What is the treatment for Acute Myeloid Leukemia (AML)?

Treatment of Acute Myeloid Leukemia (AML)

For newly diagnosed AML patients eligible for intensive therapy, initiate induction chemotherapy with an anthracycline (daunorubicin 60-90 mg/m² or idarubicin 12 mg/m² for 3 days) combined with cytarabine 100-200 mg/m² continuous infusion for 7 days (the "7+3" regimen), followed by risk-stratified consolidation therapy with high-dose cytarabine for favorable-risk patients or allogeneic stem cell transplantation for intermediate/high-risk patients in first complete remission. 1, 2

Pre-Treatment Workup and Risk Stratification

Before initiating therapy, obtain comprehensive diagnostic evaluation including:

• Peripheral blood and bone marrow samples for morphology, cytochemistry, immunophenotyping, cytogenetic analysis, and molecular testing (FLT3, NPM1, CEBPA mutations) 1, 2
• HLA typing of the patient and family members immediately to identify potential transplant donors 2
• Echocardiography for patients with cardiac risk factors or history of heart disease before anthracycline administration 1, 2
• Coagulation screening prior to central venous line insertion 1

Risk stratification determines treatment intensity:

• Favorable risk: t(8;21), inv(16)/t(16;16), mutated NPM1 without FLT3-ITD, biallelic CEBPA mutations 1
• Adverse risk: Complex karyotype (≥3 abnormalities), antecedent myelodysplastic syndrome, therapy-related AML, FLT3-ITD mutations, TP53 mutations 1
• Intermediate risk: Normal karyotype without favorable molecular markers 1

Induction Chemotherapy

Standard AML (Non-APL)

Administer the "7+3" regimen consisting of:

• Cytarabine 100-200 mg/m² continuous IV infusion days 1-7
• PLUS Daunorubicin 60-90 mg/m² IV days 1-3 (for patients <65 years) OR Idarubicin 12 mg/m² IV days 1-3 3, 1, 2, 4

This achieves complete remission in 60-85% of younger patients 5, 6. For patients >60 years, mitoxantrone may substitute for the anthracycline 7.

Emergency leukapheresis is required before chemotherapy for patients with white blood cell count >100,000/mcL to prevent leukostasis complications 3, 1.

Acute Promyelocytic Leukemia (APL)

APL requires distinct treatment. Start ATRA immediately upon clinical suspicion without waiting for genetic confirmation to prevent fatal bleeding complications 3.

For high-risk APL (WBC >10,000/mcL):

• ATRA 45 mg/m² orally in 2 divided doses daily PLUS
• Arsenic trioxide 0.15 mg/kg IV daily until bone marrow remission 3

For low/intermediate-risk APL (WBC ≤10,000/mcL):

• ATRA 45 mg/m² daily PLUS
• Daunorubicin 50 mg/m² x 4 days PLUS
• Cytarabine 200 mg/m² x 7 days 3

Monitor closely for APL differentiation syndrome and disseminated intravascular coagulation 3.

Response Assessment

Evaluate bone marrow morphology at count recovery (typically days 28-35) after induction, not earlier, as premature assessment can be misleading 3, 8.

Complete remission criteria:

• Normal bone marrow cellularity with <5% blasts
• Morphologically normal hematopoiesis
• Peripheral blood count recovery (neutrophils >1,000/μL, platelets >100,000/μL)
• No extramedullary disease 3, 2

The previous requirement for 4-week duration of response has been eliminated 3.

Consolidation Therapy

Favorable-Risk AML

Administer high-dose cytarabine consolidation without transplantation:

• Cytarabine 1-3 g/m² IV every 12 hours on days 1,3,5
• Repeat for 2-4 cycles 3, 1, 2

This approach achieves 5-year relapse-free survival of approximately 48% 9.

Intermediate and High-Risk AML

Proceed to allogeneic stem cell transplantation in first complete remission for patients with:

• HLA-identical sibling donor (preferred) 3, 1, 2
• Matched unrelated donor for patients ≤30 years or those with particularly poor risk features 3, 1

Myeloablative conditioning is recommended for younger patients (<60 years) with minimal comorbidities 1.

Reduced-intensity conditioning should be used for patients ≥60 years in first complete remission with minimal comorbidities, as this achieves 60% overall survival at 5 years post-transplant 1, 7.

APL Consolidation

For APL in complete remission:

• Arsenic trioxide 0.15 mg/kg IV daily for 5 days/week every other month for 4 cycles PLUS
• ATRA 45 mg/m² in 2 divided doses daily for 2 weeks monthly (total 7 cycles) 3

Relapsed or Refractory Disease

Primary induction failure (no remission after 1-2 cycles) or relapsed disease requires:

• Re-induction chemotherapy followed by allogeneic stem cell transplantation for patients achieving second remission 3, 8, 2
• Matched unrelated donor transplantation for patients in second or subsequent remission 3, 2
• Clinical trial enrollment whenever possible 1, 8

For relapsed APL specifically, arsenic trioxide induces remission even in ATRA-refractory disease 3, 2.

Patients who fail to respond have poor prognosis; allogeneic transplantation should be considered if an HLA-matched donor is available 8.

Treatment for Older or Unfit Patients

For patients with poor performance status, significant comorbidities, or age >65 years not eligible for intensive therapy:

• Hypomethylating agents (azacitidine, decitabine) 1
• Venetoclax combinations with hypomethylating agents 1
• Low-dose cytarabine 1
• Best supportive care including transfusions and antimicrobial prophylaxis 3, 1

Five-year survival in older patients is only one-third that of younger patients due to chemotherapy-resistant disease and limited treatment tolerance 10.

Treatment Setting Requirements

AML treatment must be conducted in specialized centers with:

• Full hematology and medical oncology services
• Bone marrow transplant unit collaboration
• Infectious disease expertise
• Adequate transfusion services
• Psycho-oncology support 3, 1, 2

Follow-Up After Achieving Remission

Monitor for relapse with:

• Bone marrow morphology every 3 months for 24 months 8
• Differential blood counts every 3 months for 5 years 8
• Molecular MRD assessment every 3 months from bone marrow (or every 4-6 weeks from peripheral blood) for 24 months in patients with molecular markers 8

Serial bone marrow examination in asymptomatic remission patients without clinical or hematological evidence of relapse is of uncertain value 3.

Critical Pitfalls to Avoid

Do not delay ATRA initiation in suspected APL while awaiting genetic confirmation—early bleeding is the most lethal complication 3.

Do not perform bone marrow assessment too early (day 10-14) after induction in APL, as differentiation requires more time and premature assessment is misleading 3.

Do not mix induction regimens from one protocol with consolidation from another—use complete treatment algorithms consistently to achieve expected outcomes 3.

Do not overlook supportive care, which is essential and includes prophylaxis for tumor lysis syndrome, infection (antimicrobial prophylaxis), bleeding, and thrombosis 8. Early mortality often results from bleeding, differentiation syndrome, or infection rather than disease progression 8.

Recognize that most patients relapse within 1-2 years despite achieving complete remission, reflecting the need for effective post-remission therapy 5. Median remission duration with standard therapy is only 9-16 months 5.