Graft-Versus-Host Disease (GVHD)

Why GVHD happens

An allogeneic transplant replaces a person's blood-forming system with stem cells from a donor, often to treat leukemia, lymphoma, myelodysplastic syndrome or bone marrow failure. The donor's immune cells, especially T cells, come with the graft. If they recognize differences in the recipient's tissue proteins, they attack.

The same donor immune cells also attack remaining cancer cells, the graft-versus-leukemia effect, which helps prevent relapse. Treatment aims to control GVHD without removing this benefit.

GVHD does not occur after autologous transplants, which use a person's own cells.

Acute vs chronic GVHD

The two forms can overlap.

Symptoms

Acute GVHD

• skin: a red, sometimes itchy or painful rash, often starting on the palms, soles, ears and face, which can spread and, in severe cases, blister
• gut: watery diarrhea (sometimes large volumes or bloody), belly cramps, nausea, vomiting and loss of appetite
• liver: jaundice and abnormal liver tests

Chronic GVHD

• mouth: dryness, sensitivity to spicy food and toothpaste, white lacy patches, sores
• eyes: dryness, grittiness, burning and light sensitivity
• skin: changes in color, thickening, tightness and scarring like scleroderma, hair and nail changes
• joints and fascia: stiffness and reduced range of motion
• lungs: bronchiolitis obliterans, causing breathlessness and dry cough. This is a serious form
• gut and liver: difficulty swallowing, weight loss, abnormal liver tests
• genitals: vaginal dryness, narrowing and pain with sex, or penile skin changes
• muscles: weakness and cramps

Risk factors

• donor and recipient not fully matched for HLA tissue type
• unrelated or mismatched donors
• peripheral blood stem cells rather than bone marrow
• a female donor who has been pregnant, for a male recipient
• older recipient or donor age
• previous acute GVHD (for chronic GVHD)
• the type and intensity of GVHD prevention used

Prevention

Every allogeneic transplant includes GVHD prevention, such as:

• calcineurin inhibitors (tacrolimus or cyclosporine) with methotrexate or mycophenolate
• post-transplant cyclophosphamide
• anti-thymocyte globulin
• careful donor selection

Diagnosis

GVHD is diagnosed by the transplant team based on symptoms and timing, often confirmed with:

• skin biopsy for rashes
• endoscopy and biopsy of the gut for diarrhea
• liver tests, and sometimes imaging or liver biopsy
• lung function tests and CT for breathing problems
• eye tests such as the Schirmer test for dryness

Infections and drug reactions can look similar and must be excluded.

Treatment

Acute GVHD

• topical steroids for mild skin-only disease
• systemic corticosteroids for more extensive acute GVHD
• ruxolitinib for steroid-refractory acute GVHD, where it is approved
• other options in clinical trials and specialist centers

Chronic GVHD

• systemic steroids, often with continued calcineurin inhibitors
• for steroid-refractory chronic GVHD: ruxolitinib, belumosudil, ibrutinib or axatilimab, plus extracorporeal photopheresis
• organ-specific care: lubricating eye drops, punctal plugs and scleral lenses for eyes, mouth rinses and dental care, physical therapy for joints, inhaled therapies for lungs, and vaginal estrogen and dilators

Supportive care

Immune-suppressing treatment increases infection risk. Patients usually take preventive antibiotics, antivirals and antifungals, receive vaccines on a post-transplant schedule, and need prompt care for any fever. Bone health, nutrition and emotional support also matter.

Outlook

Mild acute GVHD often responds well to treatment. Severe acute GVHD that does not respond to steroids carries a serious risk to life. Chronic GVHD is a leading cause of long-term illness after transplant, but many people with it eventually stop treatment after months to years. Its link with the graft-versus-leukemia effect means that people with chronic GVHD often have a lower risk of cancer relapse.

Frequently asked questions

What is graft-versus-host disease?

GVHD is a complication of a donor stem cell or bone marrow transplant in which the donor's immune cells attack the recipient's tissues, such as the skin, gut, liver, mouth, eyes and lungs. It can be acute, occurring early, or chronic, developing later.

What are the first signs of GVHD?

Early signs of acute GVHD often include a red rash on the palms, soles, ears or face, followed by diarrhea, nausea or jaundice. Chronic GVHD often starts with dry eyes, a dry or sensitive mouth, mouth sores or skin tightening.

What is the difference between acute and chronic GVHD?

Acute GVHD typically develops in the first few months after transplant and mainly affects the skin, gut and liver. Chronic GVHD usually starts later, lasts longer and can affect many organs, causing dryness, scarring and stiffness similar to autoimmune diseases.

How is GVHD treated?

Treatment starts with corticosteroids, applied to the skin or taken by mouth or IV. If GVHD does not respond, drugs such as ruxolitinib, belumosudil, ibrutinib or photopheresis may be used. Organ-specific treatments and infection prevention are also essential.

Can GVHD be cured?

Many people's GVHD goes into remission, allowing immune-suppressing treatments to be stopped, although this can take months to years for chronic GVHD. Some people have long-term organ damage, particularly to the lungs, eyes or skin, that needs ongoing care.