Objective: To evaluate the efficacy and safety of brentuximab vedotin (BV) combined with rituximab and attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma (cHL). Methods: A prospective, non-randomized, risk-assigned study. Clinical data (including age, gender, B symptoms, bulky disease, CD30 and Epstein-Barr virus-encoded RNA(EBER) expression, clinical stage, risk stratification, etc.) of 28 intermediate to high-risk cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2022 to May 2024 were collected. Immuno-targeted combined with attenuated chemotherapy was administered based on risk stratification and early treatment response. The patients were followed up until May 1st, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 28 patients, there were 22 males and 6 females, the age was 12 (5,16) years, 16 cases (57%) presented with bulky disease and 10 cases (36%) with B symptoms. The most common pathological type was nodular sclerosis (14 cases, 50%). There were 7 cases of stage Ⅱ, 14 cases of stage Ⅲ and 7 cases of stage Ⅳ according to the Ann Arbor staging system. There were 5 cases in the intermediate-risk group and 23 cases in the high-risk group. EBER was positive in 20 cases (71%) and negative in 6 cases (21%), and CD30 antigen was expressed in tumor cells of all enrolled children. Treatment duration: 5 cases (18%) received 4 courses of treatment, 21 cases (75%) received 6 courses of treatment, and 2 cases (7%) received 8 courses of treatment, 25 cases (89%) achieved complete metabolism response (CMR) through early assessment after 2 courses of chemotherapy. The CMR rates were 100% in intermediate-risk group and 87% in high-risk group, respectively. Four patients (14%) finally received residual field radiotherapy. Toxicities included grade Ⅰ-Ⅱ myelosuppression, early infusion reaction and mild peripheral neuropathy, only one case of grade 3 adverse events was recorded and did not affect sequential treatment. At the end of treatment and 3 months of follow-up, the levels of IgA, IgG and IgM were all decreased compared with the baseline before chemotherapy, and the total B cell count began to be lower than the level before chemotherapy at the early stage of treatment (after 2 courses). The total B cell count monitored during treatment was 50 (0, 101)×106/L and was 12 (0, 25)×106/L at the end of treatment. The follow-up time was 6 (3, 13) months, all 28 children had event-free survival and all achieved complete remission. At 6 and 9 months of follow-up, IgA, IgG, IgM and total B cell counts returned to pre-chemotherapy baseline levels, respectively. Conclusion: BV combined with rituximab attenuated chemotherapy has demonstrated efficacy and a tolerable safety profile in the treatment of cHL in children, and significantly reduce radiation rate.
目的： 探讨维布妥昔单抗（BV）联合利妥昔单抗及减毒化疗治疗儿童经典霍奇金淋巴瘤（cHL）的安全性和临床效果。 方法： 前瞻性、非随机、风险分配的临床研究。收集2022年10月至2024年5月在首都医科大学附属北京儿童医院初诊并完成治疗的28例中、高危cHL患儿的临床资料［包括年龄、性别、B症状、有无巨大瘤灶、肿瘤CD30及Epstein-Barr病毒编码RNA（EBER）表达、临床分期、危险度分层等］，基于危险度分层及早期治疗反应，予免疫靶向联合减毒化疗。随访至2024年5月1日，记录用药期间有无输注反应及用药后的不良反应。 结果： 28例患儿中男22例，女6例；年龄为12（5，16）岁；16例（57%）患儿伴有巨大瘤灶，10例（36%）患儿有B症状；病理分型以结节硬化型（14例，50%）最常见；Ann Arbor分期：Ⅱ期7例，Ⅲ期14例，Ⅳ期7例；危险度分组：中危组5例，高危组23例；EBER阳性20例（71%），阴性6例（21%），所有入组患儿肿瘤细胞均表达 CD30抗原。化学免疫治疗疗程包括4个疗程5例（18%），6个疗程21例（75%），8个疗程2例（7%）；25例（89%）患儿2个疗程化疗后早期评估获得代谢学完全缓解（CMR）；治疗结束后，中危组CMR率为100%；高危组CMR率为87%（20/23）；最终4例（14%）接受残留野放疗。治疗不良反应包括Ⅰ~Ⅱ级骨髓抑制、早期输液反应和轻度周围神经病变，仅1例次患儿发生3级以上的不良事件，均未影响序贯治疗。化疗结束及随访3个月时患儿IgA、IgG、IgM均较化疗前基线水平下降，总B细胞计数治疗早期（2个疗程后）即开始低于化疗前水平，治疗期间监测总B细胞计数为50（0，101）×106/L，治疗结束时为12（0，25）×106/L；随访时间6（3，13）个月，28例患儿均无事件生存，截至末次随访所有患儿持续完全反应。随访至6和9个月时，患儿IgA、IgG、IgM及总B细胞计数分别恢复至化疗前基线水平。 结论： BV联合利妥昔单抗减毒化疗治疗儿童cHL早期结果总体良好，安全性可靠，可显著降低放射治疗率。.