Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for hematological malignancies. The number of patients receiving allo-HCT continues to increase with more than 50,000 transplantations reported worldwide in 2017. The development of novel strategies, including reduced-intensity conditioning (RIC), post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis, and cord blood as an alternative stem cell source have expanded the indications for allo-HCT, decreased treatment-related mortality (TRM), and increased long-term survival. However, severe acute GVHD, a life-threatening complication of allo-HCT, remains a major obstacle occurring in more than half of allo-HCT recipients and severely impacts their quality of life (QOL).
Therefore, GVHD prevention is critical for improving allo-HCT outcomes. Acute GVHD pathophysiology is complex, but allo-reactive donor T lymphocytes play a central role. Donor allo-reactive T lymphocytes are activated by antigen presenting cells (APCs), pro-inflammatory cytokines, and damage- and pathogen- associated molecular patterns (DAMPs and PAMPs, respectively), which are released by damaged host tissues after conditioning. The regulation of these various components of alloimmunity is important for preventing GVHD. In addition to immune-related mechanisms, tissue-specific mechanisms such as tissue tolerance are increasingly recognized as important components of GVHD pathogenesis. In this regard, tissue-intrinsic and extrinsic factors, such as the gut microbiome and its metabolites, were recently shown to be important for promoting tissue homeostasis and regeneration in the setting of GVHD. While GVHD is a major obstacle to all-HCT, relapse remains the number one cause of mortality following allo-HCT for malignant disorders. The graft-versus-tumor (GVT) effect helps prevent relapse, but this effect is tightly linked to GVHD, such that GVHD treatments and prophylaxis regimens often come at the cost of increased relapse. Therefore, it is crucial to find ways of treating GVHD that also preserve GVT. In this special tissue, recent advances in the translational science of GVHD and GVT are reviewed. We welcome authors to submit manuscripts focusing on translational research for treating GVHD while preserving GVT.
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for hematological malignancies. The number of patients receiving allo-HCT continues to increase with more than 50,000 transplantations reported worldwide in 2017. The development of novel strategies, including reduced-intensity conditioning (RIC), post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis, and cord blood as an alternative stem cell source have expanded the indications for allo-HCT, decreased treatment-related mortality (TRM), and increased long-term survival. However, severe acute GVHD, a life-threatening complication of allo-HCT, remains a major obstacle occurring in more than half of allo-HCT recipients and severely impacts their quality of life (QOL).
Therefore, GVHD prevention is critical for improving allo-HCT outcomes. Acute GVHD pathophysiology is complex, but allo-reactive donor T lymphocytes play a central role. Donor allo-reactive T lymphocytes are activated by antigen presenting cells (APCs), pro-inflammatory cytokines, and damage- and pathogen- associated molecular patterns (DAMPs and PAMPs, respectively), which are released by damaged host tissues after conditioning. The regulation of these various components of alloimmunity is important for preventing GVHD. In addition to immune-related mechanisms, tissue-specific mechanisms such as tissue tolerance are increasingly recognized as important components of GVHD pathogenesis. In this regard, tissue-intrinsic and extrinsic factors, such as the gut microbiome and its metabolites, were recently shown to be important for promoting tissue homeostasis and regeneration in the setting of GVHD. While GVHD is a major obstacle to all-HCT, relapse remains the number one cause of mortality following allo-HCT for malignant disorders. The graft-versus-tumor (GVT) effect helps prevent relapse, but this effect is tightly linked to GVHD, such that GVHD treatments and prophylaxis regimens often come at the cost of increased relapse. Therefore, it is crucial to find ways of treating GVHD that also preserve GVT. In this special tissue, recent advances in the translational science of GVHD and GVT are reviewed. We welcome authors to submit manuscripts focusing on translational research for treating GVHD while preserving GVT.
