Before you dive into this article, you may want to review the basics of bone marrow transplant here. You can also review the basics of bone marrow transplant by listening to episode 279 of the Straight A Nursing podcast.

Graft-versus-host disease (GVHD) is a complication that can occur after allogeneic hematopoietic cell transplant. It is a syndrome that involves multiple organs and occurs when transplanted immune cells identify the recipient cells as foreign invaders. The result is that the transplanted (graft) cells attack the recipient (host) cells. The primary targets of GVHD are the skin, mouth, GI tract, eyes, and liver, but can affect any organ or tissue in the body. 

There are two main subtypes of GVHD: 

  • Acute GVHD (aGVHD) – In this subtype, the condition has a sudden and rapid onset within the first 100 days after transplantation. 
  • Chronic GVHD (cGVHD) – In this subtype, the condition is long-term and can involve organs throughout the entire body.

Individuals most at risk for developing acute GVHD include those with an HLA mismatch (more on this down below), receiving stem cells from a donor who is not related to the host, undergoing radiation as part of the transplant regimen, older donor or recipient, and female donor combined with a male recipient. Risk factors for chronic GVHD include those mentioned above plus having a prior incidence of acute GVHD or receiving stem cells from peripheral blood versus stem cells from bone marrow or cord blood.

HLA Typing

Prior to allogeneic transplantation, both the patient and the donor must go through extensive testing to ensure the donor’s cells are a good match. One specific test, the HLA or “tissue typing” test looks at HLA proteins that exist on the surface of cells. These proteins essentially tell white blood cells which cells are self and which cells belong to a pathogen or invader. If the HLA proteins from the donor are vastly different from that of the recipient, the immune system begins attacking the recipient’s cells because they don’t recognize them as self. 

Let’s go through the key nursing implications of GVHD using the Straight A Nursing LATTE Method.

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L: How does the patient LOOK?

The signs of symptoms of GVHD can vary from person to person and whether the individual is experiencing acute or chronic disease. 

Acute GVHD

Manifestations of acute GVHD include: 

GI tract – Patients with aGVHD can have severe diarrhea (up to several liters per day), nausea, vomiting, loss of appetite, and blood in the stool.

Skin – The most common dermatologic manifestation is a rash that starts as faint redness that may spread to involve the whole body. Mild rashes tend to resemble a sunburn while severe rashes can blister and cause the skin to peel.

Liver – In many cases, liver involvement may have no outward symptoms and only be identified on blood tests. Some individuals will show outward signs of liver impairment including jaundice, abdominal pain, dark urine, bleeding (due to low platelets), ascites, and hepatic encephalopathy.

Acute GVHD is classified by how many organs are involved and how significantly they are affected. For example, the skin is classified by how much of the body surface area is affected and the GI tract is classified by how much diarrhea the patient has each day. Patients with higher scores tend to have poorer outcomes and increased mortality.

Chronic GVHD

Individuals with chronic GVHD, which affects 40 to 50% of individuals receiving allogeneic stem cell transplant, can experience mild to life-threatening complications involving one or more organs. Manifestations of chronic GVHD include:

Skin – Skin signs and symptoms are varied and include rash, non-healing ulcers, skin thickening, dry or tight skin, itching, changes in skin color, and intolerance to temperature changes secondary to damaged sweat glands. 

GI tract – Common symptoms associated with the GI tract include nausea, vomiting, diarrhea, decreased appetite, and unintentional weight loss.

Liver – Individuals with cGVHD can suffer from long-term liver impairment and exhibit signs such as jaundice and ascites.

Lungs – Respiratory symptoms can include shortness of breath, wheezing, difficulty breathing, and a persistent cough.

Eyes – The eyes of a patient with cGVHD can be painfully dry and itchy. Individuals may also experience blurred vision, light intolerance, and may even have loss of vision.

Joints and muscles – Individuals with cGVHD may have stiff joints that are difficult to move to their full range of motion. They may also experience muscle cramps or muscle weakness.

Mouth – Dry mouth is a common symptom of cGVHD. Other symptoms include painful mouth sores, gum disease, dental caries, and difficulty swallowing. Individuals may also have sensitivity to hot, acidic or spicy foods, carbonated beverages, and mint.

Genitals – Individuals may experience genital irritation, dryness, painful intercourse, and a rash.

Hair and nails – Loss or graying of hair is common as is hardening of the nails. Nails may also become brittle and may even fall off.

A: How do you ASSESS a patient with GVHD?

