Chronic Graft-Versus-Host Disease (cGVHD)

Understanding Chronic Graft‑Versus‑Host Disease (cGVHD)

Chronic graft‑versus‑host disease (cGVHD) is a long‑term complication that can occur after an allogeneic hematopoietic stem cell transplant (a transplant using donor cells). It happens when the donor’s immune cells recognize the recipient’s tissues as foreign and mount an immune response.

cGVHD can affect multiple organs, including the skin, eyes, mouth, lungs, liver, gastrointestinal tract, joints, and genital tract. It may develop after or independently of acute GVHD, and symptoms can appear months to years after transplant.

It is one of the leading causes of long‑term illness and reduced quality of life in transplant survivors.

Common signs and symptoms of cGVHD

General symptoms

Symptoms vary depending on which organs are involved. Common manifestations include:

• Skin rash, dryness, thickening, or tightening
• Dry eyes, irritation, or sensitivity to light
• Dry mouth, mouth sores, or difficulty eating
• Joint stiffness or limited range of motion
• Muscle weakness
• Fatigue
• Shortness of breath (if the lungs are affected)
• Gastrointestinal symptoms such as nausea, diarrhea, or abdominal discomfort

Organ‑specific complications

cGVHD can cause:

• Skin sclerosis (hardening or tightening of the skin)
• Liver involvement, often detected through abnormal liver tests
• Lung involvement, including bronchiolitis obliterans syndrome
• Oral sensitivity, ulcers, or pain
• Eye dryness or inflammation
• Genital or urinary symptoms
• Weight loss due to chronic inflammation or GI involvement

Causes and Risk Factors

cGVHD occurs when donor immune cells attack the recipient’s tissues. Factors associated with increased risk include:

• Older donor or recipient age
• Use of peripheral blood stem cells (higher risk than bone marrow)
• Prior acute GVHD
• Greater HLA mismatch between donor and recipient
• Female donor to male recipient
• Donor parity (female donors who have been pregnant)

Diagnosis

Diagnosis is based on clinical findings and the NIH Consensus Criteria, which define specific features that distinguish chronic GVHD from acute GVHD.

Evaluation may include:

• Physical examination of affected organs
• Blood tests (including liver function tests)
• Pulmonary function tests
• Skin, oral, or other tissue biopsies when needed
• Imaging studies if organ involvement is suspected

Severity is classified as mild, moderate, or severe based on the number of organs involved and the degree of functional impairment.

Treatment overview

Treatment depends on disease severity, organ involvement, and response to prior therapies.

First‑line treatment

• Systemic corticosteroids (typically prednisone)
• Often combined with a calcineurin inhibitor (e.g., tacrolimus) if not already being used

Second‑line and subsequent treatments

For steroid‑refractory or steroid‑dependent cGVHD, options may include:

• JAK inhibitors (e.g., ruxolitinib)
• Bruton tyrosine kinase inhibitors (e.g., ibrutinib)
• Monoclonal antibodies targeting immune pathways
• Extracorporeal photopheresis (ECP)
• Other immunosuppressive or targeted agents

Supportive care

Because cGVHD can affect many organs, supportive care is essential and may include:

• Eye lubricants and ophthalmology care
• Physical and occupational therapy
• Skin care and dermatology support
• Infection prevention and vaccination guidance
• Nutritional support