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Graft-Versus-Host Disease

Graft-versus-host disease (GVHD) is a potentially serious complication of allogeneic stem cell transplantation and reduced-intensity allogeneic stem cell transplantation. During allogeneic stem cell transplantation, a patient receives stem cells from a donor or donated umbilical cord blood.

GVHD occurs when the donor’s T cells (the graft) view the patient’s healthy cells (the host) as foreign, and attack and damage them. Graft-versus-host disease can be mild, moderate or severe. In some cases, it can be life-threatening.

Unless the patient’s donor is an identical twin, a patient receiving an allogeneic stem cell transplant will receive some type of GVHD prevention. This may include removing T cells from the donor graft and/or giving medications to suppress the T cells in the graft so that they do not attack the patient’s cells. There is no standard regimen for the prevention of GVHD, and different combinations of medications are given at different institutions. Some common medications that are given to prevent GVHD include

  • Abatacept (Orencia®)
  • Antithymocyte globulin (ATG)
  • Alemtuzumab (Campath®)
  • Belumosudil (Rezurock™)
  • Corticosteroids (methylprednisolone or prednisone)
  • Cyclophosphamide (Cytoxan®)
  • Cyclosporine
  • Methotrexate (Trexall®)
  • Mycophenolate mofetil (CellCept®) 
  • Sirolimus (Rapamune®)
  • Tacrolimus (Prograf®)

For information about the drugs listed on this page, visit Drug Listings.

There are two main categories of GVHD: acute graft-versus-host disease and chronic graft-versus-host disease. Each type affects different organs and tissues and has different signs and symptoms. Patients may develop one type, both types, or neither type. 

Acute GVHD

This usually develops within the first 100 days after transplantation, but it can occur later. Acute GVHD can affect the skin, the gastrointestinal tract or the liver. Symptoms may include

  • A rash, with burning and redness of the skin. This may erupt on the patient’s palms or the soles of the feet, and often involves the trunk and other extremities as well. The skin may blister, and in severe cases of GVHD, the exposed surface of the skin may flake off.
  • Nausea, vomiting, abdominal cramps, loss of appetite and diarrhea indicate involvement of the gastrointestinal tract.
  • Jaundice (yellowing of the skin or eyes) may indicate that GVHD has injured the liver. Abnormalities of liver function would be noticed on blood test results.

Many patients who develop acute GVHD are successfully treated with increased immunosuppression in the form of corticosteroids (medicines such as prednisone, methylprednisolone, dexamethasone, beclomethasone and budesonide). 

Patients with mild skin-only acute GVHD will usually continue with their original medications such as cyclosporine or tacrolimus and add a topical steroid cream (topical means applied directly to a part of the body) to their treatment plan.

Treatment for patients with systemic or “whole-system” manifestations and/or more severe acute GVHD usually consists of continuing the original immunosuppressive prevention and adding a corticosteroid such as methylprednisolone or prednisone. 

The Food and Drug Administration (FDA) has approved the drug Ruxolitinib (Jakafi®) for the treatment of steroid-refractory acute GVHD in adult and pediatric patients 12 years and older.

Chronic GVHD

This is a syndrome that may involve a single organ or several organs. It is one of the leading causes of medical problems and death after an allogeneic stem cell transplantation. Symptoms may include

Mouth. Patients with GVHD may experience

  • A very dry mouth 
  • Sensitivity to hot, cold, spicy and acidic foods; mint (eg, mint flavored toothpaste); carbonated drinks
  • Painful mouth ulcers that may extend down the throat
  • Difficulty eating
  • Gum disease and tooth decay

Skin. Patients with GVHD may have

  • A rash
  • Dry, tight, itchy skin
  • Thickening and tightening of the skin, which may result in restriction of joint movement
  • A change in skin color
  • Intolerance to temperature changes due to damaged sweat glands

Nails. Patients with GVHD may experience

  • Changes in nail texture
  • Hard, brittle nails
  • Nail loss

Scalp and Body Hair. Patients with GVHD may notice

  • Loss of hair on the head
  • Premature gray hair
  • Loss of body hair

Gastrointestinal Tract. Patients with GVHD may experience

  • Loss of appetite
  • Unexplained weight loss
  • Nausea
  • Vomiting
  • Diarrhea
  • Stomach pain

Lungs. Patents with GVHD may suffer from

  • Shortness of breath and difficulty breathing
  • A persistent, chronic cough that does not go away
  • Wheezing

Liver. A patient with GVHD may have

  • Abdominal swelling
  • Jaundice (yellow discoloration of the skin and/or eyes)
  • Abnormal liver function test results

Muscles and Joints. Side effects of GVHD may include

  • Muscle weakness and cramps
  • Joint stiffness causing difficult full extension of fingers, wrists, elbows, knees, ankles.

Genitalia. Chronic GVHD can have the following effects on the genitalia of women and men:

  • Female
    • Vaginal dryness, itching and pain
    • Vaginal ulcerations and scarring
    • Narrowing of the vagina
    • Difficult /painful intercourse
  • Male
    • Narrowing and/or scarring of the urethra
    • Itching or scarring on the penis and scrotum
    • Irritation of the penis

Patients with mild symptoms of chronic GVHD, especially if the symptoms are limited to a single organ or site, can often be treated with close observation or with local/topical therapies. For example, mild cases of chronic skin GVHD may be treated with topical steroid ointments and cases of chronic ocular (eye) GVHD may be treated with immunosuppressive eye drops.

Patients with more severe symptoms or multi organ involvement chronic GVHD typically require “systemic” treatment, which travels through the bloodstream and reaches cells throughout the entire body. Prednisone is the standard first-line therapy for chronic GVHD. For patients who do not respond to prednisone or other steroid treatments, the Food and Drug Administration (FDA) has approved three drugs as second-line treatments:

  • Ibrutinib (Imbruvica®) 
  • Belumosudil (Rezurock™) 
  • Ruxolitinib (Jakafi®)

Other combinations of immune suppressive drugs may be used to control the symptoms of GVHD.

Patients must be aware of the warning signs of GVHD and should call their doctors immediately if they have any symptoms. Early detection and treatment may help limit the severity of the disease.  

For more information, download or order the free fact sheet, Graft-Versus-Host Disease.

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