Acute Graft-Versus-Host Disease After Humanized Anti-CD19-CAR T Therapy in Relapsed B-ALL Patients After Allogeneic Hematopoietic Stem Cell Transplant
We studied the acute graft-versus-host disease (GVHD) after humanized anti-CD19-CAR T therapy in relapsed B-acute lymphoblastic leukemia (ALL) patients after allogeneic hematopoietic stem cell transplant (allo-HSCT). Fifteen B-ALL patients were enrolled in our study. Thirteen patients (86.67%) achie...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.573822/full |
| _version_ | 1818843270134890496 |
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| author | Pengjiang Liu Meijing Liu Cuicui Lyu Wenyi Lu Rui Cui Jia Wang Qing Li Nan Mou Qi Deng Donglin Yang |
| author_facet | Pengjiang Liu Meijing Liu Cuicui Lyu Wenyi Lu Rui Cui Jia Wang Qing Li Nan Mou Qi Deng Donglin Yang |
| author_sort | Pengjiang Liu |
| collection | DOAJ |
| description | We studied the acute graft-versus-host disease (GVHD) after humanized anti-CD19-CAR T therapy in relapsed B-acute lymphoblastic leukemia (ALL) patients after allogeneic hematopoietic stem cell transplant (allo-HSCT). Fifteen B-ALL patients were enrolled in our study. Thirteen patients (86.67%) achieved a complete response (CR) or CR with incomplete count recovery. The donor chimerism of the 13 patients reached 99.86 ± 0.21%. The development of aGVHD was observed in 10 patients (66.67%). Six patients developed grade I-II of aGVHD, while the other four patients developed grade III-IV of aGVHD. The notable adverse events were grade 1–2 cytokine release syndrome (CRS) in 10 patients and grade 3–4 CRS in five patients. Two patients died of infection, while another patient died of sudden cardiac arrest. The anti-CD19-CAR T cells were not eliminated in peripheral blood when the patients developed aGVHD. However, we did not observe their expansion peaks again in the process of aGVHD. During the aGVHD, the peaks of IL-6 and TNF-a were correlated with aGVHD levels. By May 31, 2020, the rates of leukemia-free survival (LFS) and overall survival (OS) at 180 days were 53.846 and 61.638%, respectively. All the patients who survived to date experienced aGVHD after humanized anti-CD19-CAR T cell therapy.Trial registration: The patients were enrolled in clinical trials of ChiCTR-ONN-16009862 and ChiCTR1800019622. |
| first_indexed | 2024-12-19T04:55:12Z |
| format | Article |
| id | doaj.art-a110b4d71ea04efbac9f9d3e2660c20c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-19T04:55:12Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-a110b4d71ea04efbac9f9d3e2660c20c2022-12-21T20:35:14ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-09-011010.3389/fonc.2020.573822573822Acute Graft-Versus-Host Disease After Humanized Anti-CD19-CAR T Therapy in Relapsed B-ALL Patients After Allogeneic Hematopoietic Stem Cell TransplantPengjiang Liu0Meijing Liu1Cuicui Lyu2Wenyi Lu3Rui Cui4Jia Wang5Qing Li6Nan Mou7Qi Deng8Donglin Yang9Department of Hematology, Tianjin First Central Hospital, Tianjin, ChinaThe First Central Clinical College of Tianjin Medical University, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaShanghai Genbase Biotechnology Co., Ltd., Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaWe studied the acute graft-versus-host disease (GVHD) after humanized anti-CD19-CAR T therapy in relapsed B-acute lymphoblastic leukemia (ALL) patients after allogeneic hematopoietic stem cell transplant (allo-HSCT). Fifteen B-ALL patients were enrolled in our study. Thirteen patients (86.67%) achieved a complete response (CR) or CR with incomplete count recovery. The donor chimerism of the 13 patients reached 99.86 ± 0.21%. The development of aGVHD was observed in 10 patients (66.67%). Six patients developed grade I-II of aGVHD, while the other four patients developed grade III-IV of aGVHD. The notable adverse events were grade 1–2 cytokine release syndrome (CRS) in 10 patients and grade 3–4 CRS in five patients. Two patients died of infection, while another patient died of sudden cardiac arrest. The anti-CD19-CAR T cells were not eliminated in peripheral blood when the patients developed aGVHD. However, we did not observe their expansion peaks again in the process of aGVHD. During the aGVHD, the peaks of IL-6 and TNF-a were correlated with aGVHD levels. By May 31, 2020, the rates of leukemia-free survival (LFS) and overall survival (OS) at 180 days were 53.846 and 61.638%, respectively. All the patients who survived to date experienced aGVHD after humanized anti-CD19-CAR T cell therapy.Trial registration: The patients were enrolled in clinical trials of ChiCTR-ONN-16009862 and ChiCTR1800019622.https://www.frontiersin.org/article/10.3389/fonc.2020.573822/fullacute lymphoblastic leukemiarelapseallogeneic hematopoietic stem cell transplantationchimeric antigen receptor (CARs)graft-versus-host diseasecytokine release syndrome |
| spellingShingle | Pengjiang Liu Meijing Liu Cuicui Lyu Wenyi Lu Rui Cui Jia Wang Qing Li Nan Mou Qi Deng Donglin Yang Acute Graft-Versus-Host Disease After Humanized Anti-CD19-CAR T Therapy in Relapsed B-ALL Patients After Allogeneic Hematopoietic Stem Cell Transplant Frontiers in Oncology acute lymphoblastic leukemia relapse allogeneic hematopoietic stem cell transplantation chimeric antigen receptor (CARs) graft-versus-host disease cytokine release syndrome |
| title | Acute Graft-Versus-Host Disease After Humanized Anti-CD19-CAR T Therapy in Relapsed B-ALL Patients After Allogeneic Hematopoietic Stem Cell Transplant |
| title_full | Acute Graft-Versus-Host Disease After Humanized Anti-CD19-CAR T Therapy in Relapsed B-ALL Patients After Allogeneic Hematopoietic Stem Cell Transplant |
| title_fullStr | Acute Graft-Versus-Host Disease After Humanized Anti-CD19-CAR T Therapy in Relapsed B-ALL Patients After Allogeneic Hematopoietic Stem Cell Transplant |
| title_full_unstemmed | Acute Graft-Versus-Host Disease After Humanized Anti-CD19-CAR T Therapy in Relapsed B-ALL Patients After Allogeneic Hematopoietic Stem Cell Transplant |
| title_short | Acute Graft-Versus-Host Disease After Humanized Anti-CD19-CAR T Therapy in Relapsed B-ALL Patients After Allogeneic Hematopoietic Stem Cell Transplant |
| title_sort | acute graft versus host disease after humanized anti cd19 car t therapy in relapsed b all patients after allogeneic hematopoietic stem cell transplant |
| topic | acute lymphoblastic leukemia relapse allogeneic hematopoietic stem cell transplantation chimeric antigen receptor (CARs) graft-versus-host disease cytokine release syndrome |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.573822/full |
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