TY - JOUR
T1 - Differential elimination of anti-thymocyte globulin of Fresenius and genzyme impacts T-cell reconstitution after hematopoietic stem cell transplantation
AU - Oostenbrink, Lisa V.E.
AU - Jol-Van Der Zijde, Cornelia M.
AU - Kielsen, Katrine
AU - Jansen-Hoogendijk, Anja M.
AU - Ifversen, Marianne
AU - Müller, Klaus G.
AU - Lankester, Arjan C.
AU - Van Halteren, Astrid G.S.
AU - Bredius, Robbert G.M.
AU - Schilham, Marco W.
AU - Van Tol, Maarten J.D.
N1 - Publisher 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.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Acute GvHD
KW - ATG
KW - Fresenius
KW - Genzyme
KW - Pediatrics
KW - Serotherapy
UR - http://www.scopus.com/inward/record.url?scp=85063611662&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2019.00315
DO - 10.3389/fimmu.2019.00315
M3 - Article
C2 - 30894854
AN - SCOPUS:85063611662
SN - 1664-3224
VL - 10
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - MAR
M1 - 315
ER -