Acute Lymphocytic Leukemia

Acute Lymphocytic Leukemia (ALL) – Treatment Options

Introduction
Acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, is a malignant disorder of lymphoid precursor cells characterized by uncontrolled proliferation of immature lymphoblasts. It is the most common pediatric cancer but also occurs in adults, where prognosis is generally less favorable. Clinical presentation includes anemia, recurrent infections, bleeding, lymphadenopathy, hepatosplenomegaly, bone pain, and central nervous system (CNS) involvement. Management requires multi-phase chemotherapy, risk-adapted treatment, and long-term supportive care.

1. Initial Stabilization and Supportive Care

• Hospitalization for induction therapy.

• Transfusions: Red blood cells for symptomatic anemia; platelets for bleeding or <10,000/µL count.

• Infection management: Empiric broad-spectrum antibiotics for febrile neutropenia; antifungal/antiviral prophylaxis in high-risk patients.

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

• Central venous catheter placement for chemotherapy administration.

2. Multi-Phase Chemotherapy (Standard Regimen)

• Induction phase (4–6 weeks):

  • Goal: Achieve complete remission (CR).

  • Common agents: Glucocorticoids (prednisone or dexamethasone), vincristine, asparaginase (or peg-asparaginase), ± anthracyclines.

• Consolidation/Intensification phase:

  • Goal: Eradicate residual disease.

  • Agents: High-dose methotrexate, cytarabine, cyclophosphamide, 6-mercaptopurine, asparaginase.

• Maintenance therapy (2–3 years):

  • Goal: Prevent relapse.

  • Agents: Daily oral 6-mercaptopurine, weekly methotrexate, periodic vincristine, and corticosteroids.

• CNS prophylaxis (across all phases):

  • Intrathecal chemotherapy (methotrexate ± cytarabine, hydrocortisone).

  • Cranial irradiation reserved for high-risk or refractory CNS disease.

3. Targeted and Novel Therapies

• Tyrosine kinase inhibitors (imatinib, dasatinib): For Philadelphia chromosome–positive (Ph+) ALL.

• Monoclonal antibodies:

  • Blinatumomab (CD19 bispecific T-cell engager).

  • Inotuzumab ozogamicin (anti-CD22 antibody-drug conjugate).

• CAR-T cell therapy (tisagenlecleucel): For relapsed/refractory B-cell ALL in children and young adults.

4. Hematopoietic Stem Cell Transplantation (HSCT)

• Considered in relapsed, refractory, or high-risk disease (e.g., poor cytogenetics, MRD positivity).

• Allogeneic HSCT offers curative potential but carries risks such as graft-versus-host disease and transplant-related mortality.

5. Long-Term and Supportive Management

• Infection prophylaxis: Trimethoprim–sulfamethoxazole for Pneumocystis jirovecii, with antifungal/antiviral prophylaxis when indicated.

• Fertility preservation: Counseling prior to chemotherapy.

• Neurocognitive and psychosocial support: Especially important in pediatric survivors.

• Vaccinations: Inactivated vaccines after immune recovery; live vaccines avoided during therapy.

• Survivorship care: Monitoring for late effects (cardiac, endocrine, neurocognitive).

6. Monitoring and Prognostic Factors

• Minimal residual disease (MRD) testing: By flow cytometry or PCR; critical for prognosis and therapy adaptation.

• Cytogenetics and molecular profiling: Guides risk stratification (e.g., Ph+ ALL, MLL rearrangements, hypodiploidy).

• Bone marrow biopsies: To assess remission and detect relapse.

7. Multidisciplinary Care

• Hematology/Oncology teams: For chemotherapy and targeted therapies.

• Transplant specialists: For HSCT in appropriate patients.

• Infectious disease experts: For managing opportunistic infections.

• Cardiologists, endocrinologists, neurologists: For surveillance of treatment-related toxicities.

• Psychosocial teams: For rehabilitation, school re-entry, and mental health support.