What is the pathophysiology, diagnosis, and treatment of Graft-Versus-Host Disease (GVHD)?

From the Guidelines

Graft-versus-host disease (GVHD) is a common complication following allogeneic hematopoietic stem cell transplantation where donor immune cells attack recipient tissues, and its treatment should prioritize systemic corticosteroids as the mainstay of initial treatment, as supported by the most recent evidence 1.

Pathophysiology

The pathophysiology of GVHD involves donor T-cell recognition of recipient antigens, cytokine release, and tissue damage, explaining why immunosuppression forms the cornerstone of both prevention and treatment. This process can lead to a wide range of clinical manifestations, from mild to severe, affecting various organs such as the skin, liver, gastrointestinal tract, eyes, mouth, lungs, and joints.

Diagnosis

Diagnosis of acute GVHD involves recognizing characteristic manifestations in target organs, including skin (maculopapular rash), liver (elevated bilirubin and liver enzymes), and gastrointestinal tract (diarrhea, abdominal pain, nausea). Chronic GVHD presents with features resembling autoimmune disorders affecting multiple organs. Definitive diagnosis often requires biopsy of affected tissues showing characteristic histological findings.

Treatment

First-line treatment for acute GVHD is systemic corticosteroids, typically prednisone or methylprednisolone at 1-2 mg/kg/day, as recommended by recent guidelines 1. For steroid-refractory cases, second-line options include calcineurin inhibitors (tacrolimus, cyclosporine), mycophenolate mofetil, sirolimus, ruxolitinib, or extracorporeal photopheresis. Chronic GVHD treatment also begins with corticosteroids, often combined with calcineurin inhibitors, and may require prolonged therapy with gradual tapering. Supportive care is crucial and includes antimicrobial prophylaxis, nutritional support, and specific management for organ-specific manifestations.

Some key points to consider in the treatment of GVHD include:

• The use of systemic corticosteroids as the mainstay of initial treatment, as supported by the most recent evidence 1.
• The importance of supportive care, including antimicrobial prophylaxis, nutritional support, and specific management for organ-specific manifestations.
• The role of calcineurin inhibitors, such as tacrolimus or cyclosporine, in the treatment of steroid-refractory GVHD.
• The potential use of biologics, such as ruxolitinib, in the treatment of chronic GVHD.

Overall, the treatment of GVHD should prioritize a multidisciplinary approach, taking into account the severity of the disease, the organs involved, and the individual patient's needs and response to treatment. The most recent evidence supports the use of systemic corticosteroids as the first-line treatment for acute GVHD, and highlights the importance of supportive care and individualized treatment plans 1.

From the Research

Pathophysiology of Graft-Versus-Host Disease (GVHD)

• GVHD is a common complication of allogeneic hematopoietic cell transplantation (HCT) and is associated with significant morbidity and mortality 2
• The disease is caused by immunocompetent donor leukocytes within the transplanted organ, which become activated against recipient tissues 3
• GVHD can affect the skin, gastrointestinal tract, liver, and bone marrow, and can be acute or chronic in nature 2, 3

Diagnosis of GVHD

• The diagnosis of GVHD is often delayed, but should be confirmed by biopsy of an affected organ 3
• Evidence of donor chimerism in blood or marrow supports the diagnosis 3
• Clinical symptoms of GVHD include fever, rash, diarrhea, and pancytopenia 4, 3, 5
• The diagnostic criteria of GVHD are mainly based on time, clinical symptoms, T-lymphocyte chimerism, and histopathology 5

Treatment of GVHD

• First-line systemic treatment for GVHD remains corticosteroids, but up to 50% of patients will develop steroid-refractory GVHD and the prognosis for these patients is poor 2
• Novel therapeutic approaches have been developed, including the use of ruxolitinib, an oral selective JAK1/2 inhibitor, which has been approved for the treatment of steroid-refractory acute GVHD 2
• Other treatments for GVHD include immunosuppressant adjustment, human normal immunoglobulin, and antithymocyte globulin/IL-2 antagonists 4, 5
• Supportive care, including infection prophylaxis, is also important in optimizing response and survival in patients with GVHD 6