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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.01358/full |
| _version_ | 1819093298997886976 |
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| author | Sun Yao Chen Jianlin Liu Yarong Li Botao Wang Qinghan Fang Hongliang Zhang Lu Ning Hongmei Wang Pin Wang Pin Wang Pin Wang Pin Chen Hu Chen Hu Hu Liangding Zhang Bin |
| author_facet | Sun Yao Chen Jianlin Liu Yarong Li Botao Wang Qinghan Fang Hongliang Zhang Lu Ning Hongmei Wang Pin Wang Pin Wang Pin Wang Pin Chen Hu Chen Hu Hu Liangding Zhang Bin |
| author_sort | Sun Yao |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T23:09:18Z |
| format | Article |
| id | doaj.art-8368e5bc7788449fbfd9bda9b55e9543 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-21T23:09:18Z |
| publishDate | 2019-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-8368e5bc7788449fbfd9bda9b55e95432022-12-21T18:47:05ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-12-01910.3389/fonc.2019.01358488135Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG+ AMLSun Yao0Chen Jianlin1Liu Yarong2Li Botao3Wang Qinghan4Fang Hongliang5Zhang Lu6Ning Hongmei7Wang Pin8Wang Pin9Wang Pin10Wang Pin11Chen Hu12Chen Hu13Hu Liangding14Zhang Bin15Department of Hematopoietic Stem Cell Transplantation, The Fifth Medical Center of Chinese PLA General Hospital (Former 307th Hospital of PLA), The Research Institute of Hematopoietic Stem Cell of the People's Liberation Army, Beijing, ChinaDepartment of Hematopoietic Stem Cell Transplantation, The Fifth Medical Center of Chinese PLA General Hospital (Former 307th Hospital of PLA), The Research Institute of Hematopoietic Stem Cell of the People's Liberation Army, Beijing, ChinaR&D Department, HRAIN Biotechnology Co., Ltd., Shanghai, ChinaDepartment of Hematopoietic Stem Cell Transplantation, The Fifth Medical Center of Chinese PLA General Hospital (Former 307th Hospital of PLA), The Research Institute of Hematopoietic Stem Cell of the People's Liberation Army, Beijing, ChinaDepartment of Hematopoietic Stem Cell Transplantation, The Fifth Medical Center of Chinese PLA General Hospital (Former 307th Hospital of PLA), The Research Institute of Hematopoietic Stem Cell of the People's Liberation Army, Beijing, ChinaR&D Department, HRAIN Biotechnology Co., Ltd., Shanghai, ChinaR&D Department, HRAIN Biotechnology Co., Ltd., Shanghai, ChinaDepartment of Hematopoietic Stem Cell Transplantation, The Fifth Medical Center of Chinese PLA General Hospital (Former 307th Hospital of PLA), The Research Institute of Hematopoietic Stem Cell of the People's Liberation Army, Beijing, ChinaR&D Department, HRAIN Biotechnology Co., Ltd., Shanghai, ChinaDepartment of Biomedical Engineering, University of Southern California, Los Angeles, CA, United StatesDepartment of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, United StatesDepartment of Pharmaceutical Sciences and Pharmacology, University of Southern California, Los Angeles, CA, United StatesDepartment of Hematopoietic Stem Cell Transplantation, The Fifth Medical Center of Chinese PLA General Hospital (Former 307th Hospital of PLA), The Research Institute of Hematopoietic Stem Cell of the People's Liberation Army, Beijing, ChinaBeijing Key Laboratory of Hematopoietic Stem Cell Therapy and Transformation Research, Department of Hematopoietic Stem Cell Transplantation, The Cell and Gene Therapy Center, The Fifth Medical Center of Chinese PLA General Hospital (Former 307th Hospital of PLA), The Research Institute of Hematopoietic Stem Cell of the People's Liberation Army, Beijing, ChinaDepartment of Hematopoietic Stem Cell Transplantation, The Fifth Medical Center of Chinese PLA General Hospital (Former 307th Hospital of PLA), The Research Institute of Hematopoietic Stem Cell of the People's Liberation Army, Beijing, ChinaBeijing Key Laboratory of Hematopoietic Stem Cell Therapy and Transformation Research, Department of Hematopoietic Stem Cell Transplantation, The Cell and Gene Therapy Center, The Fifth Medical Center of Chinese PLA General Hospital (Former 307th Hospital of PLA), The Research Institute of Hematopoietic Stem Cell of the People's Liberation Army, Beijing, ChinaBackground: 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.https://www.frontiersin.org/article/10.3389/fonc.2019.01358/fullchimeric antigen receptorCD123allogeneic hematopoietic stem cell transplantationacute myeloid leukemiacytokine release syndromegraft-vs-host disease |
| spellingShingle | Sun Yao Chen Jianlin Liu Yarong Li Botao Wang Qinghan Fang Hongliang Zhang Lu Ning Hongmei Wang Pin Wang Pin Wang Pin Wang Pin Chen Hu Chen Hu Hu Liangding Zhang Bin Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG+ AML Frontiers in Oncology chimeric antigen receptor CD123 allogeneic hematopoietic stem cell transplantation acute myeloid leukemia cytokine release syndrome graft-vs-host disease |
| 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 | chimeric antigen receptor CD123 allogeneic hematopoietic stem cell transplantation acute myeloid leukemia cytokine release syndrome graft-vs-host disease |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.01358/full |
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