If you’re living with chronic graft-versus-host disease (GVHD), you have a higher risk of developing other health issues, called complications. Uncontrolled inflammation and treatments can damage tissues in your body and lead to cardiovascular (heart), bone, and joint problems.

GVHD or its treatments can lead to complications. Comorbidities, on the other hand, are separate health conditions that people with GVHD are more likely to have, even though GVHD itself doesn’t cause them. GVHD can develop after a stem cell transplant, but not everyone who receives one will have it. GVHD occurs when the donor’s cells recognize the recipient’s body as foreign and attack healthy tissues. Regardless of the reason for a transplant, the signs, symptoms, and progression of GVHD are usually the same.

This article will cover eight conditions related to GVHD and how common they are. We’ll also discuss symptoms to look out for. If you begin noticing signs of a new complication, be sure to talk to your doctor or transplant team. Early diagnosis of GVHD is key to treating your symptoms and improving your quality of life.

Complications of Graft-Versus-Host Disease

Studies show that people with chronic GVHD have an increased risk of certain complications. If left untreated, they can affect your health and how your disease progresses.

Some complications develop from the disease itself — others are due to side effects from GVHD treatments.

1. Cardiovascular Disease

People who have had a stem cell transplant are about 60 percent more likely to develop cardiovascular disease (CVD) than those who haven’t. CVD affects your heart and blood vessels, increasing the risk of heart disease, heart attacks, and strokes.

Having chronic GVHD after a transplant raises your CVD risk as well. This is because GVHD is associated with risk factors for CVD. Chronic (long-term) inflammation from GVHD leads to atherosclerosis (buildup of fatty deposits along the blood vessels). This contributes to CVD.

2. Metabolic Syndrome and Diabetes

Metabolic syndrome is a group of conditions that raise your chances of developing CVD and diabetes. You may have metabolic syndrome if you have:

• Hypertension — High blood pressure
• Excess fat around the abdomen (belly area)
• Insulin resistance — A condition in which cells can’t use sugar properly for energy
• Abnormal lipid levels — Unhealthy levels of fat in the blood

People who have chronic GVHD from a stem cell transplant are more likely to have metabolic syndrome. Researchers have also found diabetes is a common complication after a transplant. They believe this may be due to certain GVHD treatments that calm the immune system. Examples include corticosteroids (steroids) like prednisone and calcineurin inhibitors like tacrolimus (Prograf).

Studies show that long-term inflammation and chronic GVHD treatments can increase a person’s lipid levels as well. Medications like tacrolimus, cyclosporine, and steroids are known to increase blood fats.

Up to 40 percent of long-term transplant survivors develop hypothyroidism (an underactive thyroid), especially those with chronic GVHD who need immunosuppressive therapy (medications that weaken the immune system to prevent rejection). Researchers believe immunosuppressive medications may lead to hypothyroidism in people with chronic GVHD. An underactive thyroid can also increase the risk of CVD and high cholesterol.

3. Weak and Brittle Bones

Osteoporosis weakens your bones, making them less dense, more fragile, and more likely to break. People with GVHD from a transplant have a higher risk of bone loss, which can reduce bone strength. Osteoporosis is common in people who take certain immunosuppressive medications, including:

• Corticosteroids
• Chemotherapy drugs that destroy diseased blood-forming cells before a hematopoietic stem cell transplant (HSCT)
• Calcineurin inhibitors

Taking high doses of these medications for extended periods of time raises your osteoporosis risk. Other factors known to play a role in bone loss include smoking, diabetes, and older age.

4. Joint and Muscle Problems

Nearly half of people with chronic GVHD develop joint and muscle complications. You may not notice these symptoms for several months to years after your stem cell transplant. Inflammation from chronic GVHD affects the muscles, joints, and connective tissues.

