儿童霍奇金淋巴瘤的临床特点及预后分析

Analysis of clinical features and prognosis in children with Hodgkin lymphoma

目的总结儿童霍奇金淋巴瘤(HL)的临床特点及预后情况,分析儿童HL复发/进展的相关危险因素。方法选择2008年1月1日至2019年12月31日四川大学华西第二医院收治的67例HL患儿为研究对象。患儿的中位发病年龄为9.1岁(6.0,11.6岁),男、女性患儿分别为52、15例。采用回顾性研究方法,收集患儿性别、年龄、肿瘤浸润部位、B组症状、巨大肿块、病理学类型、Ann Arbor分期、危险度分组、化疗方案等临床资料,采用χ2检验对不同临床特征患者的构成比进行比较。采用Kaplan-Meier法绘制总体生存(OS)和无事件生存(EFS)曲线,采用log-rank检验进行不同临床特征患儿生存率的比较,采用Cox比例风险回归模型对HL患儿OS和EFS的影响因素进行多因素分析。采用多因素非条件logistic回归分析对儿童HL复发/进展的影响因素进行多因素分析。本研究遵循的程序符合《世界医学协会赫尔辛基宣言》要求。结果①本组67例HL患儿中,以男性(77.6%,52/67),年龄>7岁(70.1%,47/67),EB病毒编码的RNA(EBER)阳性(68.7%.46/67)为主,病理学类型主要为混合细胞型(54例,80.6%),主要浸润部位为颈部(80.6%,54/67)。②第2个疗程结束时,患儿完全缓解(CR)率为58.2%(39/67),部分缓解(PR)率为35.8%(24/67),疾病稳定(SD)率为4.5%(3/67),疾病进展(PD)率为1.5%(1/67),有效率为94.0%(63/67)。化疗结束时,CR患儿为64例(95.5%),PR为1例(1.5%),死亡为2例(3.0%)。③中位随访时间为55.6个月(26.8,99.4个月),5年OS和EFS率分别为84.6%和74.4%。单因素及多因素分析结果显示,伴B组症状、2个疗程内未达CR是影响HL患儿OS率(OR=11.281,95%CI:1.302~97.764,P=0.028;OR=14.091,95%CI:1.569~126.573,P=0.018)和EFS率(OR=6.470,95%CI:1.604~26.104,P=0.009;OR=6.834,95%CI:1.810~25.805,P=0.005)的独立危险因素。④复发/进展患儿中,伴B组症状和2个疗程未达CR患儿比例分别为78.6%(11/14)和100.0%(14/14),显著高于无复发/进展患儿的24.5%(13/53)和26.4%(14/53),并且差异均有统计学意义(χ^(2)=14.070、24.651,P<0.001、0.001)。多因素非条件logistic回归分析结果显示,伴B组症状、2个疗程内未达CR是HL患儿发生复发/进展的独立危险因素(OR=6.233,95%CI:3.008~13.488,P=0.031;OR=9.403,95%CI:2.020~22.832,P<0.001)。结论儿童HL高发于学龄期,以男性患儿多见,病理学类型以混合细胞型为主,常伴有EBV感染。早期治疗反应和伴B组症状可以预测HL患儿预后,并且提示高复发/进展风险。

Objective To summarize the clinical characteristics and prognosis of Hodgkin lymphoma(HL)in children,and analyze the risk factors affecting recurrence/progression in children with HL.Methods From January 1st,2008 to December 31st,2019,a total of 67 HL children in West China Second Hospital of Sichuan University were selected as research subjects.The median onset age of HL children was 9.1 years old(6.0,11.6 years old),and the male and female children were 52 and 15,respectively.Retrospective analysis was used to collect their clinical data,such as gender,age,tumor invasion site,with group B symptoms,giant mass,pathological type,Ann Arbor stage,risk group,chemotherapy regimen,etc.The constituent ratios of patients with different clinical characteristics were compared with the chi-square test.The Kaplan-Meire method was used to draw curves of overall survival(OS)and event-free survival(EFS).The log-rank test was used for survival rate comparisons of children with different clinical characteristics.Multivariate analysis of factors influencing OS and EFS rate of HL children were performed by Cox proportional hazards model.Multivariate unconditional logistic regression was used to analyze the influencing factors on recurrence/progression in HL children.This study was conducted in accordance with the requirements of the World Medical Association Declaration of Helsinki revised in 2013.Results①Among the 67 HL children,most of them were males(77.6%,52/67),aged>7 years(70.1%,47/67),positive for Epstein-Barr virus(EBV)encoded RNA(EBER)(68.7%,46/67).The pathological type was predominantly mixed cell types(80.6%,54/67),the main tumor invasion site was neck(80.6%,54/67).②At the end of the second course of chemotherapy,the complete response(CR)rate was 58.2%(39/67),the partial response(PR)rate was 35.8%(24/67),the disease stabilization(SD)rate was 4.5%(3/67),the disease progression(PD)rate was 1.5%(1/67),and the effective rate was 94.0%(63/67).At the end of chemotherapy,64 children(95.5%)achieved CR,1 child(1.5%)achieved PR,and 2 children(3.0%)died.③The median follow-up time was 55.6 months(26.8,99.4 months).The 5-year OS and EFS rate were 84.6% and 74.4%,respectively.With group B symptoms and incomplete response after initial 2 courses of chemotherapy were independent risk factors influencing OS rate(OR=11.281,95%CI:1.302-97.764,P=0.028;OR=14.091,95%CI:1.569-126.573,P=0.018)and EFS rate(OR=6.470,95%CI:1.604-26.104,P=0.009;OR=6.834,95%CI:1.810-25.805,P=0.005)in HL children.④The proportion of relapse/progression HL children with group B symptoms and incomplete response after initial 2 courses of chemotherapy were 78.6%(11/14)and 100.0%(14/14),respectively,which were significantly higher than those of non-relapsed/progression patients[24.5%(13/53)and 26.4%(14/53)],and the differences were statistically significant(χ^(2)=14.070,24.651;P<0.001,0.001).Multivariate unconditional logistic regression analysis showed that with group B symptoms and incomplete response after initial 2 courses of chemotherapy were independent risk factors of relapse/progression in children with HL(OR=6.233,95%CI:3.008-13.488,P=0.031;OR=9.403,95%CI:2.020-22.832,P<0.001).Conclusions HL in children is mostly observed in school-aged children and predominantly occurs in male.Children with HL are often accompanied by EBV infection.The pathological type is mainly mixed cell type.Early response to treatment and with group B symptoms can predict the prognosis of children with HL as well as indicate high risk of recurrence/progression.