How Graft-Versus-Host Disease (GvHD) Is Treated

In This Article

Graft-versus-host disease (GvHD) is a complication of a stem cell or bone marrow transplant in which transplanted cells from a donor triggers an abnormal immune response in the recipient, causing the immune system to attack its own tissues and organs. As a condition characterized by an inappropriate immune response, GvHD is primarily treated with medications called immunosuppressants.

Depending on which organ is affected, the drugs may be delivered topically (by application on the skin), orally (by mouth), or intravenously (into a vein). Due to their immune suppressive effects, the drugs carry certain long-term harm, not least of which is an increased risk of infections.

In addition to treating GvHD, immunosuppressants are typically prescribed before or after a transplant to prevent the development of GvHD.

Person with graft versus host disease meets with doctor
 FatCamera / E+ / Getty Images

Home Remedies and Lifestyle

There are no home remedies that can treat GvHD, but there are things you can do to better manage the symptoms of a condition that affects 50% to 80% of allogeneic (donor-to-recipient) bone marrow or stem cell transplants.

GvHD commonly affects the skin and gastrointestinal tract, both in the people with acute GvHD (occurring within 100 days of a transplant) and those with chronic GvHD (occurring 100 days or more after a transplant).

Though immunosuppressant drugs are the primary forms of treatment, daily skin care, diet, and oral hygiene can go a long way toward better managing the cutaneous (skin) and gastrointestinal symptoms of the disease.

Skin Symptoms

With chronic GvHD, the skin can often undergo significant changes, with the progressive tightening and hardening of the skin similar to that of scleroderma. To better manage symptoms of ichthyosis (dry, scaly skin) and cutaneous sclerosis, doctors will recommend frequent moisturizing with an emollient-rich lotion or cream.

The moisturizer will typically be applied before topical medications and can help reduce folliculitis common in people with cutaneous GvHD.

Moisturizers are best applied after bathing and throughout the day whenever the skin feels itchy or chafed. Both affected and unaffected skin should be moisturized, the practice of which may temper the progression of cutaneous symptoms.

Gastrointestinal Symptoms

Both acute and chronic GvHD are characterized by frequent bouts of diarrhea, abdominal pain, and weight loss. When diarrhea symptoms are severe, doctors will generally recommend a step-wise dietary plan to ease the loss of fluid and provide nutritional support:

Oral Symptoms

People with chronic gastrointestinal GvHD are also prone to mucosal inflammation and damage of the mouth, gums, and salivary glands, leading to xerostomia (dry mouth), gingivitis, and other potentially severe oral diseases. These problems can be minimized with good oral hygiene, including daily brushing and flossing, and regular dental cleanings at least twice annually.

Toothpastes should be free of sodium lauryl sulfate, a foaming agent that can strip oils from mucosal tissues. Mouthwashes should be unflavored and alcohol-free. To help ease mouth pain, avoid spicy, acidic, coarse, or inordinately hot or cold foods.

Cigarette smoking should also be stopped. People who have undergone an allogeneic stem cell transplant are seven to nine times more likely to develop oral cancer compared to the general public, particularly those with chronic oral GvHD. Smoking only amplifies the risk.

Over-the-Counter (OTC) Therapies

There are several OTC remedies that can aid in the management of GvHD symptoms, although they are rarely if ever used on their own. These include:

  • Artificial tears: Dry eye syndrome, a common manifestation of chronic GvHD, can be often be managed with artificial tears, ideally products that are preservative-free.
  • Oral antihistamines: OTC antihistamines like Benadryl (diphenhydramine) can help relieve itching in people with cutaneous GvHD, especially if an itch is interfering with sleep.
  • Topical benzocaine: Known by the brand name Orajel and others, these topical anesthetics can relieve mouth pain in people with oral GvHD, particularly when it interferes with eating.
  • Topical hydrocortisone: Mild cutaneous symptoms may only require a low-potency OTC hydrocortisone cream (1.0% to 2.5%). Even so, the drugs are intended for short-term use, usually for no longer than three to four weeks.

OTC medications aid in the symptomatic treatment of GvHD but do nothing to temper the underlying autoimmune-like effects of the disease.

Prescriptions

GvHD is primarily treated with prescription immunosuppressants, the choice of which varies by the severity of the disease. Once diagnosed, the disease is graded based on how extensively the skin, gastrointestinal tract, liver, and other organs are affected. These diagnostic classifications help determine how the medications are dosed and stage.

