嵌合抗原受体t细胞治疗复发/难治性急性b淋巴细胞白血病伴T315I突变1例报告并文献复习

Simeng Chen, Jiakui Zhang, Yingwei Li, Fan Wu, Qianshan Tao, Furun An, Huiping Wang, Ling-xiao Liu, Qing Zhang
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摘要

目的探讨嵌合抗原受体t细胞(CAR-T)治疗复发/难治性急性b淋巴细胞白血病(B-ALL) T315I突变的安全性和有效性。方法分析1例复发/难治性B-ALL T315I突变患者在安徽医科大学第二附属医院接受CAR-T治疗的临床资料,并复习相关文献。结果患者男,34岁。他于2017年1月被诊断患有慢性粒细胞白血病(CML),并开始口服伊马替尼。然而,4个月后,原发病转变为B-ALL。由于E355G基因突变,治疗药物调整为达沙替尼,同时给予诱导化疗。完全缓解(CR)后连续巩固化疗3次。缓解半年后,检测到T315I突变,再次诱导化疗,但无效。患者在FC方案后3天接受CAR-T治疗(氟达拉滨30 mg/m2 /天,第1天至第3天;环磷酰胺200 mg/m2,第1天至第3天)。CD19 CAR-T细胞数量1.0×109,活性度98%。输注后出现1级细胞因子释放综合征,对症治疗后缓解。未见严重不良反应。CAR-T治疗半个月后达到CR, 1个月后脐带血移植成功。末次随访时,患者无复发生存时间为396天。结论CAR-T治疗可能是一种安全有效的治疗复发/难治性B-ALL T315I突变的新方法。关键词:白血病,B淋巴细胞,急性;T315I突变;嵌合抗原受体t细胞
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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
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/m2 per day, day 1 to day 3; cyclophosphamide 200 mg/m2, day 1 to day 3). The number of CD19 CAR-T was 1.0×109, 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. Key words: Leukemia, B lymphocyte, acute; T315I mutation; Chimeric antigen receptor T-cell
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