中国儿童霍奇金淋巴瘤方案(HL-2013)多中心临床诊治报告

A multicenter study on childhood Hodgkin lymphoma treated with HL-2013 regimen in China

目的探讨中国儿童霍奇金淋巴瘤方案(HL-2013)治疗儿童霍奇金淋巴瘤(HL)的效果,并分析影响HL预后的因素。方法回顾性分析8个儿童血液肿瘤诊疗中心在2011年8月至2021年4月收治的年龄≤18岁的145例初治HL患儿的临床资料,所有患儿均经组织病理形态及免疫组织化学确诊为HL,予以HL-2013方案治疗。总结患儿临床特征及治疗结果,根据临床因素对患儿进行分组,采用Kaplan-Meier法进行生存分析,组间生存率的比较采用Log-rank检验。结果145例患儿中男115例,女30例;诊断年龄7.9(5.8,10.6)岁;疾病原发部位以颈部淋巴结肿大(114例,78.6%)最常见;57例(39.3%)患儿伴有巨大肿块;病理分型以混合细胞型(93例,64.1%)最常见;Ann Arbor分期:Ⅰ期9例,Ⅱ期62例,Ⅲ期45例,Ⅳ期29例;危险度分组:低危组14例,中危组76例,高危组55例。68例(46.9%)患儿2个疗程化疗后获完全缓解(早期完全缓解);一线治疗结束后完全缓解率达93.8%(136/145);22例(15.2%)患儿出现疾病复发或进展;随访结局:存活125例,死亡6例,失访14例。123例患儿处于持续缓解状态,随访时间55(40,76)个月。145例患儿5年总生存率(OS)为(95.3±1.9)%,5年无事件生存率(EFS)为(84.2±3.0)%。Ⅲ~Ⅳ期患儿的5年OS及EFS均低于Ⅰ~Ⅱ期患儿,差异均有统计学意义(χ^(2)=6.28、7.58,均P<0.05);高危组的5年OS及EFS均低于低、中危组,差异均有统计学意义(χ^(2)=10.93、7.79,均P<0.05)。早期完全缓解组(68例)和早期未完全缓解组(77例)的5年OS分别为100.0%和(90.9±3.6)%,5年EFS分别为(93.8±3.0)%和(75.8±5.0)%,组间差异均有统计学意义(χ^(2)=5.77、8.78,均P<0.05)。结论HL-2013方案治疗儿童HL总体效果良好,但高危组及早期未获得完全缓解的患儿容易出现疾病复发或进展,Ⅲ~Ⅳ期、早期未完全缓解是预后不良因素。

Objective To evaluate the efficacy of the Hodgkin lymphoma(HL)-2013 regimen in the treatment of children with HL,and to investigate the prognostic factors of childhood HL.Methods Clinical data of 145 children(aged≤18 years)with newly diagnosed HL,treated with HL-2013 regimen in 8 tertiary referral centers for childhood cancer from August 2011 to April 2021 were analyzed retrospectively.All the diagnosis were confirmed by histopathological morphology and immunohistochemical examination.The clinical characteristics and treatment outcomes were summarized,and the patients were divided into different groups according to clinical characteristics.Kaplan-Meier method was used for survival analysis,and the comparison of survival rates between groups was performed with Log-rank test.Results Of the 145 cases,there were 115 males and 30 females,the age at diagnosis was 7.9(5.8,10.6)years.Cervical lymph node enlargement(114 cases,78.6%)was the common symptom of the disease,and 57 patients(39.3%)were accompanied by large masses.The most common pathological classification was mixed cell type(93 cases,64.1%).According to the Ann Arbor staging system,there were 9 cases of stageⅠ,62 cases of stageⅡ,45 cases of stageⅢ,29 cases of stageⅣ.According to the risk stratification:there were 14 cases of low-risk group,76 cases of medium-risk group and 55 cases of high-risk group.Of all patients,68 cases(46.9%)achieved an early complete remission(CR)after 2 courses of chemotherapy,and the CR rate was 93.8%(136/145)after first-line treatment.Disease recurrence or progression occurred in 22 cases(15.2%).Of all patients,125 cases survived,6 cases died and 14 cases were lost to follow-up.Among the survived cases,123 cases were continuously at CR state,and the follow-up time was 55(40,76)months.The 5-year overall survival(OS)and event free survival(EFS)rates were(95.3±1.9)%and(84.2±3.0)%for the entire group,respectively.5-year OS and EFS rates for patients with stageⅢ-Ⅳwere both lower than those for patients with stageⅠ-Ⅱ(χ^(2)=6.28 and 7.58,both P<0.05),the 5-year OS and EFS rates for patients in high-risk group were both lower than those for patients in low-risk and medium-risk group(χ^(2)=10.93,7.79,both P<0.05).The 5-year OS rates for the patient with early CR and without early CR were 100.0%and(90.9±3.6)%(χ^(2)=5.77,P=0.016).EFS rates for the patient with early CR(68 cases)and without early CR(77 cases)were(93.8±3.0)%and(75.8±5.0)%(χ^(2)=8.78,P=0.003).Conclusions HL-2013 regimen is significantly effective in the treatment of pediatric HL.However,the patients in high-risk group and those without early CR are prone to disease recurrence or progression.StageⅢ-Ⅳand without early CR were associated with worse prognosis.