It’s possible to manage graft-versus-host disease (GVHD) with appropriate treatments. Your individualized treatment plan will depend on your symptoms, their severity, and the disease’s response to first-line medications.

Graft-versus-host disease (GVHD) is a potentially serious complication of allogeneic hematopoietic stem cell transplant (allo-HPSCT), a transplant of stem cells from a donor.

During this procedure, which is also called a bone marrow transplant, doctors administer special stem cell grafts to help your blood cell levels recover after chemotherapy or radiation.

In GVHD, immune cells within the donor graft react to the host cells (your cells), triggering an immune response against them. This creates an immune-mediated inflammatory reaction and can lead to various symptoms that can affect multiple parts of your body.

Timely and appropriate treatment of GVHD can help reduce your symptoms and prevent progressive organ damage.

The types of GVHD

GVHD is primarily separated into two types: acute and chronic. The types differ in how quickly symptoms develop and how the symptoms present.

In acute GVHD, symptom onset is usually sudden, within the first 100 days after an allo-HPSCT. Symptoms can be mild, moderate, or severe but are primarily limited to your skin, liver, and gastrointestinal system.

Chronic GVHD features a wider range of symptoms. It often develops more than 100 days after an allo-HPSCT, and the symptoms tend to be long term, even with management.

Corticosteroids (called steroids for short) are manufactured versions of your body’s natural steroid hormones. In GVHD, steroids are the first-line treatment for both acute and chronic symptoms because they can suppress immune system activity.

Steroids are given differently depending on which symptoms you’re experiencing and how severe they are.

For example, topical steroid drops or ointments can help manage a mild, localized skin rash or eye irritation. But when multiple organ systems are involved or your symptoms are severe, your doctor will recommend systemic (whole-body) steroid therapy.

Prednisone and methylprednisolone are common steroids used to treat GVHD.

Doctors may choose to combine steroid therapy with other immunosuppressive medications, such as:

  • cyclosporine
  • tacrolimus
  • mycophenolate mofetil

Chemotherapy is often associated with cancer treatment, but chemotherapy drugs can target many rapidly dividing cells in your body, including certain immune cells.

In GVHD, chemotherapy drugs are a part of second-line treatments. They’re used in refractory (treatment-resistant) GVHD when steroids are not enough to effectively manage symptoms or slow down organ damage. By targeting graft immune cells, chemotherapy drugs help suppress your immune response.

Common chemotherapy drugs used in GVHD include:

Monoclonal antibodies are drugs that bind to specific protein markers (antigens) on cell surfaces. Depending on the antigen being targeted, monoclonal antibodies can affect various processes that are essential to cellular function.

In GVHD, monoclonal antibodies focus on changing the processes of your immune cells — primarily T cells and B cells. Like other nonsteroidal options, they’re considered a second-line treatment for refractory GVHD.

Many types of monoclonal antibody therapies exist, differentiated by their antigen (anti) targets.

Examples of monoclonal antibodies that have been used in GVHD include:

  • anti-CD20 agents (rituximab)
  • anti-CD52 agents (alemtuzumab)
  • anti-IL-2 receptor agents (daclizumab, basiliximab)
  • anti-TNF agents (etanercept, infliximab, adalimumab)
  • anti-CD3 agents (muromonab)

Tyrosine kinase inhibitors (TKIs) are a broad category of drugs that block the activity of enzymes called tyrosine kinases. These enzymes are important in the processes of cell differentiation, growth, and survival. When TKI pathways are blocked or disrupted, immune cell activity can decrease.

TKIs are currently an area of research in the treatment of GVHD, and many different tyrosine kinase targets are included in TKI treatments.

For example, Janus kinase (JAK) inhibitors and Bruton’s tyrosine kinase (BTK) inhibitors are two types of TKIs that target very specific tyrosine kinases in GVHD.

According to a review from 2022, there are currently two TKIs approved by the Food and Drug Administration (FDA) for use in steroid-refractory GVHD: ruxolitinib and ibrutinib.

Many second-line treatments for GVHD are considered targeted therapies. These are treatments that focus on affecting a very specific point in the course of GVHD.

In addition to TKIs and monoclonal antibodies, targeted therapies that hold promise for GVHD include:

  • mechanistic target of rapamycin (mTOR) inhibitors
  • Rho-associated coiled-coil kinase 2 (ROCK2) inhibitors

Sirolimus is an mTOR inhibitor that’s sometimes used alongside steroid therapy in GVHD. It helps reduce immune cell activity by blocking mTOR kinase enzyme pathways.

Belumosudil is a ROCK2 inhibitor that’s approved by the FDA for the treatment of refractory chronic GVHD. It works by affecting Rho kinase pathways, which are involved in cellular mobility and the production of pro-inflammatory substances called cytokines.

Extracorporeal photopheresis (ECP) is a procedure sometimes used for refractory GVHD. Doctors filter your blood using a machine in a clinical setting. The machine separates lymphocytes (a type of white blood cell) from your blood and treats them with ultraviolet light that changes their function.

While it’s not clear exactly how ECP works, treating lymphocytes appears to have beneficial immune-modifying and anti-inflammatory effects in GVHD.

The success of GVHD treatments can vary from person to person depending on your diagnosis and your individual health characteristics.

According to the 2022 review mentioned earlier, as many as 50% of people with GVHD will develop steroid-refractory GVHD, and unsuccessful first-line treatments are associated with less favorable outcomes.

In general, the outlook for GVHD largely depends on how many organ systems are involved and the extent of damage to those systems. The 5-year survival rate for the most severe forms of GVHD is about 5%.

GVHD is a complex immune-mediated condition, and it’s natural to have concerns about what that diagnosis means for you. Below are some of the most commonly asked questions.

Can you recover from GVHD?

GVHD is treatable and can be managed with appropriate therapies. In some cases of acute GVHD, complete remission of symptoms is possible. Chronic GVHD typically requires long-term management that may last years.

Can you survive GVHD?

Yes, you can survive GVHD. Survival depends on how many organ systems are affected, how severe the effects are, and how the disease responds to treatment.

Does GVHD mean a transplant has failed?

GVHD is not an indication that your allo-HPSCT has failed. Transplanted stem cells from a donor can still produce healthy blood cells, even if there is a secondary immune reaction. GVHD is an indication that graft cells are active.

How serious is GVHD?

GVHD can be mild, moderate, or severe. In its most advanced forms, when multiple organs are involved or there is significant organ damage, it can be life threatening.

Are there other treatments for GVHD not mentioned?

Researchers are studying many new and emerging therapies for GVHD. One promising area of study is immunomodulation, which involves using specialized cells, such as regulatory T cells, to change immune responses in GVHD.

GVHD is a complex complication of an allo-HPSCT. First-line treatments primarily involve steroids to suppress your immune system and reduce inflammation.

If GVHD does not respond to first-line treatments, healthcare professionals may recommend chemotherapy or a variety of targeted therapies.