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

Nature Reviews Gastroenterology & Hepatology volume 14, pages 711–726 (2017)Cite this article

Subjects

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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References

  1. Gratwohl, A. et al. Hematopoietic stem cell transplantation: a global perspective. JAMA 303, 1617–1624 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Appelbaum, F. R., Forman, S. J., Negrin, R. S. & Antin, J. H. (eds) Thomas' Hematopoietic Cell Transplantation 5th Edn Ch. 83 (Wiley-Blackwell, 2016).

    Google Scholar 

  3. Seggewiss, R. & Einsele, H. Immune reconstitution after allogeneic transplantation and expanding options for immunomodulation: an update. Blood 115, 3861–3868 (2010).

    Article  CAS  PubMed  Google Scholar 

  4. Barrett, A. J. & Battiwalla, M. Relapse after allogeneic stem cell transplantation. Expert Rev. Hematol. 3, 429–441 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Bhatia, S. et al. Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study. Blood 110, 3784–3792 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Filipovich, A. H. et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol. Blood Marrow Transplant 11, 945–956 (2005).

    Article  PubMed  Google Scholar 

  7. Jagasia, M. H. et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol. Blood Marrow Transplant. 21, 389–401.e1 (2015).

    Article  PubMed  Google Scholar 

  8. Harris, A. C. et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai Acute GVHD International Consortium. Biol. Blood Marrow Transplant. 22, 4–10 (2016).

    Article  PubMed  Google Scholar 

  9. Socie, G. & Ritz, J. Current issues in chronic graft-versus-host disease. Blood 124, 374–384 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. McDonald, G. B. Hepatobiliary complications of hematopoietic cell transplantation, 40 years on. Hepatology 51, 1450–1460 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Cooke, K. R. et al. The biology of chronic graft-versus-host disease: a task force report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease. Biol. Blood Marrow Transplant. 23, 211–234 (2017).

    Article  PubMed  Google Scholar 

  12. Zeiser, R. et al. Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood 108, 390–399 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Teshima, T., Reddy, P. & Zeiser, R. Acute graft-versus-host disease: novel biological insights. Biol. Blood Marrow Transplant. 22, 11–16 (2016).

    Article  CAS  PubMed  Google Scholar 

  14. Shono, Y., Docampo, M. D., Peled, J. U., Perobelli, S. M. & Jenq, R. R. Intestinal microbiota-related effects on graft-versus-host disease. Int. J. Hematol. 101, 428–437 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Taur, Y. et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood 124, 1174–1182 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Shono, Y. et al. Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice. Sci. Transl Med. 8, 339ra71 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Alonso, C. D. & Marr, K. A. Clostridium difficile infection among hematopoietic stem cell transplant recipients: beyond colitis. Curr. Opin. Infect. Dis. 26, 326–331 (2013).

    PubMed  PubMed Central  Google Scholar 

  18. Miyoshi, J. & Chang, E. B. The gut microbiota and inflammatory bowel diseases. Transl Res. 179, 38–48 (2017).

    Article  PubMed  Google Scholar 

  19. Peled, J. U., Hanash, A. M. & Jenq, R. R. Role of the intestinal mucosa in acute gastrointestinal GVHD. Blood 128, 2395–2402 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Holler, E., Landfried, K., Meier, J., Hausmann, M. & Rogler, G. The role of bacteria and pattern recognition receptors in GVHD. Int. J. Inflam. 2010, 814326 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ting, C., Alterovitz, G., Merlob, A. & Abdi, R. Genomic studies of GVHD-lessons learned thus far. Bone Marrow Transplant. 48, 4–9 (2013).

    Article  CAS  PubMed  Google Scholar 

  22. Weisdorf, S. A., Salati, L. M., Longsdorf, J. A., Ramsay, N. K. & Sharp, H. L. Graft-versus-host disease of the intestine: a protein losing enteropathy characterized by fecal alpha 1-antitrypsin. Gastroenterology 85, 1076–1081 (1983).

    CAS  PubMed  Google Scholar 

  23. Zeiser, R., Socie, G. & Blazar, B. R. Pathogenesis of acute graft-versus-host disease: from intestinal microbiota alterations to donor T cell activation. Br. J. Haematol. 175, 191–207 (2016).

    Article  CAS  PubMed  Google Scholar 

  24. Rezvani, A. R. et al. Decreased serum albumin as a biomarker for severe acute graft-versus-host disease after reduced-intensity allogeneic hematopoietic cell transplantation. Biol. Blood Marrow Transplant. 17, 1594–1601 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ruutu, T. et al. Improved survival with ursodeoxycholic acid prophylaxis in allogeneic stem cell transplantation: long-term follow-up of a randomized study. Biol. Blood Marrow Transplant. 20, 135–138 (2014).

    Article  CAS  PubMed  Google Scholar 

  26. Dignan, F. L. et al. Diagnosis and management of acute graft-versus-host disease. Br. J. Haematol. 158, 30–45 (2012).

    Article  CAS  PubMed  Google Scholar 

  27. Schubert, M. M. & Sullivan, K. M. Recognition, incidence, and management of oral graft-versus-host disease. NCI Monogr. 135–143 (1990).

  28. Chaudhry, H. M. et al. The incidence and severity of oral mucositis among allogeneic hematopoietic stem cell transplantation patients: a systematic review. Biol. Blood Marrow Transplant. 22, 605–616 (2016).

    Article  PubMed  Google Scholar 

  29. Vera-Llonch, M., Oster, G., Ford, C. M., Lu, J. & Sonis, S. Oral mucositis and outcomes of allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies. Support. Care Cancer 15, 491–496 (2007).

    Article  PubMed  Google Scholar 

  30. Trabulo, D. et al. Esophageal stenosis with sloughing esophagitis: a curious manifestation of graft-versus-host disease. World J. Gastroenterol. 21, 9217–9222 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  31. McDonald, G. B., Sullivan, K. M., Schuffler, M. D., Shulman, H. M. & Thomas, E. D. Esophageal abnormalities in chronic graft-versus-host disease in humans. Gastroenterology 80, 914–921 (1981).

    Article  CAS  PubMed  Google Scholar 

  32. Yeh, S. P. et al. Gastric bleeding due to graft-versus-host disease: discrepancy between endoscopic and histologic assessment. Am. J. Clin. Pathol. 122, 919–925 (2004).

    Article  PubMed  Google Scholar 

  33. Weisdorf, D. J. et al. Acute upper gastrointestinal graft-versus-host disease: clinical significance and response to immunosuppressive therapy. Blood 76, 624–629 (1990).

    CAS  PubMed  Google Scholar 

  34. Wu, D. et al. Persistent nausea and anorexia after marrow transplantation: a prospective study of 78 patients. Transplantation 66, 1319–1324 (1998).

    Article  CAS  PubMed  Google Scholar 

  35. Wakui, M. et al. Prospective evaluation for upper gastrointestinal tract acute graft-versus-host disease after hematopoietic stem cell transplantation. Bone Marrow Transplant. 23, 573–578 (1999).

    Article  CAS  PubMed  Google Scholar 

  36. Cox, G. J. et al. Etiology and outcome of diarrhea after marrow transplantation: a prospective study. Gastroenterology 107, 1398–1407 (1994).

    Article  CAS  PubMed  Google Scholar 

  37. Schwartz, J. M. et al. Severe gastrointestinal bleeding after hematopoietic cell transplantation, 1987–1997: incidence, causes, and outcome. Am. J. Gastroenterol. 96, 385–393 (2001).

    CAS  PubMed  Google Scholar 

  38. Joshi, N. M. et al. Bile acid malabsorption in patients with graft-versus-host disease of the gastrointestinal tract. Br. J. Haematol. 157, 403–407 (2012).

    Article  CAS  PubMed  Google Scholar 

  39. Labrador, J. et al. Incidence and risk factors for life-threatening bleeding after allogeneic stem cell transplant. Br. J. Haematol. 169, 719–725 (2015).

    Article  PubMed  Google Scholar 

  40. Spencer, G. D., Shulman, H. M., Myerson, D., Thomas, E. D. & McDonald, G. B. Diffuse intestinal ulceration after marrow transplantation: a clinicopathologic study of 13 patients. Hum. Pathol. 17, 621–633 (1986).

    Article  CAS  PubMed  Google Scholar 

  41. Mahgerefteh, S. Y. et al. Radiologic imaging and intervention for gastrointestinal and hepatic complications of hematopoietic stem cell transplantation. Radiology 258, 660–671 (2011).

    Article  PubMed  Google Scholar 

  42. Kirkpatrick, I. D. & Greenberg, H. M. Gastrointestinal complications in the neutropenic patient: characterization and differentiation with abdominal CT. Radiology 226, 668–674 (2003).

    Article  PubMed  Google Scholar 

  43. Hepgur, M. et al. Medical management of pneumatosis intestinalis in patients undergoing allogeneic blood and marrow transplantation. Bone Marrow Transplant. 46, 876–879 (2011).

    Article  CAS  PubMed  Google Scholar 

  44. Budjan, J. et al. Assessment of acute intestinal graft versus host disease by abdominal magnetic resonance imaging at 3 Tesla. Eur. Radiol. 24, 1835–1844 (2014).

    Article  PubMed  Google Scholar 

  45. Benedetti, E. et al. Prospective qualitative and quantitative non-invasive evaluation of intestinal acute GVHD by contrast-enhanced ultrasound sonography. Bone Marrow Transplant. 48, 1421–1428 (2013).

    Article  CAS  PubMed  Google Scholar 

  46. Bodet-Milin, C. et al. 18F-FDG PET/CT for the assessment of gastrointestinal GVHD: results of a pilot study. Bone Marrow Transplant. 49, 131–137 (2014).

    Article  CAS  PubMed  Google Scholar 

  47. Ferrara, J. L. et al. Regenerating islet-derived 3-alpha is a biomarker of gastrointestinal graft-versus-host disease. Blood 118, 6702–6708 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hartwell, M. J. et al. An early-biomarker algorithm predicts lethal graft-versus-host disease and survival. JCI Insight 2, e89798 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Levine, J. E. et al. A prognostic score for acute graft-versus-host disease based on biomarkers: a multicentre study. Lancet Haematol. 2, e21–e29 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Chen, Y. B. & Cutler, C. S. Biomarkers for acute GVHD: can we predict the unpredictable? Bone Marrow Transplant. 48, 755–760 (2013).

    Article  CAS  PubMed  Google Scholar 

  51. Paczesny, S. Discovery and validation of graft-versus-host disease biomarkers. Blood 121, 585–594 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. McDonald, G. B. et al. Plasma biomarkers of acute GVHD and nonrelapse mortality: predictive value of measurements before GVHD onset and treatment. Blood 126, 113–120 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Abu Zaid, M. et al. Plasma biomarkers of risk for death in a multicenter phase 3 trial with uniform transplant characteristics post-allogeneic HCT. Blood 129, 162–170 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Apostolova, P. & Zeiser, R. The role of purine metabolites as DAMPs in acute graft-versus-host disease. Front. Immunol. 7, 439 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Holtan, S. G. et al. Circulating angiogenic factors associated with response and survival in patients with acute graft-versus-host disease: results from Blood and Marrow Transplant Clinical Trials Network 0302 and 0802. Biol. Blood Marrow Transplant. 21, 1029–1036 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Mathewson, N. D. et al. Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease. Nat. Immunol. 17, 505–513 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Lorenz, F. et al. Fecal calprotectin as a biomarker of intestinal graft versus host disease after allogeneic hematopoietic stem cell transplantation. Sci. Rep. 5, 7920 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Adam, B. et al. Endoscopic and histological findings are predicted by fecal calprotectin in acute intestinal graft-versus-host-disease. Dig. Dis. Sci. 61, 2019–2026 (2016).

    Article  CAS  PubMed  Google Scholar 

  59. van der Meij, B. S. et al. Nutritional support in patients with GVHD of the digestive tract: state of the art. Bone Marrow Transplant. 48, 474–482 (2013).

    Article  CAS  PubMed  Google Scholar 

  60. Ayuk, F. et al. Serum albumin level predicts survival of patients with gastrointestinal acute graft-versus-host disease after allogeneic stem cell transplantation. Ann. Hematol. 93, 855–861 (2014).

    Article  CAS  PubMed  Google Scholar 

  61. Ponec, R. J., Hackman, R. C. & McDonald, G. B. Endoscopic and histologic diagnosis of intestinal graft-versus-host disease after marrow transplantation. Gastrointest. Endosc. 49, 612–621 (1999).

    Article  CAS  PubMed  Google Scholar 

  62. ASGE Standards of Practice Committee et al. The role of endoscopy in the management of patients with diarrhea. Gastrointest. Endosc. 71, 887–892 (2010).

  63. Hiejima, E. et al. Diagnostic accuracy of endoscopic features of pediatric acute gastrointestinal graft-versus-host disease. Dig. Endosc. 28, 548–555 (2016).

    Article  PubMed  Google Scholar 

  64. Kreisel, W. et al. Endoscopic diagnosis of acute intestinal GVHD following allogeneic hematopoietic SCT: a retrospective analysis in 175 patients. Bone Marrow Transplant. 47, 430–438 (2012).

    Article  CAS  PubMed  Google Scholar 

  65. Velasco-Guardado, A. et al. Endoscopic evaluation and histological findings in graft-versus-host disease. Rev. Esp. Enferm. Dig. 104, 310–314 (2012).

    Article  PubMed  Google Scholar 

  66. Cruz-Correa, M. et al. Endoscopic findings predict the histologic diagnosis in gastrointestinal graft-versus-host disease. Endoscopy 34, 808–813 (2002).

    Article  CAS  PubMed  Google Scholar 

  67. Thompson, B., Salzman, D., Steinhauer, J., Lazenby, A. J. & Wilcox, C. M. Prospective endoscopic evaluation for gastrointestinal graft-versus-host disease: determination of the best diagnostic approach. Bone Marrow Transplant. 38, 371–376 (2006).

    Article  CAS  PubMed  Google Scholar 

  68. Terdiman, J. P. et al. The role of endoscopic evaluation in patients with suspected intestinal graft-versus-host disease after allogeneic bone-marrow transplantation. Endoscopy 28, 680–685 (1996).

    Article  CAS  PubMed  Google Scholar 

  69. Khan, K. et al. Diagnostic endoscopy in children after hematopoietic stem cell transplantation. Gastrointest. Endosc. 64, 379–385 (2006).

    Article  PubMed  Google Scholar 

  70. Martin, P. J. et al. First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation. Biol. Blood Marrow Transplant. 18, 1150–1163 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Ross, W. A. et al. Endoscopic biopsy diagnosis of acute gastrointestinal graft-versus-host disease: rectosigmoid biopsies are more sensitive than upper gastrointestinal biopsies. Am. J. Gastroenterol. 103, 982–989 (2008).

    Article  PubMed  Google Scholar 

  72. Ma, C., Maluf, H. M. & Liu, T. C. Acute graft-versus-host disease is more prevalent and severe in the lower than the upper gastrointestinal tract. Hum. Pathol. 46, 1480–1487 (2015).

    Article  PubMed  Google Scholar 

  73. Crowell, K. R. et al. Endoscopy in the diagnosis of intestinal graft-versus-host disease: is lower endoscopy with biopsy as effective in diagnosis as upper endoscopy combined with lower endoscopy? Pediatr. Blood Cancer 60, 1798–1800 (2013).

    Article  PubMed  Google Scholar 

  74. Lee, K. J. et al. Stepwise endoscopy based on sigmoidoscopy in evaluating pediatric graft-versus-host disease. Pediatr. Gastroenterol. Hepatol. Nutr. 19, 29–37 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Kakugawa, Y., Fukuda, T. & Saito, Y. Cautionary note on using rectosigmoid biopsies to diagnose graft-versus-host disease: necessity of ruling out cytomegalovirus colitis. Am. J. Gastroenterol. 103, 2959–2960 (2008).

    Article  PubMed  Google Scholar 

  76. Cloutier, J., Wall, D. A., Paulsen, K. & Bernstein, C. N. Upper versus lower endoscopy in the diagnosis of graft-versus-host disease. J. Clin. Gastroenterol. 51, 701–706 (2017).

    Article  PubMed  Google Scholar 

  77. Wild, D. et al. The diagnostic yield of site and symptom-based biopsies for acute gastrointestinal graft-versus-host disease: a 5-year retrospective review. Dig. Dis. Sci. 61, 806–813 (2016).

    Article  PubMed  Google Scholar 

  78. Ip, S., Marquez, V., Schaeffer, D. F. & Donnellan, F. Sensitivities of biopsy sites in the endoscopic evaluation of graft-versus-host disease: retrospective review from a tertiary center. Dig. Dis. Sci. 61, 2351–2356 (2016).

    Article  PubMed  Google Scholar 

  79. Sierra, A. et al. Biopsy-induced duodenal hematoma is not an infrequent complication favored by bone marrow transplantation. J. Pediatr. Gastroenterol. Nutr. 63, 627–632 (2016).

    Article  PubMed  Google Scholar 

  80. Committee, A. S.o. P. et al. Endoscopic mucosal tissue sampling. Gastrointest. Endosc. 78, 216–224 (2013).

    Article  Google Scholar 

  81. Welch, D. C. et al. Gastric graft-versus-host disease revisited: does proton pump inhibitor therapy affect endoscopic gastric biopsy interpretation? Am. J. Surg. Pathol. 30, 444–449 (2006).

    Article  PubMed  Google Scholar 

  82. DiMarino, A. J. & Benjamin, S. B. Gastrointestinal disease: an endoscopic approach (Slack, 2002).

    Google Scholar 

  83. Bhaijee, F., Subramony, C., Tang, S. J. & Pepper, D. J. Human immunodeficiency virus-associated gastrointestinal disease: common endoscopic biopsy diagnoses. Patholog. Res. Int. 2011, 247923 (2011).

    PubMed  PubMed Central  Google Scholar 

  84. Phadke, V. K., Friedman-Moraco, R. J., Quigley, B. C., Farris, A. B. & Norvell, J. P. Concomitant herpes simplex virus colitis and hepatitis in a man with ulcerative colitis: case report and review of the literature. Medicine (Baltimore) 95, e5082 (2016).

    Article  Google Scholar 

  85. Arai, Y. et al. Usefulness of quantitative PCR in biopsy specimens for early therapeutic intervention in gastro-intestinal cytomegalovirus infections after allogeneic stem cell transplantation. Rinsho Ketsueki 55, 2400–2407 (in Japanese) (2014).

    PubMed  Google Scholar 

  86. Bhutani, D. et al. Incidence, risk factors, and outcome of cytomegalovirus viremia and gastroenteritis in patients with gastrointestinal graft-versus-host disease. Biol. Blood Marrow Transplant. 21, 159–164 (2015).

    Article  PubMed  Google Scholar 

  87. Martinez, C. et al. Serial intestinal endoscopic examinations of patients with persistent diarrhea after allo-SCT. Bone Marrow Transplant. 47, 694–699 (2012).

    Article  CAS  PubMed  Google Scholar 

  88. Tong, M. C., Tadros, M. & Vaziri, H. Endoscopy in neutropenic and/or thrombocytopenic patients. World J. Gastroenterol. 21, 13166–13176 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Xu, C. F., Zhu, L. X., Xu, X. M., Chen, W. C. & Wu, D. P. Endoscopic diagnosis of gastrointestinal graft-versus-host disease. World J. Gastroenterol. 14, 2262–2267 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  90. ASGE Standards of Practice Committee et al. Adverse events of upper GI endoscopy. Gastrointest. Endosc. 76, 707–718 (2012).

  91. Feldman, M., Friedman, L. S. & Brandt, L. J. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management 10th Edn Ch. 41 (Saunders,2016).

