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The Effect of Stem Cell Transplantation on Immunosuppression in Living Donor Renal Transplantation: A Clinical Trial
Background/Objective: We designed a clinical trial on a group of live-donor renal transplantation (LDRT) patients subjected to pre-transplant stem cell transplantation (SCT) to minimize immunosuppression to low-dose steroid monotherapy. Methods: LDRT patients subjected to pretransplant SCT who had s...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Avicenna Organ Transplantation Institute
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089327/ https://www.ncbi.nlm.nih.gov/pubmed/25013669 |
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author | Trivedi, H. L. Vanikar, A. V. Kute, V. B. Patel, H. V. Gumber, M. R. Shah, P. R. Dave, S. D. Trivedi, V. B. |
author_facet | Trivedi, H. L. Vanikar, A. V. Kute, V. B. Patel, H. V. Gumber, M. R. Shah, P. R. Dave, S. D. Trivedi, V. B. |
author_sort | Trivedi, H. L. |
collection | PubMed |
description | Background/Objective: We designed a clinical trial on a group of live-donor renal transplantation (LDRT) patients subjected to pre-transplant stem cell transplantation (SCT) to minimize immunosuppression to low-dose steroid monotherapy. Methods: LDRT patients subjected to pretransplant SCT who had stable graft function for ≥2 years and serum creatinine (SCr) <2 mg/dL were recruited. Patients with diabetes, hepatitis C/B, rejections, or unwilling to participate, were excluded. They had been subjected to non-myeloablative conditioning of total lymphoid irradiation (TLI)/bortezomib and cyclophosphamide, rabbit-antithymocyte globulin (r-ATG) and rituximab with SCT. The maintenance immunosuppression consisted of calcineurin inhibitors (CNI) and/or anti-proliferative agents and prednisone. Donor-specific antibodies (DSA) and peripheral T-regulatory cells (CD127(low/–)/4(+)/25(high)) (p-Tregs) were studied before and after withdrawal of major immunosuppressants; graft biopsy was taken after 100 days of withdrawal in willing patients. Rejections were planned to be treated by anti-rejection therapy followed by rescue immunosuppression. Results: All immunosuppression but prednisone, 5–10 mg/day has been successfully withdrawn for a mean of 2.2 years in 76 patients with a mean age of 31.4 years and a mean donor-recipient HLA match of 2.9. The mean SCr of 1.4 mg/dL and p-Tregs of 3.5% was remained stable after withdrawal; DSA status was negative in 35.5% and positive in 47.4% patients. Protocol biopsies in all 10 patients who gave the consent were unremarkable. Conclusion: Stable graft function in LDRT on low-dose steroid monotherapy using pre-transplant SCT under non-myeloablative conditioning with generation of p-Tregs can be achieved successfully and safely. |
format | Online Article Text |
id | pubmed-4089327 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Avicenna Organ Transplantation Institute |
record_format | MEDLINE/PubMed |
spelling | pubmed-40893272014-07-10 The Effect of Stem Cell Transplantation on Immunosuppression in Living Donor Renal Transplantation: A Clinical Trial Trivedi, H. L. Vanikar, A. V. Kute, V. B. Patel, H. V. Gumber, M. R. Shah, P. R. Dave, S. D. Trivedi, V. B. Int J Organ Transplant Med Original Article Background/Objective: We designed a clinical trial on a group of live-donor renal transplantation (LDRT) patients subjected to pre-transplant stem cell transplantation (SCT) to minimize immunosuppression to low-dose steroid monotherapy. Methods: LDRT patients subjected to pretransplant SCT who had stable graft function for ≥2 years and serum creatinine (SCr) <2 mg/dL were recruited. Patients with diabetes, hepatitis C/B, rejections, or unwilling to participate, were excluded. They had been subjected to non-myeloablative conditioning of total lymphoid irradiation (TLI)/bortezomib and cyclophosphamide, rabbit-antithymocyte globulin (r-ATG) and rituximab with SCT. The maintenance immunosuppression consisted of calcineurin inhibitors (CNI) and/or anti-proliferative agents and prednisone. Donor-specific antibodies (DSA) and peripheral T-regulatory cells (CD127(low/–)/4(+)/25(high)) (p-Tregs) were studied before and after withdrawal of major immunosuppressants; graft biopsy was taken after 100 days of withdrawal in willing patients. Rejections were planned to be treated by anti-rejection therapy followed by rescue immunosuppression. Results: All immunosuppression but prednisone, 5–10 mg/day has been successfully withdrawn for a mean of 2.2 years in 76 patients with a mean age of 31.4 years and a mean donor-recipient HLA match of 2.9. The mean SCr of 1.4 mg/dL and p-Tregs of 3.5% was remained stable after withdrawal; DSA status was negative in 35.5% and positive in 47.4% patients. Protocol biopsies in all 10 patients who gave the consent were unremarkable. Conclusion: Stable graft function in LDRT on low-dose steroid monotherapy using pre-transplant SCT under non-myeloablative conditioning with generation of p-Tregs can be achieved successfully and safely. Avicenna Organ Transplantation Institute 2013 2013-11-01 /pmc/articles/PMC4089327/ /pubmed/25013669 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Trivedi, H. L. Vanikar, A. V. Kute, V. B. Patel, H. V. Gumber, M. R. Shah, P. R. Dave, S. D. Trivedi, V. B. The Effect of Stem Cell Transplantation on Immunosuppression in Living Donor Renal Transplantation: A Clinical Trial |
title | The Effect of Stem Cell Transplantation on Immunosuppression in Living Donor Renal Transplantation: A Clinical Trial |
title_full | The Effect of Stem Cell Transplantation on Immunosuppression in Living Donor Renal Transplantation: A Clinical Trial |
title_fullStr | The Effect of Stem Cell Transplantation on Immunosuppression in Living Donor Renal Transplantation: A Clinical Trial |
title_full_unstemmed | The Effect of Stem Cell Transplantation on Immunosuppression in Living Donor Renal Transplantation: A Clinical Trial |
title_short | The Effect of Stem Cell Transplantation on Immunosuppression in Living Donor Renal Transplantation: A Clinical Trial |
title_sort | effect of stem cell transplantation on immunosuppression in living donor renal transplantation: a clinical trial |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089327/ https://www.ncbi.nlm.nih.gov/pubmed/25013669 |
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