Abstract
Background aims. Anti-thymocyte globulin (ATG) is being used increasingly to prevent graft-versus-host disease (GvHD); however, its impact on immune reconstitution is relatively unknown. We (i) studied immune reconstitution after ATG-conditioned hematopoietic cell transplantation (HCT), (ii) determined the factors influencing the reconstitution, and (iii) compared it with non-ATG-conditioned HCT. Methods. Immune cell subset counts were determined at 1–24 months post-transplant in 125 HCT recipients who received ATG during conditioning. Subset counts were also determined in 46 non-ATG-conditioned patients (similarly treated). Results. (i) Reconstitution after ATG-conditioned HCT was fast for innate immune cells, intermediate for B cells and CD8 T cells, and very slow for CD4 T cells and invariant natural killer T (iNKT) (iNKT) cells. (ii) Faster reconstitution after ATG-conditioned HCT was associated with a higher number of cells of the same subset transferred with the graft in the case of memory B cells, naive CD4 T cells, naive CD8 T cells, iNKT cells and myeloid dendritic cells; lower recipient age in the case of naive CD4 T cells and naive CD8 T cells; cytomegalovirus recipient seropositivity in the case of memory/effector T cells; an absence of GvHD in the case of naive B cells; lower ATG serum levels in the case of most T-cell subsets, including iNKT cells; and higher ATG levels in the case of NK cells and B cells. (iii) Compared with non-ATG-conditioned HCT, reconstitution after ATG-conditioned HCT was slower for CD4 T cells, and faster for NK cells and B cells. Conclusions. ATG worsens the reconstitution of CD4 T cells but improves the reconstitution of NK and B cells.
Acknowledgements
The authors would like to thank the patients for participating in research that could not benefit them but only future patients. This study could not happen without the dedication of Polly Louie, Lynne Fisk, Judy Wu, Glennis Doiron, Vandana Singh, Monja Metcalf, as well as the staff of the Alberta Blood and Marrow Transplant Program, including inpatient and outpatient nurses and physicians, including Drs Ahsan Chaudhry, Nancy Zacarias, Ping Yue, Nizar Bahlis, Chris Brown, Andrew Daly, Peter Duggan, Michelle Geddes, Lynn Savoie, Douglas Stewart, Mona Shafey, Loree Larratt and Robert Turner.
This work was presented in abstract form at an American Society of Hematology meeting in San Diego, December 2011.
Disclosure of interest: JS has received a grant from Genzyme, Otherwise the authors declare no competing financial interests.
Grant support: Alberta Heritage Foundation for Medical Research, Canada Research Chair Program, Alberta Cancer Foundation, and US National Institutes of Health (CA18029).