    Google Scholar 

  92. ASGE Standards of Practice Committee et al. Antibiotic prophylaxis for GI endoscopy. Gastrointest. Endosc. 81, 81–89 (2015).

  93. Malard, F. & Mohty, M. New insight for the diagnosis of gastrointestinal acute graft-versus-host disease. Mediators Inflamm. 2014, 701013 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Neumann, S. et al. Wireless capsule endoscopy for diagnosis of acute intestinal graft-versus-host disease. Gastrointest. Endosc. 65, 403–409 (2007).

    Article  PubMed  Google Scholar 

  95. Yakoub-Agha, I. et al. Impact of small bowel exploration using video-capsule endoscopy in the-management of acute gastrointestinal graft-versus-host disease. Transplantation 78, 1697–1701 (2004).

    Article  PubMed  Google Scholar 

  96. Bojarski, C. et al. In vivo diagnosis of acute intestinal graft-versus-host disease by confocal endomicroscopy. Endoscopy 41, 433–438 (2009).

    Article  CAS  PubMed  Google Scholar 

  97. Coron, E. et al. Early detection of acute graft-versus-host disease by wireless capsule endoscopy and probe-based confocal laser endomicroscopy: results of a pilot study. United European Gastroenterol. J. 2, 206–215 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  98. Sale, G. E., Shulman, H. M., McDonald, G. B. & Thomas, E. D. Gastrointestinal graft-versus-host disease in man. A clinicopathologic study of the rectal biopsy. Am. J. Surg. Pathol. 3, 291–299 (1979).

    Article  CAS  PubMed  Google Scholar 

  99. Washington, K. & Jagasia, M. Pathology of graft-versus-host disease in the gastrointestinal tract. Hum. Pathol. 40, 909–917 (2009).

    Article  PubMed  Google Scholar 

  100. Shidham, V. B. et al. Colon biopsies for evaluation of acute graft-versus-host disease (A-GVHD) in allogeneic bone marrow transplant patients. BMC Gastroenterol. 3, 5 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  101. Fenoglio-Preiser, C. M. Gastrointestinal pathology: an atlas and text (Wolters Kluwer/Lippincott Williams & Wilkins, 2008).

    Google Scholar 

  102. Levine, J. E. et al. Low Paneth cell numbers at onset of gastrointestinal graft-versus-host disease identify patients at high risk for nonrelapse mortality. Blood 122, 1505–1509 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Lin, J., Fan, R., Zhao, Z., Cummings, O. W. & Chen, S. Is the presence of 6 or fewer crypt apoptotic bodies sufficient for diagnosis of graft versus host disease? A decade of experience at a single institution. Am. J. Surg. Pathol. 37, 539–547 (2013).

    Article  PubMed  Google Scholar 

  104. Lerner, K. G. et al. Histopathology of graft-versus-host reaction (GvHR) in human recipients of marrow from HL-A-matched sibling donors. Transplant. Proc. 6, 367–371 (1974).

    CAS  PubMed  Google Scholar 

  105. Massi, D. et al. The impact of histopathologic examination of graft-versus-host disease in the era of reduced-intensity conditioning regimen: a study from the Gruppo Italiano Trapianto di Midollo Osseo. Hum. Pathol. 42, 254–268 (2011).

    Article  PubMed  Google Scholar 

  106. Rowlings, P. A. et al. IBMTR Severity Index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br. J. Haematol. 97, 855–864 (1997).

    Article  CAS  PubMed  Google Scholar 

  107. Przepiorka, D. et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 15, 825–828 (1995).

    CAS  PubMed  Google Scholar 

  108. Goyal, R. K., Goyal, M. & Sankaranarayan, K. Grading acute graft-versus-host disease: time to reconsider. Pediatr. Transplant. 19, 252–254 (2015).

    Article  PubMed  Google Scholar 

  109. Gratwohl, A. et al. Acute graft-versus-host disease: grade and outcome in patients with chronic myelogenous leukemia. Working Party Chronic Leukemia of the European Group for Blood and Marrow Transplantion. Blood 86, 813–818 (1995).

    CAS  PubMed  Google Scholar 

  110. Lee, S. E. et al. Risk and prognostic factors for acute GVHD based on NIH consensus criteria. Bone Marrow Transplant. 48, 587–592 (2013).

    Article  PubMed  Google Scholar 

  111. MacMillan, M. L. et al. A refined risk score for acute graft-versus-host disease that predicts response to initial therapy, survival, and transplant-related mortality. Biol. Blood Marrow Transplant. 21, 761–767 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  112. Leisenring, W. M. et al. An acute graft-versus-host disease activity index to predict survival after hematopoietic cell transplantation with myeloablative conditioning regimens. Blood 108, 749–755 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Castilla-Llorente, C. et al. Prognostic factors and outcomes of severe gastrointestinal GVHD after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 49, 966–971 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Shimoni, A. et al. CT in the clinical and prognostic evaluation of acute graft-versus-host disease of the gastrointestinal tract. Br. J. Radiol. 85, e416–e423 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Calmet, F. H., Yarur, A. J., Pukazhendhi, G., Ahmad, J. & Bhamidimarri, K. R. Endoscopic and histological features of mycophenolate mofetil colitis in patients after solid organ transplantation. Ann. Gastroenterol. 28, 366–373 (2015).

    PubMed  PubMed Central  Google Scholar 

  116. Ortega, F. et al. Gastrointestinal quality of life improvement of renal transplant recipients converted from mycophenolate mofetil to enteric-coated mycophenolate sodium drugs or agents: mycophenolate mofetil and enteric-coated mycophenolate sodium. Transplantation 92, 426–432 (2011).

    Article  PubMed  Google Scholar 

  117. Star, K. V., Ho, V. T., Wang, H. H. & Odze, R. D. Histologic features in colon biopsies can discriminate mycophenolate from GVHD-induced colitis. Am. J. Surg. Pathol. 37, 1319–1328 (2013).

    Article  PubMed  Google Scholar 

  118. Kamboj, M., Mihu, C. N., Sepkowitz, K., Kernan, N. A. & Papanicolaou, G. A. Work-up for infectious diarrhea after allogeneic hematopoietic stem cell transplantation: single specimen testing results in cost savings without compromising diagnostic yield. Transpl. Infect. Dis. 9, 265–269 (2007).

    Article  CAS  PubMed  Google Scholar 

  119. Bowden, R. A., Ljungman, P. & Snydman, D. R. Transplant infections (Wolters Kluwer Health/Lippincott Williams & Wilkins, 2010).

    Google Scholar 

  120. Harano, Y., Kotajima, L. & Arioka, H. Case of cytomegalovirus colitis in an immunocompetent patient: a rare cause of abdominal pain and diarrhea in the elderly. Int. J. Gen. Med. 8, 97–100 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  121. Yagi, T. et al. Acute abdomen without cutaneous signs of varicella zoster virus infection as a late complication of allogeneic bone marrow transplantation: importance of empiric therapy with acyclovir. Bone Marrow Transplant. 25, 1003–1005 (2000).

    Article  CAS  PubMed  Google Scholar 

  122. Cho, B. S. et al. Impact of cytomegalovirus gastrointestinal disease on the clinical outcomes in patients with gastrointestinal graft-versus-host disease in the era of preemptive therapy. Ann. Hematol. 92, 497–504 (2013).

    Article  CAS  PubMed  Google Scholar 

  123. Ghosh, N., Malik, F. A., Daver, R. G., Vanichanan, J. & Okhuysen, P. C. Viral associated diarrhea in immunocompromised and cancer patients at a large comprehensive cancer center: a 10-year retrospective study. Infect. Dis. (Lond.) 49, 113–119 (2016).

    Article  CAS  Google Scholar 

  124. van Montfrans, J. et al. Viral PCR positivity in stool before allogeneic hematopoietic cell transplantation is strongly associated with acute intestinal graft-versus-host disease. Biol. Blood Marrow Transplant. 21, 772–774 (2015).

    Article  PubMed  Google Scholar 

  125. Schwartz, S. et al. Norovirus gastroenteritis causes severe and lethal complications after chemotherapy and hematopoietic stem cell transplantation. Blood 117, 5850–5856 (2011).

    Article  CAS  PubMed  Google Scholar 

  126. Trifilio, S. M., Pi, J. & Mehta, J. Changing epidemiology of Clostridium difficile-associated disease during stem cell transplantation. Biol. Blood Marrow Transplant. 19, 405–409 (2013).

    Article  PubMed  Google Scholar 

  127. Chakrabarti, S., Lees, A., Jones, S. G. & Milligan, D. W. Clostridium difficile infection in allogeneic stem cell transplant recipients is associated with severe graft-versus-host disease and non-relapse mortality. Bone Marrow Transplant. 26, 871–876 (2000).

    Article  CAS  PubMed  Google Scholar 

  128. Collini, P. J., Bauer, M., Kuijper, E. & Dockrell, D. H. Clostridium difficile infection in HIV-seropositive individuals and transplant recipients. J. Infect. 64, 131–147 (2012).

    Article  PubMed  Google Scholar 

  129. Nomura, K. et al. Absence of pseudomembranes in Clostridium difficile-associated diarrhea in patients using immunosuppression agents. Scand. J. Gastroenterol. 44, 74–78 (2009).

    Article  PubMed  Google Scholar 

  130. Surawicz, C. M. et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am. J. Gastroenterol. 108, 478–498 (2013).

    Article  CAS  PubMed  Google Scholar 

  131. King, A., Rampling, A., Wight, D. G. & Warren, R. E. Neutropenic enterocolitis due to Clostridium septicum infection. J. Clin. Pathol. 37, 335–343 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Machado, N. O. Neutropenic enterocolitis: a continuing medical and surgical challenge. N. Am. J. Med. Sci. 2, 293–300 (2010).

    PubMed  PubMed Central  Google Scholar 

  133. Nesher, L. & Rolston, K. V. Neutropenic enterocolitis, a growing concern in the era of widespread use of aggressive chemotherapy. Clin. Infect. Dis. 56, 711–717 (2013).

