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Serotherapy as Graft-Versus-Host Disease Prophylaxis in Haematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukaemia

Serotherapy comprising agents such as anti-thymocyte globulin, anti-T-lymphocyte globulin, and the anti-CD52 monoclonal antibody alemtuzumab is used widely to reduce the incidence of graft-versus-host disease (GvHD) after paediatric haematopoietic stem cell transplantation (HSCT). The outcome of tra...

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Autores principales: Keogh, Steven J., Dalle, Jean-Hugues, Admiraal, Rick, Pulsipher, Michael A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8771860/
https://www.ncbi.nlm.nih.gov/pubmed/35071142
http://dx.doi.org/10.3389/fped.2021.805189
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author Keogh, Steven J.
Dalle, Jean-Hugues
Admiraal, Rick
Pulsipher, Michael A.
author_facet Keogh, Steven J.
Dalle, Jean-Hugues
Admiraal, Rick
Pulsipher, Michael A.
author_sort Keogh, Steven J.
collection PubMed
description Serotherapy comprising agents such as anti-thymocyte globulin, anti-T-lymphocyte globulin, and the anti-CD52 monoclonal antibody alemtuzumab is used widely to reduce the incidence of graft-versus-host disease (GvHD) after paediatric haematopoietic stem cell transplantation (HSCT). The outcome of transplants using matched unrelated donors now approaches that of matched sibling donors. This is likely due to better disease control in recipients, the use of donors more closely human-leukocyte antigen (HLA)-matched to recipients, and more effective graft-versus-host disease (GvHD) prophylaxis. The price paid for reduced GvHD is slower immune reconstitution of T cells and thus more infections. This has led to studies looking to optimise the amount of serotherapy used. The balance between prevention of GvHD on one side and prevention of infections and relapse on the other side is quite delicate. Serotherapy is given with chemotherapy-/radiotherapy-based conditioning prior to HSCT. Due to their long half-lives, agents used for serotherapy may be detectable in patients well after graft infusion. This exposes the graft-infused T cells to a lympholytic effect, impacting T-cell recovery. As such, excessive serotherapy dosing may lead to no GvHD but a higher incidence of infections and relapse of leukaemia, while under-dosing may result in a higher chance of serious GvHD as immunity recovers more quickly. Individualised dosing is being developed through studies including retrospective analyses of serotherapy exposure, population pharmacokinetic modelling, therapeutic drug monitoring in certain centres, and the development of dosing models reliant on factors including the patient's peripheral blood lymphocyte count. Early results of “optimal” dosing strategies for serotherapy and conditioning chemotherapy show promise of improved overall survival.
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spelling pubmed-87718602022-01-21 Serotherapy as Graft-Versus-Host Disease Prophylaxis in Haematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukaemia Keogh, Steven J. Dalle, Jean-Hugues Admiraal, Rick Pulsipher, Michael A. Front Pediatr Pediatrics Serotherapy comprising agents such as anti-thymocyte globulin, anti-T-lymphocyte globulin, and the anti-CD52 monoclonal antibody alemtuzumab is used widely to reduce the incidence of graft-versus-host disease (GvHD) after paediatric haematopoietic stem cell transplantation (HSCT). The outcome of transplants using matched unrelated donors now approaches that of matched sibling donors. This is likely due to better disease control in recipients, the use of donors more closely human-leukocyte antigen (HLA)-matched to recipients, and more effective graft-versus-host disease (GvHD) prophylaxis. The price paid for reduced GvHD is slower immune reconstitution of T cells and thus more infections. This has led to studies looking to optimise the amount of serotherapy used. The balance between prevention of GvHD on one side and prevention of infections and relapse on the other side is quite delicate. Serotherapy is given with chemotherapy-/radiotherapy-based conditioning prior to HSCT. Due to their long half-lives, agents used for serotherapy may be detectable in patients well after graft infusion. This exposes the graft-infused T cells to a lympholytic effect, impacting T-cell recovery. As such, excessive serotherapy dosing may lead to no GvHD but a higher incidence of infections and relapse of leukaemia, while under-dosing may result in a higher chance of serious GvHD as immunity recovers more quickly. Individualised dosing is being developed through studies including retrospective analyses of serotherapy exposure, population pharmacokinetic modelling, therapeutic drug monitoring in certain centres, and the development of dosing models reliant on factors including the patient's peripheral blood lymphocyte count. Early results of “optimal” dosing strategies for serotherapy and conditioning chemotherapy show promise of improved overall survival. Frontiers Media S.A. 2022-01-06 /pmc/articles/PMC8771860/ /pubmed/35071142 http://dx.doi.org/10.3389/fped.2021.805189 Text en Copyright © 2022 Keogh, Dalle, Admiraal and Pulsipher. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Keogh, Steven J.
Dalle, Jean-Hugues
Admiraal, Rick
Pulsipher, Michael A.
Serotherapy as Graft-Versus-Host Disease Prophylaxis in Haematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukaemia
title Serotherapy as Graft-Versus-Host Disease Prophylaxis in Haematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukaemia
title_full Serotherapy as Graft-Versus-Host Disease Prophylaxis in Haematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukaemia
title_fullStr Serotherapy as Graft-Versus-Host Disease Prophylaxis in Haematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukaemia
title_full_unstemmed Serotherapy as Graft-Versus-Host Disease Prophylaxis in Haematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukaemia
title_short Serotherapy as Graft-Versus-Host Disease Prophylaxis in Haematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukaemia
title_sort serotherapy as graft-versus-host disease prophylaxis in haematopoietic stem cell transplantation for acute lymphoblastic leukaemia
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8771860/
https://www.ncbi.nlm.nih.gov/pubmed/35071142
http://dx.doi.org/10.3389/fped.2021.805189
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