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Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG+ AML
Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) following chemotherapy is part of standard treatment protocol for patients with acute myeloid leukemia (AML). FUS-ERG+ AML is rare but has an extremely poor prognosis even with allo-HSCT in remission, possibly due to its a le...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901822/ https://www.ncbi.nlm.nih.gov/pubmed/31850234 http://dx.doi.org/10.3389/fonc.2019.01358 |
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author | Yao, Sun Jianlin, Chen Yarong, Liu Botao, Li Qinghan, Wang Hongliang, Fang Lu, Zhang Hongmei, Ning Pin, Wang Hu, Chen Liangding, Hu Bin, Zhang |
author_facet | Yao, Sun Jianlin, Chen Yarong, Liu Botao, Li Qinghan, Wang Hongliang, Fang Lu, Zhang Hongmei, Ning Pin, Wang Hu, Chen Liangding, Hu Bin, Zhang |
author_sort | Yao, Sun |
collection | PubMed |
description | Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) following chemotherapy is part of standard treatment protocol for patients with acute myeloid leukemia (AML). FUS-ERG+ AML is rare but has an extremely poor prognosis even with allo-HSCT in remission, possibly due to its a leukemia stem cell (LSC)-driven disease resulting in chemotherapy resistance and a novel therapy is urgently required. It has been reported that FUS-ERG-positive AML expresses CD123, a marker of LSC, in some cases. CD123-targeted CAR T cell (CART123) is promising immunotherapy, but how to improve the complete remission (CR) rate and rescue potential hematopoietic toxicity still need to explore. Case Presentation: We used donor-derived CART123 as part of conditioning regimen for haploidentical HSCT (haplo-HSCT) in a patient with FUS-ERG+ AML who relapsed after allogeneic transplantation within 3 months, resists to multi-agent chemotherapy and donor lymphocyte infusion (DLI) and remained non-remission, aiming to reduce these chemotherapy-resistant blasts and rescue potential hematopoietic toxicity. The blasts in BM were reduced within 2 weeks and coincided with CAR copies expansion after CART123 infusion. The patient achieved full donor chimerism, CR with incomplete blood count recovery, and myeloid implantation. Conclusion: Our results hints that CART123 reduces the chemotherapy-resistant AML blasts for FUS-ERG+ AML without affecting the full donor chimerism and myeloid implantation. |
format | Online Article Text |
id | pubmed-6901822 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69018222019-12-17 Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG+ AML Yao, Sun Jianlin, Chen Yarong, Liu Botao, Li Qinghan, Wang Hongliang, Fang Lu, Zhang Hongmei, Ning Pin, Wang Hu, Chen Liangding, Hu Bin, Zhang Front Oncol Oncology Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) following chemotherapy is part of standard treatment protocol for patients with acute myeloid leukemia (AML). FUS-ERG+ AML is rare but has an extremely poor prognosis even with allo-HSCT in remission, possibly due to its a leukemia stem cell (LSC)-driven disease resulting in chemotherapy resistance and a novel therapy is urgently required. It has been reported that FUS-ERG-positive AML expresses CD123, a marker of LSC, in some cases. CD123-targeted CAR T cell (CART123) is promising immunotherapy, but how to improve the complete remission (CR) rate and rescue potential hematopoietic toxicity still need to explore. Case Presentation: We used donor-derived CART123 as part of conditioning regimen for haploidentical HSCT (haplo-HSCT) in a patient with FUS-ERG+ AML who relapsed after allogeneic transplantation within 3 months, resists to multi-agent chemotherapy and donor lymphocyte infusion (DLI) and remained non-remission, aiming to reduce these chemotherapy-resistant blasts and rescue potential hematopoietic toxicity. The blasts in BM were reduced within 2 weeks and coincided with CAR copies expansion after CART123 infusion. The patient achieved full donor chimerism, CR with incomplete blood count recovery, and myeloid implantation. Conclusion: Our results hints that CART123 reduces the chemotherapy-resistant AML blasts for FUS-ERG+ AML without affecting the full donor chimerism and myeloid implantation. Frontiers Media S.A. 2019-12-03 /pmc/articles/PMC6901822/ /pubmed/31850234 http://dx.doi.org/10.3389/fonc.2019.01358 Text en Copyright © 2019 Yao, Jianlin, Yarong, Botao, Qinghan, Hongliang, Lu, Hongmei, Pin, Hu, Liangding and Bin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Yao, Sun Jianlin, Chen Yarong, Liu Botao, Li Qinghan, Wang Hongliang, Fang Lu, Zhang Hongmei, Ning Pin, Wang Hu, Chen Liangding, Hu Bin, Zhang Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG+ AML |
title | Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG+ AML |
title_full | Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG+ AML |
title_fullStr | Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG+ AML |
title_full_unstemmed | Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG+ AML |
title_short | Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG+ AML |
title_sort | donor-derived cd123-targeted car t cell serves as a ric regimen for haploidentical transplantation in a patient with fus-erg+ aml |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901822/ https://www.ncbi.nlm.nih.gov/pubmed/31850234 http://dx.doi.org/10.3389/fonc.2019.01358 |
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