Treatment of Advanced-Stage, CD20-Positive B-Cell NHL in Pediatric and Young Adult Patients
For pediatric and young adult patients with advanced-stage, CD20-positive B-cell non-Hodgkin's lymphoma, rituximab combined with intensive chemotherapy (COG ANHL1131 regimen or equivalent) is the recommended treatment, with the specific regimen determined by risk stratification. 1
Risk Stratification Framework
Treatment selection depends on precise risk categorization:
Group B (High-Risk):
- Stage III disease with LDH >2× upper limit of normal 1
- Stage IV disease with bone marrow involvement <25% and CNS-negative 1
Group C:
- Stage IV disease with ≥25% bone marrow involvement 1
- Any CNS involvement (lymphoma cells in CSF, CNS tumor mass, cranial nerve palsy, spinal cord compression, or parameningeal extension) 1
Treatment Regimens by Risk Group
High-Risk Group B Treatment
COG ANHL1131 Regimen B with rituximab is the standard approach 1:
- COP reduction phase with rituximab (day 6) 1
- Response assessment after COP:
- Response assessment after consolidation 1:
Alternative: Equivalent BFM regimen (cytoreductive prephase followed by 6 courses of chemotherapy with intrathecal therapy; 6-year pEFS 78% ± 3%) 1
Group C Treatment
All Group C patients require rituximab 1:
- CNS-positive disease: COG ANHL1131 Arm C1 CNS-positive regimen 1
- CNS and CSF involvement: Arm C1 CNS-positive regimen OR Arm C3 regimen (relative efficacy not established) 1
- CNS-negative disease: Arm C1 CNS-negative regimen 1
Evidence Supporting Rituximab Use
The COG ANHL1131 trial demonstrated definitive survival benefit 1:
- 1-year event-free survival: 95% with rituximab vs. 81.5% with chemotherapy alone (statistically significant difference) 1
- 310 patients with high-risk mature B-cell lymphomas randomized 1
For Group C patients, the COG ANHL01P1 study showed 1:
- 3-year EFS/OS: 90% (95% CI, 76%–96%) in 40 evaluable patients with CNS/bone marrow-positive disease 1
- No serious adverse events attributed to rituximab 1
The most recent high-quality evidence (2020 NEJM trial) confirmed 2:
- 3-year event-free survival: 93.9% with rituximab-chemotherapy vs. 82.3% with chemotherapy alone 2
- Hazard ratio for events: 0.32 (95% CI, 0.15-0.66; P=0.00096) 2
- 328 patients randomized; 85.7% had Burkitt's lymphoma 2
FDA-Approved Dosing
Rituximab dosing for pediatric mature B-cell NHL/B-AL (FDA-approved) 3:
- 375 mg/m² per dose 3
- Approved for patients ≥6 months of age with previously untreated, advanced stage, CD20-positive DLBCL, Burkitt lymphoma, Burkitt-like lymphoma, or mature B-cell acute leukemia in combination with chemotherapy 3
Critical Safety Considerations
Common pitfalls to avoid:
- Do not escalate therapy based on FDG-PET alone (low positive predictive value; false-positives include inflammation, necrotic tumor, reactive lymphadenitis) 1
- Biopsy residual masses if less than complete response at end of therapy (majority are necrotic tumor) 1
- Monitor for hypogammaglobulinemia: Approximately twice as many patients in rituximab groups had low IgG levels 1 year after treatment 2
Acute toxicity profile 2:
- Grade 4+ adverse events after prephase: 33.3% with rituximab vs. 24.2% without (P=0.07) 2
- Events mainly febrile neutropenia and infection 2
- Patients <3 years had higher infection incidence 3
Mandatory monitoring 3:
- Administer only as IV infusion by healthcare professional with medical support for severe infusion reactions 3
- Screen for hepatitis B virus (risk of reactivation) 3
Response Assessment Protocol
Critical timepoints for treatment modification 1:
- After COP reduction (Group B patients) 1
- After consolidation 1 (Group B patients) 1
- End of therapy (all patients) 1
Required assessments 1: