Our Summary
Acute graft-versus-host disease (GVHD) is a dangerous side effect that can occur after a type of stem cell transplant called allogeneic hematopoietic cell transplantation (allo-HCT). This disease happens when the donated cells attack the recipient’s body. Current treatments focus on suppressing the donor’s immune system.
In this study, researchers tried a new approach, focusing on protecting and regenerating particular cells in the intestine, which can be damaged during GVHD. They found that a hormone called GLP-2, which is produced in the intestine, was reduced in mice and patients who developed GVHD.
They treated the patients with a drug called teduglutide, which acts like GLP-2, and found that it reduced the severity of GVHD without affecting the ability of the transplanted cells to fight leukemia (a type of blood cancer). This drug seemed to work by regenerating the damaged intestinal cells, increasing the production of certain infection-fighting proteins, and affecting the bacteria in the gut. It also helped grow more intestinal cells in a lab setting and reduced the activity of genes related to cell death.
Additionally, they found that patients who had fewer cells producing GLP-2 in their intestine and higher levels of GLP-2 in their blood were more likely to die from causes unrelated to their cancer after the transplantation.
Overall, this suggests that using drugs like teduglutide, which mimic the actions of GLP-2, could be a new way to treat GVHD and should be tested in clinical trials.
FAQs
- What is acute graft-versus-host disease (GVHD) and how does it relate to intestinal transplants?
- How does the GLP-2 agonist, teduglutide, aid in the treatment of GVHD?
- What are the implications of low numbers of L cells and high serum levels of GLP-2 in patients undergoing allo-HCT?
Doctor’s Tip
One helpful tip a doctor might give a patient about intestinal transplant is to consider incorporating GLP-2-based treatment, such as teduglutide, to promote the regeneration of Paneth cells and intestinal stem cells. This approach can help protect the intestinal lining and improve overall intestinal health after the transplant. It is important to discuss this option with your healthcare team to see if it is appropriate for your specific situation.
Suitable For
Patients who are typically recommended for intestinal transplant are those who have severe intestinal failure, often due to conditions such as short bowel syndrome, inflammatory bowel disease, or complications from previous surgeries. These patients may have difficulty absorbing nutrients and managing their symptoms, leading to malnutrition, dehydration, and overall poor quality of life. Intestinal transplant may be considered when other treatments have been unsuccessful in managing their condition and improving their quality of life.
Timeline
Before intestinal transplant: Patients with end-stage intestinal failure may experience symptoms such as severe diarrhea, malnutrition, weight loss, and dehydration. They may require long-term parenteral nutrition or intravenous fluids to maintain their nutritional status. In some cases, patients may develop complications such as liver failure or infections due to their weakened immune system.
During intestinal transplant: Patients undergo a thorough evaluation process to determine if they are suitable candidates for intestinal transplant. This may include medical tests, psychological evaluations, and discussions with the transplant team. Once approved for transplant, patients are placed on the waiting list for a suitable donor organ. The transplant surgery is a complex procedure that involves removing the diseased intestine and replacing it with a healthy donor intestine. Patients will require close monitoring in the intensive care unit (ICU) after surgery to prevent complications such as rejection or infection.
After intestinal transplant: Patients will need to take immunosuppressive medications for the rest of their lives to prevent rejection of the donor intestine. They will also need to undergo regular follow-up appointments with their transplant team to monitor their progress and adjust their medication regimen as needed. Patients may experience complications such as infections, organ rejection, or side effects from the immunosuppressive drugs. With proper care and monitoring, many patients can experience improved quality of life and long-term survival after intestinal transplant.
What to Ask Your Doctor
- How does acute graft-versus-host disease affect the intestines and what are the potential complications?
- What role do Paneth cells and intestinal stem cells play in maintaining intestinal health?
- How does the hormone GLP-2 protect and regenerate Paneth cells and intestinal stem cells?
- What is the mechanism of action of teduglutide, the GLP-2 agonist, in reducing acute graft-versus-host disease?
- Will teduglutide treatment compromise the graft-versus-leukemia effects?
- How does GLP-2 treatment promote regeneration of Paneth cells and intestinal stem cells?
- Are there any potential side effects or risks associated with teduglutide treatment for acute graft-versus-host disease?
- How can GLP-2-based treatment of acute graft-versus-host disease improve intestinal homeostasis and reduce nonrelapse mortality in patients undergoing allogeneic hematopoietic cell transplantation?
- Are there any ongoing clinical trials or studies investigating the use of teduglutide in the treatment of acute graft-versus-host disease?
- What is the recommended follow-up care and monitoring for patients receiving teduglutide treatment for acute graft-versus-host disease?
Reference
Authors: Norona J, Apostolova P, Schmidt D, Ihlemann R, Reischmann N, Taylor G, Köhler N, de Heer J, Heeg S, Andrieux G, Siranosian BA, Schmitt-Graeff A, Pfeifer D, Catalano A, Frew IJ, Proietti M, Grimbacher B, Bulashevska A, Bhatt AS, Brummer T, Clauditz T, Zabelina T, Kroeger N, Blazar BR, Boerries M, Ayuk F, Zeiser R. Journal: Blood. 2020 Sep 17;136(12):1442-1455. doi: 10.1182/blood.2020005957. PMID: 32542357