An allogeneic stem cell transplant or bone marrow transplant can be a lifesaving procedure. However, some people may develop acute graft-versus-host disease (aGVHD). A serious complication of stem cell transplantation, aGVHD occurs when donor immune cells attack the recipient’s healthy tissues. Severe aGVHD can have a big impact on quality of life, but new research is helping improve treatment options.

If you’ve had an allogeneic stem cell transplant or are considering one, be sure to talk to your doctor about potential complications such as aGVHD. Here are some important facts about aGVHD that you can discuss further with your doctor.

1. Acute Graft-Versus-Host Disease Can Affect Different Areas of the Body

Various organs throughout the body can be affected by aGVHD. It’s known to primarily affect the skin, liver, and the gastrointestinal tract (digestive system). Less commonly, aGVHD can affect the eyes, kidneys, lungs, and, in very rare cases, the brain and nerves (central nervous system, CNS).

Depending on where the condition occurs, acute GVHD symptoms may vary. For instance:

• Skin GVHD may cause a rash, itching, redness or discoloration, blisters, or other skin problems.
• Liver GVHD can cause jaundice (yellowing or discoloration in the eyes or skin), unusual swelling, or abnormal blood test results that show high levels of bilirubin (a substance that results from the breakdown of red blood cells) and alkaline phosphatase (an enzyme that can indicate liver or bone problems)
• Gastrointestinal GVHD affects the gut and may cause diarrhea, vomiting, bloody stool, abdominal pain, loss of appetite, or unexpected weight loss.
• GVHD in the central nervous system may resemble another neurological condition such as multiple sclerosis.

It’s essential to report any unusual symptoms after a stem cell transplant to your doctor. Make sure to go to your doctor’s office for any follow-up tests or examinations.

2. Acute Graft-Versus-Host Disease Usually Occurs Within Three Months of a Stem Cell Transplant

Acute graft-versus-host disease is one of two main types of GVHD, sometimes also called graft host disease or graft vs. host disease. It typically develops within 100 days of a hematopoietic cell transplant (HCT) and has symptoms distinct from chronic GVHD. Chronic GVHD, on the other hand, can happen at any time after HCT and has its own set of symptoms.

Doctors diagnose aGVHD only if there are no signs of chronic GVHD, like autoantibodies (proteins that attack the body by mistake). Chronic GVHD often has more symptoms, some resembling autoimmune diseases. If someone has symptoms of both, it’s called overlap chronic GVHD.

3. A Donor-Host Mismatch Increases the Risk of aGVHD

When identifying a donor for a stem cell transplant, it’s key that a particular marker in their immune system is as similar as possible to the transplant recipient. The immune system works by attacking viruses and bacteria. Proteins known as human leukocyte antigens (HLAs), found on the surface of cells, help protect healthy tissue from an abnormal immune response that can damage tissues in the body. They let the immune system know which cells belong to the body and which are foreign.

When undergoing a stem cell transplant, the donor’s HLA needs to closely match the recipient’s HLA to reduce the risk of developing aGVHD. Both related donors and unrelated donors pose an increased risk of GVHD if HLA is mismatched. Only identical twins have perfectly matched HLA.

4. Other Factors Also Raise the Risk of GVHD

There are additional risk factors for aGVHD to be aware of if you’re planning to have a stem cell transplant. Other risk factors as cited by Cleveland Clinic include:

• A donor or recipient of older age
• A donor who’s had a pregnancy
• A donor and recipient whose sex is mismatched, such as a female donor and a male recipient
• Using donor stem cells from the bloodstream rather than bone marrow
• Cancer treatment with high-dose chemotherapy or full-body irradiation with chemotherapy
• Stem cell transplant treatment that includes double therapy (methotrexate and cyclosporine) instead of triple therapy (methotrexate, cyclosporine, and prednisone)

It’s also important to know that if you’ve had aGVHD you have a higher risk of developing chronic GVHD.

5. Acute GVHD Is Common With Stem Cell Transplantation

There is a high incidence of aGVHD. In people who have a stem cell transplant with HLA-matched donor cells from a sibling, as many as 50 percent develop aGVHD. The rate of developing aGVHD is higher in cases with HLA-mismatched cells from unrelated donors and donors other than siblings.

According to the journal Blood, more severe aGVHD occurs in approximately 15 percent of all allogeneic stem cell transplants.

6. Acute Graft-Versus-Host Disease is Graded According to Its Severity

Cases of aGVHD can be mild or serious, and a system of aGVHD grading determines how severe the condition is. GVHD is first staged on a scale of 0 to 4 with grade 0 indicating no active symptoms and grade 4 indicating severe symptoms. Grading is measured according to staging of symptoms:

• How much of the skin is affected — Higher stages indicate more severe inflammation, ranging from a rash on less than 25 percent of the skin (stage 1) to inflamed skin covering more than 50 percent of the body, with blisters and severe scaling (stage 4).
• Bilirubin levels in the liver — Higher levels indicate more severe disease.
• Degree of upper gastrointestinal symptoms — More severe symptoms may include nausea, vomiting, and weight loss.
• Degree of lower gastrointestinal symptoms — More severe cases may involve increased stool volume (diarrhea), abdominal pain, and cramping.