Corticosteroids

Corticosteroids, also known as glucocorticoids or simply "steroids," are the mainstay of GvHD treatment. The drugs work by mimicking the stress hormone cortisol that the body uses to induce systemic inflammation.

When applied to the skin or delivered into the bloodstream, corticosteroids "trick" the body into thinking that there are ample supplies of cortisol. As a result, the overactive immune response is blunted, and the inflammatory symptoms are relieved.

Based on the grade of GvHD—ranging from 1 for mild disease to 4 for life-threatening disease—the corticosteroid drug may be delivered topically or systemically. Acute grade 1 GvHD may only require topical steroids. All other grades, either acute or chronic, are typically treated with oral or intravenous steroids.

The two most common systemic corticosteroids used in the treatment of GvHD are:

Systemic steroids are typically prescribed at a starting dose of anywhere from 1 milligram per kilogram of body weight per day (mg/kg/day) to 10 mg/kg/day depending on the location and severity of symptoms.

Once the symptoms are controlled, the corticosteroid dose is gradually tapered to avoid long-term complications, including cataracts, glaucoma, type 2 diabetes, osteoporosis, slow wound healing, increased risk of infection, and adrenal insufficiency. In some cases, the corticosteroid can be stopped if remission is achieved; in others, maintenance therapy may be needed.

Even a low-potency topical steroid may need to be tapered to prevent irreversible skin thinning and discoloration. Depending on the dose and duration of treatment, the tapering period can take weeks or months.

Other Immunosuppressants

As effective as corticosteroids are in reining in the symptoms of GvHD, they don't work forever. Not only are steroids stopped when the risks outweigh the benefits of treatment, but they may also stop working as the body develops a gradual resistance to them.

Referred to as steroid-refractory GvHD, this effect can occur in people with acute or chronic GvHD. In cases like these, other immunosuppressive drugs may be prescribed, either alone or in combination. Each has different indications for use, mechanisms of action, and risks.

GvHD Type Drug Drug Type Common Side Effects
Acute Antithymocyte globulin (ATG) Animal-derived antibody High fevers, chills, rigors
  Campath (alemtuzumab) Monoclonal antibody Upper respiratory infection, rapid heart rate, rash, fever, fatigue
  CellCept (mycophenolic acid) IMPDH inhibitor Stomach pain, fatigue, headaches, breathing problems, blood clots
  Cytoxan (cyclophosphamide) Chemotherapy Stomach pain, blood in urine, hair loss, diarrhea, nausea, vomiting, fatigue, easy bruising
  Nipent (pentostatin) Chemotherapy Muscle ache, nausea, vomiting, skin rash, fever, fatigue
  Rapamune (sirolimus) Macrolide immune suppressant Edema, stomach pain, headache, nausea, diarrhea, chest pain, sore throat, muscle pain, upper respiratory infection
  Remicade (Infliximab) Monoclonal antibody Serious infections, reactivation of hepatitis B and tuberculosis, psoriasis, vitiligo
  Zinbryta (daclizumab) Monoclonal antibody Rash, increased risk of infections, liver injury
Chronic Campath (alemtuzumab) Monoclonal antibody Same as above
  CellCept (mycophenolic acid) IMPDH inhibitor Same as above
  Gleevec (imatinib) Chemotherapy Nausea, vomiting, diarrhea, headaches, leg cramps, edema, rash, increased risk of infection, easy bruising
  Imbruvica (ibrutinib) Kinase inhibitor Fatigue, diarrhea, rash, blood clots, increased risk of infection, muscle and bone pain
  Nipent (pentostatin) Chemotherapy Same as above
  Rapamune (sirolimus) Macrollide immune suppressant Same as above
  Rituxan (rituximab) Monoclonal antibody Increased risk of viral infection, reactivation of hepatitis B, black stools, bleeding gums, body aches, difficulty breathing
  Thalomid (thalidomide) Chemotherapy Blood clots, tremors, dizziness, constipation, edema, birth defects
  Trexall (methotrexate) Chemotherapy Mouth ulcers, increased risk of infection, stomach pain, nausea, dizziness, fever, fatigue, liver injury

Prophylactic Therapy

Immunosuppressants are not only used to treat GvHD but to prevent it as well. Unless you received a transplant from an identical twin, some form of prophylactic (preventive) therapy will be needed.

