What is the treatment approach for an adult patient with acute myeloid leukemia (AML)?

Treatment Approach for Adult Acute Myeloid Leukemia

The optimal treatment for adult AML consists of induction chemotherapy with an anthracycline combined with cytarabine (the "7+3" regimen), followed by risk-stratified consolidation therapy—with high-dose cytarabine for favorable-risk disease and allogeneic stem cell transplantation for intermediate and high-risk patients in first remission. 1, 2

Pre-Treatment Workup and Risk Stratification

Before initiating therapy, comprehensive diagnostic evaluation is mandatory to guide treatment decisions:

Essential Diagnostic Studies

• Obtain peripheral blood and bone marrow samples for morphology, cytochemistry, immunophenotyping, cytogenetics (including FISH), and molecular analysis (FLT3, NPM1, CEBPA, IDH1/2, TP53) 3, 1, 2
• Perform HLA typing immediately on the patient and all available first- and second-degree family members to identify transplant candidates early 3, 1, 2
• Assess cardiac function with echocardiography in patients with cardiac risk factors or history of heart disease before anthracycline administration 3, 2
• Obtain coagulation screening before central venous line insertion, particularly to detect APL-associated coagulopathy 3, 2
• Perform CT chest and abdomen (or chest X-ray and abdominal ultrasound) plus dental survey to identify infectious foci 3, 2

Risk Classification

The molecular and cytogenetic profile determines prognosis and guides consolidation strategy 3, 1:

Favorable-risk features:

• APL with t(15;17) 3
• Core-binding factor AML with t(8;21) or inv(16) 3
• Biallelic CEBPA mutation with normal cytogenetics 3
• NPM1 mutation without FLT3-ITD 3

Adverse-risk features:

• Complex karyotype (>3 abnormalities) or monosomal karyotype 3
• TP53 mutations 4
• Antecedent myelodysplastic syndrome 3

Induction Chemotherapy

Standard Intensive Induction (Age <60-65 Years, Fit Patients)

Administer the "7+3" regimen: 1, 2

• Cytarabine 100-200 mg/m² continuous IV infusion for 7 days (days 1-7) 1
• Plus daunorubicin 60-90 mg/m² IV on days 1-3 OR idarubicin 12 mg/m² IV on days 1-3 1

This approach achieves complete remission in 70-80% of younger patients 5. A central venous line must be inserted before starting therapy, with platelet transfusion support if needed 3.

Special Considerations Before Starting Induction

• Delay chemotherapy until all diagnostic material is obtained 3
• Perform emergency leukapheresis in patients with excessive leukocytosis and clinical signs of leukostasis, coordinated with chemotherapy initiation 3, 2
• Administer rasburicase in patients at high risk for tumor lysis syndrome 3

Acute Promyelocytic Leukemia (APL)

APL requires distinct induction therapy: all-trans retinoic acid (ATRA) combined with an anthracycline 3, 2. This is a medical emergency requiring immediate ATRA initiation once APL is suspected, even before molecular confirmation.

Consolidation Therapy

After achieving complete remission (defined as <5% bone marrow blasts with normal hematopoiesis recovery and peripheral blood count recovery 1, 2), consolidation strategy is determined by risk stratification:

Favorable-Risk AML

Administer chemotherapy consolidation alone without transplant: 1, 2

• High-dose cytarabine 1-3 g/m² IV every 12 hours on days 1,3, and 5 for 2-4 cycles 1

This approach restricts overall relapse to approximately 50% in younger patients with favorable cytogenetics 5.

Intermediate and High-Risk AML

Proceed to allogeneic stem cell transplantation in first remission: 1, 2

• Patients with HLA-identical sibling donors should proceed to myeloablative allogeneic transplant after achieving complete remission 3, 2
• Patients without sibling donors but with poor-risk features should undergo matched unrelated donor (MUD) search immediately at diagnosis and proceed to MUD transplant in first remission 3, 1
• Reduced-intensity conditioning should be considered for patients ≥60 years with minimal comorbidities 2

The early mortality risk of intensive chemotherapy in older patients (>15% in the first month) must be weighed against median survivals of less than 1 year 6.

Treatment for Older or Unfit Patients (Age ≥60-65 Years)

Patient Selection for Intensive vs. Non-Intensive Therapy

Elderly patients face higher treatment-related mortality due to comorbidities, poor performance status, and adverse disease biology (high frequency of adverse cytogenetics, antecedent MDS, multidrug resistance) 3, 6, 7.

For patients age ≥75 or with performance status ≥2, significant comorbidities, or adverse cytogenetics:

• Avoid intensive chemotherapy 8, 6
• Administer hypomethylating agents (azacitidine or decitabine) with or without venetoclax 8, 2

Azacitidine 75 mg/m² subcutaneously daily for 7 consecutive days every 28 days demonstrated median survival of 24.5 months vs. 15.0 months with conventional care (HR 0.58, p=0.0001) in higher-risk MDS and AML patients 9.

For patients age 70-74 with good performance status, normal cytogenetics, and de novo disease:

• Consider standard anthracycline plus cytarabine if treatment-related mortality risk is acceptable 6

For patients age ≥80, poor performance status, or significant organ dysfunction:

• Provide supportive/palliative care only 6

Low-dose cytarabine shows no benefit in patients with adverse cytogenetics and should be avoided in this population 8, 6.

Relapsed or Refractory Disease

Patients achieving second remission should be considered for allogeneic transplant with matched unrelated donor 1, 2. For relapsed APL, arsenic trioxide can induce remission even in ATRA-refractory disease 1.

Treatment Setting Requirements

AML should only be treated in specialized centers with full hematology and medical oncology services, close collaboration with bone marrow transplant units, infectious disease expertise, adequate transfusion services, and high case volume 3, 1, 2. Clinical trial enrollment should be pursued whenever possible 3, 2.

Common Pitfalls to Avoid

• Do not start induction before obtaining adequate diagnostic material for cytogenetics and molecular studies, as this information is critical for consolidation planning 3
• Do not delay HLA typing—initiate at diagnosis for all potential transplant candidates to avoid delays in proceeding to allogeneic transplant 3, 1
• Do not use intensive chemotherapy in elderly patients with complex cytogenetics—the prohibitive early mortality risk (>15%) is not justified by minimal survival benefit 8, 6
• Do not overlook APL—this is a medical emergency requiring immediate ATRA initiation to prevent fatal coagulopathy 3