Initial Treatment for B-Cell Acute Lymphoblastic Leukemia in a 1-Year-Old
This 1-year-old with newly diagnosed B-ALL should receive a 4-drug induction regimen consisting of a corticosteroid (prednisone or dexamethasone), vincristine, an anthracycline (daunorubicin or doxorubicin), and pegaspargase, followed by CNS prophylaxis with intrathecal chemotherapy, consolidation therapy, and prolonged maintenance treatment. 1
Induction Therapy (First 4 Weeks)
The standard 4-drug induction backbone for pediatric B-ALL includes: 1, 2
Corticosteroid: Prednisone 60 mg/m²/day for 28 days OR dexamethasone 10 mg/m²/day for 14 days 1
- For this 1-year-old patient, prednisone is preferred over dexamethasone to minimize toxicity risk, particularly osteonecrosis, though dexamethasone provides better CNS penetration 1
Vincristine: 1.4 mg/m² IV (maximum 2 mg) weekly during induction 1
Anthracycline: Daunorubicin (typically 25-30 mg/m² IV weekly) 1, 2
L-asparaginase: Pegaspargase 2,500 IU/m² IV (doses vary by protocol, typically 1-3 doses during induction) 1
Critical consideration: Infants under 1 year with KMT2A rearrangements have particularly poor prognosis and may require intensified therapy or consideration for allogeneic hematopoietic stem cell transplantation (HSCT) in first remission 1
CNS Prophylaxis (Throughout All Treatment Phases)
CNS-directed therapy must begin during induction and continue throughout treatment: 1
- Intrathecal chemotherapy: Methotrexate, cytarabine, and dexamethasone (triple intrathecal therapy) 1
- Age-based dosing for intrathecal methotrexate: For a 1-year-old, the dose is 8 mg 3
- Systemic high-dose methotrexate: Incorporated during consolidation phases 1
Consolidation/Intensification Therapy (Post-Induction)
After achieving complete remission (typically by day 29), consolidation therapy includes: 1
- High-dose methotrexate (1,500 mg/m² over 24 hours) with leucovorin rescue 1
- Cyclophosphamide, cytarabine, and mercaptopurine in various combinations 1
- Additional pegaspargase doses 1
- Continued intrathecal chemotherapy 1
The specific consolidation regimen depends on risk stratification based on:
- End-of-induction minimal residual disease (MRD) status 1
- Cytogenetic abnormalities (particularly KMT2A rearrangements in infants) 1
- Age and white blood cell count at diagnosis 1
Maintenance Therapy (Prolonged Phase)
Standard maintenance continues for approximately 2-3 years total from diagnosis: 4, 5
- Daily oral mercaptopurine: 1.5-2.5 mg/kg/day 5
- Weekly oral methotrexate: 20 mg/m²/dose 1, 4
- Monthly vincristine pulses: 1.4 mg/m² IV 1, 4
- Pulse dexamethasone: Every 4 weeks 1, 4
Risk Stratification and Treatment Modifications
MRD assessment at end of induction is the most critical prognostic factor: 1
- MRD ≥0.01%: Requires intensified therapy with additional consolidation cycles 1
- MRD <0.01%: Standard consolidation and maintenance 1
- Persistent MRD or very high-risk features: Consider allogeneic HSCT in first remission 1
Infant-specific considerations (age <1 year): 1
- Higher incidence of KMT2A rearrangements (poor prognosis) 1
- May require dose modifications due to smaller body surface area 3
- Allogeneic HSCT should be considered for high-risk features including KMT2A rearrangements 1
Common Pitfalls and Monitoring
Avoid these critical errors:
- Do not use preserved methotrexate formulations for intrathecal administration - only preservative-free formulations are safe for CNS therapy 3
- Test for TPMT and NUDT15 deficiency if severe myelosuppression occurs during mercaptopurine maintenance, as homozygous deficiency requires 90% dose reduction 5
- Reduce mercaptopurine to 25-33% of dose if coadministered with allopurinol 5
- Monitor complete blood counts weekly during induction and consolidation to adjust doses for myelosuppression 1, 5
Treatment should be administered at a specialized pediatric cancer center with expertise in ALL management given the complexity of therapy and need for supportive care 1