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Acute graft-versus-host disease of the gut: considerations for the gastroenterologist

Key Points

  • Acute graft-versus-host disease (GVHD) of the gastrointestinal tract is a common complication in patients after haematopoietic stem cell transplantation (HSCT) that results in considerable morbidity and mortality

  • As the clinical, serological and radiographical findings in gastrointestinal acute GVHD are nonspecific, a broad differential diagnosis should be considered, particularly potential infectious causes and chemotherapeutic or immunosuppressant toxicity

  • Expedient endoscopy and histopathology are helpful in excluding possible conditions that mimic gastrointestinal acute GVHD; nevertheless, the diagnosis is ultimately based on clinical criteria

  • Several novel diagnostic, prognostic, risk and predictive biomarkers have been identified for gastrointestinal acute GVHD; however, none have yet been integrated into routine clinical practice

  • Upon diagnosis of gastrointestinal acute GVHD, timely first-line therapy with systemic corticosteroids (such as prednisone or methylprednisolone) and/or oral non-absorbable corticosteroids (such as beclomethasone or budesonide) is crucial

  • Acute GVHD leads to substantial gastrointestinal symptom burden, including profuse diarrhoea, abdominal pain, severe malnutrition and gastrointestinal bleeding; providing supportive and palliative care is a critical role of the gastroenterologist

Abstract

Haematopoietic stem cell transplantation (HSCT) is central to the management of many haematological disorders. A frequent complication of HSCT is acute graft-versus-host disease (GVHD), a condition in which immune cells from the donor attack healthy recipient tissues. The gastrointestinal system is among the most common sites affected by acute GVHD, and severe manifestations of acute GVHD of the gut portends a poor prognosis in patients after HSCT. Acute GVHD of the gastrointestinal tract presents both diagnostic and therapeutic challenges. Although the clinical manifestations are nonspecific and overlap with those of infection and drug toxicity, diagnosis is ultimately based on clinical criteria. As reliable serum biomarkers have not yet been validated outside of clinical trials, endoscopic and histopathological evaluation continue to be utilized in diagnosis. Once a diagnosis of gastrointestinal acute GVHD is established, therapy with systemic corticosteroids is typically initiated, and non-responders can be treated with a wide range of second-line therapies. In addition to treating the underlying disease, the management of complications including profuse diarrhoea, severe malnutrition and gastrointestinal bleeding is paramount. In this Review, we discuss strategies for the diagnosis and management of acute GVHD of the gastrointestinal tract as they pertain to the practising gastroenterologist.

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Figure 1: Endoscopic findings in acute GVHD of the gastrointestinal tract.
Figure 2: Recommended diagnostic algorithm for patients with suspected gastrointestinal acute GVHD after HSCT.
Figure 3: Histopathological findings in GVHD of the gastrointestinal tract.
Figure 4: Gastrointestinal cytomegalovirus infection following HSCT.

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All authors contributed equally to this manuscript.

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Correspondence to Steven Naymagon.

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Competing interests

J.F. and J.L. declare that they have a patent application for a biomarker array discussed in this Review (Title: Method of predicting graft versus host disease. Provisional Application No: 62/411,230; Filing Date: 10/21/16). The other authors declare no competing interests.

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Glossary

Allogeneic HSCT

Transplantation in which a patient receives haematopoietic stem cells from a genetically similar, but not identical, donor.

Autologous HSCT

Transplantation in which a patients haematopoietic stem cells are harvested, stored for the duration of the patient's conditioning regimen, and later returned to that same patient for re-engraftment.

Myeloablative conditioning

The complete or near complete depletion of native bone marrow cells via the administration of cytotoxic chemotherapy such as cyclophosphamide, often along with radiation therapy.

Oesophagogastroduodenoscopy

A diagnostic endoscopic procedure used to visualize, and sometimes intervene upon, regions of the upper gastrointestinal tract, down to the level of the duodenum.

Small bowel capsule endoscopy

A procedure in which a capsule containing a wireless camera is ingested by a patient and used to visualize areas of the small bowel that are difficult to access using conventional endoscopy.

Unrelated donor HSCT

A type of allogeneic transplant in which the donor is not related to the patient.

HLA-mismatched transplantation

A type of allogeneic transplantation in which the HLA typing of the donor and recipient are not identical.

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Naymagon, S., Naymagon, L., Wong, SY. et al. Acute graft-versus-host disease of the gut: considerations for the gastroenterologist. Nat Rev Gastroenterol Hepatol 14, 711–726 (2017). https://doi.org/10.1038/nrgastro.2017.126

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