One of the most common symptoms after a stem cell transplant is diarrhea, which affects 40 percent to 50 percent of people following the procedure. Diarrhea can be severe and significantly impact daily life. This isn’t just an inconvenience — it can lead to dehydration, malnutrition, and a decline in overall health. Understanding why diarrhea occurs and how to manage it is very important for maintaining well-being during graft-versus-host disease (GVHD) treatment.

Continue reading to learn more about how GVHD and other conditions can cause diarrhea, and how it’s diagnosed and treated.

How Does GVHD Cause Diarrhea?

Acute GVHD is one of the most common causes of diarrhea after a stem cell transplant. It’s estimated that about 1 in 3 cases of diarrhea after a stem cell transplant is due to acute GVHD. Diarrhea may also be associated with chronic GVHD, but this is less common.

In acute GVHD, immune cells from the donor (the graft) attack healthy tissues in the transplant recipient (the host) and cause inflammation. Donor cells most commonly attack certain organs, including:

• The gastrointestinal (GI, or digestive) tract
• The skin
• The liver

If inflammation affects the lower gastrointestinal tract — including the small and large intestines — it can cause diarrhea.

Other Causes of Diarrhea After a Stem Cell Transplant

About half of people will experience diarrhea before, during, or after having a stem cell transplant. Several factors associated with the procedure can cause diarrhea. Besides GVHD causing diarrhea, medications and infections can also cause diarrhea in people who’ve had a stem cell transplant.

Medications Associated With Diarrhea

Various medications commonly used in people who’ve had a stem cell transplant can cause diarrhea as a side effect.

Chemotherapy drugs often cause diarrhea. The conditioning regimen is the treatment given before a stem cell transplant to kill diseased blood cells and prepare the bone marrow for the transplant. Diarrhea from this transplant preparation may last for weeks, even after the transplant.

Some medications used to treat or prevent GVHD can also cause adverse reactions, like diarrhea, including:

• Cyclosporine (Gengraf, Neoral, Sandimmune)
• Mycophenolate mofetil (CellCept, Myfortic, Myhibbin)
• Sirolimus (Rapamune)
• Tacrolimus (Astagraf, Envarsus, Prograf)

You might take antibiotics after a stem cell transplant to treat or prevent an infection. Antibiotics can cause dysbiosis (a disruption in the balance of good and bad bacteria in the intestines), resulting in diarrhea. Most of the time, antibiotic-associated diarrhea isn’t serious. However, taking certain antibiotics increases your risk of diarrhea caused by the bacterium Clostridioides difficile (C. diff), which can be life-threatening in severe cases.

Other medications that can cause diarrhea include:

• Proton pump inhibitors (PPIs) — These reduce stomach acid and may disrupt gut bacteria.
• Magnesium salts — These salts found in laxatives/antacids draw water into the intestines.
• Pain medications — Nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids can irritate the stomach or affect digestion.

Infections Associated With Diarrhea

Infectious diarrhea (diarrhea caused by an infection) is common in people who have had a stem cell transplant. A 2023 study of 140 people who had an allogeneic stem cell transplant found that about 1 in 3 had diarrhea due to an infection within one year of the transplant. Researchers found that most people who developed infections did so in the hospital before their body accepted the new cells.

C. diff is an example of a healthcare-associated infection that can cause severe diarrhea. Between 10 percent to 20 percent of people develop C. diff before getting a stem cell transplant. However, the most common cause of infectious diarrhea after a stem cell transplant is a viral infection, such as cytomegalovirus.

Infectious diarrhea may be a risk factor for developing acute GVHD. For example, a C. diff infection can cause inflammation that triggers acute GVHD.

Symptoms of Diarrhea Related to GVHD

It’s usually not possible to tell what’s causing diarrhea from symptoms alone. However, some symptoms are more common in GVHD than in other causes.

Diarrhea from acute GVHD is often severe, with large volumes of stool (poop) that’s watery and bloody. In some cases, a ropelike material may be present in the stool. Abdominal pain and cramps are also common in acute GVHD. People with acute GVHD may have other symptoms related to acute GVHD in other organs, including:

• Rash
• Nausea and vomiting
• Jaundice (yellowing of the skin and whites of the eyes)

Diarrhea related to chronic GVHD may include other symptoms, such as:

• Reduced appetite
• Nausea and vomiting
• Feeling of fullness
• Bloating
• Indigestion
• Unintentional weight loss

Medicine-related diarrhea usually doesn’t appear bloody or cause abdominal cramps. The severity of infection-related diarrhea depends on what caused it. For example, a C. diff infection can also cause severe watery diarrhea, like acute GVHD.