Based on staging, GVHD grading considers the following:

• Grade A — Stage 1 skin symptoms only
• Grade B — Stage 2 skin symptoms with stage 1 or 2 liver or gastrointestinal involvement
• Grade C — Stage 3 involvement of any organ
• Grade D — Stage 4 involvement of any organ

7. Acute Graft-Versus-Host Disease Can Be Treated

If the disease gets worse, aGVHD can be life-threatening. Prophylaxis (preventive treatment) is a treatment that aims at stopping aGVHD from developing.

Preventive Treatment

After transplant, preventive treatment is given. This typically includes some combination of immunosuppressive drugs such as a calcineurin inhibitor such as tacrolimus (Astagraf, Envarsus, Prograf) and cyclosporine (Gengraf, Neoral) (a medicine that weakens the immune system to prevent it from attacking the body) with an antimetabolite such as methotrexate (Jylamvo, Otrexup) (a drug that slows down the growth of certain cells, including immune cells), or mycophenolate mofetil (a medicine that stops the immune system from making too many attacking cells). Other preventive treatments may include immunosuppressants such as:

• Antithymocyte globulin (thymoglobulin) — Used off-label, which means the drug is prescribed for a purpose not officially approved by the Food and Drug Administration (FDA)
• Posttransplant cyclophosphamide (Frindovyx) — Used off-label
• Abatacept (Orencia)

Treatment of aGVHD

For people who develop aGVHD, first-line treatment with corticosteroids is standard therapy. If steroids are not effective, second-line therapy is ruxolitinib (Jakafi), a type of drug known as a Janus kinase 2 (JAK2) inhibitor, which blocks certain signaling pathways in the immune system. Ruxolitinib is safe for both adult and pediatric transplant recipients. If ruxolitinib isn’t effective, there are currently no other standard treatments.

However, some doctors may recommend nonstandard treatment if these treatments aren’t effective. For instance, a procedure known as extracorporeal photopheresis, a blood-filtering treatment, may be recommended in some cases.

8. New Treatments for Acute GVHD Are in Development

Many clinical trials have been investigating new treatment options for aGVHD, both preventively and for people who develop the condition. Newer treatments under study are targeting immune cell pathways (cytokine pathways) that are believed to play a role in the development of aGVHD. Some medical centers are trying new drug combinations to preserve organ tissue and organ function, as well as promoting a healthy gut microbiome.

Some potential therapies that have shown promising results in treating aGVHD in combination with steroids include:

• Alpha₁-Antitrypsin
• Interleukin-22
• Itolizumab, a monoclonal antibody
• Natalizumab (Tysabri), a monoclonal antibody

For people who don’t respond to steroids, some treatments under review include:

• Neihulizumab
• Urinary-derived human chorionic gonadotropin/epidermal growth factor, a fertility drug
• Fecal microbiome transplant

Many new preventive treatments are also being studied. Clinical trials are testing different types of treatment plans that include reduced-intensity conditioning (low-dose chemotherapy or radiation before a stem cell transplant) and myeloablative conditioning (high-dose chemotherapy or radiation before a transplant) with drugs such as:

• Vedolizumab (Entyvio), a monoclonal antibody
• Sirolimus (Rapamune), an immunosuppressant
• Posttransplant cyclophosphamide

9. Acute GVHD Can Resemble Other Conditions

If aGVHD looks like another illness, doctors may need to compare symptoms and test results — a process called a differential diagnosis — to determine whether it’s GVHD or another condition. If you have concerning symptoms after a stem cell transplant, your doctor will likely rule out other causes, including:

• Skin disorders caused by drug reactions, viral rashes, or radiation dermatitis, which is a skin disorder that can occur with radiation therapy
• Liver infections such as viral hepatitis, drug-induced liver disorders, or liver cancer
• Diarrhea, nausea, and vomiting due to side effects of chemotherapy or other medications, gastrointestinal infections, and malignancies (cancer)

Acute aGVHD may be diagnosed by a physical examination and a biopsy of liver, skin, or small bowel tissue.

Learn More About Graft-Versus-Host Disease

On myGVHDteam, the site for those with graft-versus-host disease and their loved ones, people come together to ask questions, give advice, and share their stories with others who understand life with the condition.

If you’ve had a stem cell transplant, what symptoms have you discussed with your doctor that could be related to aGVHD? What concerns do you have about the risks of aGVHD before or after a transplant? Share your experience in the comments below.