Graft vs Host Disease: An Overview in Bone Marrow Transplant

Overview

What is graft versus host disease?

Graft versus host disease (GvHD) is a condition that might occur after an allogeneic transplant. In GvHD, the donated bone marrow or peripheral blood stem cells view the recipient’s body as foreign, and the donated cells/bone marrow attack the body.

There are two forms of GvHD:

  • Acute graft versus host disease (aGvHD).
  • Chronic graft versus host disease (cGvHD).

As an allogeneic transplant recipient, you might experience either form of GvHD, both forms, or neither.

Acute graft versus host disease

Risk factors

Several factors are thought to increase the development of acute GvHD (aGvHD). The most important is donor/recipient HLA (human leukocyte antigen) match, in which there are differences between you and your donor. The differences can cause donor cells to recognize your cells as foreign, and lead to an immune response against your tissues and organs.

Recipients who have received peripheral blood stem cells/bone marrow from an HLA mismatched related donor (or from an HLA matched unrelated donor) have an increased risk of developing acute GvHD.

Other donor/ recipient factors that might increase the risk of developing aGvHD include:

  • A female donor who has been pregnant in the past.
  • The advanced age of either the donor or the recipient.

When/where acute graft versus host disease might occur

Acute GvHD might occur once the donor's cells have engrafted in the transplant recipient. It might develop in your skin, liver or gastrointestinal tract, and symptoms might appear within weeks after your transplant.

Chronic graft versus host disease

Risk factors for chronic graft versus host disease

Patients who have an increased risk of developing cGvHD are:

  • Those who've received stem cells/bone marrow from an HLA (human leukocyte antigen) mismatched related donor or from an HLA matched unrelated donor.
  • Patients who may have already experienced acute GvHD.
  • Older transplant recipients.

When/where chronic graft versus host disease might occur

Chronic GvHD can appear at any time after allogenic transplant or several years after your transplant. Chronic GvHD might occur in the skin, liver, mouth, lungs, gastrointestinal tract, neuromuscular system, or genitourinary tract.

Important note about graft versus host disease: While GvHD can deeply impact your quality of life, it does have some benefit. The same immune response responsible for attacking your normal cells is also monitoring and destroying any surviving cancer cells. This is called the graft versus tumor effect. Patients who develop GvHD have lower disease relapse rates.

Symptoms and Causes

What are symptoms of acute graft versus host disease (aGvHD)?

NOTE For patients with either aGvHD or cGvHD: Because of the increased risk of developing infections. it's very important to report any physical changes and fevers of 100.4° F or higher to your bone marrow transplant team.

Symptoms of acute GvHD might include any of the following:

  • Skin rash or reddened areas on the skin (signs of aGvHD of the skin): Please report if your skin is itchy.
  • Yellow discoloration of the skin and/or eyes, and abnormal blood test results (signs of aGvHD of the liver).
  • Nausea, vomiting, diarrhea, or abdominal cramping (signs of aGvHD in the gastrointestinal tract, or “gut”).

What are symptoms of chronic graft versus host disease (cGvHD)?

Symptoms of chronic GvHD might include any of the following:

  • Rash, raised, or discolored areas, skin thickening or tightening (signs of cGvHD of the skin).
  • Abdominal swelling, yellow discoloration of the skin and/or eyes, and abnormal blood test results (signs of cGvHD of the liver).
  • Dry eyes or vision changes (signs of cGvHD of the eyes).
  • Dry mouth, white patches inside the mouth, pain or sensitivity to spicy foods (signs of oral cGvHD, of the mouth).
  • Shortness of breath or changes seen on your chest X-ray (signs of dry cough pulmonary cGvHD — of the lungs).
  • Difficulty swallowing, pain with swallowing, or weight loss (signs of cGvHD of the gastrointestinal tract or “gut”).
  • Fatigue, muscle weakness, or pain (signs of neuromuscular cGvHD, of the nerves and muscles).
  • Vaginal dryness or pain with intercourse (cGvHD of the vagina or vulva).
  • Decreased range of motion in joints or tightness in joints (cGvHD or the fascia or connective tissue).

Diagnosis and Tests

How is graft versus host disease diagnosed?

Your BMT doctor can make the diagnosis of a GvHD during a physical exam by observing certain symptoms and/or by evaluating the results of site biopsies and lab values.

In the case of chronic graft versus host disease (cGvHD), some symptoms might be very vague, which might make the diagnosis possible only after other causes are excluded.

Management and Treatment

How is acute graft versus host disease (aGvHD) treated?

If aGvHD occurs, your doctor will discuss available treatment options with you and your family. Many patients are successfully treated with increased immunosuppression in the form of oral (given by mouth) or intravenous (given through the vein) steroid medicines. If steroids are unsuccessful or are not appropriate to use, other treatment options are available.

How is chronic graft versus host disease (cGvHD) treated?

If cGvHD occurs, your doctor will discuss available treatment options with you and your family. Long-term immunosuppressive medicines are usually the treatment regimen for cGvHD. Fungal, bacterial, and viral infections are a major risk with this treatment option since your immune system will be suppressed for a very long time. Your doctor will prescribe several medicines to help prevent these life-threatening infections from occurring.

The treatment of cGvHD can take many months to years.

Prevention

How can graft versus host disease prevented?

Tissue typing labs have been developing and using more precise DNA level tests to enable your BMT Team to select the best HLA matched donor for you.

We try to lower your risk of developing GvHD by giving you preventive (prophylactic) medicines to suppress the immune system after your transplant. These medicines will decrease the ability of your donor's cells to start an immune response against your own tissues.

Fungal, bacterial, and viral infections are major risks with this prophylactic medicine regimen, since your immune system will be suppressed and have a decreased ability to fight infection. You will be on prophylactic antibiotics, antifungals and antiviral medicines to decrease infection risks.

Research

New, and hopefully better, methods to prevent GvHD are being studied in clinical trials. The use of photopheresis, different immunosuppressive drugs, and new prophylaxis medications given to recipients after transplant are examples of some of that research.

Last reviewed by a Cleveland Clinic medical professional on 06/22/2020.

References

  • American Cancer Society. Stem Cell or Bone Marrow Transplant. (https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/stem-cell-transplant.html) Accessed 7/7/2020.
  • American Society of Clinical Oncology. What is a Bone Marrow Transplant (Stem Cell Transplant)? (https://www.cancer.net/navigating-cancer-care/how-cancer-treated/bone-marrowstem-cell-transplantation/what-bone-marrow-transplant-stem-cell-transplant) Accessed 7/7/2020.
  • Leukemia and Lymphoma Society. Alloegeneic Cell Transplantation. (https://www.lls.org/treatment/types-of-treatment/stem-cell-transplantation/allogeneic-stem-cell-transplantation) Accessed 7/7/2020.
  • Gyurkocza B, Rezvani A, Storb RF. Allogeneic hematopoietic cell transplantation: the state of the art. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943393/) Expert Rev Hematol. 2010;3(3):285-299. doi:10.1586/ehm.10.21

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