Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia (ALL) – Treatment Options

Introduction
Acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells, characterized by uncontrolled proliferation of immature lymphoblasts in the bone marrow, blood, and extramedullary sites. It is the most common pediatric cancer but also occurs in adults, where prognosis is generally poorer. Clinical presentation includes anemia, bleeding, recurrent infections, lymphadenopathy, hepatosplenomegaly, bone pain, and central nervous system (CNS) involvement. Treatment is prolonged, multi-phase, and risk-adapted.

1. Initial Stabilization and Supportive Care

• Hospitalization for initiation of therapy.

• Transfusions: Red blood cells for symptomatic anemia; platelets to prevent bleeding.

• 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 long-term chemotherapy administration.

2. Multi-Phase Chemotherapy (Standard of Care)

• Induction therapy (4–6 weeks):

  • Goal: Achieve complete remission (CR).

  • Agents: Glucocorticoids (prednisone or dexamethasone), vincristine, asparaginase (or pegaspargase), ± anthracyclines (daunorubicin).

• Consolidation/Intensification therapy:

  • Goal: Eradicate residual disease.

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

• Maintenance therapy (up to 2–3 years):

  • Goal: Prevent relapse.

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

• CNS prophylaxis (throughout 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 high-risk patients (poor cytogenetics, minimal residual disease positivity, relapsed ALL).

• Allogeneic HSCT offers curative potential but carries significant risks of graft-versus-host disease (GVHD) and transplant-related mortality.

5. Supportive and Long-Term Management

• Infection prophylaxis: Trimethoprim–sulfamethoxazole for Pneumocystis jirovecii; antiviral/antifungal prophylaxis as indicated.

• Fertility preservation: Counseling before initiation of chemotherapy.

• Endocrine and growth monitoring: Especially in pediatric patients exposed to cranial irradiation or steroids.

• Neurocognitive and psychosocial support: School reintegration, counseling, and rehabilitation services.

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

6. Monitoring and Prognostic Factors

• Minimal residual disease (MRD) testing: By flow cytometry or PCR; strongest predictor of relapse risk.

• Cytogenetic/molecular testing: Philadelphia chromosome (t[9;22]), MLL rearrangements, and others influence prognosis and therapy.

• Regular bone marrow biopsies: To confirm remission and detect relapse.

7. Multidisciplinary Care

• Hematologists/oncologists: For chemotherapy and targeted therapy.

• Transplant teams: For HSCT planning.

• Infectious disease specialists: For management of opportunistic infections.

• Cardiologists, endocrinologists, and neurologists: For long-term toxicity surveillance.

• Psychologists and social workers: For emotional and social support.