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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的异基因供体来源CD19嵌合抗原受体T细胞疗法

[Allogeneic donor-derived CD19 CAR-T therapy of relapsed B-cell acute lmphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

作者信息

Ma R Z, He Y, Yang D L, Wei J L, Pang A M, Jiang E L, Wang J X, Han M Z, Zhang R L, Feng S Z

机构信息

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2021 May 14;42(5):383-389. doi: 10.3760/cma.j.issn.0253-2727.2021.05.006.


DOI:10.3760/cma.j.issn.0253-2727.2021.05.006
PMID:34218580
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8293002/
Abstract

To investigate the long term efficacy and side effects of a donor-derived CD19 chimeric antigen receptor (CAR) T-cell (HI19α-4-1BB-ζ CAR-T) therapy in the treatment of patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . A total of 9 subjects with relapsed B-ALL post allo-HSCT received donor-derived CD19 CAR-T therapy from July 2017 to May 2020. All subjects were infused with donor CD3-positive T cells after lymphodepletion chemotherapy, and a median dose of CAR-T cells was 1.79 (range, 0.86-3.53) ×10(6)/kg. ①All subjects achieved complete remission and MRD-negative at 28-42 d post CAR-T cells infusion. ②Cytokine releasing syndrome (CRS) occurrd in all subjects and was grade 3 in 2, grade 2 in 4, grade 1 in 3 cases respectively. Four subjects developed immune effector cell-associated neurotoxicity syndrome (ICANS) , which was grade 2 in 1, grade 1 in 3. One subject developed grade IV acute graft-versus-host disease (GVHD) , and side effects were all controllable. ③Four subjects relapsed at a median period of 8.6 (4.6-19.3) months, 2 subjects died of disease progression after receiving chemotherapy and another one also died of disease progression 14 months after a second transplant, only 1 subject achieved complete remission after CD22 CAR-T cell therapy. Until last follow-up date, 6 subjects were leukemia-free and achieved complete donor chimerism. The estimated 1-year and 2-year leukemia-free survival (LFS) rate was 63.5% and 50.8%, with a median LFS of 18.1 months. ④After a median follow-up of 25.1 (range, 6.9-36.7) months, the estimated 2-year and 2.5-year OS rate were 87.5% and 52.5%, respectively. The donor-derived CD19 CAR-T cell therapy obtain a high remission rate in relapsed B-ALL patients post allo-HSCT with tolerable side effects, half subjects survived more than 2 years without disease recurrence, though long-term efficacy requires further observation. Chinese Clinical Trial Registry: ChiCTR1900025419.

摘要

为研究供体来源的CD19嵌合抗原受体(CAR)T细胞(HI19α-4-1BB-ζ CAR-T)疗法治疗异基因造血干细胞移植(allo-HSCT)后复发的B细胞急性淋巴细胞白血病(B-ALL)患者的长期疗效和副作用。2017年7月至2020年5月,共有9例allo-HSCT后复发的B-ALL患者接受了供体来源的CD19 CAR-T治疗。所有受试者在淋巴细胞清除化疗后输注供体CD3阳性T细胞,CAR-T细胞的中位剂量为1.79(范围0.86-3.53)×10(6)/kg。①所有受试者在输注CAR-T细胞后28-42天均达到完全缓解且微小残留病(MRD)阴性。②所有受试者均发生细胞因子释放综合征(CRS),其中3级2例,2级4例,1级3例。4例受试者发生免疫效应细胞相关神经毒性综合征(ICANS),其中2级1例,1级3例。1例受试者发生Ⅳ级急性移植物抗宿主病(GVHD),且副作用均可控。③4例受试者在中位时间8.6(4.6-19.3)个月时复发,2例受试者在接受化疗后死于疾病进展,另1例在第二次移植后14个月也死于疾病进展,仅1例受试者在接受CD22 CAR-T细胞治疗后达到完全缓解。至最后随访日期,6例受试者无白血病且实现完全供体嵌合。估计1年和2年无白血病生存率(LFS)分别为63.5%和50.8%,中位LFS为18.1个月。④中位随访25.1(范围6.9-36.7)个月后,估计2年和2.5年总生存率(OS)分别为87.5%和52.5%。供体来源的CD19 CAR-T细胞疗法在allo-HSCT后复发的B-ALL患者中获得了较高的缓解率,副作用可耐受,半数受试者存活超过2年且无疾病复发,不过长期疗效仍需进一步观察。中国临床试验注册中心:ChiCTR1900025419。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46db/8293002/d004d1c84520/cjh-42-05-383-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46db/8293002/2bdb115283cc/cjh-42-05-383-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46db/8293002/9b1975da3764/cjh-42-05-383-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46db/8293002/d004d1c84520/cjh-42-05-383-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46db/8293002/2bdb115283cc/cjh-42-05-383-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46db/8293002/9b1975da3764/cjh-42-05-383-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46db/8293002/d004d1c84520/cjh-42-05-383-g003.jpg

