Acute Granulocytic Leukemia (Acute Myeloid Leukemia)

Acute Granulocytic Leukemia (Acute Myeloid Leukemia – AML) – Treatment Options

Introduction
Acute myeloid leukemia (AML), historically called acute granulocytic leukemia, is a clonal malignancy of myeloid precursor cells characterized by uncontrolled proliferation and impaired differentiation, leading to bone marrow failure. It typically presents with anemia, recurrent infections, bleeding, and organ infiltration. Management is intensive, combining remission-induction chemotherapy, consolidation strategies, and targeted or curative approaches depending on cytogenetic and molecular risk stratification.

1. Initial Stabilization and Supportive Care

• Hospitalization with protective isolation.

• Transfusions: Packed red blood cells for anemia; platelets to prevent bleeding (<10,000/µL or active bleeding).

• Infection management:

  • Empiric broad-spectrum antibiotics for febrile neutropenia.

  • Antifungal and antiviral prophylaxis in high-risk patients.

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

• Central venous access: For chemotherapy and supportive therapy.

2. Induction Chemotherapy (Remission Induction)

• “7 + 3” regimen (standard of care):

  • Cytarabine: Continuous IV infusion for 7 days.

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

  • Goal: Achieve complete remission (CR) with eradication of leukemic blasts.

• Alternative regimens:

  • FLAG-IDA (fludarabine, cytarabine, G-CSF, idarubicin) in selected cases.

• Targeted induction therapy (in mutation-specific AML):

  • FLT3 inhibitors (midostaurin) added in FLT3-mutated AML.

  • Gemtuzumab ozogamicin (anti-CD33) in CD33-positive AML.

3. Consolidation Therapy

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

• Allogeneic hematopoietic stem cell transplantation (HSCT):

  • Recommended in patients with high-risk cytogenetics or relapsed/refractory AML.

  • Provides curative potential but associated with transplant-related morbidity.

4. Targeted and Novel Therapies

• IDH1/IDH2 inhibitors (ivosidenib, enasidenib): For relapsed/refractory AML with IDH mutations.

• BCL-2 inhibitor (venetoclax): Combined with hypomethylating agents (azacitidine, decitabine) in elderly/unfit patients.

• Gilteritinib: Oral FLT3 inhibitor for relapsed/refractory FLT3-mutated AML.

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

5. Special Considerations

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

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

• Elderly/unfit patients:

  • Hypomethylating agents (azacitidine, decitabine) ± venetoclax.

  • Low-dose cytarabine for palliation in frail patients.

6. Monitoring and Follow-Up

• Minimal residual disease (MRD) testing: By flow cytometry or molecular assays to guide prognosis.

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

• Cardiac monitoring: Due to anthracycline cardiotoxicity.

7. Multidisciplinary Care

• Hematologists/oncologists: For chemotherapy and transplantation planning.

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

• Transplant teams: For HSCT candidates.

• Psychosocial and palliative care teams: For emotional support and quality-of-life considerations.