What is the management of Graft-Versus-Host Disease (GVHD)?

Management of Graft-Versus-Host Disease (GVHD)

Systemic corticosteroids are the mainstay of initial treatment for GVHD, typically used in conjunction with a T-cell inhibitor such as cyclosporine or tacrolimus, with specific treatment approaches tailored based on GVHD type (acute vs. chronic) and severity. 1

Acute GVHD Management

First-Line Therapy

• Systemic corticosteroids: Methylprednisolone 0.5-1 mg/kg/day or prednisone equivalent 1
• Add T-cell inhibitor (cyclosporine or tacrolimus) to corticosteroid therapy 1
• For mild, single-organ involvement: Consider topical treatments or slowing immunosuppressant taper 1

Steroid-Refractory Acute GVHD

• Ruxolitinib: FDA-approved for steroid-refractory acute GVHD with 6-month survival outcomes comparable to other agents 1
• Alternative options include:
  • Cyclophosphamide
  • Biologics
  • Photopheresis 1

Chronic GVHD Management

First-Line Therapy

• Systemic corticosteroids: 0.5-1 mg/kg/day methylprednisolone or prednisone equivalent 1
• Continue, restart, or escalate original immunosuppressive agent 1
• For mild and slowly progressive disease: Consider mycophenolate mofetil, dapsone, azathioprine, or methotrexate 1

Organ-Specific Management

Ocular GVHD

• Aggressive lubrication and punctal occlusion for keratoconjunctivitis sicca 1
• Topical corticosteroids for conjunctival hyperemia and scarring 1
• Topical T-cell modulators (cyclosporine) 1
• Autologous serum tears for dry eye syndrome 1
• Scleral lenses for vision correction and dry eye symptom relief 1

Severe or Refractory Disease

• For severe inflammation or treatment-resistant disease: Consider cyclophosphamide 1
• Additional therapies:
  • Oral tetracycline and niacinamide
  • Sulfasalazine
  • Mycophenolate mofetil
  • Intravenous immunoglobulin
  • Biologics 1
• Refractory cases: Consider combination of intravenous immunoglobulin and rituximab 1

Special Considerations

Infection Prevention

• Administer PCP and herpes viral prophylaxis during GVHD treatment and for at least 2 months after completion or until CD4+ count is ≥200 cells/µL 2
• Monitor for CMV infection during treatment and for at least 2 months following completion 2
• Administer only irradiated blood products to avoid transfusion-associated GVHD 2
• Avoid live viral vaccines in patients receiving immunosuppressive therapy 2

Monitoring

• Regular follow-up visits based on disease severity, etiology, and treatment 1
• Include interval history, visual acuity measurement, slit-lamp biomicroscopy for ocular GVHD 1
• Monitor CD4+ counts until recovery to ≥200 cells/µL 2
• Routinely monitor for CMV infection 2

Important Caveats

1. Specialist Management: Immunosuppressive therapy should be administered and monitored by a physician with expertise to minimize and manage side effects 1

2. Medication-Specific Precautions:

   • When using dapsone, exercise caution in patients with G6PD deficiency 1
   • Monitor for infusion-related reactions with certain biologics 2

3. Surgical Considerations: Ocular procedures such as cataract surgery may worsen ocular GVHD; perioperative immunosuppression and close follow-up are warranted 1

4. Long-Term Management: Patients with chronic GVHD usually receive multiple lines and years of immunosuppressive therapy, with only about one-third off immunosuppression, alive, and free of malignancy at 5 years after diagnosis 3

5. Treatment Discontinuation: Patients stopping immunosuppressive therapy should be cautioned to self-monitor and continue close medical follow-up, especially for 3-6 months after stopping treatment 3

The management of GVHD requires a multidisciplinary approach with careful monitoring for treatment response and complications, particularly infections, which are a major cause of morbidity and mortality in these patients.