In addition to drugs commonly used to treat GvHD (such as prednisone and methotrexate), there are two other immunosuppressants that can aid in the prevention of GvHD, called Prograf (tacrolimus) and Sandimmune (cyclosporine).

There is no standard treatment for GVHD prophylaxis. Different drugs and combinations of drugs may be used by different doctors and institutions.

Drug Drug Type Dosages
Antithymocyte globulin (ATG) Animal-derived antibody Between 1.5 and 2.5 mg/kg/day, given intravenously for four consecutive days 
CellCept (mycophenolic acid) IMPDH inhibitor Between 2 and 3 grams (g) daily, given orally for three weeks to four months
Methylprednisolone Corticosteroid 1 to 2 mg/kg/day for up to 12 months
Predsnisone Corticosteroid 1 to 2 mg/kg/day for up to 12 months
Prograf (tacrolimus) Macrolide Immune suppressant A starting dose of 0.02 mg/kg/day, given intravenously, eventuallly changing to an oral dose for a total duration of seven months
Rapamune (sirolimus) Macrolide immune suppressant A starting dose of 12 mg/day, taken orally, decreasing to 4 mg/day for at least two weeks
Sandimmune (cyclosporine) Non-ribosomal immune suppressnt A starting dose of 3 to 5 mg/kg/day, given intravenously, gradually tapered to one dose every two weeks for a total duratin of  six months
Trexall (methotrexate) Chemotherapy Between 10 and 15 mg per m2 (a measure of body surface area), given intravenously for four consecutive days

Surgeries and Specialist-Driven Procedures

Although immunosuppressants are the cornerstone of GvHD treatment, specialist procedures are sometimes used for people with high-grade GvHD or specific manifestations of chronic GvHD.

Extracorporeal Photophoresis

Extracorporeal photophoresis is a therapeutic procedure that was approved by the Food and Drug Administration in 1988 to treat a form of cancer known as cutaneous T-cell lymphoma. In recent years, it has proven to be effective in treating acute and chronic GvHD in combination with immunosuppressive therapies.

Extracorporeal photopheresis combines two procedures known as leukapheresis and photodynamic therapy. This involves the removal of white blood cells from the blood, which are then exposed to ultraviolet (UV) radiation before being re-infused back into the body.

The treatment tempers the autoimmune-like activity of the white blood cells, significantly reducing skin, liver, and gastrointestinal symptoms of GvHD.

Phototherapy

Phototherapy, also known as UV light therapy, is a therapeutic procedure commonly used to treat psoriasis, eczema, vitiligo, and other chronic skin condition. It can also be used in people with cutaneous GvHD to reduce the size of rashes and scaly lesions and, by doing so, reduce the need for topical or oral steroids.

The procedure is sometimes used with a photosensitizing agent called psoralen that enhances the effects of the UVA radiation (referred to a PUVA therapy).

A 2018 study in the journal Bone Marrow Transplantation reported the PUVA therapy delivered sustained remission in 70% of people with cutaneous GvHD after 31 months.

Surgery

Surgery is sometimes indicated for people with chronic GvHD, most often to repair intestinal, eye, liver, joint, kidney, or heart damage caused the disease.

Bowel resection surgery, for example, is often used for those with a severe bowel obstruction or colonic perforation. Similarly, corneal keratoplasty may be needed to replace a damaged cornea caused not only by GvHD but the corticosteroid drugs used to treat GvHD.

There are also surgeries that can preemptively treat a complication of GvHD and restore normal function. One such example is punctal occlusion, a minimally invasive procedure use to open a blocked tear duct to remedy dry eye syndrome.

To reduce pain during intercourse caused by vaginal stenosis (the narrowing of the vagina common in women with GvHD), vaginoplasty may be used in tandem with dilators to maintain the shape of the vagina.

Other surgeries may be needed to treat spinal stenosis, pericarditis, bile duct obstruction, and other complications of chronic GvHD.

A Word From Verywell

Graft-versus-host disease is not an uncommon condition in bone marrow or stem cell transplant recipients but one that can cause illness, disability, and a reduced quality of life if not treated appropriately.

Corticosteroids and non-steroid agents are extremely effective in the first-line treatment of GvHD, while newer therapies are being introduced every year that are extending remission and survival times even in those with high-grade GvHD. These include experimental proteasome inhibitors and adoptive cell therapies that block the activation of the immune system in new and novel ways.

Even if current therapies fail you, by keeping on top of the research, you can find and participate in the clinical trials that may help you live longer and better with GvHD.

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