT) 1

Monitoring During Remission

• Blood counts should be monitored every 1-3 months for the first 2 years, then every 3-6 months up to 5 years 1
• Bone marrow evaluations are typically performed every 3 months for the first 2 years within clinical trials, but may not be needed outside trials unless blood counts become abnormal 1
• MRD monitoring at standardized time points may guide further treatment decisions 1, 3

Emerging Approaches

• Maintenance therapy is being investigated, particularly in high-risk patients 6
• Targeted therapies based on molecular profiling are increasingly important for personalized treatment 7
• Hypomethylating agents combined with venetoclax have revolutionized therapy for older adults 7
• Clinical trials should be considered at all stages of treatment when available 2

Common Pitfalls and Caveats

• Delaying allogeneic HSCT in eligible intermediate or adverse-risk patients can negatively impact survival 1
• Patients with MRD positivity after induction have significantly better outcomes with allogeneic HSCT compared to chemotherapy consolidation alone 3
• Reduced-intensity conditioning regimens should be considered for older patients or those with comorbidities rather than avoiding transplant altogether 1, 2
• Early relapse (within 6 months of achieving remission) has a particularly poor prognosis and may require novel approaches 1
• Molecular testing should be repeated at relapse as mutation status can change and guide targeted therapy options 1