Acute Myeloblastic Leukemia

Acute Myeloblastic Leukemia (AML) – Treatment Options

Introduction
Acute myeloblastic leukemia (AML) is a clonal hematopoietic stem cell malignancy characterized by the uncontrolled proliferation of myeloid precursor cells with impaired differentiation. It leads to bone marrow failure, presenting with anemia, infections, bleeding, organ infiltration, and constitutional symptoms. AML is heterogeneous, with prognosis influenced by age, performance status, cytogenetics, and molecular abnormalities. Management requires intensive chemotherapy, targeted therapy, and in some cases stem cell transplantation.

1. Initial Stabilization and Supportive Care

• Hospital admission with isolation precautions.

• Transfusions:

  • Packed red blood cells for anemia.

  • Platelet transfusions to prevent or treat bleeding (<10,000/µL or symptomatic).

• Infection management:

  • Broad-spectrum antibiotics for febrile neutropenia.

  • Antifungal and antiviral prophylaxis in high-risk patients.

• Tumor lysis syndrome prevention:

  • Aggressive IV hydration.

  • Allopurinol or rasburicase.

• Central venous catheter placement for long-term therapy.

2. Induction Therapy (Remission Induction)

• Standard regimen – “7 + 3”:

  • Cytarabine (continuous IV infusion for 7 days).

  • Anthracycline (daunorubicin or idarubicin) IV for 3 days.

• Goal: Achieve complete remission (CR) with eradication of circulating and marrow blasts.

• Alternative/augmented regimens: FLAG-IDA (fludarabine, cytarabine, G-CSF, idarubicin) in refractory/relapsed cases.

• Mutation-targeted induction add-ons:

  • Midostaurin for FLT3-mutated AML.

  • Gemtuzumab ozogamicin (anti-CD33 antibody-drug conjugate) for CD33-positive AML.

3. Consolidation Therapy

• High-dose cytarabine (HiDAC):

  • Standard for younger patients with favorable/intermediate risk.

• Allogeneic hematopoietic stem cell transplantation (HSCT):

  • Indicated for high-risk cytogenetics, relapsed/refractory AML, or poor MRD clearance.

  • Provides potential cure but associated with GVHD and transplant-related mortality.

4. Targeted and Novel Therapies

• IDH inhibitors:

  • Ivosidenib (IDH1) and enasidenib (IDH2) for relapsed/refractory AML.

• BCL-2 inhibitor:

  • Venetoclax in combination with azacitidine or decitabine in elderly/unfit patients.

• FLT3 inhibitors:

  • Gilteritinib for relapsed/refractory FLT3-mutated AML.

• CPX-351 (liposomal cytarabine + daunorubicin):

  • Approved for therapy-related AML and AML with myelodysplasia-related changes.

5. Special Considerations

• Acute promyelocytic leukemia (APL, AML M3 subtype):

  • Managed separately with all-trans retinoic acid (ATRA) + arsenic trioxide, with or without chemotherapy.

• Elderly/unfit patients:

  • Low-intensity therapy (hypomethylating agents ± venetoclax, or low-dose cytarabine).

  • Focus on palliation and quality of life in frail patients.

6. Monitoring and Long-Term Care

• Minimal residual disease (MRD): Flow cytometry or molecular testing to guide prognosis and therapy intensity.

• Bone marrow biopsy: To confirm remission after induction and monitor relapse.

• Cardiac function: Echocardiogram or MUGA scans due to anthracycline cardiotoxicity.

• Long-term follow-up: For secondary malignancies, organ toxicity, and survivorship care.

7. Multidisciplinary Care

• Hematology/oncology teams: For chemotherapy and transplant planning.

• Infectious disease specialists: For prophylaxis and treatment of infections.

• Transplant teams: For HSCT in appropriate candidates.

• Cardiology, nephrology, neurology specialists: For monitoring chemotherapy toxicities.

• Palliative and psychosocial support teams: For symptom management and quality-of-life support.