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

作者信息

Jiang Y L, Li Q, Pu Y D, Jiang Y Y, Yuan T, Deng Q, Li Y M, Han M Z, Zhai W H

机构信息

Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, China.

Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, National Clinical Research Center for Blood Diseases, Tianjin 300020, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2020 Jun 14;41(6):495-501. doi: 10.3760/cma.j.issn.0253-2727.2020.06.011.


DOI:10.3760/cma.j.issn.0253-2727.2020.06.011
PMID:32654464
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7378295/
Abstract

This study aimed to evaluate the maintenance therapy following an anti-CD19-CAR T-cell therapy for a B-cell acute lymphoblastic leukemia (ALL) patient who relapsed after allogeneic hematopoietic cell transplantation (allo-HSCT) and investigate the effect of donor stem cells and donor T lymphocyte infusion on the amplification of CD19 CAR-T cells. One refractory B-ALL patient relapsed after murine CD19 CAR-T cell therapy followed by a sibling allo-HSCT. He underwent a humanized CD19 CAR-T cell therapy followed by donor stem cell and donor T lymphocytes infusions as maintenance therapy in our hospital. The level of cytokines, the proportion of CD19 CAR-T cell, the level of CAR19 DNA expression in the peripheral blood, and the proportion of leukemia cells and donor chimerism in the bone marrow were detected. Correspondingly, T lymphocytes from the C57 spleen were separated to modify the CD19 CAR lentivirus and refused into C57 mice, and after 14 days, the B lymphocytes from C57 mice were separated and refused into the same C57 mice. The CD19 CAR T cells, B cells, and CD19 CAR gene counts in the peripheral blood were evaluated at different time points. ①The patient achieved a complete response (CR) 14 days after a humanized CD19 CAR-T therapy with grade 1 cytokine release syndrome (CRS) and restored a donor chimerism to 99.76%. ② Following the remission from humanized CD19 CAR-T therapy, the patient received a maintenance therapy of donor stem cell infusion. Mild graft-versus-host disease (GVHD) manifested 24 days after infusion with an increased proportion of CD19 CAR-T cells and an increased level of CAR19 DNA expression in the peripheral blood. It fell with the remission of GVHD. The patient maintained CR and 99.69% donor chimerism during this period. ③ Throughout the subsequent donor T lymphocytes maintenance therapy, mild GVHD surfaced12 days after infusion without an increased proportion of CD19 CAR-T cells and an increased level of CAR19 DNA expression in the peripheral blood. The patient maintained CR and 99.87% donor chimerism during this period. ④ In vivo experiments on C57 mice confirmed that the proportion of CD19 CAR-T cells and the level of CAR19 DNA expression were upregulated in mice following CAR-T cell infusion, accompanied by depletion of CD19(+) B lymphocyte. After infusion of CD19(+) B lymphocyte cells, an increased proportion of CD19 CAR-T cells and an increased level of CAR19 DNA expression in the peripheral blood were observed again. The infusion of donor stem cells and donor T lymphocytes could be used as a maintenance treatment after CD19 CAR-T cell therapy for B-ALL patients who relapsed after allo-HSCT. Infusion of donor stem cells induced an increased proportion of CD19 CAR-T cells and an increased level of CAR19 DNA expression with the occurrence of GVHD. It might lead to further elimination of minimal residual disease.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afdb/7378295/9bf6d43d38d4/cjh-41-06-495-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afdb/7378295/29cae29b8908/cjh-41-06-495-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afdb/7378295/69c5a181c2c9/cjh-41-06-495-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afdb/7378295/9bf6d43d38d4/cjh-41-06-495-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afdb/7378295/29cae29b8908/cjh-41-06-495-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afdb/7378295/69c5a181c2c9/cjh-41-06-495-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afdb/7378295/9bf6d43d38d4/cjh-41-06-495-g003.jpg

相似文献

[1]
[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

[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]
[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

[4]
Donor Hematopoietic Stem Cell/Lymphocyte Maintenance Treatment After CAR T-Cell Therapy in Patients With B-Cell Acute Lymphoblastic Leukemia Relapse Following Stem Cell Transplant.

Cell Transplant. 2023

[5]
CAR19/22 T cell cocktail therapy for B-ALL relapsed after allogeneic hematopoietic stem cell transplantation.

Cytotherapy. 2022-8

[6]
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

[7]
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

[8]
[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

[9]
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

[10]
Donor-derived stem cell infusion for sustained pancytopenia after CD19 CAR-T therapy for relapsed patients post allogeneic stem cell transplantation.

Eur J Haematol. 2024-1

引用本文的文献

[1]
Donor Hematopoietic Stem Cell/Lymphocyte Maintenance Treatment After CAR T-Cell Therapy in Patients With B-Cell Acute Lymphoblastic Leukemia Relapse Following Stem Cell Transplant.

Cell Transplant. 2023

本文引用的文献

[1]
Treatment with Humanized Selective CD19CAR-T Cells Shows Efficacy in Highly Treated B-ALL Patients Who Have Relapsed after Receiving Murine-Based CD19CAR-T Therapies.

Clin Cancer Res. 2019-7-12

[2]
Construction and functional characterization of a fully human anti-CD19 chimeric antigen receptor (huCAR)-expressing primary human T cells.

J Cell Physiol. 2018-10-26

[3]
Gene-knocked out chimeric antigen receptor (CAR) T cells: Tuning up for the next generation cancer immunotherapy.

Cancer Lett. 2018-3-12

[4]
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

[5]
Long-Duration Complete Remissions of Diffuse Large B Cell Lymphoma after Anti-CD19 Chimeric Antigen Receptor T Cell Therapy.

Mol Ther. 2017-7-13

[6]
Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice.

Curr Hematol Malig Rep. 2017-8

[7]
Allogeneic CD19-CAR-T cell infusion after allogeneic hematopoietic stem cell transplantation in B cell malignancies.

J Hematol Oncol. 2017-1-31

[8]
Donor origin CAR T cells: graft versus malignancy effect without GVHD, a systematic review.

Immunotherapy. 2017-1

[9]
CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients.

J Clin Invest. 2016-6-1

[10]
The novel anti-CD19 chimeric antigen receptors with humanized scFv (single-chain variable fragment) trigger leukemia cell killing.

Cell Immunol. 2016

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