How Is Diarrhea Diagnosed in GVHD?

If you develop diarrhea after a stem cell transplant, your healthcare team will try to find the most likely cause. You may need several tests to help determine the cause.

A stool test can help check for infections that cause diarrhea. For that, you will need to give a stool sample for testing in a laboratory.

Blood tests can help determine if you’re dehydrated or have lost too many electrolytes due to diarrhea. Additionally, blood tests can check your kidney and liver function. If you have acute GVHD, you may also have elevated liver enzymes or bilirubin levels, which can mean you have liver damage.

Imaging tests can check for changes in the digestive system. Examples of imaging tests for diarrhea include a CT scan, ultrasound, and X-ray.

Additionally, your healthcare team will also review your medications to see if they may be the cause of your diarrhea.

Your healthcare team may suspect acute GVHD if you have diarrhea along with other symptoms of acute GVHD, such as a rash, jaundice, or elevated liver enzymes. However, to accurately diagnose acute GVHD, your healthcare team will need to take a biopsy (tissue sample) from your rectum to examine under the microscope.

If other causes of diarrhea can’t be found, you may need a colonoscopy. In this procedure, a thin, flexible tube is inserted into the rectum. Your healthcare provider can use the camera on the end of the tube to see the inside of your colon.

How Is GVHD-Associated Diarrhea Treated?

Corticosteroids (steroids) are the preferred treatment for acute GVHD affecting the GI tract. Steroids, such as prednisone (Rayos) or methylprednisolone (Medrol), are immunosuppressants that work by suppressing the immune system to decrease inflammation. Steroids are usually given at high doses for one to two weeks or until symptoms improve. The steroid dose will be gradually reduced over the next few weeks.

If GVHD affects only the GI tract, your healthcare team may recommend steroids that aren’t absorbed into the bloodstream, such as budesonide (available as Entocort EC, Eohilia, Ortikos, Tarpeyo, or Uceris). Because budesonide isn’t absorbed into the bloodstream, it stays in the intestines to reduce inflammation. This option can help reduce steroid side effects.

People with diarrhea from acute GVHD typically have a better prognosis (outlook) if they respond to steroid treatment in the first five days. If symptoms don’t improve with steroids, it’s known as steroid-refractory GVHD.

Treatment options for people with steroid-refractory acute GVHD include:

• Alemtuzumab (Lemtrada)
• Extracorporeal photopheresis (ECP)
• Mycophenolate mofetil
• Ruxolitinib (Jakafi)

Sirolimus (Rapamune) is also sometimes used off-label to treat diarrhea from GVHD. “Off-label” means that the U.S. Food and Drug Administration (FDA) has not specifically approved the medication for this condition. However, doctors may prescribe it when they believe it could be effective based on medical research or clinical experience. Off-label use is common in medicine, but it should only be done under a doctor’s supervision.

Supportive Care

Supportive care for diarrhea involves treatments that can help your symptoms. If you have severe or alarming symptoms of diarrhea, you may need to stay in the hospital during treatment.

The following alarm symptoms require immediate medical attention:

• Blood in your stool
• Severe abdominal pain
• Fever
• Inability to eat or drink, causing severe dehydration
• Elevated heart rate or low blood pressure that causes dizziness

If you’re dehydrated, you’ll need fluid and electrolyte replacement. If you’re able to, you can drink water with electrolytes. If you’re unable to keep fluids down, you may need fluids given intravenously (directly into your veins).

If your diarrhea isn’t caused by an infection, you may be able to take loperamide (Diamode, Imodium), a medication that can help slow or stop diarrhea. Your healthcare team may also recommend a special diet or that you avoid eating for a period of time so your bowels can heal.

Other types of supportive care may be available based on your symptoms. Talk to your healthcare team about the best treatments for you.

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 or a loved one experienced diarrhea after a stem cell transplant? How did you manage your symptoms? Share your experience in the comments below.