中国儿童淋巴瘤协作组成熟B细胞淋巴瘤2017方案治疗儿童高级别B细胞淋巴瘤中期疗效分析

Interim efficacy of a multicenter cohort study for China Net Childhood Lymphoma mature B-cell lymphoma 2017 regimen in the treatment of pediatric High-grade-B cell lymphoma

目的分析中国儿童淋巴瘤协作组成熟B细胞淋巴瘤2017(CNCL-B-NHL-2017)方案治疗儿童高级别B细胞淋巴瘤(HGBL)的中期疗效。方法回顾性收集中国儿童淋巴瘤协作组(CNCL)16家医院2017年5月至2021年4月收治的年龄≤18岁的HGBL患儿的临床及病理资料,根据2016版世界卫生组织(WHO)造血和淋巴组织肿瘤分类,分为高级别B细胞淋巴瘤伴双打击/三打击(HGBL-DH/TH)组及高级别B细胞淋巴瘤-非特指型(HGBL-NOS)组。2组患儿均根据CNCL-B-NHL-2017方案,并按照危险度分层化疗,随访截止日期为2023年12月31日。所有患儿均行染色体荧光原位杂交(FISH)检查,以明确基因MYC、BCL-2及BCL-6重排情况。分析患儿发病时临床、病理特点,比较不同临床分期、危险度分组患儿的治疗效果,采用Kaplan-Meier法绘制生存曲线,log-rank检验比较组间累积生存率的差异,多因素Cox回归模型分析预后的影响因素。结果共纳入62例患儿,发病年龄[M(Q_(1),Q_(3))]为7(4,11)岁,男48例、女14例。临床分期Ⅱ、Ⅲ、Ⅳ期分别有11例(17.7%)、33例(53.2%)、18例(29.1%)。FISH检测结果显示4例(6.5%)为HGBL-DH;3例(4.8%)为HGBL-TH;余55例(88.7%)均为HGBL-NOS,其中18例伴MYC基因重排。HGBL-DH/TH组有7例,HGBL-NOS组有55例。B1方案13例(20.9%),B2方案3例(4.8%),C1方案37例(59.6%)和C2方案9例(14.7%)。48例(77.4%)同时联合利妥昔单抗靶向治疗。5例(8.0%)治疗中进展。随访时间[M(Q_(1),Q_(3))]为43.5(36.1,53.7)个月,所有患儿的完全缓解率为91.9%(57/62)。3年总生存率和无事件生存率分别为93.5%和91.9%。HGBL-NOS组患儿的3年总生存率高于HGBL-DH/TH组(96.3%比71.4%,P=0.011)。HGBL-NOS组3年无事件生存率高于HGBL-DH/TH组(94.5%比71.4%,P=0.037)。在HGBL-NOS亚组中,伴有MYC基因重排的患儿总生存率较低(100%比88.9%,P=0.039)。多因素Cox回归分析显示,中枢神经系统侵犯(HR=6.05,95%CI:1.96~38.13,P=0.046)是总生存率的危险因素。结论应用CNCL-B-NHL-2017方案治疗儿童HGBL疗效显著,预后良好。

Objective To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017(CNCL-B-NHL-2017)regimen in treating children with high-grade B-cell lymphoma(HGBL).Methods Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children′s Lymphoma Collaborative Group(CNCL)from May 2017 to April 2021 were collected retrospectively.They were divided in to high-grade B-cell lymphoma with double hit/triple hit(HGBL-DH/TH)group and high-grade B-cell lymphoma non-specified(HGBL-NOS)group,according to the 2016 version of the World Health Organization(WHO)Hematopoietic and Lymphoid Tissues Cancer Classification.Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme.The deadline for follow-up was December 31,2023.All the patients were examined by chromosome fluorescence in situ hybridization(FISH),and the rearrangement of genes MYC,BCL-2 and BCL-6 was confirmed.The clinical and pathological characteristics of patients at disease onset were analyzed,and the therapeutic effects of patients in different clinical stages and risk groups were compared.Survival analysis was drawn by Kaplan Meier method,the log-rank test was used to compare the differences in the cumulative survival rate between different groups,and multivariate Cox regression model was used to identify the prognostic factors.Results A total of 62 patients were included,with an onset age[M(Q_(1),Q_(3))]of 7(4,11)years,including 48 males and 14 females.There were 11(17.7%)patients in stageⅡ,33(53.2%)patients in stageⅢand 18(29.1%)patients in stageⅣ.FISH testing showed that 4 cases(6.5%)were HGBL-DH and 3(4.8%)were HGBL-TH.The remaining 55 cases(88.7%)were HGBL-NOS,with 18 cases accompanied by MYC rearrangement.There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group.Thirteen cases(20.9%)were treated with the B1 regimen,3 cases(4.8%)with B2 regimen,37 cases(59.6%)with C1 regimen,and 9 cases(14.7%)with the C2 regimen.Forty-eight cases(77.4%)received rituximab therapy at the same time.Five cases(8.0%)progressed during treatment.The follow-up time[M(Q_(1),Q_(3))]was 43.5(36.1,53.7)months.The complete remission rate was 91.9%(57/62).The 3 year overall survival rate was 93.5%and event-free survival(EFS)rate was 91.9%.The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group(96.3%vs 71.4%,P=0.011).The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group(94.5%vs 71.4%,P=0.037).In the HGBL-NOS subgroup,the overall survival rate of children with MYC rearrangement was lower(100%vs 88.9%,P=0.039).Multivariate Cox regression analysis showed that central invasion(HR=6.05,95%CI:1.96-38.13,P=0.046)was a risk factor for overall survival.Conclusion CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL,with a good prognosis.