Types of Graft Versus Host Disease (GVHD)

There are two manifestations of graft versus host disease (GVHD), namely acute and chronic.

Acute GVHD

Acute GVHD develops within the first 100 days after the patient receives an allogeneic bone marrow transplant (BMT). The trigger for the disease tends to be when the new bone marrow starts to produce blood cells through the process of engraftment.

Another factor implicated appears to be during the reduction of the patient’s immunosuppressive drugs, which are designed to assist the body in accepting the donation.

GVHD affects the skin, liver and gastrointestinal (GI) tract of the patient. In mild presentations of the disease, the skin is the only area that is affected. As the disease increases in severity, the liver and gastrointestinal tract start to develop signs and symptoms. If the disease gets worse, the complications increase.

This disease can be classified into four grades, which describe how it presents in the host:

• Grade 1 – the effects are mild with the patient likely to have a skin rash that covers up to 25% of their body
• Grade 2 – the effects are moderate with the rash covering more than 25% of the body and additional mild symptoms affecting the liver and GI region
• Grade 3 – the symptoms  are severe with most of the skin affected and more intense complications associated with the liver and GI region
• Grade 4 – the effects are life-threatening with the skin producing blisters and peeling off. The liver and GI region problems are extreme.

Similarly, some doctors use 0-4 stages to describe the state of the disease. A patient in stage 0 has no rash and minor liver impairments and stool production. As the disease increases in severity, the rash increases and so does the bilirubin levels  accompanied by diarrhea.

Chronic GVHD

Chronic GVHD is characterized by generally starting more than 100 days after the transplant although this is not always the case. Sometimes it can develop as long as a year or more afterwards.

It also affects the patient much longer than the acute manifestation of GVHD and accounts for as many as a quarter of the deaths in long-term transplant patients for leukemia.

The symptoms are very similar to acute GVHD with the condition causing skin problems, issues with the liver and the GI tract. However, it can also impact most other organs including the lungs, tendons, joints, mouth and eyes.

Many patients can initially suffer from acute GVHD and then also develop chronic GVDH later. A patient whose tissue type is not a close match to their donor also tends to get the condition more severe. The patients who develop chronic GVHD usually only have a mild presentation, but about 15% will have a more severe complications.

Overlap of acute and chronic GVHD

Both acute and chronic GVHD can overlap with each other at the end of the first 100 days post transplant. This has been observed when patients go through mini transplants where they have had low doses of chemotherapy and radiotherapy before a transplant.

Differences in the development of acute and chronic GVDH

Although donor T cells, which are critical to good function in the body’s immune system, have a big role to play in both acute and chronic GVDH, the conditions do not have the same disease mechanisms.

Cytokines are proteins involved in cell to cell signaling. In acute GVHD, TH1 cytokines are implicated, whereas TH2 cytokines are primarily involved in chronic GVHD. Furthermore, B cells appear to have a more active role in chronic GVHD than acute GVHD. The disease pathway suggests that chronic GVHD has much in common with autoimmune conditions and immunodeficiency. It affects the connective tissue in patients’ bodies.

References

• Children’s Cancer and Leukaemia Group on GVHD: http://www.cclg.org.uk/write/MediaUploads/Publications/PDFs/Graft_versus_host_disease_(Jul_14).pdf
• Bone Marrow and Transplantation Journal, Chronic graft-versus-host disease: clinical manifestation and therapy: http://www.nature.com/bmt/journal/v28/n2/full/1703111a.html
• Orphanet Journal of Rare Diseases, Acute graft versus host disease: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2018687/
• Medlicalistes on GVDH: http://www.medicalistes.org/gvhd/docs/what_is_gvhd.html
• Cancer Research UK on GVHD: http://www.cancerresearchuk.org/about-cancer/coping-with-cancer/coping-physically/gvhd/about-graft-versus-host-disease#late
• Biology of Blood & Bone Marrow Transplantation, B Cells in Chronic Graft-versus-Host Disease: http://www.sciencedirect.com/science/article/pii/S1083879114006685