CAR19/22 T cell cocktail therapy for B-ALL relapsed after allogeneic hematopoietic stem cell transplantation |
| |
| Institution: | 1. Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China;2. Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China;1. Medical Affairs and Innovation, Héma-Québec, Québec City, Canada;2. Cord Blood Bank, Héma-Québec, Montréal, Canada;3. Centre for Innovation, Canadian Blood Services, Ottawa, Canada;4. Biochemistry, Microbiology and Immunology Department, University of Ottawa, Ottawa, Canada;1. Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada;2. Centre for Journalology, Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Canada;3. School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Canada;4. Department of Anesthesiology and Pain Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Canada;5. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada;6. Neonatology, Department of Pediatrics, Children''s Hospital of Eastern Ontario (CHEO) and CHEO Research Institute, Ottawa, ON, Canada;1. Center for Cancer and Immunology Research, Children''s National Hospital, Washington, DC, USA;2. Department of Neurosurgery, Georgetown University Medical Center, Washington, DC, USA;3. Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA;4. Genomics Shared Resource, Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA;5. George Washington University Cancer Center, George Washington University, Washington, DC, USA;1. Jack Copland Centre, Scottish National Blood Transfusion Service, Edinburgh, UK;2. Cell and Gene Therapy Catapult, Guy''s Hospital, London, UK;3. Autolus Therapeutics plc, London, UK;4. National Health Service Blood and Transplant, Filton, UK;5. Christie National Health Service Foundation Trust, Manchester, UK;6. GlaxoSmithKline, Stevenage, UK;7. Cell and Gene Therapy, Novartis Pharmaceuticals UK Limited, London, UK;8. eXmoor Pharma Concepts Ltd, Stoke Gifford, UK;9. Kite Pharma EU B.V., Hoofddorp, The Netherlands;10. King''s College Hospital National Health Service Foundation Trust, London, UK;11. University College London Hospital National Health Service Foundation Trust, London, UK;12. Terumo BCT Europe NV, Zaventem, Belgium;13. bluebird bio Inc, Cambridge, Massachusetts, USA;14. Great Northern Children''s Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, UK;15. National Marrow Donor Program/Be The Match, Minneapolis, Minnesota, USA;16. Cytiva, Cambridge, UK;1. Krembil Research Institute, Toronto, ON, Canada;2. Princess Margaret Cancer Centre, Toronto, ON, Canada;3. Institute of Medical Science, University of Toronto, Toronto, ON, Canada;4. Faculty of Medicine, University of Toronto, Toronto, ON, Canada;1. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA;2. Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA;3. Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA;4. Mesoblast Ltd, Melbourne, Australia;5. Biostatistics Shared Resource Facility, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA |
| |
| Abstract: | B cell acute lymphocytic leukemia (B-ALL) patients who have relapsed after hematopoietic stem cell transplantation (HSCT) have a poor prognosis, and there is currently no standard approach available. Chimeric antigen receptor (CAR)-T cells induce high rates of initial response and long-term remission among patients with B-cell malignancies, especially B-ALL. Meanwhile, sequential infusion of CAR19/22 T cells has been proven to be effective at preventing tumor immune escape. In the present study, we retrospectively analyzed 23 B-ALL patients who relapsed after allogeneic (allo)-HSCT and underwent sequential infusion of CAR19/22 T cells, including nine donor-derived and 14 recipient-derived, in our center from July 2016 to July 2020, to evaluate the safety and efficacy of the cocktail of two single-specific CAR-T cells in B-ALL patients relapsed after transplantation. Except for one patient refusing evaluation, the remaining 22 patients achieved minimal residual disease (MRD)-negative complete remission within 30 days after CAR-T infusion. Most toxicities were slight and reversible. The estimated 12-month progression-free survival (PFS) rate was 59.2% (95% confidence interval CI], 35.9% to 76.5%), and the estimated 12-month overall survival (OS) rate was 67.4% (95% CI, 43.2% to 83.1%). Only two patients had CD19-negative recurrence. In addition, early recurrence after transplantation, graft-versus-host disease (GVHD) and severe infection after CAR-T infusion were poor prognostic factors. Our results indicate that sequential infusion of CAR19/22 T cells is safe and effective for relapsed ALL patients after HSCT. This trial was registered at www.chictr.org.cn as #ChiCTR-OPN-16008526. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
