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

Treatment Plan for Acute Myeloid Leukemia (AML)

The optimal treatment for AML consists of induction chemotherapy with an anthracycline (daunorubicin or idarubicin) combined with cytarabine, followed by consolidation therapy tailored to cytogenetic and molecular risk stratification, with allogeneic stem cell transplantation reserved for intermediate and high-risk patients in first remission. 1, 2

Pre-Treatment Risk Stratification and Workup

Before initiating therapy, comprehensive molecular and cytogenetic profiling is mandatory to guide treatment decisions 1:

• Obtain peripheral blood and bone marrow samples for morphology, cytochemistry, immunophenotyping, cytogenetics, and molecular analysis (FLT3, NPM1, CEBPA, IDH1/2, TP53) 1, 2
• Perform HLA typing of the patient and family members immediately to identify candidates for allogeneic stem cell transplantation 1
• Assess cardiac function with echocardiography in patients with cardiac risk factors or history of heart disease before anthracycline administration 1
• Screen coagulation parameters before central line insertion, particularly if acute promyelocytic leukemia (APL) is suspected 1

Risk Categories

Favorable-risk AML includes 1, 2:

• t(15;17) - Acute Promyelocytic Leukemia (APL)
• t(8;21)
• inv(16) or t(16;16)
• NPM1 mutation without FLT3-ITD
• Biallelic CEBPA mutations

Adverse-risk features include 1, 2:

• Complex karyotype (≥3 abnormalities)
• Antecedent myelodysplastic syndrome
• Therapy-related AML
• FLT3-ITD mutations
• TP53 mutations
• Age >60 years

Induction Chemotherapy

Standard AML (Non-APL)

For patients <65 years old and fit for intensive therapy 1, 2, 3:

• Anthracycline (daunorubicin 60-90 mg/m² IV days 1-3 OR idarubicin 12 mg/m² IV days 1-3) 1, 3
• PLUS cytarabine 100-200 mg/m² continuous IV infusion days 1-7 (the "7+3" regimen) 1, 2

For FLT3-mutated AML specifically 4, 5, 6:

• Add midostaurin (RYDAPT) 50 mg orally twice daily with food on days 8-21 of each induction and consolidation cycle to standard 7+3 chemotherapy 4
• FLT3 mutation status must be confirmed by FDA-approved testing before initiating midostaurin 4

Critical pitfall: Do not delay chemotherapy for complete molecular results if APL is not suspected, but ensure adequate tissue is collected for later analysis 1. However, if leukocytosis is excessive (typically >100,000/μL), perform emergency leukapheresis before induction to prevent tumor lysis syndrome 1.

Acute Promyelocytic Leukemia (APL) - Special Protocol

Start ATRA immediately when APL is suspected based on morphology alone, even before molecular confirmation 1, 2:

• All-trans retinoic acid (ATRA) 45 mg/m² daily in divided doses 1
• PLUS anthracycline-based chemotherapy once diagnosis is confirmed 1, 2
• This combination is mandatory and non-negotiable for APL 1, 2

Critical pitfall: Never delay ATRA in suspected APL while awaiting molecular confirmation, as early mortality from coagulopathy is high 1, 2.

Older/Unfit Patients (>65 years or significant comorbidities)

For patients unable to tolerate intensive chemotherapy 5, 6, 7:

• Hypomethylating agent (azacitidine or decitabine) PLUS venetoclax is now the standard of care 5, 6, 7
• This combination has revolutionized therapy for older adults and extends survival compared to monotherapy 5, 7

Consolidation Therapy

Favorable-Risk AML

Chemotherapy alone without transplant 1, 2:

• High-dose cytarabine (1-3 g/m² every 12 hours on days 1,3,5) for 2-4 cycles 1
• Estimated 10-year survival rates exceed 75% with this approach in core-binding factor AML 7

For FLT3-mutated favorable-risk AML: Continue midostaurin 50 mg twice daily on days 8-21 of each consolidation cycle 4

Intermediate and High-Risk AML

Allogeneic stem cell transplantation in first remission 1, 2:

• Patients with HLA-identical sibling donors should proceed to allogeneic transplant after achieving complete remission 1
• Patients with particularly poor risk features and no sibling donor may qualify for matched unrelated donor transplant 1
• Reduced-intensity conditioning regimens are increasingly used in patients >40-45 years 1

Critical pitfall: Identify transplant candidates early during induction, not after consolidation, as this affects the entire treatment timeline 1.

APL Consolidation

Maintenance therapy is beneficial and mandatory in APL 1:

• Continue ATRA-based maintenance therapy 1
• There is no role for allogeneic transplant in APL patients in first remission 1

Response Assessment

Complete remission criteria 1, 2:

• Normal bone marrow cellularity
• <5% blasts in bone marrow
• Morphologically normal hematopoiesis
• Peripheral blood count recovery

Monitor response with bone marrow aspirate during induction-induced aplasia to assess early response or blast persistence 1.

Relapsed or Refractory Disease

For relapsed non-APL AML 1:

• Patients in second remission should be considered for allogeneic transplant with matched unrelated donor 1
• Targeted therapies (gilteritinib for FLT3-mutated, ivosidenib/enasidenib for IDH-mutated) have shown activity 5, 6, 8

For relapsed APL specifically 1:

• Arsenic trioxide can induce remission even in ATRA-refractory disease 1

Treatment Setting Requirements

AML should only be treated in specialized centers 1, 2:

• Full hematology and medical oncology services
• Close collaboration with bone marrow transplant unit
• Infectious disease expertise
• Adequate transfusion services
• Psycho-oncology support 1

Critical pitfall: Do not attempt AML treatment in community settings without immediate access to transplant services and intensive supportive care infrastructure 1, 2.