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Low-dose alemtuzumab induction in a tailored immunosuppression protocol for sensitized kidney transplant recipients

BACKGROUND: Induction therapy is crucial in kidney transplantation and constitutes an important cornerstone for long-term allograft survival. Alemtuzumab is a depleting CD52-specific antibody with T- and B-cell activity, leading to prolonged lymphocyte depletion for up to 12 months, with profound im...

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Autores principales: Guthoff, Martina, Berger, Kilian, Althaus, Karina, Mühlbacher, Thomas, Bakchoul, Tamam, Steurer, Wolfgang, Nadalin, Silvio, Königsrainer, Alfred, Heyne, Nils
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218828/
https://www.ncbi.nlm.nih.gov/pubmed/32404066
http://dx.doi.org/10.1186/s12882-020-01767-z
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author Guthoff, Martina
Berger, Kilian
Althaus, Karina
Mühlbacher, Thomas
Bakchoul, Tamam
Steurer, Wolfgang
Nadalin, Silvio
Königsrainer, Alfred
Heyne, Nils
author_facet Guthoff, Martina
Berger, Kilian
Althaus, Karina
Mühlbacher, Thomas
Bakchoul, Tamam
Steurer, Wolfgang
Nadalin, Silvio
Königsrainer, Alfred
Heyne, Nils
author_sort Guthoff, Martina
collection PubMed
description BACKGROUND: Induction therapy is crucial in kidney transplantation and constitutes an important cornerstone for long-term allograft survival. Alemtuzumab is a depleting CD52-specific antibody with T- and B-cell activity, leading to prolonged lymphocyte depletion for up to 12 months, with profound immunosuppression and an associated risk of serious infections. Current concepts aim to optimize dosing strategies to reduce side effects. Here we present data from an ongoing centre protocol consisting of low-dose alemtuzumab induction and tailored immunosuppression in sensitized patients undergoing kidney transplantation. METHODS: 10-year results of the protocol were analysed. Low-dose alemtuzumab induction consisted of a single dose of 20 mg intraoperatively, followed by tacrolimus and corticosteroids for initial immunosuppression, with mycophenolate mofetil suspended until a total lymphocyte count (TLC) >5% or 200/μl was reached. RESULTS: Between 01/2007 and 04/2017, 46 patients were treated in accordance with the protocol in 48 kidney transplantations. Median PRA(max) was 43 [22-76; IQR] %; all patients had negative CDC-crossmatch prior to transplantation. Low-dose alemtuzumab was well tolerated. Median time to TLC recovery was 77 [62-127; IQR] d. Within a median follow-up of 3.3 [1.5-5.6; IQR] years, 12 (25%) patients developed BPAR, 10 of which were antibody-mediated (3 acute, 7 chronic ABMR). Death-censored 5-year allograft survival was 79.2%, with an excellent allograft function at the end of follow-up. There was no increased rate of infections, in particular viral infections. CONCLUSIONS: Our protocol, comprising low-dose alemtuzumab induction, initial suspension of mycophenolate mofetil and triple maintenance immunosuppression, provides excellent patient and allograft outcome in sensitized renal allograft recipients.
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spelling pubmed-72188282020-05-20 Low-dose alemtuzumab induction in a tailored immunosuppression protocol for sensitized kidney transplant recipients Guthoff, Martina Berger, Kilian Althaus, Karina Mühlbacher, Thomas Bakchoul, Tamam Steurer, Wolfgang Nadalin, Silvio Königsrainer, Alfred Heyne, Nils BMC Nephrol Research Article BACKGROUND: Induction therapy is crucial in kidney transplantation and constitutes an important cornerstone for long-term allograft survival. Alemtuzumab is a depleting CD52-specific antibody with T- and B-cell activity, leading to prolonged lymphocyte depletion for up to 12 months, with profound immunosuppression and an associated risk of serious infections. Current concepts aim to optimize dosing strategies to reduce side effects. Here we present data from an ongoing centre protocol consisting of low-dose alemtuzumab induction and tailored immunosuppression in sensitized patients undergoing kidney transplantation. METHODS: 10-year results of the protocol were analysed. Low-dose alemtuzumab induction consisted of a single dose of 20 mg intraoperatively, followed by tacrolimus and corticosteroids for initial immunosuppression, with mycophenolate mofetil suspended until a total lymphocyte count (TLC) >5% or 200/μl was reached. RESULTS: Between 01/2007 and 04/2017, 46 patients were treated in accordance with the protocol in 48 kidney transplantations. Median PRA(max) was 43 [22-76; IQR] %; all patients had negative CDC-crossmatch prior to transplantation. Low-dose alemtuzumab was well tolerated. Median time to TLC recovery was 77 [62-127; IQR] d. Within a median follow-up of 3.3 [1.5-5.6; IQR] years, 12 (25%) patients developed BPAR, 10 of which were antibody-mediated (3 acute, 7 chronic ABMR). Death-censored 5-year allograft survival was 79.2%, with an excellent allograft function at the end of follow-up. There was no increased rate of infections, in particular viral infections. CONCLUSIONS: Our protocol, comprising low-dose alemtuzumab induction, initial suspension of mycophenolate mofetil and triple maintenance immunosuppression, provides excellent patient and allograft outcome in sensitized renal allograft recipients. BioMed Central 2020-05-13 /pmc/articles/PMC7218828/ /pubmed/32404066 http://dx.doi.org/10.1186/s12882-020-01767-z Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Guthoff, Martina
Berger, Kilian
Althaus, Karina
Mühlbacher, Thomas
Bakchoul, Tamam
Steurer, Wolfgang
Nadalin, Silvio
Königsrainer, Alfred
Heyne, Nils
Low-dose alemtuzumab induction in a tailored immunosuppression protocol for sensitized kidney transplant recipients
title Low-dose alemtuzumab induction in a tailored immunosuppression protocol for sensitized kidney transplant recipients
title_full Low-dose alemtuzumab induction in a tailored immunosuppression protocol for sensitized kidney transplant recipients
title_fullStr Low-dose alemtuzumab induction in a tailored immunosuppression protocol for sensitized kidney transplant recipients
title_full_unstemmed Low-dose alemtuzumab induction in a tailored immunosuppression protocol for sensitized kidney transplant recipients
title_short Low-dose alemtuzumab induction in a tailored immunosuppression protocol for sensitized kidney transplant recipients
title_sort low-dose alemtuzumab induction in a tailored immunosuppression protocol for sensitized kidney transplant recipients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218828/
https://www.ncbi.nlm.nih.gov/pubmed/32404066
http://dx.doi.org/10.1186/s12882-020-01767-z
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