Why is Graft-Versus-Host Disease dangerous?
What Is Graft-Versus-Host Disease?
After an allogeneic stem cell or bone marrow transplant, the donor's immune cells attack the recipient's body as “foreign.” This is called graft-versus-host disease (GvHD). It can affect the skin, liver, intestines, and lungs and can be either acute or chronic within 100 days.
Due to HLA variations, donor immune cells (particularly T cells) assault recipient cells as foreign. This only occurs in allogeneic transplants, not autologous ones.
Possible Risks:
- Poor donor-recipient HLA match
- Age gaps between donors and recipients
- Donor pregnancy history
- Male donor/female receiver or vice versa
- Bone marrow vs. blood stem cells
Balance Risks & Benefits
- GvHD is life-threatening, especially in chronic patients.
- The graft-versus-tumour effect occurs when the immune response that destroys healthy cells also kills leftover cancer cells. Relapse rates may be reduced in moderate GvHD.
Types of GvHD
- Acute GvHD (aGvHD) occurs within 100 days post-transplant. Skin, intestines, liver. Itching, diarrhoea, nausea, jaundice
- Long-term GvHD. Skin, mouth, liver, lungs, joints, and genitals after 100 days (frequently 2 years). Tight skin, dry mouth/eyes, cough, weariness, muscle weakness, and vaginal pain.
Self-Care & Prevention
- Preventive immunosuppressants and donor HLA matching.
- Self-care advice:
- Use SPF 50+ sunscreen and long sleeves.
- Keep teeth clean.
- Stay away from spicy, acidic foods.
- Clean your hands and avoid crowds to reduce the risk of infections.
GVHD symptoms
Symptoms of acute GVHD occur within 100 days post-transplant.
Skin:
- Sunburn-like rash (neck, shoulders, ears, palms, soles)
- Itching, redness, pain
- The gastrointestinal tract
- Nausea, vomiting
- Can be severe diarrhoea
- Stomach cramps
Liver:
- Yellowing skin/eyes
- Enhanced liver enzymes
GVHD symptoms persist for over 100 days, often within 2 years.
- Skin, hair:
- Rash, itch
- Scleroderma-like skin tightness, edema, thickening
- Hair loss, brittleness, early greying
Mouth and Dental Health:
- Mouth dry
- Gum disease, painful mouth
- Mouth white spots
Eyes:
- Gritty, dry feeling
- Vision alters
GI/Liver:
- Vomiting, diarrhoea
- Jaundice
Lungs:
- Shortness of breath
- A persistent dry cough
Musculoskeletal:
- Weak muscles, cramping, pain
- Joint stiffness, limited motion
Reproductive Organs:
- Dryness, itching, and intercourse discomfort
- Itching or pain during sex
General:
- Fatigue
- Weight loss
Key Risks and Considerations
- Symptoms range from minor to life-threatening.
- Overlap: Acute and chronic GVHD can occur.
- Complications: Immunosuppression increases infection risk.
- Chronic GVHD, along with the underlying illness, has a fatal impact on allogeneic transplants.
Monitoring and Self-Care
- Avoid sun exposure; apply SPF 50+ sunscreen.
- Cleaning your teeth regularly prevents gum disease.
- Avoid hot or acidic foods that irritate the mouth/GI tract.
- Keep your hands clean and avoid crowds to avoid infection.
- Follow-up: Report new rashes, jaundice, cough, or GI concerns immediately.
What causes GVHD most often?
Graft-versus-host disease (GVHD) is most often caused by donor T lymphocytes attacking recipient tissues after an allogeneic stem cell or bone marrow transplant.
Key Cause
Differences in human leukocyte antigens cause donor immune cells, especially T lymphocytes, to detect receiving cells as foreign.
This mismatch causes an immunological attack on the recipient's skin, liver, GI tract, and other organs.
Contributing Risks
- HLA mismatch: Minor variances raise risk.
- Differences between donors and recipients
Age gap
- Mismatched sexes (particularly female donor-male receiver)
- Donor pregnancy history (multiparous women suffer immunological reactions)
- Peripheral blood stem cells are more GVHD-prone than bone marrow.
- Conditioning regimen: GVHD risk depends on chemotherapy/radiation intensity before transplant.
Why is GVHD dangerous?
- GVHD can severely harm the skin, liver, gastrointestinal tract, lungs, and other organs.
- Treatment with strong immunosuppressive medicines makes patients susceptible to bacterial, viral, and fungal infections.
- Treatment resistance: Some cases resist corticosteroids, making them difficult to treat.
- Scarring, organ dysfunction, and disability can result from chronic GVHD.
