嵌合抗原受体T细胞治疗伴T315I突变的复发难治急性B淋巴细胞白血病一例并文献复习

Chimeric antigen receptor T-cell therapy for relapsed/refractory acute B-cell lymphoblastic leukemia with T315I mutation:report of one case and review of literature

目的探讨嵌合抗原受体T细胞(CAR-T)治疗伴有T315I突变的复发难治急性B淋巴细胞白血病(B-ALL)患者的疗效及安全性。方法回顾性分析安徽医科大学第二附属医院收治的1例接受CD19 CAR-T治疗的伴T315I突变的复发难治B-ALL患者的临床资料,并复习相关文献。结果患者为34岁男性,2017年1月确诊为慢性粒细胞白血病(CML)并开始口服伊马替尼,4个月后转化为B-ALL,因检出E355G耐药基因突变调整治疗药物为达沙替尼,同时行诱导化疗,获得完全缓解(CR)后序贯巩固化疗3次。患者CR半年后复发并检出T315I突变,予再诱导化疗未缓解。随后接受CD19 CAR-T治疗(细胞数1.0×10^9,活性度98%),输注前予FC(氟达拉滨每天30 mg/m^2,第1天至第3天;环磷酰胺每天200 mg/m^2,第1天至第3天)方案预处理,输注后发生1级细胞因子释放综合征,对症处理后好转,未出现严重不良反应。CAR-T治疗后半个月评估原发病达CR,CR后1个月成功行脐带血移植。截至末次随访时患者无复发生存时间已达396 d。结论对于复发难治B-ALL合并T315I突变的患者,CAR-T治疗可能是一种新的有效治疗手段,安全性较好。

Objective To explore the safety and efficacy of chimeric antigen receptor T-cell(CAR-T)therapy for relapsed/refractory acute B-cell lymphoblastic leukemia(B-ALL)with T315I mutation.Methods The clinical data of a patient with relapsed/refractory B-ALL with T315I mutation who underwent CAR-T therapy in the Second Affiliated Hospital of Anhui Medical University was analyzed,and the related literature was reviewed.Results The patient was a 34-year-old man.He was diagnosed with chronic myelogenous leukemia(CML)in January 2017 and started to take imatinib orally.However,the primary affection transformed to B-ALL 4 months later.Because of the E355G gene mutation,the treatment drug was adjusted to dasatinib,and induction chemotherapy was given at the same time.The sequential consolidation chemotherapy was given for 3 times after complete remission(CR).After half a year of remission,T315I mutation was detected and re-induced chemotherapy was given,but ineffective.The patient was treated with CAR-T 3 days after FC regimen(fludarabine 30 mg/m^2 per day,day 1 to day 3;cyclophosphamide 200 mg/m^2,day 1 to day 3).The number of CD19 CAR-T was 1.0×10^9,98%activity degree.Grade 1 cytokine-releasing syndrome appeared after infusion,and was resolved after symptomatic treatment.No serious adverse reactions were observed.CR was achieved half-month after CAR-T treatment,and umbilical cord blood transplantation was successfully performed 1 month later.At the last follow-up,the relapse-free survival time of the patient was 396 days.Conclusion CAR-T therapy may be a new,safe and effective therapy for patients with relapsed/refractory B-ALL with T315I mutation.