北京儿童医院-2009-淋巴母细胞淋巴瘤方案治疗儿童青少年T淋巴母细胞淋巴瘤远期疗效及预后分析

Long-term efficacy and prognostic factors of Beijing Children′s Hospital-2009-lymphoblastic lymphoma in the treatment of T-lymphoblastic lymphoma in children and adolescents

目的分析北京儿童医院-2009-淋巴母细胞淋巴瘤(BCH-2009-LBL)方案治疗儿童青少年T淋巴母细胞淋巴瘤(T-LBL)的远期疗效,探讨预后相关因素。方法回顾性纳入2009年1月至2017年4月首都医科大学附属北京儿童医院收治的T-LBL患儿,根据临床分期、预后相关基因和治疗反应,将患儿分为低、中、高危三组,均按照BCH-2009-LBL方案分层治疗,随访截至2023年12月31日。比较各组患儿的临床特征及治疗疗效。采用Kaplan-Meier法绘制生存曲线,log-rank检验比较组间生存率的差异。采用多因素Cox回归模型分析预后的影响因素。结果共纳入146例患儿,发病年龄[M(Q_(1),Q_(3))]为8.0(1.5,14.0)岁;男107例(73.3%),女39例(26.7%)。临床分期:Ⅰ、Ⅱ期各1例(各0.7%);Ⅲ期41例(28.1%);Ⅳ期103例(70.5%)。低、中、高危组分别有1例(0.7%)、93例(63.7%)、52例(35.6%)。随访时间121(80,180)个月,5、10年无事件生存率分别为76.4%、75.0%。低、中、高危组5年无事件生存率分别为100.0%、81.3%、67.3%,中危组和高危组激素预治疗第8天、诱导结束时缓解情况差异均有统计学意义(均P<0.05)。复发/进展29例(复发率19.9%),复发时间15(3,74)个月,其中26例死亡,3例存活;感染相关死亡6例(4.1%)。激素预治疗第8天治疗无效或进展(HR=10.089,95%CI:1.266~80.387,P=0.029)、诱导结束时(中期评估)未达完全缓解(HR=7.638,95%CI:2.411~24.199,P=0.001)为中危组无事件生存率的危险因素;以上指标对高危组无事件生存率的影响均无统计学意义(均P>0.05)。结论儿童T-LBL采用BCH-2009-LBL方案化疗取得良好疗效;激素预治疗第8天治疗无效或进展、诱导结束时(中期评估)未达完全缓解是无事件生存率的危险因素。

Objective To summarize the long-term efficacy of Beijing Children′s Hospital-2009-lymphoblastic lymphoma(BCH-2009-LBL)in the treatment of T-lymphoblastic lymphoma(T-LBL)in children and adolescents and to explore the prognostic factors.Methods T-LBL children admitted to Beijing Children′s Hospital Affiliated to Capital Medical University from January 2009 to April 2017 were retrospectively included.According to clinical stage,prognostic genes and treatment response,the children were divided into low,intermediate and high risk groups,and stratified treatment was performed according to the BCH-2009-LBL protocol,with follow-up until December 31,2023.The clinical characteristics and therapeutic effect of each group were compared.Survival curve was drawn by Kaplan-Meier method,and the difference in survival rate between groups was compared by log-rank test.Multivariate Cox regression model was used to analyze the prognostic factors.Results A total of 146 patients were included,the age of disease onset[M(Q_(1),Q_(3))]was 8.0(1.5,14.0)years old.There were 107(73.3%)males and 39(26.7%)females.Clinical staging:1 case in stageⅠand 1 case in stageⅡ(0.7%each),41 cases(28.1%)cases in stageⅢand 103 cases(70.5%)in stageⅣ.There were 1 case(0.7%),93 cases(63.7%),and 52 cases(35.6%)in the low,intermediate,and high-risk groups,respectively.The follow-up time was 121(80,180)months,and the 5-year and 10-year event-free survival(EFS)rates were 76.4%and 75.0%,respectively.The 5-year EFS rates of low,intermediate and high risk groups were 100.0%,81.3%and 67.3%,respectively.There was significant difference in remission between the middle-risk group and the high-risk group on the 8th day of hormone pretreatment and at the end of induction(both P<0.05).Recurrence/progression occurred in 29 cases(recurrence rate 19.9%),and the recurrence time was 15(3,74)months,in which 26 cases died and only 3 cases survived.Infection-related death occurred in 6 cases(4.1%).The failure or progression of hormone pretreatment at d8(HR=10.089,95%CI:1.266-80.387,P=0.029)and the failure to achieve complete remission at the end of induction(mid-term evaluation)(HR=7.638,95%CI:2.411-24.199,P=0.001)were the risk factors for EFS rate of intermediate risk group.The above indexes had no statistical significance on EFS rate in high-risk groups(all P>0.05).Conclusions BCH-2009-LBL regimen shows good efficacy in the treatment of pediatric T-LBL.The failure or progression of hormone pretreatment at d8 and the failure to achieve complete remission at the end of induction(mid-term evaluation)were the risk factors for EFS rate.