相似文献

[1]
[Allogeneic donor-derived CD19 CAR-T therapy of relapsed B-cell acute lmphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Zhonghua Xue Ye Xue Za Zhi. 2021-5-14

[2]
Donor-derived CD19 CAR-T Cells versus Chemotherapy Plus Donor Lymphocyte Infusion for Treatment of Recurrent CD19-positive B-ALL After Allogeneic Hematopoietic Stem Cell Transplantation.

Curr Med Sci. 2023-8

[3]
Humanized Anti-CD19 CAR-T Cell Therapy and Sequential Allogeneic Hematopoietic Stem Cell Transplantation Achieved Long-Term Survival in Refractory and Relapsed B Lymphocytic Leukemia: A Retrospective Study of CAR-T Cell Therapy.

Front Immunol. 2021

[4]
Integrating CAR T-Cell Therapy and Transplantation: Comparisons of Safety and Long-Term Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation After CAR T-Cell or Chemotherapy-Based Complete Remission in B-Cell Acute Lymphoblastic Leukemia.

Front Immunol. 2021

[5]
[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].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2019-8

[6]
[Maintenance therapy following CD19 CAR-T treatment for relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Zhonghua Xue Ye Xue Za Zhi. 2020-6-14

[7]
[Safety and efficacy of donor-derived chimeric antigen receptor T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Zhonghua Xue Ye Xue Za Zhi. 2024-1-14

[8]
Combination of CD19 and CD22 CAR-T cell therapy in relapsed B-cell acute lymphoblastic leukemia after allogeneic transplantation.

Am J Hematol. 2021-6-1

[9]
Safety and efficacy of co-administration of CD19 and CD22 CAR-T cells in children with B-ALL relapse after CD19 CAR-T therapy.

J Transl Med. 2023-3-22

[10]
[Efficacy and safety of chimeric antigen receptor T-cell therapy followed by allogeneic hematopoietic stem cell transplantation in 21 patients with Ph-like acute lymphoblastic leukemia].

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引用本文的文献

[1]
[Safety and efficacy of donor-derived chimeric antigen receptor T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Zhonghua Xue Ye Xue Za Zhi. 2024-1-14

[2]
Role of allogeneic haematopoietic stem cell transplantation in the treatment of adult acute lymphoblastic leukaemia in the era of immunotherapy.

Chin Med J (Engl). 2022-4-20

本文引用的文献

[1]
Acute Graft-Versus-Host Disease After Humanized Anti-CD19-CAR T Therapy in Relapsed B-ALL Patients After Allogeneic Hematopoietic Stem Cell Transplant.

Front Oncol. 2020-9-29

[2]
Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant.

Leukemia. 2021-6

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Efficacy and safety of CD19 CAR T constructed with a new anti-CD19 chimeric antigen receptor in relapsed or refractory acute lymphoblastic leukemia.

J Hematol Oncol. 2020-9-7

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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.

Cytotherapy. 2020-12

[5]
Allogeneic Donor-Derived Anti-CD19 CAR T Cell Is a Promising Therapy for Relapsed/Refractory B-ALL After Allogeneic Hematopoietic Stem-Cell Transplantation.

Clin Lymphoma Myeloma Leuk. 2020-9

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Blood. 2019-12-26

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Clinical trials of dual-target CAR T cells, donor-derived CAR T cells, and universal CAR T cells for acute lymphoid leukemia.

J Hematol Oncol. 2019-2-14

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Programmed cell death protein 1 activation preferentially inhibits CD28.CAR-T cells.

Cytotherapy. 2018-10-9

[9]
Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia.

N Engl J Med. 2018-2-1

[10]
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.

Br J Haematol. 2017-11

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