Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation

Anti-thymocyte globulin (ATG) is a lymphocyte depleting agent applied in hematopoietic stem cell transplantation (HSCT) to prevent rejection and Graft-vs.-Host Disease (GvHD). In this study, we compared two rabbit ATG products, ATG-Genzyme (ATG-GENZ), and ATG-Fresenius (ATG-FRES), with respect to do...

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Main Authors: Lisa V. E. Oostenbrink, Cornelia M. Jol-van der Zijde, Katrine Kielsen, Anja M. Jansen-Hoogendijk, Marianne Ifversen, Klaus G. Müller, Arjan C. Lankester, Astrid G. S. van Halteren, Robbert G. M. Bredius, Marco W. Schilham, Maarten J. D. van Tol
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-03-01
Series:Frontiers in Immunology
Subjects:
ATG
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2019.00315/full
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spelling doaj-8044e135e7df45b3a36d392be8be61d72020-11-25T02:18:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-03-011010.3389/fimmu.2019.00315435886Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell TransplantationLisa V. E. Oostenbrink0Cornelia M. Jol-van der Zijde1Katrine Kielsen2Katrine Kielsen3Anja M. Jansen-Hoogendijk4Marianne Ifversen5Klaus G. Müller6Klaus G. Müller7Arjan C. Lankester8Astrid G. S. van Halteren9Robbert G. M. Bredius10Marco W. Schilham11Maarten J. D. van Tol12Department of Pediatrics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Pediatrics, Leiden University Medical Center, Leiden, NetherlandsInstitute for Inflammation Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, DenmarkDepartment of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, DenmarkDepartment of Pediatrics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, DenmarkInstitute for Inflammation Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, DenmarkDepartment of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, DenmarkDepartment of Pediatrics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Pediatrics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Pediatrics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Pediatrics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Pediatrics, Leiden University Medical Center, Leiden, NetherlandsAnti-thymocyte globulin (ATG) is a lymphocyte depleting agent applied in hematopoietic stem cell transplantation (HSCT) to prevent rejection and Graft-vs.-Host Disease (GvHD). In this study, we compared two rabbit ATG products, ATG-Genzyme (ATG-GENZ), and ATG-Fresenius (ATG-FRES), with respect to dosing, clearance of the active lymphocyte binding component, post-HSCT immune reconstitution and clinical outcome. Fifty-eigth pediatric acute leukemia patients (n = 42 ATG-GENZ, n = 16 ATG-FRES), who received a non-depleted bone marrow or peripheral blood stem cell graft from an unrelated donor were included. ATG-GENZ was given at a dosage of 6–10 mg/kg; ATG-FRES at 45–60 mg/kg. The active component of ATG from both products was cleared at different rates. Within the ATG-FRES dose range no differences were found in clearance of active ATG or T-cell re-appearance. However, the high dosage of ATG-GENZ (10 mg/kg), in contrast to the low dosage (6–8 mg/kg), correlated with prolonged persistence of active ATG and delayed T-cell reconstitution. Occurrence of serious acute GvHD (grade III–IV) was highest in the ATG-GENZ-low dosage group. These results imply that dosing of ATG-GENZ is more critical than dosing of ATG-FRES due to the difference in clearance of active ATG. This should be taken into account when designing clinical protocols.https://www.frontiersin.org/article/10.3389/fimmu.2019.00315/fullATGGenzymeFreseniusserotherapypediatricsacute GvHD
collection DOAJ
language English
format Article
sources DOAJ
author Lisa V. E. Oostenbrink
Cornelia M. Jol-van der Zijde
Katrine Kielsen
Katrine Kielsen
Anja M. Jansen-Hoogendijk
Marianne Ifversen
Klaus G. Müller
Klaus G. Müller
Arjan C. Lankester
Astrid G. S. van Halteren
Robbert G. M. Bredius
Marco W. Schilham
Maarten J. D. van Tol
spellingShingle Lisa V. E. Oostenbrink
Cornelia M. Jol-van der Zijde
Katrine Kielsen
Katrine Kielsen
Anja M. Jansen-Hoogendijk
Marianne Ifversen
Klaus G. Müller
Klaus G. Müller
Arjan C. Lankester
Astrid G. S. van Halteren
Robbert G. M. Bredius
Marco W. Schilham
Maarten J. D. van Tol
Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation
Frontiers in Immunology
ATG
Genzyme
Fresenius
serotherapy
pediatrics
acute GvHD
author_facet Lisa V. E. Oostenbrink
Cornelia M. Jol-van der Zijde
Katrine Kielsen
Katrine Kielsen
Anja M. Jansen-Hoogendijk
Marianne Ifversen
Klaus G. Müller
Klaus G. Müller
Arjan C. Lankester
Astrid G. S. van Halteren
Robbert G. M. Bredius
Marco W. Schilham
Maarten J. D. van Tol
author_sort Lisa V. E. Oostenbrink
title Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation
title_short Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation
title_full Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation
title_fullStr Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation
title_full_unstemmed Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation
title_sort differential elimination of anti-thymocyte globulin of fresenius and genzyme impacts t-cell reconstitution after hematopoietic stem cell transplantation
publisher Frontiers Media S.A.
series Frontiers in Immunology
issn 1664-3224
publishDate 2019-03-01
description Anti-thymocyte globulin (ATG) is a lymphocyte depleting agent applied in hematopoietic stem cell transplantation (HSCT) to prevent rejection and Graft-vs.-Host Disease (GvHD). In this study, we compared two rabbit ATG products, ATG-Genzyme (ATG-GENZ), and ATG-Fresenius (ATG-FRES), with respect to dosing, clearance of the active lymphocyte binding component, post-HSCT immune reconstitution and clinical outcome. Fifty-eigth pediatric acute leukemia patients (n = 42 ATG-GENZ, n = 16 ATG-FRES), who received a non-depleted bone marrow or peripheral blood stem cell graft from an unrelated donor were included. ATG-GENZ was given at a dosage of 6–10 mg/kg; ATG-FRES at 45–60 mg/kg. The active component of ATG from both products was cleared at different rates. Within the ATG-FRES dose range no differences were found in clearance of active ATG or T-cell re-appearance. However, the high dosage of ATG-GENZ (10 mg/kg), in contrast to the low dosage (6–8 mg/kg), correlated with prolonged persistence of active ATG and delayed T-cell reconstitution. Occurrence of serious acute GvHD (grade III–IV) was highest in the ATG-GENZ-low dosage group. These results imply that dosing of ATG-GENZ is more critical than dosing of ATG-FRES due to the difference in clearance of active ATG. This should be taken into account when designing clinical protocols.
topic ATG
Genzyme
Fresenius
serotherapy
pediatrics
acute GvHD
url https://www.frontiersin.org/article/10.3389/fimmu.2019.00315/full
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