From January 16–18, 2026, the CSCO Leukemia, Lymphoma, and Myeloma Expert Committee Working Meeting and the 2026 CSCO Hematologic Oncology Conference were held in Haikou. Leading experts and scholars from across China presented advances in both basic and clinical research in leukemia, lymphoma, and myeloma, addressing key challenges in real-world practice and exploring new therapeutic directions.During the meeting, Oncology Frontier – Hematology Frontier invited Professor Xiuli Ju from Qilu Hospital of Shandong University to share the latest progress in the diagnosis and management of pediatric mature B-cell lymphoma.
Overview: Current Landscape of Pediatric Mature B-Cell NHL
Pediatric mature B-cell non-Hodgkin lymphoma (B-NHL) is the most common subtype of childhood and adolescent NHL, accounting for approximately 50–60% of cases. Major subtypes include Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and high-grade B-cell lymphoma (HGBL).
Thanks to intensive short-course combination chemotherapy and the widespread use of rituximab, overall survival rates have improved markedly over the past three decades, reaching ~90%. However, 10–15% of patients develop refractory or relapsed disease, with poor prognosis.
Current research priorities are shifting toward:
- Molecular pathology–based precision diagnosis
- Optimized risk stratification
- Development of novel immune and targeted therapies
01. Precision Diagnosis and the Central Role of Molecular Pathology
While histopathology remains the gold standard, modern diagnosis increasingly integrates immunophenotyping and molecular genetics.
According to the WHO 5th Edition classification, high-grade B-cell lymphoma is now further refined into molecularly defined entities, such as:
- IRF4-rearranged lymphoma
- 11q-aberrant lymphoma
- MYC/BCL2-rearranged lymphoma
These distinctions carry important prognostic and therapeutic implications.
Molecular Profiling and Prognostic Stratification
- The traditional cutoff distinguishing B-ALL vs. B-NHL based on ≥25% marrow blasts has limitations
- Integration of fusion genes and driver mutations enables more accurate classification
Notably, Chinese pediatric patients exhibit distinct mutational patterns, with lower frequencies of ID3 and CCND3 mutations compared with Western cohorts, underscoring the need for population-specific genomic research.
High-Risk Molecular Markers
Mutations in TP53 and ARID1A, particularly TP53/ARID1A co-mutations, are strongly associated with:
- Chemotherapy resistance
- Inferior CAR-T outcomes
- Poor overall prognosis
These markers provide critical tools for early high-risk identification and treatment intensification.
02. Refined Staging and Risk Stratification
Pediatric NHL staging follows the International Pediatric NHL Staging System, which differs from the adult Ann Arbor system. For example, primary thoracic, abdominal, or paraspinal disease is classified as Stage III.
The updated staging system provides more precise definitions of bone marrow and CNS involvement, incorporating morphologic, immunologic, and genetic data.
This refined staging approach improves:
- Tumor burden assessment
- Biologic risk characterization
- CNS prophylaxis planning
- Personalized treatment intensity
Key Adverse Prognostic Factors
Poor-risk features include:
- Short disease course
- Bulky tumors
- CNS involvement
- Stage IV or leukemic presentation
- Markedly elevated LDH
- High-risk genetic alterations (e.g., TP53)
- Poor early treatment response
Multidimensional risk stratification is essential for precision therapy.
03. Optimization of Conventional Chemotherapy and Ongoing Challenges
Risk-adapted intensive chemotherapy combined with rituximab remains the standard first-line treatment.
Large multicenter studies—including CCCG-BNHL-2015 and CNCL-B-NHL-2017—have demonstrated that adding rituximab significantly improves event-free survival (EFS), with long-term EFS approaching 90%.
Persistent High-Risk Subgroups
Despite progress, outcomes remain suboptimal in:
- Stage IV patients with both bone marrow and CNS involvement
- Stage III/IV patients with high LDH and incomplete mid-treatment response
04. Strategy Shift: “De-escalation with Efficacy” and “Precision Intensification”
Reducing Toxicity While Preserving Efficacy
International studies show that anti-CD20 antibodies allow reduced chemotherapy intensity in selected risk groups without compromising outcomes.
Precision Intensification for Ultra-High-Risk Patients
The CCCG-BNHL-2025 trial introduces key refinements:
- Expanding the high-risk (R4) group to include Stage III cases with LDH 2–4× ULN
- Increasing rituximab dosing to 6 total cycles, with intensified early administration
- Adding additional chemotherapy cycles for extremely high-risk patients
Goal: Improve 3-year EFS from ~70% to ~90%, representing a cutting-edge effort to overcome outcome plateaus through targeted intensification.
05. Emerging Immunotherapies and Targeted Innovations in R/R Disease
1. Next-Generation Anti-CD20 Antibodies
Obinutuzumab (Type II anti-CD20) enhances ADCC through Fc glycoengineering. Early studies combining obinutuzumab + ICE in pediatric R/R B-NHL show favorable safety and efficacy, serving as a bridge to transplantation in some cases.
2. CAR-T Cell Therapy
CD19-directed CAR-T therapy achieves ORR of 60–90% in pediatric R/R B-NHL.
To address antigen escape and durability, strategies under investigation include:
- Dual-target CAR-T
- Sequential CAR-T infusions
Chinese studies demonstrate high response rates in refractory Burkitt lymphoma, including patients with CNS involvement and bulky disease, with manageable toxicity.
3. CAR-NK Cell Therapy
iPSC-derived CAR-NK cells show:
- Strong antitumor activity
- Low CRS and neurotoxicity
- Promising efficacy even after CAR-T failure
4. Bispecific T-Cell Engagers (BiTEs)
CD20×CD3 BiTE molecules redirect T cells to tumor cells. Early trials show durable complete responses in some R/R pediatric patients.
5. Small-Molecule Targeted Therapies and Combination Strategies
- Ibrutinib (BTK inhibitor) did not improve survival in pediatric Phase III trials
- Tazemetostat (EZH2 inhibitor) shows activity in mutation-positive patients
- Venetoclax (BCL-2 inhibitor) is under pediatric evaluation
- Combination approaches are prioritized, including: CAR-T + PD-1 inhibitors CAR-T + BTK inhibitors or lenalidomide Targeted therapy as bridging or consolidation
06. Summary and Future Directions
Pediatric mature B-cell lymphoma has entered the era of precision oncology and immunotherapy.
Key Strategic Priorities
- Strengthen China-specific pediatric genomic research
- Build more accurate prognostic models
- Integrate novel targeted agents early in frontline high-risk therapy
- Expand CAR-T, BiTE, and CAR-NK use in R/R disease
- Optimize combination regimens to enhance depth and durability of response
Remaining Challenges
- Drug accessibility
- Cost burden
- Long-term toxicity management
- Need for deeper multidisciplinary collaboration
The ultimate goal is to increase cure rates while preserving long-term quality of life, ensuring that innovative therapies benefit more children worldwide.
