What is the treatment for Acute Lymphoblastic Leukemia (ALL)?

Treatment of Acute Lymphoblastic Leukemia (ALL)

The treatment of Acute Lymphoblastic Leukemia (ALL) requires intensive multiagent chemotherapy regimens administered in distinct phases (induction, consolidation, and maintenance) with specific modifications based on patient age, disease subtype, and risk stratification. 1

Risk Stratification

Risk stratification is essential for treatment planning:

• Poor prognostic factors include: 1
  • Elevated WBC count (≥30×10⁹/L for B-cell lineage; ≥100×10⁹/L for T-cell lineage)
  • Hypodiploidy
  • MLL/KMT2A rearrangements
  • Philadelphia chromosome positivity
  • Age ≥65 years or substantial comorbidities

Treatment Phases

1. Induction Therapy

• For adults <65 years with Ph-negative ALL: 1

  • Multiagent regimens based on a backbone of:
    • Vincristine
    • Anthracyclines (daunorubicin or doxorubicin)
    • Corticosteroids (prednisone or dexamethasone)
    • L-asparaginase
  • High-intensity options include CALGB 9111, ECOG 1910, and dose-adjusted hyper-CVAD

• For adults ≥65 years or with substantial comorbidities: 1

  • Low-intensity options: vincristine and prednisone or POMP
  • Moderate-intensity options: ALLOLD07, EWALL, GMALL, or GRAALL regimens
  • Immunotherapy options: ALL-INITIAL-1 (InO/dexamethasone) or InO mini-hyper-CVD

• For pediatric patients: 1, 2

  • Standard-risk: 3-drug induction (without anthracyclines)
  • High-risk: 4-drug induction including anthracyclines

2. Consolidation Therapy

• Typically includes high-dose methotrexate, cytarabine, and other agents 1
• CNS prophylaxis with intrathecal chemotherapy is essential in all treatment regimens 1, 2
• Minimal residual disease (MRD) assessment guides further therapy 1, 3

3. Maintenance Therapy

• Mercaptopurine 1.5-2.5 mg/kg orally once daily as part of combination maintenance regimen 4
• Typically continues for 2-3 years 3, 5

Special Considerations

Philadelphia Chromosome-Positive ALL

• Combination of tyrosine kinase inhibitors with chemotherapy or blinatumomab 3
• Has dramatically improved 5-year survival rates to >80% 3

T-Cell ALL

• Requires combination chemotherapy incorporating pegylated asparaginase and nelarabine 3
• Early T-cell precursor (ETP) ALL is high-risk and may benefit from allogeneic stem cell transplantation 3

Relapsed/Refractory Disease

• Combination therapy including chemo- and immuno-therapies 3
• Consider CAR T-cell therapy followed by allogeneic stem cell transplantation 3

Treatment Modifications

• Dose adjustments needed for patients with TPMT or NUDT15 deficiency 4
• Patients with renal or hepatic impairment require lower starting doses 4
• Dexamethasone shows better CNS penetration than prednisone but has higher toxicity risk 2

Outcomes

• Pediatric patients: 80-90% long-term survival 3, 5
• Adult patients: 40-50% long-term survival 3, 6
• Adolescent and young adult patients treated with modern immunotherapy-chemotherapy regimens: 80-85% 4-year survival 3

Monitoring

• Regular assessment of complete blood counts to adjust dosing 4
• MRD monitoring to guide therapy intensification and consideration for stem cell transplantation 1, 3
• Bone marrow evaluation for patients with prolonged or repeated myelosuppression 4