Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Yao, Sun, Jianlin, Chen, Yarong, Liu, Botao, Li, Qinghan, Wang, Hongliang, Fang, Lu, Zhang, Hongmei, Ning, Pin, Wang, Hu, Chen, Liangding, Hu, Bin, Zhang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
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
_version_ 1783477566508630016
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
work_keys_str_mv AT yaosun donorderivedcd123targetedcartcellservesasaricregimenforhaploidenticaltransplantationinapatientwithfusergaml
AT jianlinchen donorderivedcd123targetedcartcellservesasaricregimenforhaploidenticaltransplantationinapatientwithfusergaml
AT yarongliu donorderivedcd123targetedcartcellservesasaricregimenforhaploidenticaltransplantationinapatientwithfusergaml
AT botaoli donorderivedcd123targetedcartcellservesasaricregimenforhaploidenticaltransplantationinapatientwithfusergaml
AT qinghanwang donorderivedcd123targetedcartcellservesasaricregimenforhaploidenticaltransplantationinapatientwithfusergaml
AT hongliangfang donorderivedcd123targetedcartcellservesasaricregimenforhaploidenticaltransplantationinapatientwithfusergaml
AT luzhang donorderivedcd123targetedcartcellservesasaricregimenforhaploidenticaltransplantationinapatientwithfusergaml
AT hongmeining donorderivedcd123targetedcartcellservesasaricregimenforhaploidenticaltransplantationinapatientwithfusergaml
AT pinwang donorderivedcd123targetedcartcellservesasaricregimenforhaploidenticaltransplantationinapatientwithfusergaml
AT huchen donorderivedcd123targetedcartcellservesasaricregimenforhaploidenticaltransplantationinapatientwithfusergaml
AT liangdinghu donorderivedcd123targetedcartcellservesasaricregimenforhaploidenticaltransplantationinapatientwithfusergaml
AT binzhang donorderivedcd123targetedcartcellservesasaricregimenforhaploidenticaltransplantationinapatientwithfusergaml