Survey of transfusion-associated graft-versus-host disease in immunocompetent recipients

During pregnancy, a bidirectional transfer of molecules and cells takes place through the placenta, which can be considered a transfusion. For decades, we have wondered whether said transfusion can lead to a true TA-GVHD. We propose several factors that may influence production of TA-GVHD during pregnancy. In order to achieve this, we shall take into account possible destinations for transfused leukocytes, which represent extremely different scenarios and may include transfusion associated-graft versus host disease (TA-GVHD).

Transfusion-associated graft-versus-host disease (TA-GVHD), a rare but usually fatal adverse effect of transfusion, is hypothesized here as a two-hit phenomenon: 1) predisposing “cytokine weather” irrespective of immunocompetence, plus 2) consequence of a (partial or total) one-way (donor to recipient) HLA match of viable donor T lymphocytes with proliferation potential. Since the introduction of irradiation, universal leukoreduction with third or later generation filters, and avoidance of transfusion from blood relatives, TA-GVHD has been successfully prevented in developed countries. However, potassium release from stored red blood cells is accelerated after irradiation, increasing the likelihood of hyperkalemia-associated mortality during rapid, and/or high-volume RBC transfusions, including exchange transfusions and extracorporeal circuit priming. Pathogen inactivation technologies may effectively prevent T lymphocyte replication, but have not yet been perfected for whole blood or red cell components. Protection against organ transplantation-associated GVHD (mainly from liver transplants) would likewise be improved by knowing and avoiding HLA one-way matched organ donors.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare life-threatening complication of blood transfusion caused by donor T cells that escape rejection by the recipient immune system. These donor T cells drive recipient tissue damage in response to host antigens. On the other hand, GVHD occurring after allogeneic hematopoietic cell transplantation (HCT-GVHD) is also caused by donor T cells, but its pathophysiology is more complex and differs due to the effects of tissue damage caused by pre−HCT conditioning and profound immunosuppression. Both TA-GVHD and HCT-GVHD can be fatal; however, mortality is higher with TA-GVHD due to the paucity of treatment options. Here, we compare and summarize the presentation, diagnosis, pathophysiology, prevention, and treatment of TA-GVHD and HCT-GVHD.

Graft-versus-host disease (GVHD) is a rare, usually fatal complication following blood transfusion or organ transplantation, namely transfusion-associated GVHD (TA-GVHD) and organ transplantation-associated GVHD (OA-GVHD). The dominant mechanism of GVHD is exposure to viable donor lymphocytes that are not recognized as foreign by, but able to respond to, the recipient. The clinical features and relative risk factors of either TA-GVHD or OA-GVHD are yet to be fully understood. The current review article aims to discuss and summarize the similarities and differences between TA-GVHD and OA-GVHD to gain a deeper understanding of the pathogenesis.

It is evident that the shared human leukocyte antigens (HLA) between donor and recipient and immunocompromised status of the recipient are the two main risk factors for the development of both TA-GVHD and OA-GVHD. In particular, the homozygous donor with donor-dominant one-way matching at the three loci HLA-A, -B, and -DR has a high risk of developing GVHD following liver transplantation, and such donors should be excluded to prevent it. However, the development of GVHD is thought to be related to a combination of several risk factors, and the contribution of each risk factor remains unknown. Further studies are warranted to determine the important contributing factors that lead to an accurate prediction of GVHD development.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare immune-mediated complication of transfusion that is associated with high mortality. This chapter provides information regarding the immune pathophysiology and clinical implications of TA-GVHD and explores both long-standing and emerging interventions that reduce the risk of TA-GVHD from transfused cellular blood components. New areas of research related to TA-GVHD are described in an effort to explore how our understanding of this complication has evolved.