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Outcomes of Anti-CD19 CAR-T Treatment of Pediatric B-ALL with Bone Marrow and Extramedullary Relapse

PURPOSE: Anti-CD19 chimeric antigen receptor T-cell (19CAR-T) immunotherapy has achieved impressive clinical results in adult and pediatric relapsed/refractory (r/r) B-lineage acute lymphoblastic leukemia (B-ALL). However, the application and effect of CAR-T therapy in B-ALL patients with extramedul...

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Autores principales: Wan, Xinyu, Yang, Xiaomin, Yang, Fan, Wang, Tianyi, Ding, Lixia, Song, Lili, Miao, Yan, Wang, Xiang, Ma, Yani, Luo, Chengjuan, Tang, Jingyan, Gu, Longjun, Chen, Jing, Tang, Yanjing, Lu, Jun, Li, Benshang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Cancer Association 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296935/
https://www.ncbi.nlm.nih.gov/pubmed/34583462
http://dx.doi.org/10.4143/crt.2021.399
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author Wan, Xinyu
Yang, Xiaomin
Yang, Fan
Wang, Tianyi
Ding, Lixia
Song, Lili
Miao, Yan
Wang, Xiang
Ma, Yani
Luo, Chengjuan
Tang, Jingyan
Gu, Longjun
Chen, Jing
Tang, Yanjing
Lu, Jun
Li, Benshang
author_facet Wan, Xinyu
Yang, Xiaomin
Yang, Fan
Wang, Tianyi
Ding, Lixia
Song, Lili
Miao, Yan
Wang, Xiang
Ma, Yani
Luo, Chengjuan
Tang, Jingyan
Gu, Longjun
Chen, Jing
Tang, Yanjing
Lu, Jun
Li, Benshang
author_sort Wan, Xinyu
collection PubMed
description PURPOSE: Anti-CD19 chimeric antigen receptor T-cell (19CAR-T) immunotherapy has achieved impressive clinical results in adult and pediatric relapsed/refractory (r/r) B-lineage acute lymphoblastic leukemia (B-ALL). However, the application and effect of CAR-T therapy in B-ALL patients with extramedullary relapse are rarely issued even disqualified in some clinical trials. Here, we examined the efficacy of 19CAR-T in patients with both bone marrow and extramedullary involvement. MATERIALS AND METHODS: CAR-T cells were generated by transfection of primary human T lymphocytes with a lentiviral vector expressing anti-CD19 single-chain antibody fragments with the cytoplasmic domains of 4-1BB and CD3ζ, and used to infuse patients diagnosed as having r/r B-ALL with extramedullary origination. Clinical responses were evaluated by the use of bone marrow aspiration, imaging, and flow cytometry. RESULTS: Eight patients received 19CAR-T infusion and all attained complete remission (CR). Only one patient was bridged to hematopoietic stem cell transplantation (HSCT). Although three patients relapsed after infusion, they received 19/22CAR-T infusion sequentially and attained a second remission. To date, five patients are in continuous CR and all eight patients are still alive. The mean follow-up time was 21.9 months, while the 24-month estimated event-free survival is 51.4%. CONCLUSION: 19CAR-T therapy can lead to clinical remission for extramedullary relapsed pediatric B-ALL patients. However, the problem of CD19(+) relapses after CAR-T remained to be solved. For patients relapsing after CAR-T, a second CAR-T therapy creates another opportunity for remission for subsequent HSCT.
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spelling pubmed-92969352022-07-20 Outcomes of Anti-CD19 CAR-T Treatment of Pediatric B-ALL with Bone Marrow and Extramedullary Relapse Wan, Xinyu Yang, Xiaomin Yang, Fan Wang, Tianyi Ding, Lixia Song, Lili Miao, Yan Wang, Xiang Ma, Yani Luo, Chengjuan Tang, Jingyan Gu, Longjun Chen, Jing Tang, Yanjing Lu, Jun Li, Benshang Cancer Res Treat Original Article PURPOSE: Anti-CD19 chimeric antigen receptor T-cell (19CAR-T) immunotherapy has achieved impressive clinical results in adult and pediatric relapsed/refractory (r/r) B-lineage acute lymphoblastic leukemia (B-ALL). However, the application and effect of CAR-T therapy in B-ALL patients with extramedullary relapse are rarely issued even disqualified in some clinical trials. Here, we examined the efficacy of 19CAR-T in patients with both bone marrow and extramedullary involvement. MATERIALS AND METHODS: CAR-T cells were generated by transfection of primary human T lymphocytes with a lentiviral vector expressing anti-CD19 single-chain antibody fragments with the cytoplasmic domains of 4-1BB and CD3ζ, and used to infuse patients diagnosed as having r/r B-ALL with extramedullary origination. Clinical responses were evaluated by the use of bone marrow aspiration, imaging, and flow cytometry. RESULTS: Eight patients received 19CAR-T infusion and all attained complete remission (CR). Only one patient was bridged to hematopoietic stem cell transplantation (HSCT). Although three patients relapsed after infusion, they received 19/22CAR-T infusion sequentially and attained a second remission. To date, five patients are in continuous CR and all eight patients are still alive. The mean follow-up time was 21.9 months, while the 24-month estimated event-free survival is 51.4%. CONCLUSION: 19CAR-T therapy can lead to clinical remission for extramedullary relapsed pediatric B-ALL patients. However, the problem of CD19(+) relapses after CAR-T remained to be solved. For patients relapsing after CAR-T, a second CAR-T therapy creates another opportunity for remission for subsequent HSCT. Korean Cancer Association 2022-07 2021-09-17 /pmc/articles/PMC9296935/ /pubmed/34583462 http://dx.doi.org/10.4143/crt.2021.399 Text en Copyright © 2022 by the Korean Cancer Association https://creativecommons.org/licenses/by-nc/4.0/This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Wan, Xinyu
Yang, Xiaomin
Yang, Fan
Wang, Tianyi
Ding, Lixia
Song, Lili
Miao, Yan
Wang, Xiang
Ma, Yani
Luo, Chengjuan
Tang, Jingyan
Gu, Longjun
Chen, Jing
Tang, Yanjing
Lu, Jun
Li, Benshang
Outcomes of Anti-CD19 CAR-T Treatment of Pediatric B-ALL with Bone Marrow and Extramedullary Relapse
title Outcomes of Anti-CD19 CAR-T Treatment of Pediatric B-ALL with Bone Marrow and Extramedullary Relapse
title_full Outcomes of Anti-CD19 CAR-T Treatment of Pediatric B-ALL with Bone Marrow and Extramedullary Relapse
title_fullStr Outcomes of Anti-CD19 CAR-T Treatment of Pediatric B-ALL with Bone Marrow and Extramedullary Relapse
title_full_unstemmed Outcomes of Anti-CD19 CAR-T Treatment of Pediatric B-ALL with Bone Marrow and Extramedullary Relapse
title_short Outcomes of Anti-CD19 CAR-T Treatment of Pediatric B-ALL with Bone Marrow and Extramedullary Relapse
title_sort outcomes of anti-cd19 car-t treatment of pediatric b-all with bone marrow and extramedullary relapse
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296935/
https://www.ncbi.nlm.nih.gov/pubmed/34583462
http://dx.doi.org/10.4143/crt.2021.399
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