Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) – Treatment Options

Introduction
Acute myeloid leukemia (AML) is a clonal hematopoietic stem cell malignancy characterized by uncontrolled proliferation and impaired differentiation of myeloid precursors. It leads to bone marrow failure, presenting with anemia, bleeding, infections, and sometimes organ infiltration (skin, gums, CNS). AML is heterogeneous, with prognosis determined by age, performance status, cytogenetics, and molecular mutations (e.g., FLT3, NPM1, IDH1/2). Management includes intensive chemotherapy, targeted agents, supportive care, and stem cell transplantation in selected patients.

1. Initial Stabilization and Supportive Care

• Hospital admission with protective precautions.

• Blood product support:

  • Red blood cells for symptomatic anemia.

  • Platelets to maintain >10,000–20,000/µL, higher if bleeding.

• Infection control:

  • Broad-spectrum antibiotics for febrile neutropenia.

  • Antifungal/antiviral prophylaxis in prolonged neutropenia.

• Tumor lysis syndrome prevention: IV fluids, allopurinol, or rasburicase.

• Leukostasis management (if WBC >100,000/µL): Leukapheresis and/or hydroxyurea.

• Central venous catheter placement for therapy delivery.

2. Induction Therapy (Remission Induction)

• Standard regimen – “7 + 3”:

  • Cytarabine (continuous IV for 7 days).

  • Anthracycline (daunorubicin or idarubicin) for 3 days.

• Goal: Achieve complete remission (CR) with <5% blasts in bone marrow and recovery of normal hematopoiesis.

• Alternative regimens:

  • CPX-351 (liposomal cytarabine + daunorubicin) for therapy-related AML or AML with myelodysplasia-related changes.

  • FLAG-IDA (fludarabine, cytarabine, G-CSF, idarubicin) for relapsed/refractory AML.

• Targeted induction add-ons:

  • Midostaurin in FLT3-mutated AML.

  • Gemtuzumab ozogamicin in CD33-positive AML.

3. Consolidation Therapy

• High-dose cytarabine (HiDAC): Standard for younger patients with favorable/intermediate risk.

• Allogeneic hematopoietic stem cell transplantation (HSCT):

  • Recommended for high-risk or relapsed disease.

  • Potentially curative but associated with graft-versus-host disease and transplant-related mortality.

4. Targeted and Novel Therapies

• FLT3 inhibitors: Midostaurin (frontline), gilteritinib (relapsed/refractory).

• IDH inhibitors: Ivosidenib (IDH1) and enasidenib (IDH2).

• BCL-2 inhibitor: Venetoclax with azacitidine, decitabine, or low-dose cytarabine, particularly in older/unfit patients.

• Hypomethylating agents: Azacitidine or decitabine for elderly or poor-performance patients.

5. Special Considerations

• Acute promyelocytic leukemia (APL, AML-M3): Managed uniquely with all-trans retinoic acid (ATRA) + arsenic trioxide, achieving high cure rates.

• Elderly/unfit patients: Low-intensity therapy (venetoclax + hypomethylating agents, or low-dose cytarabine).

• Pregnancy: Requires specialized risk-adapted management with careful chemotherapy selection.

6. Monitoring and Long-Term Care

• Minimal residual disease (MRD): Monitored by flow cytometry or PCR for relapse prediction.

• Bone marrow biopsies: After induction and during follow-up to confirm remission.

• Toxicity surveillance:

  • Cardiac (anthracyclines).

  • Renal/hepatic function.

  • Fertility considerations (preservation counseling before therapy).

• Survivorship care: Monitoring for relapse, secondary malignancies, and late treatment toxicities.

7. Multidisciplinary Care

• Hematologists/oncologists: For chemotherapy and targeted therapy planning.

• Transplant teams: For HSCT evaluation.

• Infectious disease specialists: For antimicrobial prophylaxis and infection management.

• Cardiology, nephrology, endocrinology specialists: For monitoring organ toxicity.

• Psychosocial and palliative care: For quality-of-life and supportive management.