What is the management of Acute Myeloid Leukemia (AML)?

Management of Acute Myeloid Leukemia (AML)

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

Initial Diagnostic Workup and Risk Stratification

Before initiating any therapy, obtain comprehensive diagnostic evaluation including peripheral blood and bone marrow samples for morphology, cytochemistry, immunophenotyping, cytogenetic analysis, and molecular testing (specifically FLT3, NPM1, and CEBPA mutations). 1, 2 Do not delay treatment waiting for all results—begin induction once morphology suggests AML, but obtain molecular testing immediately to guide subsequent therapy. 1

Essential Pre-Treatment Assessments:

• HLA typing of patient and family members immediately to identify potential transplant donors 1, 2
• Echocardiography for patients with cardiac risk factors before anthracycline administration 1, 2
• Coagulation screening prior to central venous line insertion 1, 2

Risk Stratification Categories:

Favorable risk features include: 1, 2

• t(8;21) or inv(16)/t(16;16) translocations
• Mutated NPM1 without FLT3-ITD
• Biallelic CEBPA mutations

Adverse risk features include: 1, 2

• Complex karyotype (≥3 abnormalities)
• Monosomal karyotype
• FLT3-ITD mutations
• Antecedent myelodysplastic syndrome

Induction Therapy

Standard "7+3" Regimen:

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

Critical Modifications:

For FLT3-mutation positive AML: Add midostaurin 50 mg orally twice daily with food on days 8-21 of each induction and consolidation cycle. 3 Midostaurin is FDA-approved specifically for this indication and should not be used as single-agent induction therapy. 3

For hyperleukocytosis (WBC >100,000/mcL): Perform emergency leukapheresis before chemotherapy to prevent leukostasis complications. 1, 2

Response Assessment:

Evaluate bone marrow morphology at count recovery (typically days 28-35) after induction—do not assess earlier as premature evaluation is misleading. 2 Complete remission requires: 2

• Normal bone marrow cellularity with <5% blasts
• Morphologically normal hematopoiesis
• Neutrophils >1,000/μL and platelets >100,000/μL
• No extramedullary disease

Consolidation Therapy

For Favorable-Risk AML:

Administer high-dose cytarabine consolidation without transplantation: cytarabine 1-3 g/m² IV every 12 hours on days 1,3,5, repeated for 2-4 cycles. 1, 2 This approach achieves excellent long-term survival without the morbidity of transplantation.

For Intermediate and High-Risk AML:

Allogeneic stem cell transplantation in first complete remission is the standard of care. 1, 2 Specific recommendations:

• Myeloablative allogeneic transplant from HLA-compatible sibling for children with intermediate-high risk cytogenetics or who achieved CR after second induction course 1
• Matched unrelated donor transplantation for adults ≤30 years in first CR 1
• Reduced-intensity conditioning allogeneic transplant for patients ≥60 years in first CR with minimal comorbidities 1
• Autologous stem cell transplantation for patients <60 years who are not candidates for allogeneic transplant or lack a donor (though this remains controversial) 1

Treatment for Older or Unfit Patients

For patients with poor performance status, significant comorbidities, or age >65 years not eligible for intensive therapy, the treatment landscape has evolved substantially. 4, 5 Options include: 2, 6

• Hypomethylating agents (azacitidine or decitabine) with median OS of 9.9 months 6
• Venetoclax combinations with hypomethylating agents (highly effective newer option) 5
• Low-dose cytarabine with median OS of 7.9 months 6
• Best supportive care with median OS of 2.5 months 6

The choice between these options should be based on molecular profile, with targeted therapies increasingly available for specific mutations. 5

Relapsed or Refractory Disease

Primary induction failure or relapsed disease requires re-induction chemotherapy followed by allogeneic stem cell transplantation for patients achieving second remission. 2 Options include: 1, 2

• Clinical trial enrollment (strongly preferred when available)
• Matched unrelated donor transplantation for patients in second or subsequent remission
• Low-intensity therapy for patients not candidates for intensive re-induction
• Best supportive care

Special Considerations for Acute Promyelocytic Leukemia (APL)

APL is a medical emergency requiring immediate action upon suspicion—do not wait for genetic confirmation. 7

Immediate Management:

• Start ATRA (all-trans retinoic acid) immediately the same day APL is suspected 7
• Aggressive coagulation support: maintain platelets >30-50 × 10⁹/L and fibrinogen >150 mg/dL 7
• Avoid invasive procedures (central lines, lumbar puncture, bronchoscopy) until coagulopathy corrects 7
• Add chemotherapy immediately for hyperleukocytosis (WBC >10 × 10⁹/L) even before genetic confirmation 7

APL Differentiation Syndrome Management:

Start dexamethasone 10 mg IV twice daily at the earliest sign of: 7

• Dyspnea, unexplained fever, weight gain, peripheral edema
• Unexplained hypotension, acute renal failure
• Chest radiograph showing interstitial infiltrates or effusions

Do not wait for full-blown syndrome—early treatment is critical. Temporarily discontinue ATRA/ATO only for severe cases requiring ICU admission. 7

Treatment Setting Requirements

AML treatment must be conducted in specialized centers with: 2

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

Centers should treat at least 5 AML patients per year with intensive chemotherapy. 7

Follow-Up After Achieving Remission

Monitor for relapse with: 2

• Bone marrow morphology every 3 months for 24 months
• Differential blood counts every 3 months for 5 years
• 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

Critical Pitfalls to Avoid

Do not delay ATRA initiation in suspected APL while awaiting genetic confirmation—early bleeding is the most lethal complication. 2

Do not perform bone marrow assessment too early (day 10-14) after induction—wait until count recovery (days 28-35) as premature assessment is misleading. 2

Do not mix induction regimens from one protocol with consolidation from another—use complete treatment algorithms consistently to achieve expected outcomes. 2

Do not overlook supportive care, which is essential and includes prophylaxis for tumor lysis syndrome, infection (antimicrobial prophylaxis), bleeding, and thrombosis. 2