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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.00315

Differential elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme impacts T cell reconstitution after hematopoietic stem cell transplantation

 Lisa V. Oostenbrink1*,  Cornelia M. Jol-van der Zijde1, Katrine Kielsen2, 3, Anja M. Jansen-Hoogendijk1, Marianne Ifversen3, Klaus G. Müller2, 3,  Arjan C. Lankester1,  Astrid G. van Halteren1, Robbert G. Bredius1,  Marco W. Schilham1 and  Maarten J. van Tol1
  • 1Willem-Alexander Children's Hospital, Leiden University Medical Center, Netherlands
  • 2Institute for Inflammation Research, Department of Rheumatology and Rheumatology, Rigshospitalet, Denmark
  • 3Department of Paediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Denmark

Anti-thymocyte globulin (ATG) is a lymphocyte depleting agent applied in hematopoietic stem cell transplantation (HSCT) to prevent rejection and Graft-versus-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.

Keywords: Atg, Genzyme, Fresenius, Serotherapy, Pediatrics, acute GVHD

Received: 09 Nov 2018; Accepted: 06 Feb 2019.

Edited by:

Ulrike Koehl, Hannover Medical School, Germany

Reviewed by:

Philippe Saas, INSERM U1098 Interactions Hôte-Greffon-Tumeur & Ingénierie Cellulaire et Génique, France
Bjarne K. Møller, Aarhus University Hospital, Denmark  

Copyright: © 2019 Oostenbrink, Jol-van der Zijde, Kielsen, Jansen-Hoogendijk, Ifversen, Müller, Lankester, van Halteren, Bredius, Schilham and van Tol. 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.

* Correspondence: MD. Lisa V. Oostenbrink, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, 2300, Netherlands, v.e.oostenbrink@lumc.nl