Treatment of Acute Myeloid Leukemia (AML)
Initial Risk Stratification
Treatment decisions in AML must be guided by cytogenetic and molecular risk classification, with favorable risk including Core Binding Factor (CBF) AML, NPM1+/FLT3-, and CEBPA+; intermediate risk including normal karyotype without favorable mutations; and adverse risk including complex karyotype, -5/5q-, -7/7q-, MLL rearrangements, and FLT3+ disease. 1
Patient performance status and comorbidities determine eligibility for intensive versus lower-intensity therapy. 1
Induction Therapy for Fit Patients
FLT3-Mutated AML (FLT3-ITD or FLT3-TKD)
For FLT3-mutated AML, administer standard 7+3 (cytarabine 100-200 mg/m²/day continuous infusion for 7 days with daunorubicin 60-90 mg/m² for 3 days) plus midostaurin 50 mg twice daily on days 8-21, which improves 4-year overall survival by 7.1% to 51.4%. 2, 1
Therapy-Related AML or AML with Myelodysplasia-Related Changes (t-AML/MRC-AML)
For patients ≥60 years with t-AML or MRC-AML, 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%. 2, 1 CPX-351 is approved in Europe independent of age, though prospective data in younger patients are limited. 2 Note that CPX-351 showed no benefit in patients previously treated with hypomethylating agents for MDS. 2
CD33-Positive Core Binding Factor (CBF) AML
For CD33-positive CBF-AML (RUNX1-RUNX1T1 or CBFB-MYH11), administer 7+3 plus gemtuzumab ozogamicin (GO) 3 mg/m² on days 1,4, and 7, which improves 6-year overall survival by 20.7% to 75.5%. 2, 1 Maintain at least 2 months between the last GO dose and allogeneic transplantation to reduce sinusoidal obstruction syndrome risk. 2, 1
Standard Risk AML
For remaining patients without the above features, use standard 7+3 induction (cytarabine 100-200 mg/m²/day for 7 days with daunorubicin 60-90 mg/m² or idarubicin 10-12 mg/m²/day for 3 days). 1, 3 Consider adding GO to 7+3 in younger CD33-positive patients with ELN favorable or intermediate risk, which improves 6-year overall survival by 5.7% in intermediate-risk cytogenetics. 2 Do not add GO in adverse-risk cytogenetics, as it provides no benefit. 2
Post-Induction Assessment
Perform bone marrow assessment 14-21 days after induction to evaluate response. 1 Assess for complete remission (CR) after 4-6 weeks following hematologic recovery. 2
Consolidation Therapy
Favorable Risk Patients
Administer 3-4 cycles of high-dose cytarabine consolidation; allogeneic hematopoietic cell transplantation (alloHCT) is not justified in first remission as transplant-related mortality exceeds benefit in this group with ≤35% relapse risk. 2, 1
Intermediate Risk Patients
Proceed to alloHCT with HLA-matched sibling or unrelated donor if available, or administer high-dose cytarabine if transplant is not feasible. 2, 1
Adverse Risk Patients
Proceed to alloHCT with HLA-matched sibling or unrelated donor if age and performance status permit; this is the only curative option for this high-risk group. 2, 1
Administer 1-2 consolidation cycles before proceeding to transplantation. 1
Treatment for Older or Unfit Patients
For patients ineligible for intensive chemotherapy, administer hypomethylating agents (azacitidine or decitabine) combined with venetoclax, which has revolutionized therapy in older adults and extends survival over monotherapy. 2, 4 Alternative options include low-dose cytarabine with or without targeted agents. 2, 1
For patients with IDH1 mutations, consider ivosidenib or olutasidenib; for IDH2 mutations, consider enasidenib. 2, 4
Special Considerations
Hyperleukocytosis (WBC >100 × 10⁹/L)
Administer cytoreduction with hydroxycarbamide, cytarabine, or daunorubicin before starting induction to prevent leukostasis and tumor lysis syndrome. 1 Consider emergency leukapheresis coordinated with chemotherapy initiation. 2
CNS Involvement
Administer intrathecal cytarabine twice weekly until clearance of blasts from cerebrospinal fluid. 1
Coagulopathy
Obtain coagulation studies before central line insertion, particularly in acute promyelocytic leukemia (APL). 2
Monitoring and Follow-Up
Perform bone marrow morphology every 3 months for 24 months and differential blood counts every 3 months for 5 years after treatment. 1 Assess measurable residual disease (MRD) after 2 cycles of chemotherapy and at end of treatment. 1