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

• Published in: Frontiers in immunology Vol. 10; p. 315
• Main Authors: Oostenbrink, Lisa V E, Jol-van der Zijde, Cornelia M, Kielsen, Katrine, Jansen-Hoogendijk, Anja M, Ifversen, Marianne, Müller, Klaus G, Lankester, Arjan C, van Halteren, Astrid G S, Bredius, Robbert G M, Schilham, Marco W, van Tol, Maarten J D
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 06.03.2019
• Subjects: acute GvHD; Animals; Antilymphocyte Serum - immunology; ATG; Fresenius; Genzyme; Graft vs Host Disease - immunology; Hematopoietic Stem Cell Transplantation - methods; Humans; Immunology; Leukemia, Myeloid, Acute - immunology; Lymphocyte Depletion - methods; pediatrics; Rabbits; serotherapy; Stem Cells - immunology; T-Lymphocytes - immunology; Transplantation Conditioning - methods; Unrelated Donors; acute GvHD; serotherapy; ATG; Genzyme; Fresenius; pediatrics
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.00315

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 ( = 42 ATG-GENZ, = 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.