Dynamic immune profiling identifies the stronger graft-versus-leukemia (GVL) effects with haploidentical allografts compared to HLA-matched stem cell transplantation.
Haploidentical stem cell transplantation (haplo-SCT) achieves superior or at least comparable clinical outcomes to HLA-matched sibling donor transplantation (MSDT) in treating hematological malignancies. To define the underlying regulatory dynamics, we analyzed time courses of leukemia burden and immune abundance of haplo-SCT or MSDT from multiple dimension. First, we employed two nonirradiated leukemia mouse models which carried human AML-ETO or MLL-AF9 fusion gene to establish haplo-identical and major histocompatibility (MHC)-matched transplantation models and investigated the immune cell dynamic response during leukemia development in vivo. We found that haplo-matching the MHCs of leukemia cells with recipient mouse T cells prolonged leukemic mice survival and reduced leukemia burden. The stronger graft-versus-leukemia activity in haplo-SCT group mainly induced by decreased apoptosis and increased cytotoxic cytokine secretion including tumor necrosis factor-α, interferon-γ, pore-forming proteins and CD107a secreted by T cells or natural killer cells. Furthermore, we conducted a prospective clinical trial which enrolled 135 patients with t(8;21) acute myeloid leukemia that displayed minimal residual disease before transplantation and underwent either haplo-SCT or MSDT. The results showed that the haplo-SCT slowed the kinetics of the leukemia burden in vivo and reduced the cumulative incidence of relapse compared with MSDT. Ex vivo experiments showed that, 1 year after transplantation, cytotoxic T lymphocytes from the haplo-SCT group had higher cytotoxicity than those from the MSDT group during the same period. Our results unraveled the role of immune cells in superior antileukemia effects of haplo-SCT compared with MSDT.
['Guo|Huidong|H|', 'Chang|Ying-Jun|YJ|', 'Hong|Yan|Y|', 'Xu|Lan-Ping|LP|', 'Wang|Yu|Y|', 'Zhang|Xiao-Hui|XH|', 'Wang|Ming|M|', 'Chen|Huan|H|', 'Chen|Yu-Hong|YH|', 'Wang|Feng-Rong|FR|', 'Wei-Han|||', 'Sun|Yu-Qian|YQ|', 'Yan|Chen-Hua|CH|', 'Tang|Fei-Fei|FF|', 'Mo|Xiao-Dong|XD|', 'Liu|Kai-Yan|KY|', 'Huang|Xiao-Jun|XJ|']
Graft-versus-leukemia Haplo-SCT MSDT AML MRD