Frontiers in Immunology (Mar 2019)

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

  • 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

DOI
https://doi.org/10.3389/fimmu.2019.00315
Journal volume & issue
Vol. 10

Abstract

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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.

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