Acute Nonlymphocytic Leukemia

Acute Nonlymphocytic Leukemia (ANLL) – Treatment Options

Introduction
Acute nonlymphocytic leukemia (ANLL) is an older term that corresponds to acute myeloid leukemia (AML). It encompasses leukemias of myeloid lineage characterized by uncontrolled proliferation of immature myeloid blasts and impaired differentiation. Patients typically present with bone marrow failure—manifesting as anemia, bleeding/bruising, and recurrent infections—along with organ infiltration in some cases (gums, skin, CNS). Prognosis varies depending on cytogenetic and molecular abnormalities, as well as patient age and comorbidities.

1. Initial Stabilization and Supportive Care

• Hospital admission with protective isolation.

• Transfusions:

  • Packed red blood cells for symptomatic anemia.

  • Platelets for thrombocytopenia (<10,000/µL or higher if bleeding).

• Infection prevention and management:

  • Empiric broad-spectrum antibiotics for febrile neutropenia.

  • Antifungal/antiviral prophylaxis in high-risk cases.

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

• Leukostasis management (if hyperleukocytosis): Leukapheresis and/or hydroxyurea.

• Central venous catheter placement for chemotherapy and transfusion support.

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 marrow and recovery of blood counts.

• Targeted add-ons:

  • Midostaurin for FLT3-mutated AML.

  • Gemtuzumab ozogamicin for CD33-positive AML.

• Alternative regimens:

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

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

3. Consolidation Therapy

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

• Allogeneic hematopoietic stem cell transplantation (HSCT):

  • Indicated for high-risk cytogenetics or relapsed disease.

  • Offers curative potential but carries transplant-related morbidity and mortality.

4. Targeted and Novel Therapies

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

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

• BCL-2 inhibitor: Venetoclax with azacitidine, decitabine, or low-dose cytarabine (especially for older or unfit patients).

• Hypomethylating agents: Azacitidine or decitabine in patients unsuitable for intensive chemotherapy.

5. Special Considerations

• Acute promyelocytic leukemia (APL, AML M3): Managed distinctly with all-trans retinoic acid (ATRA) + arsenic trioxide, with or without anthracyclines.

• Elderly/unfit patients:

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

  • Emphasis on quality of life and palliative intent if frail.

6. Monitoring and Long-Term Care

• Minimal residual disease (MRD): Monitored with flow cytometry or molecular assays for prognosis and therapy decisions.

• Bone marrow evaluations: After induction and periodically during remission.

• Toxicity surveillance:

  • Cardiac monitoring (anthracyclines).

  • Renal/hepatic function monitoring.

  • Fertility preservation discussions pre-therapy.

• Survivorship care: Screening for relapse, secondary cancers, and long-term toxicities.

7. Multidisciplinary Care

• Hematologists/oncologists: For chemotherapy and HSCT planning.

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

• Transplant teams: For patients proceeding to HSCT.

• Cardiology, nephrology, endocrinology specialists: For managing treatment-related toxicities.

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