The impact of different doses of antithymocyte globulin conditioning on immune reconstitution upon hematopoietic stem cell transplantation

Abstract

Introduction: Anti-thymocyte globulin (ATG) is used prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) for graft-versus-host disease (GVHD) prophylaxis. Two different ATG doses (7.5 or 10 mg/kg) were evaluated in comparison with a group without ATG therapy.

Methods: We retrospectively analyzed 132 patients who were transplanted with HSCT without ATG (non-ATG), or who received 7.5 mg/kg ATG (ATG-7.5) or 10 mg/kg ATG (ATG-10) prior to transplantation. The immune cells (CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, CD19⁺ B cells and CD16⁺CD56⁺ NK cells) were examined in peripheral blood every three months post-HSCT for 12 months.

Results: Compared with non-ATG group, combined ATG-7.5/ATG-10 groups had significantly lower CD3⁺CD4⁺ T cells and higher CD3⁺CD8⁺ T cells at 3, 6, 9, 12 months post-HSCT; thus, displaying a lower CD4/CD8 ratio in the ATG groups compared to non-ATG group. The ratio of CD19⁺ B cells was statistically lower (at 3rd month, p = .014; at 6th month, p = .025) in combined ATG-7.5/ATG-10 groups at 3 and 6 months post-HSCT, but not at 9 and 12 months after HSCT. The ratios of CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, CD19⁺ B cells and CD16⁺CD56⁺ NK cells were similar between the ATG-7.5 and ATG-10 groups at all examined time points. The overall survival (OS), progression-free survival (PFS), relapse and acute GVHD (aGVHD) were comparable among recipients without ATG therapy and with ATG-7.5 or/and ATG-10 therapies. Multivariate analysis revealed that immune cells ratios were not independent factors affecting prognosis.

Conclusion: The ATG therapy at higher and lower doses led to a delayed reconstitution of T cells and the inversion of CD4/CD8 ratio for at least one year after HSCT.

Keywords: Allogeneic hematopoietic stem cell transplantation; Anti-thymocyte globulin; Conditioning regimen; Immune reconstitution.