The role of graft T-cell size in patients receiving alemtuzumab serotherapy for non-malignant disorders: results of an institutional protocol
Abstract Although graft T cells assist in engraftment, mediate antiviral immune-reconstitution, and cause graft-versus-host disease, graft size is not determined by T-cell content of the graft. The conventional method of graft size determination based on CD34+ cells with alemtuzumab serotherapy is a...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-50416-6 |
| _version_ | 1797274742887022592 |
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| author | Ambreen Pandrowala Sanna Khan Darshan Kataria Manasa Kakunje Varsha Mishra Dhruv Mamtora Sangeeta Mudaliar Minnie Bodhanwala Bharat Agarwal Prashant Hiwarkar |
| author_facet | Ambreen Pandrowala Sanna Khan Darshan Kataria Manasa Kakunje Varsha Mishra Dhruv Mamtora Sangeeta Mudaliar Minnie Bodhanwala Bharat Agarwal Prashant Hiwarkar |
| author_sort | Ambreen Pandrowala |
| collection | DOAJ |
| description | Abstract Although graft T cells assist in engraftment, mediate antiviral immune-reconstitution, and cause graft-versus-host disease, graft size is not determined by T-cell content of the graft. The conventional method of graft size determination based on CD34+ cells with alemtuzumab serotherapy is associated with delayed immune reconstitution, contributing to an increased risk of viral infections and graft failure. Alemtuzumab, a long half-life anti-CD52 monoclonal antibody is a robust T-cell depleting serotherapy, and relatively spares memory-effector T cells compared to naïve T cells. We therefore hypothesized that graft size based on T-cell content in patients receiving peripheral blood stem cell graft with alemtuzumab serotherapy would facilitate immune-reconstitution without increasing the risk of graft-versus-host disease. We retrospectively analysed twenty-six consecutive patients with non-malignant disorders grafted using alemtuzumab serotherapy and capping of graft T cells to a maximum of 600 million/kg. The graft T-cell capping protocol resulted in early immune-reconstitution without increasing the risk of severe graft-versus-host disease. Graft T-cell content correlated with CD4+ T-cell reconstitution and acute graft-versus-host disease. The course of CMV viraemia was predictable without recurrence and associated with early T-cell recovery. No patient developed chronic graft-versus-host disease. Overall survival at one year was 100% and disease-free survival was 96% at a median of 899 days (range: 243–1562). Graft size determined by peripheral blood stem cell graft T-cell content in patients receiving alemtuzumab serotherapy for non-malignant disorders is safe and leads to early T-cell immune-reconstitution with excellent survival outcomes. |
| first_indexed | 2024-03-07T15:02:38Z |
| format | Article |
| id | doaj.art-b5ba33fa012e4043923f8d3e79eddf03 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:02:38Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b5ba33fa012e4043923f8d3e79eddf032024-03-05T19:04:28ZengNature PortfolioScientific Reports2045-23222024-01-011411810.1038/s41598-023-50416-6The role of graft T-cell size in patients receiving alemtuzumab serotherapy for non-malignant disorders: results of an institutional protocolAmbreen Pandrowala0Sanna Khan1Darshan Kataria2Manasa Kakunje3Varsha Mishra4Dhruv Mamtora5Sangeeta Mudaliar6Minnie Bodhanwala7Bharat Agarwal8Prashant Hiwarkar9Department of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for ChildrenDepartment of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for ChildrenDepartment of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for ChildrenDepartment of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for ChildrenDepartment of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for ChildrenDepartment of Pathology, Bai Jerbai Wadia Hospital for ChildrenDepartment of Paediatric Haematology, Bai Jerbai Wadia Hospital for ChildrenDepartment of Paediatrics, Bai Jerbai Wadia Hospital for ChildrenDepartment of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for ChildrenDepartment of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for ChildrenAbstract Although graft T cells assist in engraftment, mediate antiviral immune-reconstitution, and cause graft-versus-host disease, graft size is not determined by T-cell content of the graft. The conventional method of graft size determination based on CD34+ cells with alemtuzumab serotherapy is associated with delayed immune reconstitution, contributing to an increased risk of viral infections and graft failure. Alemtuzumab, a long half-life anti-CD52 monoclonal antibody is a robust T-cell depleting serotherapy, and relatively spares memory-effector T cells compared to naïve T cells. We therefore hypothesized that graft size based on T-cell content in patients receiving peripheral blood stem cell graft with alemtuzumab serotherapy would facilitate immune-reconstitution without increasing the risk of graft-versus-host disease. We retrospectively analysed twenty-six consecutive patients with non-malignant disorders grafted using alemtuzumab serotherapy and capping of graft T cells to a maximum of 600 million/kg. The graft T-cell capping protocol resulted in early immune-reconstitution without increasing the risk of severe graft-versus-host disease. Graft T-cell content correlated with CD4+ T-cell reconstitution and acute graft-versus-host disease. The course of CMV viraemia was predictable without recurrence and associated with early T-cell recovery. No patient developed chronic graft-versus-host disease. Overall survival at one year was 100% and disease-free survival was 96% at a median of 899 days (range: 243–1562). Graft size determined by peripheral blood stem cell graft T-cell content in patients receiving alemtuzumab serotherapy for non-malignant disorders is safe and leads to early T-cell immune-reconstitution with excellent survival outcomes.https://doi.org/10.1038/s41598-023-50416-6 |
| spellingShingle | Ambreen Pandrowala Sanna Khan Darshan Kataria Manasa Kakunje Varsha Mishra Dhruv Mamtora Sangeeta Mudaliar Minnie Bodhanwala Bharat Agarwal Prashant Hiwarkar The role of graft T-cell size in patients receiving alemtuzumab serotherapy for non-malignant disorders: results of an institutional protocol Scientific Reports |
| title | The role of graft T-cell size in patients receiving alemtuzumab serotherapy for non-malignant disorders: results of an institutional protocol |
| title_full | The role of graft T-cell size in patients receiving alemtuzumab serotherapy for non-malignant disorders: results of an institutional protocol |
| title_fullStr | The role of graft T-cell size in patients receiving alemtuzumab serotherapy for non-malignant disorders: results of an institutional protocol |
| title_full_unstemmed | The role of graft T-cell size in patients receiving alemtuzumab serotherapy for non-malignant disorders: results of an institutional protocol |
| title_short | The role of graft T-cell size in patients receiving alemtuzumab serotherapy for non-malignant disorders: results of an institutional protocol |
| title_sort | role of graft t cell size in patients receiving alemtuzumab serotherapy for non malignant disorders results of an institutional protocol |
| url | https://doi.org/10.1038/s41598-023-50416-6 |
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