AML (Acute Myeloid Leukemia)

Acute Myeloid Leukemia (AML) – Treatment Overview

Introduction
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by clonal proliferation of immature myeloid precursors (blasts) in the bone marrow, leading to bone marrow failure (anemia, infections, bleeding). AML is more common in adults and is associated with cytogenetic and molecular abnormalities that influence prognosis and treatment decisions.

Management requires rapid initiation of therapy, often in specialized centers, and includes induction chemotherapy, consolidation, targeted therapies, and supportive care.

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Treatment Options and Doses

1. Induction Therapy (Goal: Remission – <5% blasts in bone marrow)

• “7+3” regimen (standard of care for fit patients):

  • Cytarabine: 100–200 mg/m²/day continuous IV infusion for 7 days.

  • Anthracycline (daunorubicin or idarubicin):

    • Daunorubicin: 60–90 mg/m² IV daily on days 1–3.

    • Idarubicin: 12 mg/m² IV daily on days 1–3.

• CPX-351 (liposomal daunorubicin + cytarabine): For secondary AML or therapy-related AML.

  • Dose: 44 mg/m² daunorubicin + 100 mg/m² cytarabine IV on days 1, 3, and 5.

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2. Consolidation Therapy (Goal: Eradicate residual disease)

• High-dose cytarabine (HiDAC):

  • 3 g/m² IV every 12 hours on days 1, 3, and 5 for 3–4 cycles (younger, fit patients).

  • Reduced dose (1–1.5 g/m²) in older patients to reduce neurotoxicity.

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3. Targeted Therapies (Molecularly guided)

• FLT3 mutation: Midostaurin 50 mg orally twice daily (days 8–21 of each induction/consolidation cycle).

• IDH1 mutation: Ivosidenib 500 mg orally once daily.

• IDH2 mutation: Enasidenib 100 mg orally once daily.

• BCL-2 inhibitor (older/unfit patients): Venetoclax in combination with azacitidine or decitabine.

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4. Hematopoietic Stem Cell Transplant (HSCT)

• Considered for patients with intermediate- or high-risk cytogenetics or those with relapsed/refractory disease.

• Allogeneic HSCT offers the best chance of cure in selected patients.

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5. Supportive Care

• Infections: Broad-spectrum antibiotics for febrile neutropenia; antifungal prophylaxis (e.g., posaconazole).

• Transfusions: Red blood cells and platelets as required.

• Tumor lysis syndrome prevention: Allopurinol 300 mg daily or Rasburicase in high-risk patients.

• Growth factors (G-CSF): Occasionally used in post-chemotherapy neutropenia.

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Special Situations

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

  • All-trans retinoic acid (ATRA) + arsenic trioxide ± anthracycline.

  • High cure rates compared to other AML subtypes.

• Older/unfit patients: Low-intensity regimens with azacitidine, decitabine, or low-dose cytarabine ± venetoclax.

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Prognosis

• Prognosis depends on age, cytogenetics, and molecular mutations.

• Favorable-risk AML (e.g., t(8;21), inv(16)) has better long-term outcomes.

• Adverse-risk AML (e.g., TP53 mutation, complex karyotype) has poor prognosis, often requiring HSCT or novel therapies.