Improved Survival From Graft-versus-host Disease Following Pediatric Small Intestinal Transplantation Through Reduction in Systemic Immunosuppression Altering T-cell Chimerism Dynamics
Background. Graft-versus-host-disease (GvHD) is an infrequent but serious complication of small intestinal transplantation in children, which is associated with a very poor prognosis. This study evaluated a novel strategy of managing GvHD in these patients through a reduction in immunosuppression. M...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer
2025-07-01
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| Series: | Transplantation Direct |
| Online Access: | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001830 |
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| author | Sandeep Potluri, FRCPath, PhD Sarah Lawson, FRCPath Shyla Kishore, FRCPCH Malobi Ogboli, FRCP Jane Hartley, FRCPCH Arun Alfred, FRCPath Yvonne Wilson, FRCSG (Plast) Darius F. Mirza, FRCS Khalid Sharif, FRCS Girish Gupte, FRCPCH |
| author_facet | Sandeep Potluri, FRCPath, PhD Sarah Lawson, FRCPath Shyla Kishore, FRCPCH Malobi Ogboli, FRCP Jane Hartley, FRCPCH Arun Alfred, FRCPath Yvonne Wilson, FRCSG (Plast) Darius F. Mirza, FRCS Khalid Sharif, FRCS Girish Gupte, FRCPCH |
| author_sort | Sandeep Potluri, FRCPath, PhD |
| collection | DOAJ |
| description | Background. Graft-versus-host-disease (GvHD) is an infrequent but serious complication of small intestinal transplantation in children, which is associated with a very poor prognosis. This study evaluated a novel strategy of managing GvHD in these patients through a reduction in immunosuppression.
Methods. We conducted a retrospective review 108 consecutive pediatric patients at our center between 2005 and 2021, who had small intestinal transplantation. We assessed clinical features and outcomes as well as laboratory chimerism studies in cohorts of patients before and following a change in treatment strategy for GvHD from intensification to reduction in immunosuppression.
Results. Fourteen percent of pediatric patients developed GvHD after small intestinal transplantation. A change in treatment strategy to a reduction in immunosuppression led to significantly improved overall survival (log rank P = 0.015). This improved survival correlated biologically with altered T-cell chimerism dynamics in blood; in patients who had a reduction in immunosuppression, there was abrogation of the rise in donor T-cell chimerism over time seen in the blood of patients who instead had intensification of their immunosuppression. This may be because of permitting recipient lymphocytes to have a host-versus-graft effect and outcompete donor-derived lymphocytes.
Conclusions. Our results demonstrate that that altering the immunosuppressive therapy strategy, following clinical manifestations of GvHD such as a typical skin rash, from intensification to a reduction in immunosuppression led to significantly improved survival. |
| format | Article |
| id | doaj-art-d903d95ebb0841d6bd030656a8e8013b |
| institution | Kabale University |
| issn | 2373-8731 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Transplantation Direct |
| spelling | doaj-art-d903d95ebb0841d6bd030656a8e8013b2025-08-20T03:35:36ZengWolters KluwerTransplantation Direct2373-87312025-07-01117e183010.1097/TXD.0000000000001830202507000-00007Improved Survival From Graft-versus-host Disease Following Pediatric Small Intestinal Transplantation Through Reduction in Systemic Immunosuppression Altering T-cell Chimerism DynamicsSandeep Potluri, FRCPath, PhD0Sarah Lawson, FRCPath1Shyla Kishore, FRCPCH2Malobi Ogboli, FRCP3Jane Hartley, FRCPCH4Arun Alfred, FRCPath5Yvonne Wilson, FRCSG (Plast)6Darius F. Mirza, FRCS7Khalid Sharif, FRCS8Girish Gupte, FRCPCH91 Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United Kingdom.1 Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United Kingdom.1 Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United Kingdom.1 Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United Kingdom.1 Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United Kingdom.3 Department of Haematology, The Rotherham NHS Foundation Trust, Rotherham, United Kingdom.1 Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United Kingdom.4 Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.1 Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United Kingdom.1 Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United Kingdom.Background. Graft-versus-host-disease (GvHD) is an infrequent but serious complication of small intestinal transplantation in children, which is associated with a very poor prognosis. This study evaluated a novel strategy of managing GvHD in these patients through a reduction in immunosuppression. Methods. We conducted a retrospective review 108 consecutive pediatric patients at our center between 2005 and 2021, who had small intestinal transplantation. We assessed clinical features and outcomes as well as laboratory chimerism studies in cohorts of patients before and following a change in treatment strategy for GvHD from intensification to reduction in immunosuppression. Results. Fourteen percent of pediatric patients developed GvHD after small intestinal transplantation. A change in treatment strategy to a reduction in immunosuppression led to significantly improved overall survival (log rank P = 0.015). This improved survival correlated biologically with altered T-cell chimerism dynamics in blood; in patients who had a reduction in immunosuppression, there was abrogation of the rise in donor T-cell chimerism over time seen in the blood of patients who instead had intensification of their immunosuppression. This may be because of permitting recipient lymphocytes to have a host-versus-graft effect and outcompete donor-derived lymphocytes. Conclusions. Our results demonstrate that that altering the immunosuppressive therapy strategy, following clinical manifestations of GvHD such as a typical skin rash, from intensification to a reduction in immunosuppression led to significantly improved survival.http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001830 |
| spellingShingle | Sandeep Potluri, FRCPath, PhD Sarah Lawson, FRCPath Shyla Kishore, FRCPCH Malobi Ogboli, FRCP Jane Hartley, FRCPCH Arun Alfred, FRCPath Yvonne Wilson, FRCSG (Plast) Darius F. Mirza, FRCS Khalid Sharif, FRCS Girish Gupte, FRCPCH Improved Survival From Graft-versus-host Disease Following Pediatric Small Intestinal Transplantation Through Reduction in Systemic Immunosuppression Altering T-cell Chimerism Dynamics Transplantation Direct |
| title | Improved Survival From Graft-versus-host Disease Following Pediatric Small Intestinal Transplantation Through Reduction in Systemic Immunosuppression Altering T-cell Chimerism Dynamics |
| title_full | Improved Survival From Graft-versus-host Disease Following Pediatric Small Intestinal Transplantation Through Reduction in Systemic Immunosuppression Altering T-cell Chimerism Dynamics |
| title_fullStr | Improved Survival From Graft-versus-host Disease Following Pediatric Small Intestinal Transplantation Through Reduction in Systemic Immunosuppression Altering T-cell Chimerism Dynamics |
| title_full_unstemmed | Improved Survival From Graft-versus-host Disease Following Pediatric Small Intestinal Transplantation Through Reduction in Systemic Immunosuppression Altering T-cell Chimerism Dynamics |
| title_short | Improved Survival From Graft-versus-host Disease Following Pediatric Small Intestinal Transplantation Through Reduction in Systemic Immunosuppression Altering T-cell Chimerism Dynamics |
| title_sort | improved survival from graft versus host disease following pediatric small intestinal transplantation through reduction in systemic immunosuppression altering t cell chimerism dynamics |
| url | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001830 |
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