Under the leadership of Professor Zhang Yonghong,who has worked in pediatric hematologic oncology for over 30 years,the Pediatric Lymphoma Department was established in 2017 at Beijing GoBroad Boren Hospital.The team focuses on the treatment of refractory/recurrent pediatric lymphoma,continuously exploring the individual application of new methods such as CAR-T,targeted therapy,and precision treatment based on molecular stratification,seeking new hopes for curing children with lymphoma.In six years,the team has treated over 1000 children with lymphoma,with about 80%being refractory/recurrent cases.

To promote standardized diagnosis and treatment of pediatric lymphoma and improve the overall treatment level of pediatric lymphoma nationwide:

• Professor Zhang Yonghong led the establishment of the China-Net Childhood Lymphoma(CNCL)in 2017,aiming to promote the homogenization and standardization of precise stratification and integrated treatment of pediatric lymphoma in China.

• Initially comprising 11 hospitals,CNCL now includes 42 top-tier hospitals across provinces and cities.

From the treatment of over 2000 patients across various hospitals,different types of therapies have seen a 15%-25%improvement over the original baseline,marking a rapid advancement in the overall therapeutic effect of pediatric lymphoma in China,especially for B-cell lymphoma.

1.Continuous Innovation and Breakthroughs-Targeting the Dilemma of Refractory/Recurrent Pediatric Lymphoma

(1)Exploration of CAR-T Therapy in R/R MBL

Previously,the team innovated by using sequential infusion of CD19/CD22/CD20 CAR-T cells for the treatment of refractory/recurrent Burkitt lymphoma(R/R BL),achieving an 18-month progression-free survival(PFS)rate of 78%.These results have been published in BLOOD and Blood Advances.

Based on the classical treatment protocol for pediatric mature B-cell lymphoma(MBL),the LMB89/96 protocol,the team modified the CNCL-B-NHL-2017 protocol.The CAR-T treatment group showed significantly higher efficacy than the non-CAR-T group(including second-line chemotherapy,targeted drug therapy,or monoclonal antibody),confirming the excellent therapeutic effect of sequential CAR-T treatment for R/R MBL.These results were orally presented at the 17th International Conference on Malignant Lymphoma(ICML 2023).

(2)Prognostic Assessment of CAR-T Treatment in R/R MB-NHL

Continuing exploration,in 2023,the team reported for the first time internationally the occurrence frequency of ARID1A in mature B-cell non-Hodgkin lymphoma(MB-NHL)and its impact on CAR-T treatment.The study found that MB-NHL children carrying ARID1A mutation or concurrent TP53 and ARID1A mutations were insensitive to initial standard chemotherapy and subsequent CAR-T treatment,and it was associated with disease progression or relapse.This suggests that detecting ARID1A and TP53 mutation status has prognostic assessment value and may predict poor treatment outcomes for CAR-T treatment in R/R MB-NHL.These results have been published in Cancer Cell International this year.Supported by these findings,clinical consideration of alternative treatments,such as chemotherapy combined with targeted therapy or transplantation for children with corresponding mutations,is necessary,along with active exploration of new treatment protocols.