ALL Leukemia (Acute Lymphocytic Leukemia)

Introduction

Acute Lymphocytic Leukemia (ALL) is a rapidly progressing malignancy of the bone marrow and blood, characterized by the uncontrolled proliferation of immature lymphoid cells (lymphoblasts). It is the most common childhood cancer, but it also affects adults. Advances in chemotherapy, targeted therapy, and supportive care have significantly improved outcomes, particularly in children. Treatment is typically multi-phase, aiming to induce remission, eradicate minimal residual disease, and prevent relapse in the central nervous system (CNS).

---

Treatment Options and Doses

1. Induction Therapy (goal: achieve complete remission)

• Vincristine: 1.4 mg/m² IV weekly (maximum 2 mg per dose).

• Prednisone or Dexamethasone:

  • Prednisone 60 mg/m² orally daily for 28 days,

  • or Dexamethasone 6 mg/m²/day orally in divided doses.

• Daunorubicin: 25–45 mg/m² IV once weekly (depending on protocol).

• L-Asparaginase (E. coli-derived or PEGylated form):

  • Native L-Asparaginase: 6,000–10,000 units/m² IV or IM, 2–3 times per week.

  • PEG-Asparaginase: 2,500 units/m² IV or IM every 2 weeks.

---

2. Consolidation / Intensification Therapy (goal: eradicate residual disease)

• Cytarabine (Ara-C): 75 mg/m² IV or SC daily for 4 weeks, or in high-dose regimens (2–3 g/m² IV every 12 hours on days 1–4).

• Methotrexate:

  • Standard dose: 20–40 mg/m² IV weekly.

  • High-dose protocols: 1–5 g/m² IV over 24 hours with leucovorin rescue.

• Cyclophosphamide: 1,000 mg/m² IV on day 1 of a cycle.

• 6-Mercaptopurine (6-MP): 50–75 mg/m² orally daily.

---

3. CNS Prophylaxis (essential in ALL)

• Intrathecal Methotrexate: 12–15 mg per dose (age- and protocol-adjusted).

• May be combined with intrathecal cytarabine (30 mg) and/or hydrocortisone (50 mg) in triple therapy regimens.

---

4. Maintenance Therapy (goal: prevent relapse, usually 2–3 years)

• 6-Mercaptopurine (6-MP): 50–75 mg/m² orally daily.

• Methotrexate: 20 mg/m² orally or IV weekly.

• Vincristine: 1.4 mg/m² IV monthly (maximum 2 mg).

• Prednisone: 40 mg/m² orally for 5 days each month.

---

5. Targeted and Novel Agents (for Ph+ ALL or relapsed disease)

• Imatinib (for Philadelphia chromosome–positive ALL): 400–600 mg orally once daily, combined with chemotherapy.

• Dasatinib: 100 mg orally daily (adults).

• Blinatumomab (BiTE monoclonal antibody): 28 mcg/day continuous IV infusion for 4 weeks, followed by 2-week rest.

• Inotuzumab ozogamicin: 1.8 mg/m² per cycle, divided across days 1, 8, and 15 of a 28-day cycle.

• CAR-T cell therapy (e.g., Tisagenlecleucel): single IV infusion, dose weight-based (0.2–5 × 10⁶ CAR+ viable T cells/kg).

---

Key Considerations

• Protocols vary (e.g., Hyper-CVAD for adults, Berlin-Frankfurt-Münster [BFM] for children).

• Supportive care is essential: infection prophylaxis, transfusions, tumor lysis prevention (allopurinol or rasburicase).

• Dosing adjustments: depend on age, risk stratification, and organ function.

• Monitoring: bone marrow aspirates, MRD testing, and CNS evaluation guide treatment modifications.