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Graft versus host disease (GvHD)

Dr. Anurag Shahi (AIIMS)MBBS,MD

September 01, 2020

September 01, 2020

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Graft versus host disease
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Graft versus host disease (GvHD) is a medical complication that may occur after a hematopoietic stem cell transplant or an allogeneic bone marrow transplant.

This occurs when the donated stem cells or bone marrow consider the host or recipient's body to be foreign, and instead of providing protection, they begin to attack the receiver's body.

Hematopoietic stem cells, found inside most bones, make blood cells in the body. They can be transplanted from the patient himself/herself (autologous) or from another donor (allogeneic). An allogeneic transplant refers to the process in which the donor is different from the recipient.

According to a study published in the Orphanet Journal of Rare Diseases in 2007, GvHD is rare, affecting less than 100 per 100,000 people around the world, although the prevalence of this condition hasn't been extensively studied in developing countries. 

One of the primary reasons is that bone marrow transplants or stem cell transplants are highly specialised procedures that happen in countries or centres equipped for them. Between 4,795 and 6,850 cases were recorded around the world in 2003, and an average of about 5,500 cases are recorded in a year.

Even though GvHD is a rare disorder, the incidence of patients developing this condition after undergoing stem cell transplants is a high 35% to 50%, and it tends to affect men more than women. There isn't a specific age group where it develops more commonly, although older people are said to develop this condition especially after receiving stem cells from female donors.

Most stem cell transplants occur during treatment for certain types of cancer in addition to radiation therapy and chemotherapy. The condition can be fatal—the annual case fatality is about 25% from GvHD.

Graft versus host disease (GvHD) types

Graft versus host disease occurs in two different ways:

  • Acute graft versus host disease (aGvHD), where the recipient develops the condition weeks (within 100 days) after receiving the stem cell transplant, often as the bone marrow and stem cells from the donor do not work well with the recipient's due to a combination of factors.
    Some estimates suggest that nearly 80% of people who undergo such transplants develop GvHD. This is because the new bone marrow begins to develop new blood cells that end up attacking the host's healthy cells.
  • Chronic graft versus host disease (cGvHD) is a condition that may develop after the patient has already had acute GvHD. While acute GvHD sets in shortly after receiving a stem cell transplant, chronic GvHD takes longer to develop— usually between three months to a year after the transplant.

Graft versus host disease (GvHD) symptoms

Acute GvHD patients are known to develop problems in their liver and gut, as well as rashes on the skin along with diarrhoea, stomach pain and vomiting, causing a rapid increase in the liver enzymes. Acute GvHD patients can also go on to develop chronic GvHD.

Chronic GVHD presents with symptoms such as rashes, drying, scarring, hardening and darkening of the skin, trouble in the joints, hair loss, ulcers in the mouth and inside the stomach, reddening and irritation in the eyes, vaginal dryness among women, scarring in the lungs, and damage to the liver. However, chronic GvHD isn’t considered to be as severe as acute GvHD.

Read more: Liver disease

Graft versus host disease (GvHD) causes

GvHD typically occurs because the host or recipient's body is severely immunocompromised due to the disease he or she has been suffering from and due to the resulting treatment they have already been receiving (for example, cancer and chemotherapy, respectively), while the donor's healthy cells from the donated bone marrow thrive in the receiver's body or are immunocompetent, thus attacking the host's cells.

Other than bone marrow or stem cell transplants, GvHD can also occur in transplants of other organs that contain lymphoid tissues and blood products.

GvHD is also described as an undesirable immune response as the donor T cells—usually the white blood cells that are responsible for the body's immune response to infections—mistake the host body's cells in the affected organ for a foreign body. The donor's T cells are triggered to fight the cells of the recipient's body, which leads to a greater or more significant inflammatory response.

Read more: Study links muscle mass to strong immune system

Human leukocyte antigens (HLA) are proteins that can be different from person to person—the recipient's HLA must match the donor's HLA before a transplant or transfusion can take place, as any mismatch can lead to the development of GvHD.

The chances of GvHD are usually higher when the recipient and donor are not blood relatives, the donor is older or of the opposite sex, or even when stem cells of the donor have a higher T cell count.

As GvHD affects nearly half the people who undergo some form of bone marrow or stem cell transplant, it is commonly seen in patients of leukemia, as they have to undergo such transplants. Different kinds of leukemia (blood cancer), depending on the stage or severity of the condition, are treated with bone marrow transplants.

Diagnosis of graft versus host disease (GvHD)

It is important for patients who are stem cell recipients or of other organ donations to be in regular contact with their specialist to be aware of symptoms of GvHD, and to alert them as soon as possible if any symptoms do arise. As GvHD often develops within a few weeks to months of receiving a bone marrow transplant, the symptoms of GvHD in case of a mismatch can also develop fairly quickly.

Blood tests to check for high white blood cell counts are usually indicative of the development of such a condition, which may prompt the doctor to order a biopsy of the affected tissue in the body. In some cases, a urine test can also indicate signs of infection, but it is also performed to rule out other infections or conditions of the bladder or diabetes.

Graft versus host disease (GVHD) treatment

GvHD can affect multiple systems around the body. Doctors usually advise the use of steroids or other anti-inflammatory medications to suppress the immune system, based on which type of GvHD the patient has developed.

Treatment for GvHD can last for a long time, often up to a year or more as it depends on how the patient is responding to the medicines.

Acute GvHD is usually treated with glucocorticosteroids and drugs like cyclosporine that suppress the immune system in the body. A host of other medications are also being researched and scrutinized for their effects on the body in the management of GvHD.

Recent research on the role of T cells in GvHD, published in the Journal of Clinical Investigation, shows that the host's original T cells become activated after receiving donor stem cells and can be found in the skin and gastrointestinal tract, leading to tissue injury. 

The researchers discovered that although T cells in the host's blood were depleted, there was a presence of T cells in the tissues of the skin and the gut, which according to them could be game-changing in the treatment of GvHD, and may even prevent the onset of the condition.



References

  1. Jacobsohn DA and Vogelsang GB. Acute graft versus host disease. Orphanet Journal of Rare Diseases. 2007 Sep; 2: 35.
  2. Pandey N et al. Graft-versus-host disease: Rare complication postliver transplant. Indian Journal of Transplantation. 2019 Jun; 13(2): 130-133.
  3. Jacobs R et al. Prevalence and risk factors associated with development of ocular GVHD defined by NIH consensus criteria. Bone Marrow Transplantation. 2012 Apr; 47: 1470-1473.
  4. Divito SJ et al. Peripheral host T cells survive hematopoietic stem cell transplantation and promote graft-versus-host disease. The Journal of Clinical Investigation. 2020 Jun; 1-14.


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