    Article  PubMed  Google Scholar 

  134. Gupta, N. K. & Masia, R. Cord colitis syndrome: a cause of granulomatous inflammation in the upper and lower gastrointestinal tract. Am. J. Surg. Pathol. 37, 1109–1113 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  135. Bhatt, A. S. et al. Sequence-based discovery of Bradyrhizobium enterica in cord colitis syndrome. N. Engl. J. Med. 369, 517–528 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Herrera, A. F. et al. Cord colitis syndrome in cord-blood stem-cell transplantation. N. Engl. J. Med. 365, 815–824 (2011).

    Article  CAS  PubMed  Google Scholar 

  137. Shimoji, S. et al. Evaluating the association between histological manifestations of cord colitis syndrome with GVHD. Bone Marrow Transplant. 48, 1249–1252 (2013).

    Article  CAS  PubMed  Google Scholar 

  138. Milano, F. et al. Late-onset colitis after cord blood transplantation is consistent with graft-versus-host disease: results of a blinded histopathological review. Biol. Blood Marrow Transplant. 20, 1008–1013 (2014).

    Article  PubMed  Google Scholar 

  139. Renteria, A. S., Levine, J. E. & Ferrara, J. L. M. Therapeutic targets and emerging treatment options in gastrointestinal acute graft-versus-host disease. Expert Opin. Orphan Drugs 4, 469–484 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Ruutu, T. et al. Prophylaxis and treatment of GVHD after allogeneic haematopoietic SCT: a survey of centre strategies by the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 47, 1459–1464 (2012).

    Article  CAS  PubMed  Google Scholar 

  141. Inamoto, Y. et al. A retrospective comparison of tacrolimus versus cyclosporine with methotrexate for immunosuppression after allogeneic hematopoietic cell transplantation with mobilized blood cells. Biol. Blood Marrow Transplant. 17, 1088–1092 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Ringden, O. et al. Decreased incidence of graft-versus-host disease and improved survival with methotrexate combined with cyclosporin compared with monotherapy in recipients of bone marrow from donors other than HLA identical siblings. Bone Marrow Transplant. 9, 19–25 (1992).

    CAS  PubMed  Google Scholar 

  143. Perkins, J. et al. A randomized phase II trial comparing tacrolimus and mycophenolate mofetil to tacrolimus and methotrexate for acute graft-versus-host disease prophylaxis. Biol. Blood Marrow Transplant. 16, 937–947 (2010).

    Article  CAS  PubMed  Google Scholar 

  144. Weber, T., Niestadtkotter, J., Wienke, A., Muller-Tidow, C. & Muller, L. P. Enteric-coated mycophenolate sodium containing GvHD prophylaxis reduces GvHD rate after allogeneic HSCT. Eur. J. Haematol. 97, 232–238 (2016).

    Article  CAS  PubMed  Google Scholar 

  145. Theurich, S. et al. Polyclonal anti-thymocyte globulins for the prophylaxis of graft-versus-host disease after allogeneic stem cell or bone marrow transplantation in adults. Cochrane Database Syst. Rev. 9, CD009159 (2012).

    Google Scholar 

  146. Klein, O. R. et al. Alternative-donor hematopoietic stem cell transplantation with post-transplantation cyclophosphamide for nonmalignant disorders. Biol. Blood Marrow Transplant. 22, 895–901 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Ruutu, T. et al. Prophylaxis and treatment of GVHD: EBMT-ELN working group recommendations for a standardized practice. Bone Marrow Transplant. 49, 168–173 (2014).

    Article  CAS  PubMed  Google Scholar 

  148. Mielcarek, M. et al. Effectiveness and safety of lower dose prednisone for initial treatment of acute graft-versus-host disease: a randomized controlled trial. Haematologica 100, 842–848 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Van Lint, M. T. et al. Early treatment of acute graft-versus-host disease with high- or low-dose 6-methylprednisolone: a multicenter randomized trial from the Italian Group for Bone Marrow Transplantation. Blood 92, 2288–2293 (1998).

    CAS  PubMed  Google Scholar 

  150. McDonald, G. B. et al. Oral beclomethasone dipropionate for treatment of intestinal graft-versus-host disease: a randomized, controlled trial. Gastroenterology 115, 28–35 (1998).

    Article  CAS  PubMed  Google Scholar 

  151. Hockenbery, D. M. et al. A randomized, placebo-controlled trial of oral beclomethasone dipropionate as a prednisone-sparing therapy for gastrointestinal graft-versus-host disease. Blood 109, 4557–4563 (2007).

    Article  CAS  PubMed  Google Scholar 

  152. Castilla, C. et al. Oral beclomethasone dipropionate for the treatment of gastrointestinal acute graft-versus-host disease (GVHD). Biol. Blood Marrow Transplant. 12, 936–941 (2006).

    Article  CAS  PubMed  Google Scholar 

  153. Sandborn, W. J. et al. Once-daily budesonide MMX(R) extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study. Gastroenterology 143, 1218–1226.e2 (2012).

