White blood cells of the donor's immune system which remain within the donated tissue (the graft) recognize the recipient (the host) as foreign (non-self).

[1] In the clinical setting, graft-versus-host disease is divided into acute and chronic forms, and scored or graded on the basis of the tissue affected and the severity of the reaction.

[3][4] In the classical sense, acute graft-versus-host disease is characterized by selective damage to the liver, skin (rash), mucosa, and the gastrointestinal tract.

[8] The acute or fulminant form of the disease (aGvHD) is normally observed within the first 10 to 100 days post-transplant,[9][10] and is a major challenge to transplants owing to associated morbidity and mortality.

[23] While donor T-cells are undesirable as effector cells of graft-versus-host disease, they are valuable for engraftment by preventing the recipient's residual immune system from rejecting the bone marrow graft (host-versus-graft).

In addition, as bone marrow transplantation is frequently used to treat cancer, mainly leukemias, donor T-cells have proven to have a valuable graft-versus-tumor effect.

[24] A great deal of current research on allogeneic bone marrow transplantation involves attempts to separate the undesirable graft-vs-host disease aspects of T-cell physiology from the desirable graft-versus-tumor effect.

[27] Autoimmune disease is a frequent complication after human allogeneic thymus transplantation, found in 42% of subjects over one year post-transplantation.

Prior to haematopoietic stem cell transplantation, radiation or chemotherapy results in damage and activation of host tissues, especially intestinal mucosa.

In the final phase, these effector cells migrate to target organs and mediate tissue damage, resulting in multiorgan failure.

[41] The use of these glucocorticoids is designed to suppress the T-cell-mediated immune onslaught on the host tissues; however, in high doses, this immune-suppression raises the risk of infections and cancer relapse.

Therefore, it is desirable to taper off the post-transplant high-level steroid doses to lower levels, at which point the appearance of mild GVHD may be welcome, especially in HLA mis-matched patients, as it is typically associated with a graft-versus-tumor effect.

[42] An increasing number of recent treatment options for SR-GVHD have been investigated, such as extracorporeal photopheresis (ECP), mesenchymal stem cell (MSCs), fecal microbial transplantation (FMT), and the medication Ruxolitinib.

These complexes inhibit calcineurin, block dephosphorylation of the transcription factor NFAT of activated T-cells and its translocation into the nucleus.

[47] Given the complex systemic condition and immunosuppression of the chronic GVHD patients, non-drug therapies, are a significant advancement, and may be preferred whenever possible.

[48] There are a large number of clinical trials either ongoing or recently completed in the investigation of graft-versus-host disease treatment and prevention.

[49] On 17 May 2012, Osiris Therapeutics announced that Canadian health regulators approved Prochymal, its drug for acute graft-versus-host disease in children who have failed to respond to steroid treatment.

[50] In January 2016, Mesoblast released results of a phase 2 clinical trial on 241 children with acute Graft-versus-host disease, that was not responsive to steroids.