Differential impact of two doses of antithymocyte globulin conditioning on lymphocyte recovery upon haploidentical hematopoietic stem cell transplantation

Jiangying Liu, Lan-Ping Xu, Zhilei Bian, Ying-Jun Chang, Yu Wang, Xiao-Hui Zhang, Xiao-Jun Huang

In 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. This 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. We 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. The 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.