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 administered in distinct phases (induction, consolidation, and maintenance), with specific modifications based on patient age, disease subtype, and risk stratification. 1

Risk Stratification

Risk assessment is crucial for determining treatment intensity:

• Poor prognostic factors include:
  • Elevated WBC count (≥30×10⁹/L for B-cell lineage; ≥100×10⁹/L for T-cell lineage) 1, 2
  • Hypodiploidy 1, 3
  • MLL/KMT2A rearrangements 1, 3
  • Age ≥35 years 2
  • Time to complete remission >4 weeks 2
  • Philadelphia chromosome positivity 2

Standard Treatment Protocol

1. Induction Therapy

• For adults <65 years with Ph-negative ALL: Multiagent regimens based on a backbone of vincristine, anthracyclines, corticosteroids, and L-asparaginase 1, 3
• For adults ≥65 years or with substantial comorbidities: Low-intensity options (vincristine and prednisone or POMP) or moderate-intensity regimens (ALLOLD07, EWALL, GMALL, or GRAALL) 1
• For pediatric patients:
  • Standard-risk: 3-drug induction without anthracyclines 1, 3
  • High-risk: 4-drug induction including anthracyclines 1, 3

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, 3
• For Philadelphia chromosome-positive ALL, tyrosine kinase inhibitors should be added to standard chemotherapy 2
• BLINCYTO (blinatumomab) is indicated for CD19-positive B-cell precursor ALL in the consolidation phase of multiphase chemotherapy 4

3. Maintenance Therapy

• Standard maintenance regimens include daily mercaptopurine, weekly methotrexate, monthly vincristine, and pulse dexamethasone 1

Special Considerations

Philadelphia Chromosome-Positive ALL

• Addition of tyrosine kinase inhibitors can improve 3-year event-free survival from 35% to 80% 2
• Allogeneic HSCT should be considered in first complete remission 2

Minimal Residual Disease (MRD)

• MRD monitoring guides therapy intensification and consideration for stem cell transplantation 1, 2
• BLINCYTO is indicated for MRD-positive B-cell precursor ALL in first or second complete remission with MRD ≥0.1% 4

Relapsed/Refractory Disease

• FDA-approved targeted therapies include:
  • BLINCYTO (blinatumomab) for relapsed or refractory CD19-positive B-cell precursor ALL 4
  • BESPONSA (inotuzumab ozogamicin) for relapsed or refractory CD22-positive B-cell precursor ALL 5
• Combination of high-dose Ara-C and an anthracycline has shown efficacy in achieving second remission 6
• Chimeric antigen receptor (CAR) T-cell therapy shows promising results in the relapsed/refractory setting 7, 8

Age-Specific Considerations

• Adolescents and young adults: Pediatric-inspired regimens have improved outcomes 7
• Older adults (≥60 years): Reduced intensity approaches using inotuzumab ozogamicin and blinatumomab in lieu of intensive chemotherapy have improved safety and efficacy 7
• Chronologic age alone should not determine fitness for therapy 3, 2

Treatment Outcomes

• Long-term survival rates:
  • Pediatric patients: 80-90% 7
  • Adult patients: 40-50% 7
  • Philadelphia chromosome-positive ALL with TKIs: 80+% 7
  • Immunotherapy-chemotherapy regimens in younger adults: 80-85% 7

Common Pitfalls and Considerations

• Dexamethasone shows better CNS penetration than prednisone but has higher toxicity risk (induction mortality, neuropsychiatric events, myopathy) 1, 3
• Early T-cell precursor (ETP) ALL is a high-risk subgroup requiring consideration for allogeneic stem cell transplantation 7
• Novel immunotherapies (blinatumomab, CAR T-cells) are associated with distinct adverse reactions requiring specialized management 8