CD19/CD22 chimeric antigen receptor T-cell therapy for refractory acute B-cell lymphoblastic leukemia with FLT3-ITD mutations
CD19/CD22 chimeric antigen receptor T-cell therapy for refractory acute B-cell lymphoblastic leukemia with FLT3-ITD mutations
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DOI：
10.1038/s41409-020-0807-7
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发表时间：
2020-01-31
影响因子：
4.8
通讯作者：
Huang, He
中科院分区：
文献类型：
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作者：
Jin, Aiyun;Feng, Jingjing;Huang, He
急性淋巴细胞白血病（ALL）的治疗经过多年的研究仍是一个挑战，特别是对预后不良的患者。Zhang和他的团队最近证明，在5%的ALL中发现了FLT 3基因突变，并且突变谱与AML不同。近年来，嵌合抗原受体T细胞（CART）疗法在治疗难治性白血病方面显示出巨大的疗效。我们报告了一例FLT 3-ITD突变和不利核型的难治性ALL患者，该患者对化疗和小分子酪氨酸激酶抑制剂无效，经CART治疗成功。FLT 3-ITD突变在输注后3天显著下调至14.1%阳性，并且直到现在仍保持阴性。MRD从第10天起一直保持阴性。该病例提示CART细胞治疗FLT 3-ITD阳性难治性ALL可能有效，这意味着有可能克服传统的白血病预后评分系统，并为其他预后因素较差的白血病患者提供新的机会。
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.