Kinetics of immune reconstitution after anti-CD19 chimeric antigen receptor T cell therapy in relapsed or refractory acute lymphoblastic leukemia patients
Ying Wang
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorHujun Li
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorXuguang Song
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorKunming Qi
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorHai Cheng
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorJiang Cao
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorMing Shi
Cancer Institute, Xuzhou Medical University, Xuzhou, China
Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Search for more papers by this authorZhiling Yan
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorBin Pan
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorWei Sang
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorXiangmin Wang
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorKai Zhao
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorChong Chen
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorWei Chen
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorCorresponding Author
Junnian Zheng
Cancer Institute, Xuzhou Medical University, Xuzhou, China
Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Correspondence
Kailin Xu, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Zhenyu Li, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Junnian Zheng, Cancer Institute, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Zhenyu Li
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Correspondence
Kailin Xu, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Zhenyu Li, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Junnian Zheng, Cancer Institute, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Kailin Xu
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Correspondence
Kailin Xu, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Zhenyu Li, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Junnian Zheng, Cancer Institute, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Search for more papers by this authorYing Wang
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorHujun Li
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorXuguang Song
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorKunming Qi
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorHai Cheng
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorJiang Cao
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorMing Shi
Cancer Institute, Xuzhou Medical University, Xuzhou, China
Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Search for more papers by this authorZhiling Yan
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorBin Pan
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorWei Sang
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorXiangmin Wang
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorKai Zhao
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorChong Chen
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorWei Chen
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Search for more papers by this authorCorresponding Author
Junnian Zheng
Cancer Institute, Xuzhou Medical University, Xuzhou, China
Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Correspondence
Kailin Xu, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Zhenyu Li, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Junnian Zheng, Cancer Institute, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Zhenyu Li
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Correspondence
Kailin Xu, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Zhenyu Li, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Junnian Zheng, Cancer Institute, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Kailin Xu
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
Correspondence
Kailin Xu, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Zhenyu Li, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Junnian Zheng, Cancer Institute, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou 221002, China.
Email: [email protected]
Search for more papers by this authorAbstract
Introduction
Anti-CD19 chimeric antigen receptor (CAR) -T cells, which recognize and kill both B lymphoblasts and normal B cells, result in B cell aplasia and humoral immunodeficiency. However, there were only a few detailed reports on the profile of immune reconstitution after anti-CD19 CAR-T cell therapy.
Methods
Thirty nine patients with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (ALL) receiving anti-CD19 CAR-T cell therapy were enrolled. Subjects died, relapsed, received other treatment, or lost to follow-up within 60 days post-infusion were excluded. 21 patients were finally selected. Laboratory and clinical data were collected for analysis of immune reconstitution.
Results
CD8+ cells were the first to recover with a median time on day 21(7-87), followed by CD16/CD56+ cells on day 28(14-87), and finally CD4+ cells with only 5(23.81%) patients recovered within 60 days post-infusion. CD4/CD8 ratio was inverted, sustaining for at least 1 year. B cell aplasia occurred in all patients and CD19+ cells returned to normal on a median time of day 79(41-118). All patients developed hypogammaglobulinemia with a median onset time of 2 weeks post-infusion. IgG recovered in 6 patients with a median time on day 184(89-346). IgM recovered on days 212, 242, and 346 in 3 patients. IgA recovered most slowly and remained low >1 year postinfusion. A total of 9 infections occurred in 6(28.57%) patients.
Conclusions
Our data showed prolonged reconstitution of immune function, especially humoral immunity, in R/R B cell ALL patients receiving anti-CD19 CAR-T cell therapy.
CONFLICT OF INTEREST
GJ is an employee of iCARTAB Biomedical Co Ltd. All other authors declare no competing interests.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| ijlh13375-sup-0001-SupInfo.docWord document, 491 KB | Supplementary Material |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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