【摘要】 背景:近年来肿瘤免疫治疗发展迅速,大部分学者研究方向主要是自体嵌合抗原受体T细胞的单抗体治疗,存在培养细胞质量差、数目少的问题。因此,异体嵌合抗原受体T细胞的研究更具发展潜力。目的:探讨异基因嵌合抗原受体T细胞治疗异基因造血干细胞移植后复发白血病的疗效及安全性。方法:应用异基因嵌合抗原受体T细胞治疗2例异基因造血干细胞移植后复发的难治慢性粒细胞白血病急淋变患者,对其临床资料进行分析并结合国内外文献复习。结果与结论:例1因"发热、乏力5 d"入院,经骨髓细胞形态学、流式分析、染色体、融合基因等相关检查确诊为慢性粒细胞白血病急淋变,口服伊马替尼联合小剂量化疗后,行单倍体移植(女供母,HLA10/10相合)过程顺利,移植后3个月复发,BCR-ABL(p210)阳性,嵌合体:供者细胞占67.4%。给予氟达拉滨+环磷酰胺方案处理后,输注抗CD19嵌合抗原受体T细胞5×10~6/kg。2周后复查BCR-ABL(p210)转阴,嵌合体:供者细胞占99.62%,期间出现1级细胞因子释放综合征,对症处理。随访持续缓解6个月。例2因"左上腹饱胀1年,盗汗15d"于2011年4月就诊当地医院,1年后进展为慢性粒细胞白血病急淋变伴T315I突变,经化疗缓解后行弟供兄HLA7/10相合单倍体造血干细胞移植,2018年二次复发时输注抗CD19嵌合抗原受体T细胞2×105/kg,期间出现4级细胞因子释放综合征,慢性粒细胞白血病持续缓解2个月余复发死亡。由此可见,慢性粒细胞白血病急淋变患者行异基因造血干细胞移植后复发,可以考虑供者来源嵌合抗原受体T细胞治疗,可反复输注,安全有效,移植物抗宿主病发生率低。抗CD22嵌合抗原受体T细胞序贯治疗安全、有效。更多还原

【Abstract】 BACKGROUND: In recent years, tumor immunotherapy has developed rapidly. Most scholars have focused on the single antibody treatment with autologous chimeric antigen receptor T-cell(CAR-T), but poor quality and small number of cultured cells are encountered. Therefore, allogeneic CAR-T cells have a better developmental potential. OBJECTIVE: To investigate the efficacy and safety of allogeneic CAR-T cells in the treatment of recurrent leukemia after allogeneic hematopoietic stem cell transplantation. METHODS: Two patients with relapsed refractory chronic myeloid leukemia in lymphoid blast crisis after allogeneic hematopoietic stem cell transplantation were treated with allogeneic CAR-T cells. Their clinical data were analyzed and relevant literature was reviewed. RESULTS AND CONCLUSION: Case 1 was hospitalized because of fever and fatigue for 5 days, and was diagnosed as chronic myeloid leukemia in lymphoid blast crisis by bone marrow cell morphology, flow cytometry, chromosome analysis, fusion gene and other related examinations. After oral imatinib combined with low dose chemotherapy, HLA10/10 matched haploid transplantation from daughter to mother proceeded smoothly. Three months after transplantation, BCR-ABL(p210) was positive, and chimera: donor cells accounted for 67.4%. After treatment with fludarabine+cyclophosphamide regimen, anti-CD19 CAR-T cells were infused at a dose of 5 ×10~6 cells/kg. Two weeks later, BCR-ABL(p210) turned negative and chimera: donor cells accounted for 99.62%. During the period, cytokine release syndrome level 1 appeared and symptomatic treatment was performed. The follow-up lasted for 6 months. Case 2 was treated in the local hospital in April 2011 because of left upper abdomen fullness for 1 year and night sweat for 15 days. One year later, it progressed to chronic myeloid leukemia in lymphoid blast crisis with T315 I mutation. HLA 7/10 matched haploid stem cell transplantation from little brother to brother was performed after remission by chemotherapy. Anti-CD19 CAR-T cells were transfused at 2×10~5/kg in the second relapse in 2018. During this period, cytokine release syndrome level 4 appeared. Chronic myeloid leukemia continued to alleviate for over 2 months and then relapsed resulting in death. Thus, the donor-derived CAR-T cells can be considered for the treatment of recurrent chronic myeloid leukemia in lymphoid blast crisis after allogeneic hematopoietic stem cell transplantation. It can be transfused repeatedly. It is safe and effective, and the incidence of Graft-versus-host disease is low. Sequential treatment with anti-CD22 CAR-T cells is safe and effective.更多还原