Separating Graft-Versus-Leukemia From Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Routine methods to maximize the graft-versus-leukemia (GvL) activity of allogeneic hematopoietic stem cell transplantation (HSCT) without the detrimental effects of graft-versus-host disease (GvHD) are lacking. Depletion or inhibition of alloreactive T cells is partially effective in preventing GvHD, but usually leads to decreased GvL activity. The current model for the pathophysiology of acute GvHD describes a series of immune pathways that lead to activation of donor T cells and inflammatory cytokines responsible for tissue damage in acute GvHD. This model does not account for how allotransplant can lead to GvL effects without GvHD, or how the initial activation of donor immune cells may lead to counter-regulatory effects that limit GvHD. In this review, we will summarize new findings that support a more complex model for the initiation of GvHD and GvL activities in allogeneic HSCT, and discuss the potential of novel strategies to enhance GvL activity of the transplant.

Predicting the risk of acute kidney injury after hematopoietic stem cell transplantation: development of a new predictive nomogram

“…The descriptions of transplant characteristics, such as donor, race, TBI, nephrotoxic agents, and post-transplant adverse events, such as aGVHD and infection, were inconsistently described as risk factors for the development of AKI 21 – 23 . Studies had shown that unrelated donors were closely associated with AKI (HR, 6.26; P = 0.042) 20 .It had been reported that transplantation of hematopoietic stem cells from unrelated donors was associated with a significant increase in the risk of infection, severe aGVHD, and organ toxicity 24 – 29 . Calcineurin inhibitor (CNIs) caused AKI by arteriolar vasoconstriction, reducing kidney perfusion, tubular toxicity, and endothelial injury 30 , 31 .…”

Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

“…Cytokines are critical drivers of both GVHD and GVL, and current evidence indicates that different cytokines may play different roles in GVHD vs the GVL effect[ 122 - 133 ]. In a recent study, Tugues et al [ 108 ] used an MHC-mismatched HSCT mouse model and found that donor T cell-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) can drive GVHD pathology by licensing donor-derived phagocytes to produce inflammatory mediators such as IL-1 and reactive oxygen species (ROS).…”

Stem Cell Transplant As an Immunomodulatory Tool for Children with Hematologic Malignancies

“…For example, depletion of ␣␤ T cells and naive T cells decreases GVHD while increasing numbers of ␥␦ or memory T cells, or CD4 ϩ CD25 ϩ regulatory T cells (Tregs) enhance GVL and/or suppress GVHD. 10 T cells are no longer thought to be the only immune cells responsible for GVL; donor-derived natural killer (NK) and dendritic (DC) cells also playing key roles. 11,12 Early efforts to identify the timing and the immunologic mechanisms responsible for GVHD focused on augmenting the GVL response through donor lymphocyte infusions.…”