硼替佐米联合化疗治疗复发难治及高危儿童急性淋巴细胞白血病11例病例系列报告

Bortezomib combined with chemotherapy in the treatment of 11 children with relapsed,refractory or high-risk acute lymphoblastic leukemia:A case series report

背景儿童复发/难治性急性淋巴细胞白血病(ALL)临床治疗较困难、预后差。硼替佐米联合化疗显示出一定的有效性,目前国内相关报道较少。目的探讨硼替佐米联合化疗对复发难治及高危儿童ALL的疗效及安全性。设计病例系列报告。方法纳入2017年9月至2019年9月北京大学人民医院儿科收治的接受硼替佐米联合化疗的复发难治及高危ALL患儿,分析其临床特征、实验室检查、治疗情况和预后。主要结局指标总反应率(ORR)、2年无事件生存(EFS)、总生存(OS)、不良反应。结果11例患儿纳入分析,男9例,女2例,诊断中位年龄10(3~15)岁。7例T-ALL,2例T淋巴母细胞淋巴瘤Ⅳ期,2例B-ALL。复发2例,难治4例,高危5例。经硼替佐米联合化疗1个疗程后,8例(B-ALL 1例,T-ALL 7例)治疗有反应,ORR 72.7%。治疗前骨髓形态未缓解3例,部分缓解4例,治疗后完全缓解率85.7%(6/7);治疗前骨髓微小残留病(MRD)阳性10例,治疗后均有下降,其中1例MRD转阴。不良反应总体可耐受,主要为骨髓抑制、感染、胃肠道反应、肝功能异常等,无化疗相关死亡病例。9例行异基因造血干细胞移植治疗,其中7例无病存活,2例死于移植后复发;2例患儿继续化疗,长期随访均死亡。中位随访时间15(2~29)个月,2年EFS为(45.5±15)%,OS为(63.6±14.5)%。结论硼替佐米联合化疗是复发难治及高危ALL患儿的一种有效、耐受性良好的治疗选择。

Background The treatment of children with relapsed,refractory acute lymphoblastic leukemia(ALL)is difficult and the prognosis is poor.Bortezomib combined with chemotherapy shows promising effect,but there are few reports in China at present.Objective To investigate the efficacy and safety of bortezomib combined with chemotherapy in the treatment of children with relapsed,refractory or high-risk ALL.Design Case series report.Methods Eleven children with relapsed,refractory or high-risk ALL who were treated with bortezomib combined with chemotherapy in the Department of Pediatrics,Peking University People's Hospital from September 2017 to September 2019 were included.Their clinical characteristics,laboratory examinations,treatment and prognosis were analyzed.Main outcome measures Overall response rate(ORR),2-year event-free survival(EFS),overall survival(OS)and adverse events.Results Eleven children were included into the analysis,including 9 males and 2 females,with a median age of 10(3-15)years old.We evaluated bortezomib in combination with chemotherapy in 7 cases of T-ALL,2 cases of T lymphoblastic lymphoma stage IV,2 cases of B-ALL.Among these patients,there were 2 cases of relapse,4 cases of refractory and 5 cases of high-risk disease.After one course,8 cases showed response,with an ORR of 72.7%,including B-ALL 50%(1/2)and T-ALL 77.8%(7/9).Before treatment,there were 3 cases of bone marrow non-remission and 4 cases of partial remission,and the complete remission(CR)rate was 85.7%(6/7).Before treatment,10 cases were positive for bone marrow minimal residual disease(MRD),and all decreased after treatment,of which one case turned negative.The main adverse events were myelosuppression,infection,gastrointestinal disorder and abnormal liver function associated with combination chemotherapy.Nine cases were subsequently treated with allogeneic hematopoietic stem cell transplantation,seven of which survived without disease and two of which died of relapse after transplantation.Two cases continued chemotherapy and both died at the last follow-up.The median follow-up time was 15(2-29)months,the 2-year EFS was 45.5±15%,and OS was 63.6±14.5%.Conclusion Bortezomib combined with chemotherapy is an effective and well-tolerated treatment option for relapsed,refractory or high-risk children with ALL.