Acute Graft Versus Host Disease in Intestine
Acute graft versus host disease affecting the intestine is a serious complication that can occur after receiving donated stem cells, where the donor’s immune cells attack the recipient’s digestive system, causing severe symptoms and requiring careful management.
Table of contents
- What Is Acute Graft Versus Host Disease of the Intestine?
- Who Is at Risk?
- Symptoms and Effects
- How It Is Diagnosed
- Understanding Severity Grades
- Treatment Options
- The Role of Gut Bacteria
- Managing Complications and Daily Life
What Is Acute Graft Versus Host Disease of the Intestine?
Acute graft versus host disease (acute GVHD) of the intestine is a condition that occurs after someone receives a stem cell transplant from a donor. In a stem cell transplant, also called a bone marrow transplant, a patient receives healthy stem cells from another person to help treat diseases like leukemia, lymphoma, or other blood disorders[1].
In acute GVHD, the donated immune cells see the recipient’s body as foreign and begin to attack it. The gastrointestinal system, which includes the stomach, small intestine, and large intestine, is one of the most common areas affected by this immune attack[1]. When GVHD affects the gut, it can cause significant damage to the intestinal lining and lead to serious complications[7].
Acute GVHD typically occurs within the first 100 days after transplant, though it can sometimes appear later[2][5]. The condition is different from chronic GVHD, which usually develops after 100 days and has different symptoms and treatments[2].
Who Is at Risk?
Acute GVHD of the gut affects approximately 30% to 50% of patients who undergo an allogeneic transplant, which means a transplant using cells from a donor rather than the patient’s own cells[4]. About 40% of patients who develop acute GVHD will have gastrointestinal involvement[6].
Several factors can increase the risk of developing acute intestinal GVHD[4]. These include having an unrelated or mismatched donor, receiving a transplant from a female donor, and undergoing total body radiation before the transplant. The intensity of chemotherapy and radiation treatments before transplant can also raise the risk[4].
Other risk factors include infections during the transplant period and damage to the gut microbiome, which is the community of bacteria living in the intestines[4]. Transplant patients often have a less diverse gut microbiome because they have received multiple courses of chemotherapy and antibiotics[4].
Symptoms and Effects
The most common symptoms of acute GVHD affecting the intestines include severe diarrhea, nausea, vomiting, abdominal cramping, and abdominal pain[2][4]. Many patients experience loss of appetite and significant weight loss[4].
The diarrhea associated with intestinal GVHD is often profuse and watery in nature[1][6]. This type of severe diarrhea can lead to dangerous dehydration and can leave patients feeling extremely weak. Some patients may experience such severe symptoms that they pass out on the toilet for extended periods[13].
In severe cases, GVHD can cause bleeding in the gastrointestinal tract, with blood appearing in the stool[13]. The condition can also cause malnutrition because it prevents the body from properly absorbing nutrients, calories, and fluids from food[14].
The symptoms of intestinal GVHD can range from mild to potentially fatal[2]. Severe gastrointestinal GVHD has the highest mortality rate compared to GVHD affecting the skin or liver, and it significantly contributes to death after transplant[8][9].
How It Is Diagnosed
Diagnosing acute GVHD of the intestine can be challenging because the symptoms overlap with those of infections and reactions to medications[1]. Diagnosis is primarily based on clinical criteria, meaning doctors consider the patient’s symptoms, risk factors, and timing after transplant[1][7].
To confirm the diagnosis, doctors often perform an endoscopic examination, which involves using a flexible tube with a camera to look inside the digestive tract[6]. During this procedure, doctors can see changes in the intestinal lining and take small tissue samples called biopsies[6].
When examining the tissue under a microscope, the characteristic finding of GVHD is damage to the intestinal cells, particularly a type of cell death called apoptosis affecting the lining of the gut[6]. However, it’s important to note that even intestinal tissue that looks normal during the endoscopy can show GVHD when examined under a microscope[6].
One limitation of endoscopic biopsy is that it may not always detect GVHD because the disease can affect the intestine in a patchy pattern. Up to 26% of patients who need treatment for gastrointestinal GVHD may have negative biopsy results[6]. For this reason, doctors must also rule out other possible causes of symptoms, such as infections or medication side effects[7].
Researchers are working on developing blood tests and other biomarkers that could help diagnose GVHD more reliably, but these have not yet been validated for routine use outside of clinical trials[1].
Understanding Severity Grades
Doctors grade acute GVHD of the intestine to determine how severe it is and what treatment is needed[4][11]. The grading system ranges from grade 1 (mild) to grade 4 (very severe).
