What is the treatment for acute myeloid leukemia (AML)?

Treatment of Acute Myeloid Leukemia

Initial Workup and Risk Stratification

Before initiating any therapy, obtain comprehensive molecular and cytogenetic profiling from peripheral blood and bone marrow samples, including morphology, cytochemistry, immunophenotyping, cytogenetics, and molecular testing for FLT3, NPM1, CEBPA, IDH1, IDH2, and TP53 mutations to guide treatment decisions. 1, 2

• Perform HLA typing of the patient and family members immediately to identify potential transplant donors 1, 2
• Obtain echocardiography for patients with cardiac risk factors or history of heart disease before anthracycline administration 1, 2
• Perform coagulation screening prior to central venous line insertion 2, 3
• Administer emergency leukapheresis before chemotherapy for patients with white blood cell count >100,000/mcL to prevent leukostasis complications 2, 3

Risk classification determines treatment intensity:

• Favorable risk: Core Binding Factor AML (t(8;21), inv(16)/t(16;16)), NPM1-mutated without FLT3-ITD, biallelic CEBPA mutations 2, 3
• Intermediate risk: Normal karyotype without favorable mutations 3
• Adverse risk: Complex karyotype, -5/5q-, -7/7q-, MLL rearrangements, FLT3-mutated disease 3

Induction Chemotherapy for Fit Patients

FLT3-Mutated AML (Highest Priority)

For FLT3-mutated AML, administer standard 7+3 chemotherapy (cytarabine 100-200 mg/m²/day continuous infusion for 7 days with daunorubicin 60-90 mg/m² for 3 days) PLUS midostaurin 50 mg orally twice daily with food on days 8-21 of each induction and consolidation cycle. 3, 4

• This combination improves 4-year overall survival by 7.1% to 51.4% 3
• Midostaurin is FDA-approved specifically for this indication and must be used with standard chemotherapy, not as monotherapy 4

Therapy-Related or MRC-AML in Patients ≥60 Years

For patients ≥60 years with therapy-related AML or AML with myelodysplasia-related changes, use CPX-351 (liposomal daunorubicin 29 mg/m² and cytarabine 65 mg/m²), which improves 2-year overall survival by 18.8% to 31.1%. 3

CD33-Positive Core Binding Factor AML

For CD33-positive CBF-AML (RUNX1-RUNX1T1 or CBFB-MYH11), administer 7+3 plus gemtuzumab ozogamicin 3 mg/m² on days 1,4, and 7, which improves 6-year overall survival by 20.7% to 75.5%. 3

Standard Induction for All Other Fit Patients

For patients without the above features, use standard 7+3 induction: cytarabine 100-200 mg/m² continuous IV infusion days 1-7 with daunorubicin 60-90 mg/m² IV days 1-3 (for patients <65 years) or idarubicin 12 mg/m² IV days 1-3. 1, 2, 3, 5

• Consider adding gemtuzumab ozogamicin to 7+3 in younger CD33-positive patients with favorable or intermediate risk, which improves 6-year overall survival by 5.7% in intermediate-risk cytogenetics 3

Response Assessment

Evaluate bone marrow morphology at count recovery (typically days 28-35) after induction, NOT earlier, as premature assessment can be misleading. 2

Complete remission criteria include:

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

Consolidation Therapy (Risk-Stratified Approach)

Favorable-Risk AML

For favorable-risk AML, administer 3-4 cycles of high-dose cytarabine consolidation (1-3 g/m² IV every 12 hours on days 1,3,5) WITHOUT allogeneic stem cell transplantation in first remission. 1, 2, 3

• Allogeneic transplant is NOT justified in first remission for favorable-risk patients, as transplant-related mortality exceeds benefit in this group with ≤35% relapse risk 3

Intermediate-Risk AML

For intermediate-risk AML, proceed to allogeneic stem cell transplantation with HLA-matched sibling or unrelated donor if available; if transplant is not feasible, administer high-dose cytarabine consolidation. 1, 2, 3

Adverse-Risk AML

For adverse-risk AML, proceed to allogeneic stem cell transplantation with HLA-matched sibling or unrelated donor if age and performance status permit—this is the only curative option for this high-risk group. 1, 3

Treatment for Older or Unfit Patients

For patients ineligible for intensive chemotherapy (age >65 years, poor performance status, significant comorbidities), administer hypomethylating agents (azacitidine or decitabine) combined with venetoclax, which has revolutionized therapy in older adults and extends survival over monotherapy. 2, 3, 6

• Alternative options include low-dose cytarabine with or without targeted agents 2, 3
• Best supportive care alone results in median overall survival of only 2.5 months 7

Relapsed or Refractory Disease

For relapsed non-APL AML, patients achieving second remission should proceed to allogeneic transplant with matched unrelated donor. 1, 2

• Primary induction failure or relapsed disease requires re-induction chemotherapy followed by allogeneic stem cell transplantation for patients achieving second remission 2
• Clinical trial enrollment should be considered whenever possible 2

Treatment Setting Requirements

AML must be treated ONLY in specialized centers with full hematology and medical oncology services, close collaboration with bone marrow transplant unit, infectious disease expertise, adequate transfusion services, and psycho-oncology support. 1, 2

Follow-Up After Achieving Remission

Monitor for relapse with:

• Bone marrow morphology every 3 months for 24 months 2, 3
• Differential blood counts every 3 months for 5 years 2, 3
• Molecular measurable residual disease (MRD) assessment every 3 months from bone marrow (or every 4-6 weeks from peripheral blood) for 24 months in patients with molecular markers 2

Critical Pitfalls to Avoid

Do not delay ATRA initiation in suspected acute promyelocytic leukemia (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, as differentiation requires more time and 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