程序性死亡受体1抗体在儿童难治或复发霍奇金淋巴瘤中的应用探索

Application of anti-programmed cell death protein 1 antibody in children with refractory or relapsed Hodgkin lymphoma

目的探索程序性死亡受体1(PD-1)抗体用于儿童难治或复发霍奇金淋巴瘤的治疗反应。方法回顾性病例总结,选择2017年12月至2021年6月就诊于首都医科大学附属北京儿童医院的采用PD-1抗体治疗的6例霍奇金淋巴瘤患儿为研究对象。收集患儿的临床资料,评估近期、远期随访疗效及不良反应。疗效评估分为完全反应、部分反应、疾病稳定、疾病进展和无反应。结果6例患儿中男5例、女1例,开始PD-1抗体治疗时年龄为11.6(10.2,13.3)岁。病理类型为混合细胞型3例、结节硬化型2例、结节淋巴细胞为主型1例。分期Ⅳ期4例、Ⅲ期2例;危险度分组均为高危组,5例患儿存在B组症状,所有患儿在开始PD-1治疗前状态均为难治或复发。PD-1抗体首次用药后12周内早期评估3例部分反应、3例疾病稳定,用药16周后晚期评估5例完全反应、1例部分反应,无一例患儿治疗期间出现进展。随访时间27(21,41)个月,5例患儿无事件生存,持续缓解状态,1例患儿停药4周后发热,后确认为转化为介于弥漫大B细胞和经典霍奇金淋巴瘤的B细胞淋巴瘤。6例患儿用药耐受性较好,输注期间未见高热、寒战、皮疹等输注反应,无一例患儿因不良反应延迟、减量或停药。2例在治疗过程中出现反应性皮肤血管增生,不伴疼痛或痒感,未给予特殊处理,停药后自行恢复。结论PD-1抗体用于难治或复发霍奇金淋巴瘤患儿治疗应答较好且不良反应可耐受。

Objective To explore the efficacy of anti-programmed cell death protein 1(PD-1)antibody for children with refractory or relapsed Hodgkin lymphoma.Methods Clinical data including short-term efficacy,long-term efficacy and adverse reaction of Hodgkin lymphoma children treated with anti-PD-1 antibody in Beijing Children′s Hospital,Capital Medical University from December 2017 to June 2021 were analyzed retrospectively.Efficacy was evaluated as complete remission(CR),partial remission(PR),stable disease(SD),progressed disease(PD)and no response.Results A total of 6 cases were included,including 5 males and 1 female.The age at the start of anti-PD-1 antibody treatment was 11.6(10.2,13.3)years,including 3 cases of mixed cellularity type,2 cases of nodular sclerosis type,and 1 case of nodular lymphocyte-predominant type.There were 4 cases of stageⅣand 2 cases of stageⅢ.All cases were assigned to the high-risk group,and 5 cases had B symptoms,all cases were refractory or relapsed Hodgkin lymphoma before the start of anti-PD-1 antibody treatment.Early evaluation showed that within 12 weeks of the treatment,3 cases achieved PR and 3 cases achieved SD,while late evaluation showed that after 16 weeks of the treatment,5 cases achieved CR and 1 case achieved PR.None of the children progressed during treatment.The follow-up time was 27(21,41)months.Among all cases,5 cases had event-free survival and sustained remission,1 case had fever about 4 weeks after the drug withdrawal,finally he was confirmed to be transformed to B cell lymphoma between diffuse B cells and classic Hodgkin lymphoma.All the patients were well tolerated with anti-PD-1 antibody therapy.No adverse reactions such as high fever,chills,rash,etc.were observed during infusion.None of the patients were delayed,dose reduction or withdrawal due to adverse reactions.Two cases had reactive skin vascular hyperplasia during the treatment,without pain or itching,and they recovered on their own after stopping anti-PD-1 antibody therapy without other special treatment.Conclusion Anti-PD-1 monoclonal antibody for children with refractory or relapsed Hodgkin lymphoma have good efficacy and tolerable side effects.