What to Know About Graft-Versus-Host Disease (GVHD)
Graft-versus-host disease (GVHD) is one of the most common complications of bone marrow or stem cell transplants.
GVHD can range from mild to life-threatening, can have a sudden onset or develop over time, and may affect multiple systems of the body at once. While bone marrow transplant centers are well-versed in treating GVHD in adults, few are accustomed to caring for children and adolescents.
As one of the largest pediatric bone marrow transplant centers in the West, the Transplantation and Cellular Therapy team at Children’s Hospital Los Angeles regularly receives patient referrals from within California and beyond for multi-organ or difficult-to-treat chronic GVHD.
“While the disease can manifest similarly in adults and children, treatment for children often requires a more specialized approach that prioritizes long-term management to support their development and psychological well-being as they grow up.”
Ashley N. Gray, MD, MS, a physician in the Cancer and Blood Disease Institute
Dr. Gray shares what caregivers should know about graft-versus-host disease, and the leading treatments and management options available to families at CHLA.
What is Graft-Versus-Host disease?
When someone gets a bone marrow transplant, they’re essentially getting a new immune system. The immune system’s core job is to detect and fight anything foreign or potentially damaging within the body. The immune cells responsible for this are called T-cells.
When that new immune system (the graft) enters the recipient’s body (the host), those transplanted T-cells may mistake the host as an invader. This is how GVHD forms: The new immune system begins attacking the host’s tissues and organ systems.
Organ systems affected by GVHD can include:
Gut
Skin
Lungs
Liver
Acute GVHD
Acute GVHD most often forms within the first 3 months after transplant. The new immune system sees “foreign” body tissue—most commonly skin and gut tissue—and overreacts with an intense inflammatory response.
This inflammatory response can be life threatening, especially when the greatest inflammation is in the gut and causes a secondary infection.
Symptoms of acute GVHD include:
Burning rash and/or blisters on the skin
Nausea, loss of appetite, or vomiting
Diarrhea and belly pain
Jaundice
Chronic GVHD
Chronic GVHD develops and progresses over time—typically 3 months or more after transplant. “Long-term inflammation can create chronic irritation that leads to scarring or permanent damage of organ systems, so treatment to minimize damage is essential,” Dr. Gray explains.
Symptoms of chronic GVHD include:
Changes to the skin, nails, and hair (rash, thickening skin, itchiness)
Eye irritation (dryness or teariness) that won’t go away
Mouth sores, dryness, or sensitivity
Nausea, vomiting, or diarrhea
Cough, shortness of breath, or trouble breathing
Pain in the joints and muscles
Irritation or dryness in the genital area
Who is most likely to get GVHD?
Anyone receiving a bone marrow transplant from a donor can develop GVHD. The more differences there are between the donor’s DNA and the recipient’s DNA, the higher the risk.
The gold standard for bone marrow transplantation involves finding a “fully matched” donor. This is someone who has 10 of the same cell surface markers called human leukocyte antigens (HLAs).
A sibling donor is the recipient’s most likely match—but even then, the chance of a perfect 10/10 match is only about 25%. Finding a non-relative donor with enough HLAs in common can be difficult, especially for people of Hispanic or Latino, Asian or Pacific Islander, and Black or African American descent.
Advanced treatments like cord blood and “half match” transplants from family members have helped provide a lifeline to patients who can’t find a perfect donor match, but these procedures can carry a higher risk of the donor or “graft” immune system attacking the recipient or “host.”
People with a higher risk for developing GVHD include:
Adolescents and adults
Recipients without a fully matched donor
Recipients with an older donor
Male patients with female donors
Patients who have received a lot of radiation and chemotherapy
Preventing GHVD
“As a center that treats patients from a wide variety of ethnic backgrounds, we’re well versed in helping patients whose transplant is from a mismatched donor and have a higher risk for developing GVHD,” Dr. Gray explains. “Using advanced donor cell manipulation in our stem laboratory, we can greatly reduce the risk of GVHD from mismatched transplants.”
The majority of these preventive treatments involve removing or suppressing GVHD-causing T-cells in either the donor’s bone marrow or the recipient.
Alpha/beta T-cell depletion: In this highly specialized treatment, doctors bring the donor bone marrow to a lab, where they remove the T-cells cells that cause GVHD before transplanting them.
GVHD prophylaxis: Doctors treat the recipient with at least 2 types of medications that suppress these new T-cells allowing the donor cells time to get used to living in the receipent’s body. The amount of medication needed decreases over time.
Since these treatments suppress the immune system, they can increase a person’s risk of other illness, infection, and even relapse, so clinicians weigh whether that risk is absolutely necessary for each individual before suggesting preventive treatment.
Treatment for GVHD
Both acute and chronic GVHD require specialized, multidisciplinary care. Since the condition can affect multiple organ systems, one patient may need coordinated care from multiple specialists, like an ophthalmologist, dentist, dermatologist, hepatologist, pulmonologist, and gastroenterologist. At CHLA, patients have access to all these specialties within the same hospital.
Front-line therapy: Corticosteroids are the first-line treatment for GVHD. They help suppress the immune system, reducing inflammation to prevent damage to tissues, and are effective for about half of all people with GVHD.
Alternative therapies: When a patient doesn’t respond to corticosteroids, they have steroid-refractory GVHD. A number of additional treatments are available if this happens. One newly FDA-approved therapy is Ryoncil, a life-saving cellular therapy for patients 2 months or older who have acute steroid-refractory GVHD.
Emerging therapies: As a leading pediatric academic medical center, CHLA offers multiple clinical trials for therapies that aren’t available to children at other sites. Many of these therapies have already been FDA-approved and work well for adults and children over 12.
Often, these medications are only available in pill form, so doctors at CHLA participate in clinical trials that provide drugs in liquid or intravenous forms to help younger patients gain access to these treatments.
Long-term management for chronic GVHD
Patients with chronic GVHD require coordinated care over several years. Their treatment and management may require coming to the hospital or clinic every 1-3 months for regular follow up.
Specialized psychological and social support is also key for children and adolescents dealing with the pain, discomfort, and cosmetic challenges of chronic GVHD. Patients can access these resources at CHLA as part of the Cancer and Blood Disease Institute’s Survivorship and Supportive Care Program.
It can take several years for GVHD to resolve, but coordinated, multidisciplinary treatment with trained specialists can make the condition manageable.
“The beauty of having a blood system transplant is that the donor immune system will adapt and learn to live in their body,” reassures Dr. Gray. “But until then, we want to prevent any long-term side effects by recognizing early signs of GVHD and intervening early.”
(Newswise/HG)
