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[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].[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]
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Donor-derived CAR-T Cells Serve as a Reduced-intensity Conditioning Regimen for Haploidentical Stem Cell Transplantation in Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: Case Report and Review of the Literature.供体来源的 CAR-T 细胞作为减轻强度预处理方案,用于治疗复发/难治性急性淋巴细胞白血病的单倍体相合干细胞移植:病例报告及文献复习。
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Donor-derived CD19-targeted T cell infusion induces minimal residual disease-negative remission in relapsed B-cell acute lymphoblastic leukaemia with no response to donor lymphocyte infusions after haploidentical haematopoietic stem cell transplantation.供体来源的靶向CD19的T细胞输注可诱导复发的B细胞急性淋巴细胞白血病患者达到微小残留病阴性缓解,这些患者在单倍体造血干细胞移植后对供体淋巴细胞输注无反应。
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Case report: Two pediatric cases of long-term leukemia-free survival with relapsed acute T-lymphoblastic leukemia treated with donor CD7 CAR-T cells bridging to haploidentical stem cell transplantation.病例报告:两例复发急性 T 淋巴细胞白血病患儿在接受供体 CD7 CAR-T 细胞桥接单倍体造血干细胞移植后实现长期无白血病生存。
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Anti-CD19 chimeric antigen receptor-modified T-cell therapy bridging to allogeneic hematopoietic stem cell transplantation for relapsed/refractory B-cell acute lymphoblastic leukemia: An open-label pragmatic clinical trial.抗 CD19 嵌合抗原受体修饰 T 细胞疗法桥接异基因造血干细胞移植治疗复发/难治性 B 细胞急性淋巴细胞白血病:一项开放标签实用临床试验。
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Long-term follow-up of CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation.异基因造血干细胞移植后复发/难治性急性淋巴细胞白血病的 CD19 嵌合抗原受体 T 细胞治疗的长期随访。
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[Efficacy of CD19 Chimeric Antigen Receptors T Cells in the Treatment of Relapsed Patients with B Cell Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation].CD19嵌合抗原受体T细胞治疗异基因造血干细胞移植后复发的B细胞急性淋巴细胞白血病患者的疗效
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Umbilical cord blood: A promising source for allogeneic CAR-T cells.脐带血:同种异体嵌合抗原受体T细胞的一个有前景的来源。
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2
Allogeneic CD19-CAR-T cell infusion after allogeneic hematopoietic stem cell transplantation in B cell malignancies.异基因造血干细胞移植后在B细胞恶性肿瘤中输注异基因CD19嵌合抗原受体T细胞。
J Hematol Oncol. 2017 Jan 31;10(1):35. doi: 10.1186/s13045-017-0405-3.

本文引用的文献

1
CD33-specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia.CD33特异性嵌合抗原受体T细胞对人类急性髓系白血病表现出强大的临床前活性。
Leukemia. 2015 Aug;29(8):1637-47. doi: 10.1038/leu.2015.52. Epub 2015 Feb 27.
2
Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies.迅速传播:嵌合抗原受体T细胞疗法治疗血液系统恶性肿瘤
Immunol Rev. 2015 Jan;263(1):68-89. doi: 10.1111/imr.12243.
3
Chimeric antigen receptor T cells for sustained remissions in leukemia.用于白血病持续缓解的嵌合抗原受体T细胞。
N Engl J Med. 2014 Oct 16;371(16):1507-17. doi: 10.1056/NEJMoa1407222.
4
Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia.一名复发难治性急性髓系白血病患者接受CD33导向嵌合抗原受体修饰T细胞治疗。
Mol Ther. 2015 Jan;23(1):184-91. doi: 10.1038/mt.2014.164. Epub 2014 Sep 1.
5
CD123 AML targeting by chimeric antigen receptors: A novel magic bullet for AML therapeutics?嵌合抗原受体靶向CD123急性髓系白血病:一种用于急性髓系白血病治疗的新型神奇药物?
Oncoimmunology. 2014 May 14;3:e28835. doi: 10.4161/onci.28835. eCollection 2014.
6
How do we prepare ourselves for a new paradigm of medicine to advance the treatment of pediatric acute lymphoblastic leukemia?我们如何为推进儿童急性淋巴细胞白血病治疗的新医学范式做好准备?
Blood Res. 2014 Mar;49(1):3-4. doi: 10.5045/br.2014.49.1.3.
7
Design and implementation of adoptive therapy with chimeric antigen receptor-modified T cells.嵌合抗原受体修饰 T 细胞过继免疫疗法的设计与实施。
Immunol Rev. 2014 Jan;257(1):127-44. doi: 10.1111/imr.12139.
8
[A clinical study of drug-related toxicities of CCLG-ALL 08 protocol for childhood acute lymphoblastic leukemia].CCLG-ALL 08方案治疗儿童急性淋巴细胞白血病药物相关毒性的临床研究
Zhongguo Dang Dai Er Ke Za Zhi. 2013 Sep;15(9):737-42.
9
TanCAR: A Novel Bispecific Chimeric Antigen Receptor for Cancer Immunotherapy.TanCAR:用于癌症免疫治疗的新型双特异性嵌合抗原受体。
Mol Ther Nucleic Acids. 2013 Jul 9;2(7):e105. doi: 10.1038/mtna.2013.32.
10
Chimeric antigen receptor-modified T cells for acute lymphoid leukemia.嵌合抗原受体修饰的 T 细胞治疗急性淋巴细胞白血病。
N Engl J Med. 2013 Apr 18;368(16):1509-1518. doi: 10.1056/NEJMoa1215134. Epub 2013 Mar 25.

[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.

DOI:10.3760/cma.j.issn.0253-2727.2016.02.006
PMID:27014980
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7348202/
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。