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[嵌合抗原受体T细胞治疗复发性儿童急性淋巴细胞白血病,异基因造血干细胞移植后复发:病例报告及文献复习]

[Chimeric antigen receptors T cells in treatment of a relapsed pediatric acute lymphoblastic leukemia, relapse after allogenetic hematopoietic stem cell transplantation: case report and review of literature review].

作者信息

Zuo Yingxi, Wang Jingbo, Lu Aidong, Jia Yueping, Wu Jun, Dong Lujia, Chang Lungji, Zhang Leping

机构信息

Pediatrics Department, Peking University People's Hospital, Beijing 100044, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2016 Feb;37(2):115-8. doi: 10.3760/cma.j.issn.0253-2727.2016.02.006.

Abstract

OBJECTIVE

To evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL).

METHODS

A relapsed B-ALL child after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was treated with CAR-T, and the related literatures were reviewed.

RESULT

An 11-year-old girl with TEL-AML1 fusion gene positive BALL who suffered a bone marrow relapse 28 months after remission from conventional chemotherapy. During the second remission, the patient received haploidentical allo-HSCT. She relapsed with detectable TEL-AML1 fusion gene even after chemotherapy and donor leukocyte infusions. She received an experimental donor-derived fourth generation CD19 CAR-T therapy. After infusion of 1 × 10(6)/kg CAR-T cells, she experienced only mild or moderate cytokine-release syndrome and the minimal residual disease turned negative. Then three maintenance of CAR-T cell infusions [(0.83-1.65)×10(6)/kg] was administered, and the disease-free survival had lasted for 10 months. However, the TEL-AML1 copies in her blood still increased and she died with leukemia relapse after additional CAR-T cell infusion.

CONCLUSION

Treatment of relapsed B-ALL with the fourth generation CAR-T cells directed against CD19 was effective and safe. CAR-T therapy is a novel therapeutic approach that could be useful for patients with relapsed and refractory B-ALL who have failed all other treatment options.

摘要

目的

评估嵌合抗原受体T细胞(CAR-T)治疗儿童急性B淋巴细胞白血病(B-ALL)的安全性和有效性。

方法

对1例异基因造血干细胞移植(allo-HSCT)后复发的B-ALL患儿进行CAR-T治疗,并复习相关文献。

结果

1例11岁TEL-AML1融合基因阳性的B-ALL女童,在接受传统化疗缓解28个月后出现骨髓复发。第二次缓解期,患者接受了单倍体allo-HSCT。即使在化疗和供者淋巴细胞输注后,她仍因可检测到的TEL-AML1融合基因而复发。她接受了实验性供者来源的第四代CD19 CAR-T治疗。输注1×10(6)/kg CAR-T细胞后,她仅出现轻度或中度细胞因子释放综合征,微小残留病转为阴性。随后进行了3次CAR-T细胞维持输注[(0.83-1.65)×10(6)/kg],无病生存期持续了10个月。然而,她血液中的TEL-AML1拷贝数仍增加,在再次输注CAR-T细胞后因白血病复发死亡。

结论

用针对CD19的第四代CAR-T细胞治疗复发的B-ALL是有效且安全的。CAR-T疗法是一种新型治疗方法,对所有其他治疗方案均失败的复发难治性B-ALL患者可能有用。

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