What is the management approach for Acute Myeloid Leukemia (AML)?

Management of Acute Myeloid Leukemia (AML)

The management of AML should follow a structured approach including induction chemotherapy with an anthracycline and cytarabine, followed by risk-stratified consolidation therapy that may include high-dose cytarabine, allogeneic stem cell transplantation, or targeted agents based on molecular profile. 1

Diagnosis and Risk Assessment

• AML diagnosis requires examination of peripheral blood and bone marrow samples with morphological examination, cytochemistry, immunophenotyping, cytogenetic and molecular analysis 1
• Risk stratification should consider:
  • Patient factors: age, performance status, comorbidities 1
  • Disease factors: initial leukocyte count, AML subtype, karyotype, molecular markers 1
  • Favorable risk features include: t(8;21), t(16;16), mutations in C/EBPa and nucleophosmin genes 1
  • Adverse risk features include: complex karyotype, antecedent myelodysplastic syndrome, FLT3 mutations 1
• Pre-treatment evaluation should include:
  • Cardiac assessment with echocardiography for patients with cardiac risk factors 1
  • Coagulation screening prior to central venous line insertion 1
  • HLA typing for potential transplant candidates and their family members 1

Treatment Strategy

Induction Therapy

• First-line therapy for all newly diagnosed patients eligible for intensive treatment should include one cycle of induction with standard-dose cytarabine and an anthracycline 1
• Patients with acute promyelocytic leukemia (APL) should receive all-trans retinoic acid (ATRA) in addition to chemotherapy 1
• Emergency leukapheresis may be required for patients presenting with hyperleukocytosis 1
• Response evaluation should be performed through clinical examination, serial peripheral blood counts, and bone marrow aspirates 1
• Complete remission (CR) is defined as normal bone marrow cellularity with <5% blasts and recovery of normal hematopoiesis 1
• Time to CR achievement is prognostic - patients achieving CR after a lengthy time (>29 days) have higher relapse rates 2

Consolidation Therapy

• After achieving CR, patients should receive consolidation therapy based on risk stratification 1:
  • Patients with favorable risk features should receive chemotherapy consolidation, preferably with high-dose cytarabine 1
  • Patients aged <60 years with intermediate or high-risk features should be considered for allogeneic stem cell transplantation 1

Specific Recommendations for Allogeneic Stem Cell Transplantation

• Myeloablative allogeneic stem cell transplantation from an HLA-compatible sibling should be performed in first CR for 1:
  • Children with intermediate-high risk cytogenetics or who achieved CR after second course of therapy
  • Adults <40 years with intermediate-risk disease
  • Adults <55 years with high-risk cytogenetics or who achieved CR after second course of therapy
• Stem cell transplantation from an unrelated donor is recommended in first CR for 1:
  • Adults ≤30 years
  • Children with very high-risk disease lacking a sibling donor
• Reduced-intensity conditioning allogeneic HCT should be considered for patients ≥60 years in first CR with minimal comorbidities 1
• Allogeneic HCT can significantly improve outcomes in patients with detectable measurable residual disease (MRD) after induction therapy 3

Autologous Stem Cell Transplantation

• Patients aged <60 years who are not candidates for allogeneic stem cell transplantation or lack a donor should be considered for autologous stem cell transplantation 1
• The role of autologous transplantation remains controversial in AML 1

Therapy for Relapsed or Refractory Disease

• Options for relapsed/refractory disease include 1:
  • Clinical trials (preferred)
  • Low-intensity therapy (azacitidine, decitabine)
  • Allogeneic HCT
  • Best supportive care
• Patients in second or subsequent remission may qualify for allogeneic transplantation with an unrelated donor 1

Older Adults and Lower-Intensity Approaches

• For older patients or those unfit for intensive chemotherapy, lower-intensity options include 1:
  • Hypomethylating agents (azacitidine, decitabine)
  • Venetoclax combinations
  • Targeted therapies for specific mutations (enasidenib for IDH2, ivosidenib for IDH1)
  • Best supportive care

Special Considerations

• Treatment should be conducted in centers with multidisciplinary expertise and adequate infrastructure 1
• Clinical trials should be considered whenever possible 1
• Supportive care is crucial and includes transfusion support, antimicrobial prophylaxis, and management of treatment-related complications 1
• Molecular testing is increasingly important for targeted therapy selection and MRD monitoring 1

Pitfalls and Caveats

• Delaying treatment initiation for diagnostic workup completion is appropriate to ensure proper risk stratification 1
• Age alone should not exclude patients from intensive therapy; fitness for treatment should be assessed holistically 4
• Untreated AML is uniformly fatal with median survival <3 months; even older or comorbid patients should be considered for appropriate treatment options 5
• MRD status after induction is a critical prognostic factor that should guide consolidation strategy - patients with detectable MRD benefit significantly more from allogeneic HCT than chemotherapy alone 3