Abstract：
BACKGROUND: The risk of second tumors after chimeric antigen receptor (CAR) T-cell therapy, especially the risk of T-cell neoplasms related to viral vector integration, is an emerging concern.
METHODS: We reviewed our clinical experience with adoptive cellular CAR T-cell therapy at our institution since 2016 and ascertained the occurrence of second tumors. In one case of secondary T-cell lymphoma, a broad array of molecular, genetic, and cellular techniques were used to interrogate the tumor, the CAR T cells, and the normal hematopoietic cells in the patient.
RESULTS: A total of 724 patients who had received T-cell therapies at our center were included in the study. A lethal T-cell lymphoma was identified in a patient who had received axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma, and both lymphomas were deeply profiled. Each lymphoma had molecularly distinct immunophenotypes and genomic profiles, but both were positive for Epstein-Barr virus and were associated with DNMT3A and TET2 mutant clonal hematopoiesis. No evidence of oncogenic retroviral integration was found with the use of multiple techniques.
CONCLUSIONS: Our results highlight the rarity of second tumors and provide a framework for defining clonal relationships and viral vector monitoring. (Funded by the National Cancer Institute and others.).
METHODS: We reviewed our clinical experience with adoptive cellular CAR T-cell therapy at our institution since 2016 and ascertained the occurrence of second tumors. In one case of secondary T-cell lymphoma, a broad array of molecular, genetic, and cellular techniques were used to interrogate the tumor, the CAR T cells, and the normal hematopoietic cells in the patient.
RESULTS: A total of 724 patients who had received T-cell therapies at our center were included in the study. A lethal T-cell lymphoma was identified in a patient who had received axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma, and both lymphomas were deeply profiled. Each lymphoma had molecularly distinct immunophenotypes and genomic profiles, but both were positive for Epstein-Barr virus and were associated with DNMT3A and TET2 mutant clonal hematopoiesis. No evidence of oncogenic retroviral integration was found with the use of multiple techniques.
CONCLUSIONS: Our results highlight the rarity of second tumors and provide a framework for defining clonal relationships and viral vector monitoring. (Funded by the National Cancer Institute and others.).
摘要：
背景：嵌合抗原受体（CAR）T细胞治疗后发生第二肿瘤的风险，特别是与病毒载体整合相关的T细胞肿瘤的风险，是一个新兴的问题。
方法：我们回顾了自2016年以来在我们机构进行过继性细胞CART细胞治疗的临床经验，并确定了第二种肿瘤的发生。在一例继发性T细胞淋巴瘤中，广泛的分子，遗传,细胞技术被用来询问肿瘤，CAR-T细胞,和病人体内的正常造血细胞.
结果：共有724名在我们中心接受过T细胞治疗的患者被纳入研究。在接受axicabtageneciloleucel治疗弥漫性大B细胞淋巴瘤的患者中发现了致死性T细胞淋巴瘤，两种淋巴瘤都有很深的轮廓。每个淋巴瘤都有不同的分子免疫表型和基因组谱，但两者均为EB病毒阳性,且与DNMT3A和TET2突变克隆造血相关.使用多种技术没有发现致癌逆转录病毒整合的证据。
结论：我们的结果突出了第二肿瘤的罕见性，并为定义克隆关系和病毒载体监测提供了框架。（由国家癌症研究所和其他机构资助。).
方法：我们回顾了自2016年以来在我们机构进行过继性细胞CART细胞治疗的临床经验，并确定了第二种肿瘤的发生。在一例继发性T细胞淋巴瘤中，广泛的分子，遗传,细胞技术被用来询问肿瘤，CAR-T细胞,和病人体内的正常造血细胞.
结果：共有724名在我们中心接受过T细胞治疗的患者被纳入研究。在接受axicabtageneciloleucel治疗弥漫性大B细胞淋巴瘤的患者中发现了致死性T细胞淋巴瘤，两种淋巴瘤都有很深的轮廓。每个淋巴瘤都有不同的分子免疫表型和基因组谱，但两者均为EB病毒阳性,且与DNMT3A和TET2突变克隆造血相关.使用多种技术没有发现致癌逆转录病毒整合的证据。
结论：我们的结果突出了第二肿瘤的罕见性，并为定义克隆关系和病毒载体监测提供了框架。（由国家癌症研究所和其他机构资助。).
