Steroid therapy is the first-line treatment for graft-versus-host disease (GVHD). If GVHD does not respond to initial therapies, doctors may consider chemotherapy, monoclonal antibodies, and other targeted drugs.
GVHD is a possible complication of allogeneic (donor) hematopoietic stem cell transplant (allo-HPSCT).
In GVHD, immune cells from the donor graft react to the innate cells of the host body, creating an immune-mediated inflammatory reaction. Healthcare professionals categorize GVHD as one of two types — acute or chronic — depending on how quickly symptoms develop and how they present.
Because both types of GVHD can be mild, moderate, or severe, they have many of the same treatment protocols.
This article looks at the most common treatments for GVHD as well as secondary and novel therapies.
One of the primary goals of GVHD treatment is to reduce the activity of T and B immune cells from the allo-HPSCT graft. Healthcare professionals typically accomplish this through the use of immunosuppressants (medications that suppress the immune system).
Corticosteroids (steroids) are the first-line immunosuppressive treatment for GVHD. They replicate the body’s natural steroid hormones to decrease immune activity and reduce inflammation.
Healthcare professionals determine how to administer steroid therapy based on the severity of GVHD.
If symptoms are localized and mild, such as a rash on the skin, topical products might be the only treatment necessary. However, if multiple organs are involved or if symptoms are severe, healthcare professionals will recommend systemic (whole-body) steroid therapy.
Prednisone and methylprednisolone are common medications.
Healthcare professionals may add other immunosuppressant medications to steroid therapy,
- mycophenolate mofetil
- cyclosporine
- tacrolimus
Chemotherapy uses chemicals to target rapidly dividing cells in the body. These drugs are effective against certain cancers and can also work on the immune cells that underlie GVHD.
Chemotherapy is a second-line treatment for GVHD. It is one option if a person is experiencing steroid-refractory GVHD, which means the condition is resistant to steroids.
By destroying immune cells, chemotherapy agents reduce the overall immune response that causes inflammation and tissue damage.
Common chemotherapy agents that healthcare professionals may recommend for GVHD include:
- pentostatin
- cyclophosphamide
- methotrexate
Monoclonal antibodies are one of several targeted therapies that show promise for treating GVHD. These medications are designed to bind to antigens (protein sites) on immune cells and disrupt processes essential to the cells’ function.
In GVHD, monoclonal antibodies can have different antigen targets. Each target affects a very specific point in the cell’s function.
Tyrosine kinase inhibitors (TKIs), another targeted therapy, are a broad variety of drugs that inhibit tyrosine kinase enzymes and their pathways. Tyrosine kinases are involved in processes of immune cell differentiation, growth, and survival.
TKIs include drugs that target specific types of tyrosine kinase, such as Janus kinase (JAK) inhibitors and Bruton’s tyrosine kinase (BTK) inhibitors.
Currently, there are two TKIs that the Food and Drug Administration (FDA) has
Mechanistic target of rapamycin (mTOR) inhibitors and Rho-associated coiled-coil kinase 2 (ROCK2) inhibitors target unique kinase pathways that affect immune cells.
ROCK2 inhibitors affect Rho kinase pathways, which regulate the movement of cells and the production of pro-inflammatory chemicals called cytokines. Belumosudil is a ROCK2 inhibitor that the
The protein kinase mTOR is known for promoting cellular growth and metabolism. Sirolimus is an mTOR inhibitor that healthcare professionals
ECP uses ultraviolet light to alter the function of white blood cells called lymphocytes. The procedure takes place in a clinical setting and involves filtering a person’s blood through a specialized machine.
The machine returns the treated lymphocytes to the person’s bloodstream, where their altered function
Supportive care in GVHD may include:
- antimicrobial agents to prevent infection
- bone-strengthening medications to prevent steroid-related bone loss
- nutritional support
People with GVHD may also benefit from mental health support.
The success of GVHD treatment varies and can depend on GVHD type and severity, treatment response, and individual health and lifestyle factors.
According to a
Even with treatment, the 5-year survival rate for the most severe forms of GVHD is
GVHD affects each person differently. Below are some common questions about this immune-mediated condition.
Can you recover from GVHD?
Recovery from GVHD is possible with appropriate treatment. Outcomes depend on the severity of GVHD and the response to initial therapies. Some people with acute GVHD may experience full remission of symptoms.
Can you survive GVHD?
GVHD is not always life threatening. People can manage the symptoms with timely and appropriate treatment, and symptoms may fully resolve in some cases.
Does GVHD mean a transplant has failed?
GVHD is not an indication that an allo-HPSCT has failed. It is a complication that can affect a person’s outcome, but it does not prevent grafted stem cells from producing healthy blood cells.
Are there other treatments available for GVHD?
GVHD treatment is an area of ongoing research. Researchers are investigating many novel and emerging therapies. Some studies are looking at new ways to modify the body’s immune responses, such as immunomodulatory agents.
GVHD is an immune-mediated complication of allo-HPSCT. It develops when immune cells in a donor graft trigger an immune response in the host body.
Immunosuppressive therapy with steroids is the primary treatment for GVHD. However, when first-line therapies are not effective, chemotherapy, monoclonal antibodies, and other targeted drugs may help improve outcomes.