Abstract
BackgroundIn vivo depletion of host T cells with antithymocyte globulin (ATG) is a common strategy for preventing graft-versus-host disease in allogeneic hematopoietic stem cell transplantation (HSCT). The total dose of ATG in conditioning regimens appears to be an important factor that influences the outcome in recipients of transplants. However, the optimal ATG dosage has not been established to date. It remains unclear whether, in the setting of haploidentical HSCT (haploHSCT), different doses of ATG might exert differential influences on the recovery of lymphocyte subpopulations.MethodsThis retrospective study analyzed lymphocyte recovery and its correlation to viral infection in two groups of patients that received different doses of ATG before haploHSCT. We performed flowcytometry to determine immunophenotypes of CD19+ B cells and CD3+, CD4+, CD8+, CD4+CD45RA+, CD4+CD45RO+, CD4+CD28+, CD8+CD28+, and CD4−CD8− T cells.ResultsWe found that, compared to 6 mg/kg, 10 mg/kg ATG significantly hampered the recoveries of CD4+, CD4+CD45RA+, and CD4+CD45RO+ T cells in the first 2 months following haploHSCT. Similarly, compared to 6 mg/kg, the 10 mg/kg dose of ATG negatively influenced the recoveries of CD4−CD8− and CD8+CD28+ T cells; recovery was delayed for 6 and 12 months after transplantation, respectively. Moreover, we showed that an increase in Epstein-Barr virus (EBV) infections, associated with the higher dose of ATG, was correlated with the delayed recovery of CD4−CD8− double negative T cells.ConclusionsThe present study revealed a differential impact of different ATG conditioning doses on the recoveries of T cell subpopulations post-haploHSCT. This study was the first to connect the recovery of CD4−CD8− T cells to the risk of EBV infection after HSCT. These findings will facilitate optimization of the ATG conditioning dosage and improve the outcome of patients with leukemia that receive haploHSCT.
Highlights
In vivo depletion of host T cells with antithymocyte globulin (ATG) is a common strategy for prevent‐ ing graft-versus-host disease in allogeneic hematopoietic stem cell transplantation (HSCT)
Recoveries of T lymphocyte subpopulations were delayed with 10 mg/kg ATG We first analyzed the peripheral white blood cell (WBC) and the absolute lymphocyte counts determined in routine blood tests from day 30 to 360 after haploHSCT
High dose ATG conditioning was associated with a lower incidence of acute graft-versus-host disease (GVHD) but increased Epstein-Barr virus (EBV) reactivation after haploHSCT we evaluated whether different doses of ATG administration pre-transplantation might impact the incidence of acute GVHD
Summary
In vivo depletion of host T cells with antithymocyte globulin (ATG) is a common strategy for prevent‐ ing graft-versus-host disease in allogeneic hematopoietic stem cell transplantation (HSCT). The optimal ATG dosage has not been established to date It remains unclear whether, in the setting of hap‐ loidentical HSCT (haploHSCT), different doses of ATG might exert differential influences on the recovery of lympho‐ cyte subpopulations. The total dose of ATG appears to have an important influence on the overall clinical outcome of transplantation, studies on the impact of different ATG doses have produced inconsistence [9,10,11], and an optimal dose has not been established. In the haploHSCT setting, our previous prospective study reported that, compared to 6 mg/kg ATG, 10 mg/kg ATG conditioning regimen increased the risk of EBV infection, but reduced the incidence of grades III–IV acute GVHD [15]. The cause-consequence relationship between immunodeficiency and the occurrence of viral infections was not demonstrated in this context
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