Prognostic for CNS3 Control in Children with Lymphoblastic Lymphoma Treated with Chemotherapy without Cranial Irradiation:a Multicenter, China Net-Childhood Lymphoma-NHL-2017-Lbl Program
Authors: Wang Lingzhen , Jin Ling , Zhang Yonghong , Sun Lirong , Li Fu , Zheng Mincui , Dai Yunpeng , Zhang Leping , Liu Ansheng , Wang Jian , Yuan Xiaojun , Liu Rong , Zhu Xiaofan 
Published: December 2024

PURPOSE:To analyze the prognosis of children with central nervous system 3 lymphoblastic lymphoma (LBL) treated with increased four courses of high-dose methotrexate and the times of intrathecal injection, without prophylactic cranial irradiation.
PATIENTS AND METHODS: From April 2017 to September 2023, 883 Chinese children with LBL were registered in the China Net-Childhood Lymphoma-NHL-2017-LBL program in the multicenter hospitals or medical centers of China and were treated with risk-adjusted therapy. Patients with CNS3 were given increased 2 times intrathecal injection in the induction phase and 2 times intrathecal injection in the reintensification phase. Their clinical outcome were evaluated. This Time to event analyses were conducted to evaluate event-free survival and to identify risk factors for treatment failure.
RESULITS: CNS involvement was diagnosed in 113(12.7%) of 883 patients. 55 patients were CNS positive by flow cytometry and conventional cytology (CC) of cerebrospinal fluid (CSF), 13 patients had intracerebral mass(IM), 15 patients werer cranial nerve palsy, 11 were epidural tumors with bone lesions, and 2 paitents were epidural tumors with CSF+. The 5-year event-free survival rate was 75.7% (95% confidence interval [CI], 66.3-86.4%), and the overall survival rate was 85.0% (95% CI, 77.0-93.8%). The cumulative risk of any central nervous system relapse is 3.17% (95% CI, 0 - 6.64%). The event-free survival rate for patients older than ten years was significantly lower than for those ten years old or younger (57.4%; 95% CI, 41.0-80.4% vs. 85.8%; 95% CI, 76.8-95.9%; P &lt; 0.005). Male patients also had a significantly lower event-free survival rate compared to female patients (69.9%; 95% CI, 58.4-83.7% vs. 86.7%; 95% CI, 72.5-100%; P &lt; 0.05). The presence of a large tumor significantly decreased the 5-year event-free survival rate in pediatric patients. Among CNS3 pediatric patients treated with regimen for non-Hodgkin lymphoma, there were no significant differences in the 5-year event-free survival and overall survival rates between high-risk and intermediate-risk groups, as well as between B-cell LBL (B-LBL) and T-cell LBL(T-LBL). Hazard Ratios (HR) showed higher risk for males and patients older than ten years, but failed to retain independent significance in multivariate analysis. From the literature, the overall survival and event-free survival associated with the addition of cranial irradiation ranged from 70-90%.
CONCLUSION: Among 113 pediatric patients with CNS3, the application of chemotherapy and increased times of intrathecal injection as an alternative to cranial irradiation in childhood lymphoblastic leukemia resulted in comparable overall survival and event-free survival rates, without increasing the risk of central nervous system relapse. This suggests that prophylactic cranial irradiation can be safely omitted.