Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report
Abstract Background Mixed phenotype acute leukemia (MPAL) is a rare leukemia and is regarded as a high-risk entity with a poor prognosis. Induction therapy of an acute lymphoblastic leukemia type or hybrid regimen and hematopoietic stem cell transplantation has been recommended for MPAL. However, th...
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2020-08-01
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Series: | Biomarker Research |
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Online Access: | http://link.springer.com/article/10.1186/s40364-020-00216-1 |
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doaj-94106da34ed2401093bcb170a914ec9a |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Meng-Yun Li Zhi-Hong Lin Ming-Ming Hu Li-Qing Kang Xiao-xia Wu Qi-wei Chen Xin Kong Jian Zhang Hui-Ying Qiu De-Pei Wu |
spellingShingle |
Meng-Yun Li Zhi-Hong Lin Ming-Ming Hu Li-Qing Kang Xiao-xia Wu Qi-wei Chen Xin Kong Jian Zhang Hui-Ying Qiu De-Pei Wu Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report Biomarker Research CD19 Chimeric antigen receptor T cells Donor-derived Humanized Mixed phenotype acute leukemia |
author_facet |
Meng-Yun Li Zhi-Hong Lin Ming-Ming Hu Li-Qing Kang Xiao-xia Wu Qi-wei Chen Xin Kong Jian Zhang Hui-Ying Qiu De-Pei Wu |
author_sort |
Meng-Yun Li |
title |
Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report |
title_short |
Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report |
title_full |
Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report |
title_fullStr |
Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report |
title_full_unstemmed |
Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report |
title_sort |
secondary donor-derived humanized cd19-modified car-t cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report |
publisher |
BMC |
series |
Biomarker Research |
issn |
2050-7771 |
publishDate |
2020-08-01 |
description |
Abstract Background Mixed phenotype acute leukemia (MPAL) is a rare leukemia and is regarded as a high-risk entity with a poor prognosis. Induction therapy of an acute lymphoblastic leukemia type or hybrid regimen and hematopoietic stem cell transplantation has been recommended for MPAL. However, the optimal therapies for relapsed or refractory MPAL remain unclear, especially for relapse after stem cell transplantation. Donor-derived chimeric antigen receptor T (CAR-T) cell therapy may be a promising therapeutic option for patients with MPAL who express target antigens and have relapsed after stem cell transplantation. However, recurrence remains a challenge, and reinfusion of CAR-T cells is not always effective. An infusion of secondary donor-derived humanized CD19-modified CAR-T cells may be effective in inducing remission. Case presentation We report a case of MPAL with CD19 expression. The patient was treated with acute lymphoblastic leukemia-like induction and consolidation therapies but remained positive for SET-NUP214 fusion gene transcript. He subsequently underwent a haploidentical stem cell transplantation but relapsed within 6 months. He then underwent donor-derived CD19-targeted CAR-T cell therapy and achieved a sustained, complete molecular remission. Unfortunately, he developed a CD19-positive relapse after 2 years. Donor-derived humanized CD19-directed CAR-T cells induced a second complete molecular remission without severe cytokine release syndrome or acute graft-versus-host disease. Conclusion This case demonstrated the efficacy and safety of humanized donor-derived CD19-modified CAR-T cell infusion for treating the recurrence of MPAL previously exposed to murine-derived CD19-directed CAR-T cells. |
topic |
CD19 Chimeric antigen receptor T cells Donor-derived Humanized Mixed phenotype acute leukemia |
url |
http://link.springer.com/article/10.1186/s40364-020-00216-1 |
work_keys_str_mv |
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doaj-94106da34ed2401093bcb170a914ec9a2020-11-25T02:25:03ZengBMCBiomarker Research2050-77712020-08-01811610.1186/s40364-020-00216-1Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case reportMeng-Yun Li0Zhi-Hong Lin1Ming-Ming Hu2Li-Qing Kang3Xiao-xia Wu4Qi-wei Chen5Xin Kong6Jian Zhang7Hui-Ying Qiu8De-Pei Wu9Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Soochow UniversitySuzhou Yongding HospitalSuzhou Yongding HospitalInstitute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal UniversityJiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Soochow UniversityJiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Soochow UniversityJiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Soochow UniversityJiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Soochow UniversityJiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Soochow UniversityJiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Soochow UniversityAbstract Background Mixed phenotype acute leukemia (MPAL) is a rare leukemia and is regarded as a high-risk entity with a poor prognosis. Induction therapy of an acute lymphoblastic leukemia type or hybrid regimen and hematopoietic stem cell transplantation has been recommended for MPAL. However, the optimal therapies for relapsed or refractory MPAL remain unclear, especially for relapse after stem cell transplantation. Donor-derived chimeric antigen receptor T (CAR-T) cell therapy may be a promising therapeutic option for patients with MPAL who express target antigens and have relapsed after stem cell transplantation. However, recurrence remains a challenge, and reinfusion of CAR-T cells is not always effective. An infusion of secondary donor-derived humanized CD19-modified CAR-T cells may be effective in inducing remission. Case presentation We report a case of MPAL with CD19 expression. The patient was treated with acute lymphoblastic leukemia-like induction and consolidation therapies but remained positive for SET-NUP214 fusion gene transcript. He subsequently underwent a haploidentical stem cell transplantation but relapsed within 6 months. He then underwent donor-derived CD19-targeted CAR-T cell therapy and achieved a sustained, complete molecular remission. Unfortunately, he developed a CD19-positive relapse after 2 years. Donor-derived humanized CD19-directed CAR-T cells induced a second complete molecular remission without severe cytokine release syndrome or acute graft-versus-host disease. Conclusion This case demonstrated the efficacy and safety of humanized donor-derived CD19-modified CAR-T cell infusion for treating the recurrence of MPAL previously exposed to murine-derived CD19-directed CAR-T cells.http://link.springer.com/article/10.1186/s40364-020-00216-1CD19Chimeric antigen receptor T cellsDonor-derivedHumanizedMixed phenotype acute leukemia |