What is the recommended chemotherapy schedule for a 5-year-old patient with T-cell Acute Lymphoblastic Leukemia (T-cell ALL) and a mediastinal mass?

Chemotherapy Schedule for T-cell ALL in a 5-Year-Old with Mediastinal Mass

A 5-year-old with T-cell ALL and mediastinal mass should be treated with a pediatric-inspired intensive multiagent chemotherapy protocol following the BFM framework, consisting of 4-drug induction (vincristine, anthracycline, corticosteroid, L-asparaginase), consolidation, and prolonged maintenance therapy for approximately 2 years, with CNS prophylaxis throughout. 1

Treatment Framework and Phases

Induction Phase (Weeks 1-4)

The primary goal is to achieve complete remission, defined as <5% bone marrow blasts and resolution of extramedullary disease including the mediastinal mass. 2

• Four-drug induction regimen includes: 1

  • Vincristine (weekly) 1
  • Anthracycline (daunorubicin or doxorubicin) 1
  • Corticosteroid (prednisone or dexamethasone) 1
  • L-asparaginase or pegaspargase 1

• Corticosteroid selection considerations: Dexamethasone significantly reduces CNS relapse risk compared to prednisone but carries higher risks of induction mortality, neuropsychiatric events, and myopathy. 1 However, no conclusive overall survival advantage has been demonstrated. 1

• Expected response: Rapid early response (defined as <25% marrow blasts on Day 8) occurs in approximately 86% of T-ALL patients. 2 Complete remission should be achieved in 98% of patients by Day 28. 2

Consolidation/Intensification Phase (Weeks 5-20)

This phase eliminates residual leukemic cells and includes: 3

• Cyclophosphamide 3
• Cytarabine (high-dose) 3
• Mercaptopurine 3
• Methotrexate (high-dose with leucovorin rescue) 3
• L-asparaginase 3

CNS Prophylaxis (Throughout All Phases)

T-ALL patients are at particularly high risk for CNS relapse, requiring aggressive CNS-directed therapy. 4

• Intrathecal chemotherapy with methotrexate, cytarabine, and/or corticosteroids should be administered throughout induction, consolidation, and maintenance phases. 3

• Cranial irradiation indications: 2

  • CNS leukemia at diagnosis (present in 11% of T-ALL cases) 2
  • CNS2 status (<5 cells/µL CSF with blasts on cytospin, present in 17% of cases) 2
  • Cranial nerve palsies (present in 5% of cases) 2
  • Initial WBC >100,000/µL 2

Maintenance Therapy (Until 24 Months from Diagnosis)

Prolonged maintenance is essential to prevent relapse. 3, 5

• Daily oral mercaptopurine 5
• Weekly oral or intramuscular methotrexate 5
• Monthly vincristine pulses 5
• Monthly prednisone pulses 5
• Periodic intrathecal chemotherapy 3

Mediastinal Mass-Specific Considerations

The mediastinal mass (present in 71% of T-ALL cases) typically resolves with chemotherapy alone and does not require upfront radiation. 6, 7

• Incomplete local response of the mediastinal mass on Day 35 or Day 70 does NOT predict worse prognosis and is NOT an indication for treatment intensification such as local irradiation or high-dose chemotherapy. 7

• For T-cell lymphoblastic lymphoma with primary mediastinal presentation, residual masses should be irradiated. 3 However, this patient has T-ALL (not lymphoma), so radiation is typically not indicated unless there is CNS involvement or other high-risk features. 2

• Monitor mediastinal mass response with thoracic imaging at Day 35 and Day 70, but do not alter therapy based solely on incomplete regression. 7

Risk Stratification and Prognostic Factors

T-ALL in children carries specific risk features that should be monitored: 1

• Elevated WBC count (>100×10⁹/L for T-cell lineage indicates poor prognosis) 1
• MRD (minimal residual disease) assessment should guide therapy intensity 1
• Bone marrow involvement predicts lower event-free survival 8

Expected Outcomes and Relapse Patterns

With modern intensive protocols, 5-year event-free survival is 75% and 5-year overall survival is 80-91%. 4, 2

• T-ALL patients remain at increased risk for: 4

  • Induction failure (higher than B-ALL) 4
  • Early relapse (median time 1.2 years vs 2.5 years for B-ALL) 4
  • Isolated CNS relapse 4

• Most relapses occur early: 81% within 2 years of diagnosis and 57% while still receiving therapy. 8

Critical Pitfalls to Avoid

• Do not reduce treatment intensity based on incomplete mediastinal mass regression - this does not predict outcome. 7

• Do not omit CNS prophylaxis - T-ALL has significantly higher CNS relapse rates than B-ALL. 4

• Do not delay therapy for mediastinal mass concerns - chemotherapy effectively treats both systemic disease and mediastinal involvement. 6

• Ensure adequate asparaginase dosing - this is a critical component of T-ALL therapy and should not be omitted due to toxicity concerns without careful consideration. 1

• Monitor for early relapse - most relapses occur within the first 2 years, requiring vigilant surveillance. 8