Immunological properties of bone marrow microenvironment 1 year after allogeneic hematopoietic stem cell transplantation

Post‐hematopoietic stem cell transplantation relapse: Role of checkpoint inhibitors

“… 9 Although regulatory T cells (T regs) effectively prevent GVHD, they may prohibit GVL. 10 Consistent with this, it has been demonstrated in a study that a higher dose of CD34+ cells correlates with a higher rate of relapse, which proposed that it could be due to more malignant cells and T regs, decreasing antileukemic effects. 11 Because of a higher percentage of T cells in peripheral blood HSCT, the relapse rate is lower at the expense of a higher incidence of GVHD.…”

“…Reduced dendritic cells (DCs) have been associated with relapse after HSCT 9 . Although regulatory T cells (T regs) effectively prevent GVHD, they may prohibit GVL 10 . Consistent with this, it has been demonstrated in a study that a higher dose of CD34+ cells correlates with a higher rate of relapse, which proposed that it could be due to more malignant cells and T regs, decreasing antileukemic effects 11 .…”

Targeting the CD27-CD70 Pathway to Improve Outcomes in Both Checkpoint Immunotherapy and Allogeneic Hematopoietic Cell Transplantation

“…In a study of the bone marrow microenvironment in 28 patients undergoing alloHCT for hematologic malignancies, dramatic changes were noted over the course of one year. In six patients undergoing a myeloablative conditioning regimen, bone marrow samples were obtained on the day of transplantation (day 0) to determine the effect of conditioning, which demonstrated a statistically significant increase in Tregs and a 30-fold increase in IFNγ concentration ( 9 ). However, the concentration of IL-2, IL-6, IL-10, and IL-17A were not significantly different, while IL-1b, IL-4, IL-11, and TNFα were mostly undetectable.…”

“…The initiation phase of GVHD is believed to be mediated by both surviving host and donor Antigen Presenting Cells (APCs) (5,6). The insult of conditioning chemotherapy and Total Body Irradiation (TBI) has been shown to cause significant changes in hematopoiesis, activation of host APCs, and host tissue damage, leading to an inflammatory environment, which sets the stage for the development of acute GVHD (7)(8)(9)(10). This inflammatory milieu includes cytokine release in both hematopoietic and nonhematopoietic compartments, leading to both host and donor Tcell activation and proliferation and alloreactivity which subsequently damages host tissue as GVHD manifests (9)(10)(11)(12)(13).…”

“…The insult of conditioning chemotherapy and Total Body Irradiation (TBI) has been shown to cause significant changes in hematopoiesis, activation of host APCs, and host tissue damage, leading to an inflammatory environment, which sets the stage for the development of acute GVHD (7)(8)(9)(10). This inflammatory milieu includes cytokine release in both hematopoietic and nonhematopoietic compartments, leading to both host and donor Tcell activation and proliferation and alloreactivity which subsequently damages host tissue as GVHD manifests (9)(10)(11)(12)(13). A multitude of diverse therapies to alter these underlying mechanisms of GVHD have been adopted into standard clinical practice.…”