Assessments for GVHD will be tailored to the individual’s specific manifestations. Some general assessments include: 

  • Perform a full skin assessment, making note of non-healing wounds and areas where the skin has peeled as these may require specific wound interventions. 
  • Monitor the amount of diarrhea and for the presence of blood in the stool.
  • Assess the patient for signs of volume depletion, which can occur due to dehydration and decreased oral intake secondary to oral complications. These can include tachycardia, hypotension, poor skin turgor and dry mucous membranes.
  • Take your patient’s temperature as they are at higher risk for infection.
  • Assess the patient for liver involvement by observing for things like jaundice, hypoglycemia and bleeding. If ascites is present, measure abdominal girth and assess for shortness of breath.
  • Assess the oral cavity as mouth sores may be present that make eating painful and difficult. 
  • Ask the patient about their appetite and food preferences.
  • Assess ROM, noting that limited ROM can affect ability to perform ADLs as well as gait (which can increase risk for falls). 

T: What TESTS are conducted for a patient with GVHD?

The diagnosis of GVHD is typically arrived at through physical examination and may also involve a biopsy of the skin or affected organs. 

Ongoing evaluation will depend on the patient’s unique manifestations. For example, a patient with liver involvement will have their liver enzymes monitored as well as bilirubin and ammonia levels. Cultures will be sent in cases of suspected infection, such as from a non-healing wound. In cases of severe diarrhea, the stool may be cultured or tested for c. diff and cytomegalovirus. In addition, upper endoscopy and/or colonoscopy may be utilized and biopsies taken for further evaluation of the GI tract.

T: What TREATMENTS are provided for GVHD?

Treatments for GVHD are aimed at suppressing the donor T cells, which are the cells primarily responsible for the attack on the body’s tissues. However, a complicating factor is that the same T cells are also the cells that mediate the immune response against the tumor. What this means is that treatment must be carefully balanced to reduce GVHD without decreasing the immune reaction against the tumor. 

A key treatment of acute GVHD is prophylaxis. Preferred methods vary based on a variety of factors including the graft source, the conditioning regimen utilized, and the degree of matching between donor and recipient. A common combination of prophylactic medications is a calcineurin inhibitor, such as tacrolimus or cyclosporine, and an antimetabolite, such as methotrexate. Other medications may be utilized depending on the patient’s specific transplant details. 

Another method of GVHD prophylaxis is T-cell depletion which aims to eliminate the donor’s T-cells. This can be achieved by giving the recipient certain medications (such as antithymocyte globulin) right before or right after transplant. Another method utilizes external removal of the T-cells before the stem cells are transplanted in the recipient.

Should aGVHD develop, treatments include optimizing the prophylactic regimen as well as the following: 

  • Topical corticosteroids are often utilized for grade 1 aGVHD involving a rash. Other skin treatments may include antihistamines and moisturizers to relieve itching. Topical tacrolimus may also be utilized if a topical corticosteroid is ineffective. 
  • A systemic glucocorticoid (ex: methylprednisolone) is often utilized for grade 2 and higher aGVHD.
  • Beclomethasone or budesonide, which are oral nonabsorbable steroids, may be used for GI tract involvement.
  • In cases of glucocorticoid-resistant GVHD, ruxolitinib may be utilized. Ruxolitinib (Jakifi) is an antineoplastic medication that can cause anemia, thrombocytopenia, infection and other serious adverse effects.
  • Supportive care for GI tract involvement includes optimizing nutrition. Parenteral nutrition may be utilized in patients with high volume diarrhea (in excess of 500 ml/day). In some cases, octreotide may be administered on a short-term basis to treat diarrhea. Because the volume losses with diarrhea can be significant, it’s vital to replenish fluids and electrolytes as needed. In addition, ensure the patient’s skin remains clean and dry, especially if areas of blistering or peeling are nearby.
  • Other medications used to treat acute GVHD include other immunosuppressants such as mycophenolate mofetil (CellCept) and biologics that can slow or even halt inflammation such as abatacept (Orencia) and alemtuzumab (Campath).

Chronic GVHD treatments will vary depending on the affected tissue and severity. Mild skin symptoms, for example, may be managed with a topical corticosteroid. Moderate cGVHD may be treated with prednisone, which is a systemic medication taken by mouth. Individuals with severe cGVHD will require more extensive treatment that typically involves prednisone plus ruxolitinib. 

Another option that may be utilized for chronic GVHD is extracorporeal photopheresis (ECP). In this procedure, blood is removed and the white blood cells are separated from the other components. A drug that has been exposed to UV light (a photoactive drug) is combined with the WBCs and this combination is returned to the patient.

Specific symptoms and complications will be managed and vary depending on the patient’s specific disease course. This can include things like skin ointments and creams, medicated eye drops and artificial tears, oral rinses, bronchodilators, supplemental oxygen, physical therapy, and antibiotics as needed.

E: How do you EDUCATE the patient about GVHD?

