What is the standard treatment for a patient with B-cell Acute Lymphoblastic Leukemia (B ALL) classified as standard risk (SR)?

Standard Treatment for B-Cell Acute Lymphoblastic Leukemia (B-ALL) Standard Risk

For pediatric patients with standard-risk B-ALL, treatment consists of a 3-drug induction regimen (dexamethasone, vincristine, and pegaspargase) without anthracyclines, followed by risk-adapted consolidation based on end-of-induction minimal residual disease (MRD), and prolonged maintenance therapy with daily mercaptopurine and weekly methotrexate plus monthly vincristine and pulse dexamethasone. 1, 2

Risk Stratification Criteria

Standard-risk B-ALL is defined by the Children's Oncology Group (COG) as:

• Age 1 to <10 years AND
• WBC count <50×10⁹ cells/L 1

Additional favorable features that may classify patients as low-risk within the standard-risk category include:

• DNA index ≥1.16 with ETV6-RUNX1 fusion 1
• Simultaneous trisomies of chromosomes 4,10, and 17 1

Induction Therapy (Weeks 1-4)

Standard-risk patients receive a 3-drug induction without anthracyclines: 1, 2

• Dexamethasone 10 mg/m²/day for 14 days (or prednisone 60 mg/m²/day for 28 days) 1, 3
• Vincristine 1.4 mg/m² IV weekly (maximum 2 mg) 3
• Pegaspargase 2,500 IU/m² IV (typically 1 dose during induction) 1, 3, 4

Critical consideration: Dexamethasone provides superior CNS penetration compared to prednisone but carries higher risk of osteonecrosis in patients ≥10 years old. 1, 5 For younger children (<10 years), dexamethasone improves outcomes; for patients ≥10 years, prednisone may be preferred to reduce toxicity. 1

CNS Prophylaxis (Initiated During Induction)

All patients require CNS-directed therapy: 2, 3

• Intrathecal chemotherapy with methotrexate, cytarabine, and dexamethasone (triple intrathecal therapy) 3
• Timing of lumbar puncture should coincide with initial intrathecal therapy administration 1

Post-Induction Risk Stratification

MRD assessment at end-of-induction (Day 29) is the most critical prognostic factor and determines subsequent therapy intensity: 1, 2

Standard-Risk Low (SR-Low):

• MRD <0.01% at end of induction 1
• 5-year event-free survival: 95% 1
• Receive standard consolidation therapy 1

Standard-Risk Average (SR-Average):

• MRD 0.01% to <0.1% at end of induction 1
• 5-year event-free survival: 89-95% 1
• Receive standard consolidation therapy 1

Standard-Risk High (SR-High):

• MRD ≥0.1% at end of induction 1
• 5-year event-free survival: 85% 1
• Require intensified consolidation with cyclophosphamide, cytarabine, 6-mercaptopurine, vincristine, pegaspargase, and intrathecal methotrexate 1

Consolidation Therapy

For SR-Low and SR-Average patients, standard consolidation includes: 1, 2

• 6-mercaptopurine
• Vincristine
• Intrathecal methotrexate 1

For SR-High patients, intensified consolidation includes: 1

• Cyclophosphamide
• Cytarabine
• 6-mercaptopurine
• Vincristine
• Pegaspargase
• Intrathecal methotrexate 1

High-dose methotrexate (1,500 mg/m²) is incorporated during consolidation phases for CNS prophylaxis. 1, 2, 3

Maintenance Therapy (Continues for 2-3 Years Total from Diagnosis)

Standard maintenance regimen includes: 2, 3

• Daily oral mercaptopurine 2, 3
• Weekly oral methotrexate (20 mg/m²/dose is standard; escalation to 40 mg/m²/dose does not improve outcomes) 1
• Monthly vincristine pulses 2, 3
• Pulse dexamethasone 2, 3

Important finding: Reducing vincristine and dexamethasone pulses from every 4 weeks to every 12 weeks does not compromise outcomes (3-year disease-free survival 95.1% vs 94.1%). 1

Recent Advances: Blinatumomab Integration

For newly diagnosed standard-risk B-ALL with average or higher relapse risk, adding blinatumomab to chemotherapy significantly improves outcomes: 6

• 3-year disease-free survival: 96.0% with blinatumomab plus chemotherapy vs 87.9% with chemotherapy alone (P<0.001) 6
• Administered as two nonsequential 28-day cycles 6
• Caveat: Higher incidence of nonfatal sepsis and catheter-related infections in patients receiving blinatumomab 6

Common Pitfalls and Monitoring

Key toxicities to monitor during treatment: 4

• Elevated transaminases (66% grade ≥3) 4
• Febrile neutropenia (40% grade ≥3) 4
• Hypertriglyceridemia (30% grade ≥3) 4
• Pancreatitis (24% grade ≥3) 4
• Hyperglycemia (24% grade ≥3) 4
• Thrombotic events (8% grade ≥3) 4

Cardiac assessment: Echocardiogram should be performed at baseline given that anthracyclines may be added for patients who develop high-risk features. 1

Treatment setting: Therapy should be administered at a specialized pediatric cancer center with expertise in ALL management due to treatment complexity and supportive care requirements. 3