What is graft-versus-host disease (GVHD)?

In a donor transplant, the new blood-forming cells come from another person, and the donor’s immune system comes with them. GVHD happens when the donor’s cells (the graft) see the patient’s cells (the host) as different and attack them, NMDP explains.

It happens only after an allogeneic, or donor, transplant. MedlinePlus, from the US National Library of Medicine, says it does not happen after an autologous transplant, which uses the patient’s own cells.

The same donor cells can also help. The US National Cancer Institute says that in leukemia, white blood cells from the donor may attack cancer cells left after treatment. This is called the graft-versus-tumor or graft-versus-leukemia effect. NMDP says doctors may even see mild GVHD as a good thing after a transplant for blood cancer, because patients with some GVHD may have a lower risk of the cancer coming back.

Doctors describe two forms. Acute GVHD usually develops in the first weeks and months after transplant. Chronic GVHD usually develops within the first year but can appear years later, NMDP says. MedlinePlus says chronic GVHD can last a lifetime.

The old dividing line was day 100 after transplant. The EBMT Handbook says that line has blurred, because acute GVHD can appear after day 100. Doctors go by the pattern of signs, not only the date.

Acute GVHD mainly affects the skin, the gut and the liver. NMDP lists signs such as a rash that can look like sunburn, nausea that doesn’t go away, diarrhea, belly pain, blood in the stool, and yellow skin or eyes (jaundice).

Chronic GVHD can affect many parts of the body. NMDP lists thickening or itching of the skin, mouth sores, and dry or irritated eyes. Other signs are a cough or shortness of breath that doesn’t go away, stiff and painful joints, muscle cramps or weakness, and dryness or irritation of the genitals.

Anyone who has a donor transplant can develop GVHD, but some things make it more likely. MedlinePlus says the chance is higher when the donor and the patient are not related.

The EBMT Handbook lists the main risk factors for chronic GVHD. They are an unrelated or mismatched donor, stem cells collected from the blood rather than the marrow, an older donor, an older patient, and a female donor for a male patient.

The strongest warning sign for chronic GVHD is having had acute GVHD, especially severe acute GVHD. Children under 12 rarely develop chronic GVHD without acute GVHD first, the handbook says.

After a donor transplant, care teams give medicines to lower the risk of GVHD. St. Jude Children’s Research Hospital lists common ones: cyclophosphamide, cyclosporine, sirolimus, tacrolimus, methotrexate, mycophenolate, antithymocyte globulin (ATG) and alemtuzumab. NMDP notes that these medicines lower the risk but do not guarantee GVHD won’t happen.

For years, a standard approach was tacrolimus or cyclosporine plus methotrexate. A newer approach gives cyclophosphamide after the transplant, called post-transplant cyclophosphamide (PTCy), to clear out donor immune cells that have been switched on. It has been used especially in half-matched family transplants, the EBMT Handbook notes.

A large trial compared the two in 431 adults with blood cancers. They had a matched or nearly matched donor and lower-dose conditioning. At one year, more people were alive without severe acute GVHD, chronic GVHD needing treatment, or relapse with PTCy-based prevention than with the older standard. Overall survival did not differ much between the groups.

Other options exist. In December 2021, the US Food and Drug Administration (FDA) approved abatacept (Orencia) as the first medicine to prevent acute GVHD. It is used with other medicines for people 2 and older who get cells from an unrelated donor. In June 2026, the FDA approved Tregzi, a donor cell product built around regulatory T cells. It is for some adults with blood cancers who have a matched donor and strong (myeloablative) conditioning, to improve survival without chronic GVHD.

Steroids, such as prednisone, are the most common treatment for acute GVHD, NMDP says. They calm the immune system. The EBMT Handbook notes that infections are frequent with long steroid treatment and says medicines to prevent infection should be considered.

Steroids do not work for everyone. A 2022 review in The Oncologist says up to half of patients develop GVHD that does not respond to steroids, called steroid-refractory GVHD, and their outlook is poor. The EBMT Handbook says severe acute GVHD that does not respond to first treatment has an extremely poor outlook.

In the US, ruxolitinib (Jakafi) is approved for steroid-refractory acute GVHD in people 12 and older. The FDA first approved it for this use in 2019. In December 2024, the FDA approved remestemcel-L (Ryoncil), a cell therapy, for steroid-refractory acute GVHD in children 2 months and older. In the European Union, ruxolitinib (Jakavi) is approved for acute GVHD from 28 days of age when steroids or other treatments have not worked well enough.

NMDP says extracorporeal photopheresis (ECP) may be an option when steroids are not working. Blood is drawn, treated with light and returned to the body. NMDP describes it as an outpatient procedure that treats GVHD affecting the skin.

Steroids are also the standard first treatment for chronic GVHD, according to the EBMT Handbook. NMDP says treatment for chronic GVHD may last months or years.

When the first treatment is not enough, several medicines are approved in the US. Ibrutinib (Imbruvica) became the first for chronic GVHD in 2017 and is now approved from age 1 after at least one earlier treatment. Ruxolitinib (Jakafi) is approved from age 12 after one or two earlier treatments.

Belumosudil (Rezurock), approved by the FDA in July 2021, is for people 12 and older after at least two earlier treatments. In the EU it received a conditional approval in March 2026. It covers people 12 and older weighing at least 40 kg (88 pounds) when other options have not helped enough or are not suitable.

Axatilimab (Niktimvo), approved by the FDA in August 2024, is for adults and children weighing at least 40 kg after at least two earlier treatments. It is given into a vein every 2 weeks. In the EU, ruxolitinib (Jakavi) is also approved for chronic GVHD from 6 months of age when steroids or other treatments have not worked well enough.

Chronic GVHD can be a long road. St. Jude says it can last months or years and sometimes needs long-term treatment. It can affect many organs, and people often don’t report changes until an organ is already affected. So the EBMT Handbook calls regular checks of every organ that could be affected essential.

NMDP asks patients to call the transplant team right away about any new or worsening symptom. For children, St. Jude suggests families check the skin and notice changes in eating, breathing, eyes, mouth, movement and energy.

Daily care often focuses on particular organs. St. Jude says sun exposure may trigger GVHD or make skin symptoms worse, so care teams give guidance on sunscreen, protective clothing and time outdoors. Dry eyes and mouth sores are watched and treated.

Infections stay a concern while GVHD and its treatment weaken the immune system. The EBMT Handbook says repeat vaccination with inactivated vaccines is strongly recommended once chronic GVHD is under control, and live vaccines are avoided. It also notes that long-lasting chronic GVHD of the skin raises the risk of skin cancers.

Support is available. NMDP’s Patient Support Center offers information, professional and peer support and free education materials before, during and after transplant. Its number is 1 (888) 999-6743.