Impact of Pre-Transplant Anti-T Cell Globulin (ATG) on Immune Recovery after Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation

PLoS One. 2015 Jun 22;10(6):e0130026. doi: 10.1371/journal.pone.0130026. eCollection 2015.

Abstract

Background: Pre-transplant infusion of rabbit anti-T cell globulin (ATG) is increasingly used as prevention of graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (PBSCT). However, the precise impact of pre-transplant ATG on immune recovery after PBSCT is still poorly documented.

Methods: In the current study, we compared immune recovery after myeloablative PBSCT in 65 patients who either received (n = 37) or did not (n = 28) pre-transplant ATG-Fresenius (ATG-F). Detailed phenotypes of circulating T, B, natural killer (NK) and invariant NKT (iNKT) cells were analyzed by multicolor flow cytometry at serial time-points from day 40 to day 365 after transplantation. Thymic function was also assessed by sjTREC quantification. Serious infectious events were collected up to 2 years post-transplantation.

Results: Pre-transplant ATG-F had a prolonged (for at least up to 1-year) and selective negative impact on the T-cell pool, while it did not impair the recovery of B, NK nor iNKT cells. Among T cells, ATG-F selectively compromised the recovery of naïve CD4+, central memory CD4+ and naïve CD8+ cells, while it spared effector memory T and regulatory T cells. Levels of sjTRECs were similar in both cohorts at 1-year after PBSCT, suggesting that ATG-F unlikely impaired thymopoiesis at long-term after PBSCT. Finally, the incidence and rate of serious infections were similar in both groups, while ATG-F patients had a lower incidence of grade II-IV acute graft-versus-host disease.

Conclusions: Pre-transplant ATG-F induces long-lasting modulation of the circulating T-cell pool after myeloablative PBSCT, that may participate in preventing graft-versus-host disease without deeply compromising anti-pathogen defenses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • B-Lymphocytes / immunology
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Globulins / immunology*
  • Graft vs Host Disease / immunology*
  • Granulocyte Precursor Cells / immunology*
  • Humans
  • Killer Cells, Natural / immunology
  • Male
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation / adverse effects*
  • Retrospective Studies
  • T-Lymphocytes / immunology*
  • Transplantation Conditioning / adverse effects
  • Young Adult

Substances

  • Globulins

Grants and funding

FB is a senior research associate of the National Fund for Scientific Research (FNRS) Belgium. This study was supported by funds from the Leon Fredericq fund and Anti-Cancer Center at the University of Liège. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.