Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy
Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy
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DOI：
10.1182/blood-2015-08-665547
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发表时间：
2016-05-19
期刊：
影响因子：
20.3
通讯作者：
Turtle, Cameron J.
中科院分区：
文献类型：
--
作者：
Gardner, Rebecca;Wu, David;Turtle, Cameron J.
施用淋巴细胞清除化疗，然后施用CD 19特异性嵌合抗原受体（CAR）修饰的T细胞是治疗复发性和难治性CD 19 1 B细胞恶性肿瘤患者的非常有效的方法。我们用CD 19 CAR-T细胞治疗了7例携带混合系白血病（MLL）基因重排的B细胞急性淋巴细胞白血病（B-ALL）患者。在CD 19 CAR-T细胞治疗后，通过流式细胞术，所有患者的骨髓均达到完全缓解（CR）;然而，在CAR-T细胞输注1个月内，2例患者发生了与其B-ALL克隆相关的急性髓性白血病（AML），这是一种CD 19阴性免疫逃逸的新机制。这些报告对接受CD 19 CAR-T细胞治疗的复发性和难治性MLL-B-ALL患者的管理具有意义。
Administration of lymphodepletion chemotherapy followed by CD19-specific chimeric antigen receptor (CAR)-modified T cells is a remarkably effective approach to treating patients with relapsed and refractory CD19 1 B-cell malignancies. We treated 7 patients with B-cell acute lymphoblastic leukemia (B-ALL) harboring rearrangement of the mixed lineage leukemia (MLL) gene with CD19 CAR-T cells. All patients achieved complete remission (CR) in the bone marrow by flow cytometry after CD19 CAR-T-cell therapy; however, within 1 month of CAR-T-cell infusion, 2 of the patients developed acute myeloid leukemia (AML) that was clonally related to their B-ALL, a novel mechanism of CD19-negative immune escape. These reports have implications for the management of patients with relapsed and refractory MLL-B-ALL who receive CD19 CAR-T-cell therapy.