Outcomes
Mild GVHD: Manageable and may enhance graft-versus-tumour effects.
Moderate to severe GVHD: Can be lethal if uncontrolled, and chronic GVHD is one of the primary causes of death after allogeneic stem cell transplants (excluding recurrence).
Diagnostics of GVHD
Rash, diarrhoea, jaundice, dry eyes/mouth, lung difficulties, etc.
Blood tests:
- To diagnose liver disease, liver function tests
- Complete blood counts
- Biopsies:
- Rash skin biopsy
- GI biopsy for diarrhea or abdominal pain
- Liver biopsy if liver involvement is suspected
- Imaging: Chest CT or pulmonary function tests for lung GVHD.
- Specialized tests:
- GI symptoms, endoscopy/colonoscopy with tissue samples
- Dry-eye Schirmer test of tear production
GVHD treatment
Main Treatment Methods
1. Prophylactic
- Immunosuppressive medicines lower GVHD risk shortly after transplant.
- Cyclosporine, tacrolimus, methotrexate, and mycophenolate mofetil.
- Stop donor T cells from attacking recipient tissues.
2. Treating acute GVHD
- First-line:
- Corticosteroids (oral, IV, or topical) decrease inflammation and immunological response.
- Second-line (steroid-resistant):
- Ruxolitinib (Jakafi®) lowers immunological activation by inhibiting JAK.
- Novel medicines may undergo clinical testing.
3. Treatment for cGVHD
- Typical immunosuppressants last long.
- Resistance or severity:
- Belumosudil (Rezurock™) inhibits ROCK2, reducing fibrosis and inflammation.
- BTK inhibitor Ibrutinib (Imbruvica®) alters immune cell signaling.
- Chronic cases take ruxolitinib (Jakafi®).
- Photopheresis (ECP) reduces immunological attack with blood-filtering light.
Supportive therapies:
- Skin GVHD steroid creams
- Eye drops for dry eyes
- Joint-stiffness physical therapy
- GI medicines for nausea, diarrhoea, appetite loss
Comparing Acute and Chronic GVHD Treatment
- Acute GVHD, Corticosteroids, Ruxolitinib, clinical trials Topical steroids, GI relief
- Chronic GVHD Long-term immunosuppressantsBelumosudil, Ibrutinib, Ruxolitinib, Photopheresis, Skin creams, eye drops, PT, GI medications.
Risks, side effects
- Immunosuppressants exacerbate fungal, bacterial, and viral infections.
- Long-term steroid use can cause bone loss, diabetes, hypertension, and weight gain.
- Ruxolitinib, ibrutinib, and belumosudil may cause low blood counts, liver enzyme abnormalities, and bleeding.
Key Takeaway
- Steroids are key to treating GVHD.
- Newer targeted therapies (ruxolitinib, belumosudil, and ibrutinib) improve steroid-resistant results.
- Symptom management and quality of life require supportive treatment.
- Glucksberg/Modified Seattle Criteria for Acute GVHD Staging
Acute GVHD severity is categorised I–IV:
Stage I (Mild): Skin rash encompassing <25% of the body
- Liver enzyme rise or mild diarrhoea
Stage 2: Moderate
- 25%–50% body rash
- Daily diarrhoea 500–1000 mL
- Bilirubin 2–3 mg/dL, moderate liver involvement
Stage 3: Severe
- More than 50% body rash
- Daily diarrhea >1000 mL
- Bilirubin 3–6 mg/dL liver damage
Life-threatening Stage IV:
- Blistering throughout the skin
- Severe diarrhea, stomach discomfort, blood
- Severe liver failure (bilirubin >15 mg/dL)
Chronic GVHD Staging (NIH Consensus)
Stages of chronic GVHD include organ involvement and severity.
Mild:
- 1–2 organs, minimal symptoms (dry mouth, rash).
Moderate:
- A minimum of 3 organs or one with moderate symptoms (e.g., skin tightness, eye dryness requiring drops).
Severe:
- Major organ malfunction (lungs, liver, GI tract) or severe disability (skin sclerosis, joint contractures, severe eye/mouth involvement).
Why Staging Matters
- Helps doctors choose therapy intensity.
- Predicts problems and survival.
- It determines whether to use steroids alone or with targeted therapy.
Conclusion
Graft-versus-host disease (GVHD) is a serious complication of allogeneic stem cell or bone marrow transplants, caused when donor immune cells attack the recipient’s tissues.
GVHD is both a dangerous complication and a potential therapeutic ally against cancer relapse. Its management requires a careful balance between controlling immune attacks and preserving anti-tumour benefits.