    Article  CAS  PubMed  Google Scholar 

  154. Deeg, H. J. How I treat refractory acute GVHD. Blood 109, 4119–4126 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. MacMillan, M. L. et al. Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems. Biol. Blood Marrow Transplant. 8, 387–394 (2002).

    Article  CAS  PubMed  Google Scholar 

  156. Trigg, M. E. & Inverso, D. M. Nausea and vomiting with high-dose chemotherapy and stem cell rescue therapy: a review of antiemetic regimens. Bone Marrow Transplant. 42, 501–506 (2008).

    Article  CAS  PubMed  Google Scholar 

  157. Navari, R. M. & Aapro, M. Antiemetic prophylaxis for chemotherapy-induced nausea and vomiting. N. Engl. J. Med. 374, 1356–1367 (2016).

    Article  CAS  PubMed  Google Scholar 

  158. Tuncer, H. H., Rana, N., Milani, C., Darko, A. & Al-Homsi, S. A. Gastrointestinal and hepatic complications of hematopoietic stem cell transplantation. World J. Gastroenterol. 18, 1851–1860 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  159. Dodd, M. J. et al. Randomized clinical trial of the effectiveness of 3 commonly used mouthwashes to treat chemotherapy-induced mucositis. Oral Surg. Oral Med. Oral Pathol. Oral Radiol Endod. 90, 39–47 (2000).

    Article  CAS  PubMed  Google Scholar 

  160. Lalla, R. V. et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 120, 1453–1461 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  161. McDonald, G. B. How I treat acute graft-versus-host disease of the gastrointestinal tract and the liver. Blood 127, 1544–1550 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Lauro, A., De Giorgio, R. & Pinna, A. D. Advancement in the clinical management of intestinal pseudo-obstruction. Expert Rev. Gastroenterol. Hepatol. 9, 197–208 (2015).

    Article  CAS  PubMed  Google Scholar 

  163. Thomas, J. et al. Methylnaltrexone for opioid-induced constipation in advanced illness. N. Engl. J. Med. 358, 2332–2343 (2008).

    Article  CAS  PubMed  Google Scholar 

  164. Khanna, I. K. & Pillarisetti, S. Buprenorphine - an attractive opioid with underutilized potential in treatment of chronic pain. J. Pain Res. 8, 859–870 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  165. DuPont, H. L. & Hornick, R. B. Adverse effect of lomotil therapy in shigellosis. JAMA 226, 1525–1528 (1973).

    Article  CAS  PubMed  Google Scholar 

  166. Ippoliti, C. et al. Use of octreotide in the symptomatic management of diarrhea induced by graft-versus-host disease in patients with hematologic malignancies. J. Clin. Oncol. 15, 3350–3354 (1997).

    Article  CAS  PubMed  Google Scholar 

  167. Beatson, N. Atropine and paralytic ileus. Postgrad. Med. J. 58, 451–453 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Akpek, G., Valladares, J. L., Lee, L., Margolis, J. & Vogelsang, G. B. Pancreatic insufficiency in patients with chronic graft-versus-host disease. Bone Marrow Transplant. 27, 163–166 (2001).

    Article  CAS  PubMed  Google Scholar 

  169. Papadopoulou, A., Lloyd, D. R., Williams, M. D., Darbyshire, P. J. & Booth, I. W. Gastrointestinal and nutritional sequelae of bone marrow transplantation. Arch. Dis. Child. 75, 208–213 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Guieze, R. et al. Enteral versus parenteral nutritional support in allogeneic haematopoietic stem-cell transplantation. Clin. Nutr. 33, 533–538 (2014).

    Article  PubMed  Google Scholar 

  171. Imataki, O. et al. Nutritional support for patients suffering from intestinal graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Am. J. Hematol. 81, 747–752 (2006).

    Article  PubMed  Google Scholar 

  172. Ohashi, K. et al. Use of octreotide in the management of severe duodenal bleeding after unrelated-donor bone marrow transplantation. Int. J. Hematol. 78, 176–177 (2003).

    Article  PubMed  Google Scholar 

  173. Chen, R. Z., Zhao, G., Jin, N., Chen, B. A. & Ding, J. H. Superselective arterial embolization of the superior mesenteric artery for the treatment of gastrointestinal hemorrhage following allogeneic hematopoietic stem cell transplantation. Patient Prefer. Adherence 8, 1581–1585 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  174. Kably, I. M., Ziga, E. D. & Andreansky, M. Intra-arterial platelet infusion for intractable hemorrhage and refractory thrombocytopenia in children with gastrointestinal graft-versus-host disease. Pediatr. Blood Cancer 62, 2226–2228 (2015).

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, 10029, New York, USA

    Steven Naymagon, Serre-Yu Wong, Huaibin Mabel Ko & Jean-Frederic Colombel

  2. Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, 10029, New York, USA

    Leonard Naymagon, Anne Renteria, John Levine & James Ferrara

  3. Lillian and Henry M. Stratton-Hans Popper Department of Pathology and Laboratory Medicine, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, 10029, New York, USA

    Huaibin Mabel Ko

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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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