Graft-versus-Host Disease

Graft-versus-host disease (GVHD) is a complex and potentially life-threatening complication that can occur after a hematopoietic stem cell or bone marrow transplant. It arises when donor cells recognize the recipient's tissues as foreign and mount an immune response against them. GVHD can affect various organs and systems in the body, and its severity can vary.
To understand GVHD, it's essential to understand the fundamentals of stem cell and bone marrow transplantation. These procedures are often performed to treat conditions such as leukemia, lymphoma, or certain genetic disorders. The goal is to replace the recipient's malfunctioning or cancerous cells with healthy donor cells to restore normal blood cell production. However, the donor's immune cells, including T cells, can recognize the recipient's tissues as foreign, leading to GVHD.

Causes and Risk Factors
GVHD primarily occurs after allogeneic transplants, where the donor and recipient are not genetically identical (such as a sibling or unrelated donor). The risk factors and causes of GVHD include:

• HLA Disparities: Differences in human leukocyte antigen (HLA) types between the donor and recipient increase the risk of GVHD.
• Age and Sex: Younger donors and male donors tend to increase the risk of severe GVHD.
• Conditioning Regimen: The intensity of the pre-transplant conditioning regimen, which includes chemotherapy and radiation, can affect GVHD risk.
• Stem Cell Source: Peripheral blood stem cells are associated with a higher risk of acute GVHD compared to bone marrow.
• Chronic GVHD: Acute GVHD can evolve into chronic GVHD, a distinct condition with its own set of complications.

Symptoms of GVHD
GVHD can manifest in two forms: acute and chronic, each with its unique set of symptoms.

• Acute GVHD Symptoms:
  • Skin Rash: Skin involvement is common, leading to a rash that can be painful and itchy.
  • Gastrointestinal Symptoms: Diarrhoea, abdominal pain, and nausea are common, as GVHD can affect the gut lining.
  • Jaundice: Liver involvement can lead to yellowing of the skin and eyes.
  • Fever: Elevated body temperature may be present.
  • Mouth Sores: Painful sores in the mouth and throat can develop.

• Chronic GVHD Symptoms:
  • Skin Changes: Persistent skin problems, including thickening, tightening, and changes in skin colour.
  • Oral and Eye Dryness: Dry mouth and dry eyes can be chronic issues.
  • Joint Pain: Musculoskeletal symptoms like joint pain and stiffness.
  • Pulmonary Symptoms: Breathing difficulties and a chronic cough can occur.
  • Fatigue: Ongoing fatigue and weakness may be present.

Diagnosis of GVHD
Diagnosing GVHD requires a combination of clinical evaluation and diagnostic tests, including:

• Clinical Assessment: A healthcare provider will examine the patient for physical signs and symptoms of GVHD.
• Biopsy: Tissue samples from affected areas, such as the skin, may be examined under a microscope to confirm the presence of GVHD.
• Blood Tests: Blood tests can reveal changes in blood cell counts and liver function, which may be indicative of GVHD.
• Endoscopy: In cases of gastrointestinal GVHD, endoscopy may be performed to directly visualize and assess the condition of the digestive tract.

Treatment Options
Treatment for GVHD is complex and aims to suppress the donor immune response while preserving the graft's anti-cancer effect. Common approaches include:
Immunosuppressive Medications:

• Corticosteroids: Prednisone and similar drugs are often the first-line treatment for GVHD.
• Calcineurin Inhibitors: Medications like tacrolimus and cyclosporine can be used in combination with corticosteroids.
• Methotrexate: This drug is sometimes employed as part of the GVHD prophylaxis regimen.

Biological Therapies:

• Antithymocyte Globulin (ATG): ATG can help reduce the activity of T cells involved in GVHD.
• Alemtuzumab: This antibody targets specific immune cells and can be used in certain cases.
• Donor Lymphocyte Infusion (DLI): In cases of relapsed cancer, a controlled infusion of donor lymphocytes can help stimulate graft-versus-leukemia (GVL) effects.

Photopheresis:

• Extracorporeal Photopheresis (ECP): ECP is a procedure that involves removing white blood cells, treating them with ultraviolet light, and returning them to the patient. It can be used to treat chronic GVHD.

Prognosis and Outlook
The prognosis for GVHD varies depending on the severity of the disease and the effectiveness of treatment. Acute GVHD can often be controlled with immunosuppressive therapy, while chronic GVHD may require ongoing management. With advancements in transplantation techniques and GVHD treatment, more patients are achieving successful outcomes after these procedures.

Graft-versus-host disease is a complex and challenging complication of stem cell and bone marrow transplantation. Understanding the causes, risk factors, symptoms, diagnosis, and treatment options for GVHD is essential for both healthcare providers and patients. While GVHD presents significant challenges, ongoing research and medical advancements offer hope for improved outcomes and a better quality of life for individuals who undergo transplantation.