Understanding Graft-versus-Host Disease (GVHD)

Graft Versus Host Disease (GVHD): A Comprehensive Guide

Introduction

Graft versus host disease (GVHD) is a potentially life-threatening complication that can arise after a stem cell or bone marrow transplant. It occurs when donor immune cells (T cells) recognize and attack the recipient’s (host) body tissues, leading to inflammation and tissue damage. GVHD can affect various organs and systems, including the skin, gastrointestinal tract, liver, lungs, and immune system.

Causes of GVHD

GVHD is caused by the interaction between donor T cells and host tissue antigens (HLA molecules). These antigens are expressed on the surface of cells and are responsible for immune recognition. In a successful transplant, the donor T cells should recognize and attack foreign molecules (e.g., cancer cells) while sparing host tissues. However, in GVHD, donor T cells mistakenly identify host antigens as foreign and mount an immune attack against them.

Several factors can contribute to the development of GVHD, including:

• Degree of HLA mismatch: The greater the HLA mismatch between donor and recipient, the higher the risk of GVHD.
• Type of transplant: Allogeneic transplants (from a different donor) carry a higher risk of GVHD than autologous transplants (from the patient’s own cells).
• Recipient pre-transplant conditioning: Prior treatment with chemotherapy or radiation before transplantation can weaken the host’s immune system, making them more susceptible to GVHD.
• Donor characteristics: Certain donor characteristics, such as younger age and female sex, may increase the risk of GVHD.

Types of GVHD

GVHD is classified into two main types based on the time of onset and clinical presentation:

• Acute GVHD: Occurs within 100 days of the transplant and commonly affects the skin, gastrointestinal tract, and liver.
• Chronic GVHD: Develops more than 100 days after the transplant and can involve a wider range of organs, including the lungs, immune system, and connective tissues.

Symptoms of GVHD

The symptoms of GVHD can vary depending on the affected organs and severity of the disease. Common symptoms include:

• Skin: Rash, itching, blisters, ulceration
• Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain
• Liver: Jaundice, liver failure
• Lungs: Shortness of breath, cough, interstitial pneumonitis
• Immune system: Immunodeficiency, infections
• Other: Joint pain, fatigue, weight loss

Diagnosis of GVHD

The diagnosis of GVHD is based on a combination of clinical symptoms, physical examination, and laboratory tests. A skin biopsy may be performed to confirm the diagnosis. Other tests may include:

• Complete blood count
• Liver function tests
• Pulmonary function tests
• Immunological assays

Treatment of GVHD

The primary treatment for GVHD is immunosuppressive medication, which aims to suppress the activity of donor T cells. Commonly used medications include:

• Corticosteroids (e.g., prednisone)
• Calcineurin inhibitors (e.g., tacrolimus, cyclosporine)
• Mycophenolate mofetil
• Methotrexate

In severe cases, additional treatments may be necessary, such as:

• Photopheresis: A procedure that involves removing and treating patient’s immune cells with ultraviolet light to suppress their activity.
• Stem cell transplant: A second transplant using stem cells from a different donor who has a better HLA match.
• Gene therapy: Experimental approaches to target and modify donor T cells.

Prevention of GVHD

Several strategies can be used to reduce the risk of GVHD, including:

• HLA matching: Selecting a donor with a high degree of HLA compatibility.
• T-cell depletion: Removing T cells from the donor stem cell or bone marrow before transplantation.
• Post-transplant immunosuppression: Administering immunosuppressive medications to prevent the activation of donor T cells.
• Donor cell infusions: Introducing regulatory immune cells from the donor to suppress GVHD reactions.

Prognosis of GVHD

The prognosis of GVHD depends on several factors, including the severity of the disease, the affected organs, and the patient’s overall health. Acute GVHD is generally more treatable than chronic GVHD. The overall survival rate for patients with GVHD is approximately 50-70%.

Conclusion

Graft versus host disease is a serious complication of stem cell and bone marrow transplantation. It is caused by the activation of donor immune cells against host tissues, leading to inflammation and tissue damage. The symptoms and severity of GVHD can vary widely, depending on the affected organs. Early diagnosis and aggressive treatment are crucial to improve the prognosis. While GVHD remains a challenging condition, ongoing research and advancements in treatment strategies are offering new hope for patients.