There is a lot of potential teaching surrounding the topic of GVHD. Things you want to ensure your patient or their family understand are numerous and include: 

  • GVHD can be acute or chronic. Acute GVHD usually occurs within three months of the transplant and is more likely to affect individuals receiving stem cells from an unrelated donor. 
  • Individuals with aGVHD have a 50% chance of developing the chronic form. Chronic GVHD usually develops three to 18 months after transplant and affects about 30% of individuals with an HLA matched sibling donor. 
  • If GVHD occurs in recipients who received HLA matched cells from a sibling donor, the disease is usually less severe and responds more readily to treatment.
  • The signs and symptoms of GVHD can be varied and include a skin rash, diarrhea, nausea/vomiting, abdominal cramps and jaundice.
  • GVHD can affect many organs throughout the body including the lungs, liver and kidneys. 
  • Monitor the volume or occurrences of diarrhea as excessive losses may require additional treatment including fluids, electrolyte replacement, or parenteral nutrition.
  • Drink at least 8 to 10 8-oz glasses of water each day to avoid dehydration. More fluids may be needed if diarrhea is significant. 
  • Avoid beverages and foods that promote diarrhea such as caffeine, chocolate, greasy foods, and high-sugar foods, as well as vegetables that promote gas (ex: cauliflower, beans, and onions).
  • The mint in toothpaste can cause pain in a sensitive mouth. Kingfisher Natural Toothpaste and Tom’s of Maine both offer toothpaste flavors that do not contain mint or menthol.
  • Choose an alcohol-free mouthwash or make your own by mixing 1 tsp salt and 1 tsp baking soda in 4 cups of water. Rinsing the mouth with this solution can help soothe the pain associated with mucositis.
  • Avoid foods and beverages that can irritate the mouth. This includes hot items, spicy foods, acidic foods and beverages, carbonated beverages and very dry or rough textures.
  • Sugarless candies and chewing gum may help alleviate dry mouth.
  • If loss of taste is a factor, enhance nutritional intake by choosing foods that are most appealing. Additionally, adding non-irritating seasonings to foods can help boost flavor. 
  • Some individuals are sensitive to the odor of foods. If this is the case, avoid foods that have strong odors (such as fish) and open windows while cooking. Other options include eating foods that are served cold or at room temperature.
  • To combat unintentional weight loss, eat small meals frequently, drink beverages that are high in calories, add more calories and protein to the diet, eat the foods you enjoy most, and add good-smelling foods to meals such as fresh-baked bread.
  • Use lukewarm or cool water for bathing/showering and use gentle, moisturizing soaps that are free of fragrance. Applying moisturizer immediately afterwards helps lock in moisture and relieve dry skin.
  • Protect the skin from UV exposure by wearing sunscreen with UPF of 30 or higher along with protective clothing.
  • Physical activity can help preserve joint mobility and improve symptoms of fatigue. A combination of aerobic exercise, strength-training, and stretching are advised.

For an excellent resource for patient education that includes these tips and many more, visit the Memorial Sloan Kettering Cancer Center website.

I hope this overview of GVHD helps you understand this complex condition. If you enjoyed learning using the Straight A Nursing LATTE Method, you can download a free LATTE template here.

Take this topic on the go by tuning in to episode 323 of the Straight A Nursing podcast. Listen from any podcast platform, or straight from the website here.


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References:

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Cleveland Clinic. (n.d.). Graft vs. Host Disease (GvHD). Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/10255-graft-vs-host-disease-an-overview-in-bone-marrow-transplant
Davis’s Drug Guide. (n.d.). Ruxolitinib (Jakafi). Davis’s Drug Guide. https://www.drugguide.com/ddo/view/Davis-Drug-Guide/109616/all/ruxolitinib?refer=true
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Leukemia & Lymphoma Society. (n.d.). Stem Cell Transplantation | Graft-Versus-Host Disease | LLS. Leukemia & Lymphoma Society. https://www.lls.org/treatment/types-treatment/stem-cell-transplantation/graft-versus-host-disease
Zeiser, R. (n.d.-a). Treatment of acute graft-versus-host disease. UpToDate. https://www.uptodate.com/contents/treatment-of-acute-graft-versus-host-disease?search=graft%20versus%20host%20disease%20treatment&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
Zeiser, R. (n.d.-b). Treatment of chronic graft-versus-host disease. UpToDate. https://www.uptodate.com/contents/treatment-of-chronic-graft-versus-host-disease?search=chronic%20graft%20versus%20host%20disease%20treatment&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
Zeiser, R. (2022, June 16). Prevention of graft-versus-host disease. UpToDate. https://www.uptodate.com/contents/prevention-of-graft-versus-host-disease?search=graft%20versus%20host%20disease%20treatment&topicRef=3543&source=see_link