Wang Songmi, Liu Aiguo, Wang Na, Wang Yaqin, Zhang Ai, Wang Li, Yu Wen, Li Chunrui, Zhang Yicheng, Hu Qun
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Pediatr. 2023 Jan 16;10:1100404. doi: 10.3389/fped.2022.1100404. eCollection 2022.
The 5-year event-free survival rate for childhood acute lymphoblastic leukemia (ALL) has increased to more than 85%. However, the 5-year overall survival rate in children with relapsed/refractory ALL did not exceed 50%. In the past decade, immunotherapies (such as blinatumomab and chimeric antigen receptor T-cell therapy) were approved for relapsed/refractory B-ALL, transforming the treatment environment for children with relapsed/refractory ALL.
This study aimed to explore how immunotherapy can be incorporated into salvage regimens for pediatric patients with relapsed/refractory ALL by retrospectively analyzing the diagnosis and treatment process of seven children with relapsed/refractory leukemia and observing the side effects of the two strategies and long-term survival.
The clinical features and treatment responses of patients aged <14 years with relapsed/refractory leukemia who received immunotherapy (including Chimeric Antigen Receptor T cell treatment and blinatumomab) at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology between February 2014 and April 2022 were retrospectively analyzed.
Seven children underwent immunotherapy. Five patients received immunotherapy and sequential allogeneic hematopoietic stem cell transplantation (HSCT), whereas the other two received only immunotherapy. Five patients achieved complete remission (71.4%). None of the patients had severe cytokine release syndrome. However, one developed grade 3 immune effector cell-associated neurotoxicity syndrome with prior leukoencephalopathy. The median follow-up period was 541 days (range, 186-3,180 days). No deaths were related to treatment. Three patients relapsed, two had CD19-negative recurrences, and the third showed CD19 antigen reduction. One patient died after disease progression, whereas the other died of HSCT-related complications. One patient abandoned the treatment after relapse and was lost to follow-up.
Blinatumomab and CAR T-cell therapy showed excellent remission rates and manageable toxicity in pediatric patients with relapsed/refractory leukemia. However, the duration of the remission was limited. Therefore, further prospective randomized clinical studies should be conducted to improve the long-term efficacy of immunotherapy.
儿童急性淋巴细胞白血病（ALL）的5年无事件生存率已提高到85%以上。然而，复发/难治性ALL患儿的5年总生存率不超过50%。在过去十年中，免疫疗法（如博纳吐单抗和嵌合抗原受体T细胞疗法）被批准用于复发/难治性B-ALL，改变了复发/难治性ALL患儿的治疗环境。
本研究旨在通过回顾性分析7例复发/难治性白血病患儿的诊断和治疗过程，观察两种治疗策略的副作用和长期生存情况，探讨免疫疗法如何纳入小儿复发/难治性ALL的挽救治疗方案。
回顾性分析2014年2月至2022年4月在华中科技大学同济医学院附属同济医院接受免疫疗法（包括嵌合抗原受体T细胞治疗和博纳吐单抗）的14岁以下复发/难治性白血病患者的临床特征和治疗反应。
7例儿童接受了免疫治疗。5例患者接受免疫治疗并序贯异基因造血干细胞移植（HSCT），另外2例仅接受免疫治疗。5例患者达到完全缓解（71.4%）。所有患者均未发生严重的细胞因子释放综合征。然而，1例患者发生3级免疫效应细胞相关神经毒性综合征，既往有白质脑病。中位随访期为541天（范围186 - 3180天）。无治疗相关死亡。3例患者复发，2例为CD19阴性复发，第3例表现为CD19抗原减少。1例患者在疾病进展后死亡，另1例死于HSCT相关并发症。1例患者复发后放弃治疗并失访。
博纳吐单抗和CAR T细胞疗法在小儿复发/难治性白血病患者中显示出优异的缓解率和可控制的毒性。然而，缓解期有限。因此，应开展进一步的前瞻性随机临床研究，以提高免疫疗法的长期疗效。
