What is the treatment for Graft Versus Host Disease (GVHD)?

Treatment for Graft Versus Host Disease (GVHD)

The standard treatment for acute GVHD is systemic corticosteroids (0.5-1 mg/kg/day methylprednisolone or prednisone equivalent), while chronic GVHD management typically involves immunosuppressive agents with ruxolitinib now considered the standard of care for steroid-refractory cases. 1

Types of GVHD and Initial Management

Acute GVHD

• Occurs within 100 days of hematopoietic stem cell transplantation (HSCT) or donor lymphocyte infusion
• Affects primarily the skin (rash/dermatitis), liver (hepatitis/jaundice), and gastrointestinal tract (abdominal pain/diarrhea) 2
• Graded from I-IV based on organ involvement and severity

First-line Treatment:

• Low-dose corticosteroids (0.5-2 mg/kg/day) 3
• Lower steroid doses (0.5 mg/kg/day) may be appropriate for grade 2 acute GVHD with isolated skin or upper GI tract involvement 4
• Topical steroids may be used for localized skin involvement

Steroid-Refractory Acute GVHD:

• Ruxolitinib is now FDA-approved and considered the standard of care 5
• Response to methylprednisolone occurs in only about 50% of patients 2

Chronic GVHD

• Occurs beyond 100 days post-transplant
• Leading cause of non-relapse mortality in HSCT survivors 1
• Characterized by fibrosis and features resembling autoimmune disorders
• Affects multiple organ systems including skin, eyes, mouth, lungs (bronchiolitis obliterans), and other organs

First-line Treatment:

• Systemic corticosteroids (0.5-1 mg/kg/day methylprednisolone or prednisone equivalent)
• Options include restarting, continuing, or escalating original immunosuppressive agents 1
• Organ-specific topical treatments:
  • Skin: Triamcinolone, clobetasol
  • Oral: Dexamethasone oral rinse
  • Vulvovaginal: Topical estrogen
  • Lung involvement: Inhaled steroids (budesonide or fluticasone) ± azithromycin 1

Steroid-Refractory Chronic GVHD:

• Ruxolitinib is the standard of care 5
• Belumosudil is another approved option 5

GVHD Prevention Strategies

Prevention is critical and preferable to treatment. Methods include:

1. T-cell depletion approaches:

   • Ex vivo: Remove donor T cells from the transplant
   • In vivo: Administer T-cell antibodies to the recipient 3
   • Rabbit anti-T-cell globulin is recommended for peripheral blood stem cell transplantations from unrelated donors 5

2. Post-transplant immunosuppression:

   • Calcineurin inhibitors: Cyclosporine or tacrolimus
   • Methotrexate
   • Mycophenolate mofetil
   • Post-transplantation cyclophosphamide 5

3. Combination approaches:

   • Most frequently, cyclosporine or tacrolimus is administered with other immunosuppressive agents (methotrexate or corticosteroids) 1

Special Considerations

Risk Factors for GVHD

• Patient age >15 years (44% probability vs <14% for children under 5) 1
• Use of total body irradiation 1
• Peripheral blood stem cell source (higher risk than bone marrow) 1
• HLA-mismatched or unrelated donors 1

Complications of GVHD and Treatment

• Infections are a major cause of morbidity and mortality
• Prophylaxis, early diagnosis, and treatment of infections are essential 3
• Cyclosporine use increases risk of infectious complications and potential disease relapse 1

Long-term Outcomes

• Chronic GVHD significantly impacts overall health status, causing functional impairment, activity limitation, and pain 1
• Resolution of chronic GVHD can result in long-term health outcomes comparable to survivors who never developed GVHD 1
• HSCT survivors are at increased risk for recurrent infections, secondary cancers, cardiac dysfunction, growth failure, and other end-organ dysfunction 1

Management Algorithm

1. Assess GVHD type and severity:

   • Acute vs. chronic
   • Organ involvement
   • Grading (acute: I-IV; chronic: mild, moderate, severe)

2. First-line therapy:

   • Acute GVHD: Systemic corticosteroids (0.5-2 mg/kg/day)
   • Chronic GVHD: Systemic corticosteroids (0.5-1 mg/kg/day) plus appropriate topical treatments

3. Monitor response after 3-7 days:

   • If improved: Continue treatment with gradual taper
   • If no improvement after 7 days or progression after 3 days: Initiate second-line therapy

4. Second-line therapy:

   • Acute GVHD: Ruxolitinib (FDA-approved)
   • Chronic GVHD: Ruxolitinib or belumosudil

5. Supportive care:

   • Infection prophylaxis
   • Wound care for skin GVHD
   • Fluid/nutrition management for GI GVHD
   • Multidisciplinary care to preserve organ function

The management of GVHD requires close monitoring and may need adjustment based on clinical response, with the goal of minimizing long-term complications while preserving the graft-versus-tumor effect.