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CD19/CD22嵌合抗原受体T细胞疗法治疗伴有FLT3-ITD突变的难治性急性B淋巴细胞白血病

CD19/CD22 chimeric antigen receptor T-cell therapy for refractory acute B-cell lymphoblastic leukemia with FLT3-ITD mutations.

作者信息

Jin Aiyun, Feng Jingjing, Wei Guoqing, Wu Wenjun, Yang Luxin, Xu Huijun, Zhang Yanlei, Cui Jiazhen, Chang Alex Hongsheng, Hu Yongxian, Huang He

机构信息

Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, China.

Institute of Hematology, Zhejiang University, Hangzhou, China.

出版信息

Bone Marrow Transplant. 2020 Apr;55(4):717-721. doi: 10.1038/s41409-020-0807-7. Epub 2020 Jan 31.

Abstract

Treatment of acute lymphoblastic leukemia (ALL) is still a challenge despite years of researching, especially for those of poor prognosis. Zhang and his team recently proved that FLT3 gene mutation was identified in ~5% of ALL and the mutation spectrum is different from AML. Recently, chimeric antigen receptor T cells (CART) therapy presents great efficacy in treating refractory leukemia. We report a case of a refractory ALL patient with FLT3-ITD mutations and unfavorable karyotypes, who failed to respond to chemotherapy and small molecule tyrosine kinase inhibitors, successfully treated by CART therapy. FLT3-ITD mutations were downregulated dramatically into 14.1% positive 3 days after the infusion and remained negative until now. MRD has stayed to be negative from the 10th day. This case suggests that CART-cell therapy might be effective in treating FLT3-ITD positive refractory ALL, implying the possibility to overcome the traditional prognosis scoring system for leukemia and providing a new chance for other leukemia patients with inferior prognosis factors.

摘要

尽管经过多年研究,急性淋巴细胞白血病(ALL)的治疗仍然是一项挑战,尤其是对于那些预后较差的患者。张及其团队最近证明,在约5%的ALL患者中发现了FLT3基因突变,且突变谱与急性髓系白血病(AML)不同。最近,嵌合抗原受体T细胞(CART)疗法在治疗难治性白血病方面展现出巨大疗效。我们报告了一例难治性ALL患者,该患者存在FLT3-ITD突变且核型不佳,对化疗和小分子酪氨酸激酶抑制剂均无反应,经CART疗法成功治疗。输注后3天,FLT3-ITD突变显著下调至阳性率为14.1%,至今仍为阴性。微小残留病(MRD)从第10天起一直保持阴性。该病例表明,CART细胞疗法可能对治疗FLT3-ITD阳性难治性ALL有效,这意味着有可能克服白血病传统的预后评分系统,并为其他具有不良预后因素的白血病患者提供新的机会。

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