Grade 1, or mild GVHD, may cause minimal symptoms and might not require treatment beyond careful monitoring[11]. In contrast, grade 4 represents the most severe form of intestinal GVHD, causing extreme abdominal symptoms, severe cramping, and intense pain[4].
While most cases of acute GVHD are mild, approximately 10% of patients experience more severe symptoms[4]. The severity of GVHD can differ depending on which parts of the gastrointestinal tract are affected[6].
The grade of GVHD directly influences treatment decisions and helps doctors predict outcomes. Over the past 20 years, the incidence of severe acute GVHD has declined substantially, which is significant because historically only 5% to 20% of patients with severe acute GVHD survived[4].
Treatment Options
Once a diagnosis of intestinal acute GVHD is established, treatment typically begins with systemic corticosteroids, which are powerful medications that suppress the immune system[1][7]. Steroids remain the standard first-line therapy for acute GVHD, with about 50% of patients responding well to this treatment[8].
For patients with mild GVHD (grade 1), doctors may use lower and shorter courses of immune suppression, which has proven to be safe and effective[7]. However, for moderate to severe GVHD (grades 2 to 4), more aggressive treatment is necessary[11].
When steroids don’t control the GVHD, a condition called steroid-resistant GVHD, doctors turn to second-line therapies[1][11]. The medication ruxolitinib (Jakafi), which blocks certain immune system signals, has been approved as an effective second-line therapy for steroid-resistant acute GVHD[8][9].
Other treatment options for steroid-resistant GVHD include various medications that suppress the immune system, such as monoclonal antibodies like infliximab or rituximab, and drugs like methotrexate or mycophenolate mofetil[11]. Some patients may benefit from a specialized light therapy called extracorporeal photopheresis[11].
Newer approaches include the use of vedolizumab (Entyvio), which specifically targets the intestinal immune system[4], and teduglutide, a medication that may help heal the intestinal lining[9]. In a recent study, 64.7% of patients with treatment-resistant intestinal GVHD showed some response to teduglutide, including complete resolution in 41.2% of cases[9].
The Role of Gut Bacteria
The community of bacteria, fungi, and other microorganisms living in the intestines, called the gut microbiome, plays a crucial role in the development and severity of intestinal GVHD[3][17].
Transplant patients typically have a much less diverse gut microbiome than healthy people because they have undergone extensive chemotherapy and have often received multiple courses of antibiotics[4]. Research has shown that patients who maintain certain beneficial bacteria in their gut, particularly a species called Blautia, have a lower risk of developing acute GVHD[4].
The key strategy to manage acute GVHD of the gut includes prevention, which depends heavily on maintaining a healthy gut microbiome[4]. A healthy microbiome can be supported by substances called prebiotics, which are compounds that feed beneficial bacteria. However, over-the-counter probiotics available at stores are generally not sufficient to restore a healthy gut microbiome in transplant patients[4].
Some researchers are studying fecal microbiota transplantation, a procedure where stool from a healthy donor is transferred to the patient to restore beneficial gut bacteria. This approach is considered the most effective way to replace the microbiome because it contains all the necessary bacteria, fungi, and viruses. However, this treatment comes with risks and requires careful consideration[4].
Clinical trials are currently underway to learn more about how to modify the gut microbiota and improve treatment responses for patients with intestinal GVHD[10].
Managing Complications and Daily Life
Beyond treating the underlying disease, managing the complications of intestinal GVHD is essential. Patients often need intravenous fluids to prevent and treat dehydration caused by severe diarrhea[11]. Pain medications may be necessary to control abdominal discomfort[11].
Maintaining proper nutrition is critical for patients with intestinal GVHD because poor nutrition and loss of muscle mass can increase the risk of complications[14]. When the body’s weight is healthy, it supports immune function and other important bodily processes, including digestion[14].
Dietary modifications can help ease symptoms. Patients are often advised to follow a bland diet that includes foods that are easy to digest[15]. This specialized GVHD diet avoids foods that might irritate the damaged intestinal lining and helps reduce symptoms like diarrhea, nausea, and abdominal pain[15].
Living with acute intestinal GVHD can be overwhelming and has been described by patients as a “full-time job”[16]. The condition can affect physical functioning, cause extreme fatigue, and lead to psychological distress including depression and anxiety[16]. Patients who are struggling with these challenges should tell their healthcare providers, who can refer them to supportive care services including mental health professionals[16].
Treating GVHD requires a team effort involving multiple healthcare practitioners, including gastroenterologists, transplant specialists, nutritionists, and mental health providers[10]. This multidisciplinary approach ensures comprehensive care for patients dealing with this complex condition.