Common complications from this disease include:

• Joint pain and inflammation
• Muscle cramping
• Swelling or edema
• Fibrosis — Joint stiffness from scar tissue

5. Sexual Dysfunction and Fertility Problems

In some cases, chronic GVHD affects the genitals. This can negatively affect your sexual health and even lead to fertility problems. An article in Clinical Hematology International found that women are more likely than men to experience genital symptoms of chronic GVHD. Symptoms affecting the vagina can include:

• Fibrosis
• Ulcers (open sores)
• Bleeding after sexual intercourse
• Pain around the genitals
• Vaginal dryness

The same article stated that chronic GVHD can cause symptoms like inflammation of the head of the penis. Skin changes and rashes are also common. Erectile dysfunction can develop in people also affected by other problems like CVD and low hormone levels.

Comorbidities of Graft-Versus-Host Disease

Chronic GVHD develops in people who have had an allogeneic HSCT. Also known as a bone marrow transplant (BMT), this procedure replaces diseased blood-forming cells with healthy cells. The term “allogeneic” means the cells come from a donor.

There are several reasons why you may have a stem cell transplant. Doctors use transplants to treat a variety of diseases — including cancers and immune-related conditions.

6. Blood Cancers

Blood cancers develop in your blood-forming stem cells. These cells normally live in your bone marrow, the spongy tissue inside your bones. Your stem cells eventually turn into one of three cell types:

• Red blood cells (RBCs) that carry oxygen throughout your body
• White blood cells (WBCs) that fight infections
• Platelets that help blood clots form

Certain changes alter how stem cells grow and divide. The abnormal cells can’t fully mature into functional blood cells — leading to cancer. They grow out of control and eventually crowd out the healthy cells in your bone marrow. People with blood cancers can’t make enough RBCs or WBCs to perform their normal functions.

If you’ve had a stem cell transplant to treat your blood cancer, you may eventually develop GVHD. Studies show that 30 percent to 70 percent of transplant recipients develop acute GVHD. Of those, about half will later develop chronic GVHD.

Examples of blood cancers associated with transplants and GVHD include:

• Leukemia — Creates abnormal WBCs that can’t fight infections as well as they should
• Lymphoma — Affects WBCs called lymphocytes (T cells) that collect in your body and weaken your immune system
• Myeloma — Stops immune cells called plasma cells from making enough antibodies to fight infections
• Myelodysplastic syndromes — Conditions caused by the buildup of immature blood cells

7. Aplastic Anemia

Aplastic anemia occurs when your bone marrow can’t make enough new RBCs. The fewer RBCs you have, the less oxygen reaches your tissues. This can leave you feeling fatigued and short of breath. Other symptoms of aplastic anemia include:

• Frequent infections that last longer than usual
• Dizziness and headaches
• Pale skin and new rashes
• A fast, irregular heartbeat
• Bruising or bleeding easily from nosebleeds, cuts, or your gums
• Unexplained fevers

Doctors treat aplastic anemia with stem cell transplants. The goal is to replace the old bone marrow cells with healthy ones that can make new RBCs. Unfortunately, some people develop GVHD after a transplant for aplastic anemia. Studies show that you can try to prevent GVHD with certain treatments, like alemtuzumab (Campath).

8. Other Comorbidities

Some comorbid conditions relate to how severe your acute GVHD symptoms are. One study of over 2,900 people looked at GVHD after a stem cell transplant. Researchers found that having more comorbidities led to more severe acute GVHD. For example, people who had at least five comorbid conditions had a 24 percent chance of developing moderate to severe acute GVHD.

Examples of comorbidities associated with acute GVHD include:

• Lung problems like shortness of breath
• Congestive heart failure
• Diabetes
• Liver and kidney diseases
• History of cancer or stroke
• Other inflammatory diseases like lupus or rheumatoid arthritis

Ask Your Doctor

Living with GVHD can bring health challenges beyond the disease itself. But staying informed and working with your healthcare team can help you manage symptoms, prevent complications, and improve your quality of life. If you notice any new or worsening health issues, ask your doctor about the best ways to manage them. Regular checkups and early treatment can help you stay as healthy as possible.

Talk With Others Who Understand

On myGVHDteam, the site for people 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.

Have you had any of these complications with your GVHD? Share your experience in the comments below.