Rabbit Anti–T Cell Globulin in Allogeneic Hematopoietic Cell Transplantation

Abstract

Anti-T cell globulin (ATG) is polyclonal IgG from rabbits immunized with human thymocytes or a human T cell line. Prophylaxis using ATG infused with conditioning for adult marrow or blood stem cell transplantation reduces both acute and chronic graft-versus-host disease (GVHD). However, ATG is not or minimally efficacious in steroid refractory GVHD treatment. Regarding preemptive therapy, ATG is promising; however, further work is needed on establishing adequate biomarkers to be used as triggers for preemptive therapy before it can be used routinely. Relapse is not increased by ATG, except possibly in the setting of reduced-intensity conditioning. Infections are probably increased when using high but not low-dose ATG, except for Epstein-Barr virus-driven post-transplantation lymphoproliferative disorder, which may be increased even with low-dose ATG. Survival is not improved with ATG; however, survival free of immunosuppressive therapy is improved. Pharmacokinetics of ATG are highly variable, resulting in highly variable areas under the time-concentration curves. Optimized dosing of ATG might improve transplantation outcomes. In conclusion, ATG reduces GVHD and, thus, may improve quality of life, without compromising survival.

Lower dose anti-thymocyte globulin for GvHD prophylaxis results in improved survival after allogeneic stem cell transplantation

“…In summary, our results are consistent with previous studies, including randomized trials and observational studies, showing in the majority that ATG as part of the conditioning reduces GvHD, particularly cGvHD without increasing relapse but without a survival benefit, as reviewed by Storek et al 26 In our cohort though, there is a survival benefit in patients with unrelated donor HSCT and with related donor HSCT at high risk of GvHD receiving lower dose ATG-F with less TRM in spite of higher risks of infectious complications.…”

The patient’s CMV serological status affects clinical outcome after T-cell replete haplo-HSCT and post-transplant cyclophosphamide

“…Despite being indirect, the data may suggest a better immune reconstitution after PT-Cy than after anti-thymocyte globulin (ATG), 8,9 infections (in particular of viral origin) occur frequently in the early post-transplant period after PT-Cy; 10 this may explain our findings of higher NRM and worse survival among CMV+ patients, events that are possibly related to the high cumulative incidence of CMV infectious episodes observed here in the cohorts 3 and 4. In addition, unfortunately the treatment with the available anti-CMV agents may be complicated by myelotoxicity and/or renal impairment, therefore this may conduct ultimately to fatal complications, even if the final event is different from the CMV infection itself.…”

Anti-thymocyte globulin as graft- versus -host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…21 ATGAM (ATG-h) consists of polyclonal IgG obtained from hyperimmune sera of horses immunized with human thymic cells. The two other brands of ATG consist of polyclonal IgG obtained from hyperimmune sera of rabbits immunized either with human thymocytes recovered from patients undergoing cardiac surgery (Thymoglobuline, ATG-T) or with the human Jurkat leukemic T-cell line (which was derived from the peripheral blood of a 14-year old boy suffering from acute T-cell leukemia 22 ) [ATG Fresenius/Neovii (ATG-F)].…”