Graft Versus Host Disease After Intestinal Transplantation: A Single-center Experience

Kaufman, Stuart S.; Hussan, Elsadig; Kroemer, Alexander; Timofeeva, Olga; Pasieka, Helena B.; Guerra, Juan Francisco; Yazigi, Nada; Khan, Khalid; Ekong, Udeme D.; Subramanian, Sukanya; Hawksworth, Jason; Girlanda, R.; Ghobrial, Shahira; Fishbein, Thomas M.; Matsumoto, Cal

doi:10.1097/txd.0000000000001187

Cited by 15 publications

(31 citation statements)

References 52 publications

(101 reference statements)

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“…Patients underwent routine loop ileostomy creation at the time of transplant for post-transplant monitoring, with planned restoration of intestinal continuity and closure of the ileostomy three to six months later. Post-transplant monitoring included endoscopy and biopsy twice weekly for the first 6 weeks, weekly until month three, biweekly until month six, and monthly thereafter, as previously described [ 14 , 15 ].…”

Section: Methodsmentioning

confidence: 99%

The Microbiome and Metabolomic Profile of the Transplanted Intestine with Long-Term Function

et al. 2022

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We analyzed the fecal microbiome by deep sequencing of the 16S ribosomal genes and the metabolomic profiles of 43 intestinal transplant recipients to identify biomarkers of graft function. Stool samples were collected from 23 patients with stable graft function five years or longer after transplant, 15 stable recipients one-year post-transplant and four recipients with refractory rejection and graft loss within one-year post-transplant. Lactobacillus and Streptococcus species were predominant in patients with stable graft function both in the short and long term, with a microbiome profile consistent with the general population. Conversely, Enterococcus species were predominant in patients with refractory rejection as compared to the general population, indicating profound dysbiosis in the context of graft dysfunction. Metabolomic analysis demonstrated significant differences between the three groups, with several metabolites in rejecting recipients clustering as a distinct set. Our study suggests that the bacterial microbiome profile of stable intestinal transplants is similar to the general population, supporting further application of this non-invasive approach to identify biomarkers of intestinal graft function.

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Section: Methodsmentioning

confidence: 99%

The Microbiome and Metabolomic Profile of the Transplanted Intestine with Long-Term Function

et al. 2022

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“…Certain induction and maintenance immunosuppressive regimens may affect the subsequent incidence of GVHD. In one series, early use of sirolimus was protective against subsequent GVHD [35 ▪ ]. In a large case series from the University of Miami, the use of alemtuzumab was shown to significantly decrease the later incidence of GVHD when used as part of induction therapy for ITx [36 ▪ ].…”

Section: Treatment Of Graft-versus-host Diseasementioning

confidence: 99%

“…The incidence of GVHD after intestinal transplant ranges from approximately 5–15%, far exceeding that of other solid organ transplants [2,35 ▪ ,36 ▪ ]. Increased graft volume (especially liver-containing or colon-including grafts) is the most definitive risk factor, with other risk factors, such as recipient age and certain induction regimens, varying between centers [35 ▪ ,36 ▪ ,37]. GVHD is a major contributor to morbidity and mortality that is frequently refractory to modern medical management, with >50% mortality in some series [35 ▪ ,37].…”

Section: Treatment Of Graft-versus-host Diseasementioning

confidence: 99%

“…In the absence of clinical trials or multicenter studies, there is no current standard of care treatment regimen for GVHD, even within individual intestinal transplant programs [36 ▪ ]. Corticosteroids remain the cornerstone of both acute and chronic GVHD treatment after all forms of transplantation, including intestinal [35 ▪ ], but outcomes are variable [38,39].…”

Section: Treatment Of Graft-versus-host Diseasementioning

confidence: 99%

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Update on immunosuppressive strategies in intestinal transplantation

Merola

Shamim

Weiner

2022

Current Opinion in Organ Transplantation

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Purpose of reviewThe intestine is the most immunologically complex solid organ allograft with the greatest risk of both rejection and graft-versus-host disease (GVHD). High levels of immunosuppression are required, further increasing morbidity. Due to low volume of transplants and few centers with experience, there is paucity of evidence-based, standardized, and effective therapeutic regimens. We herein review the most recent data about immunosuppression, focusing on novel and emerging therapies.Recent findingsRecent data are moving the field toward increasing use of basilixumab and consideration of alemtuzumab for induction and inclusion of mammalian target of rapamycin inhibitors and antimetabolites for maintenance. For rejection, we highlight novel roles for tumor necrosis factor-α inhibition, α4β7 integrin inhibition, microbiome modulation, desensitization protocols, and tolerance induction strategies. We also highlight emerging novel therapies for GVHD, especially the promising role of Janus kinase inhibition.SummaryNew insights into immune pathways associated with rejection and GVHD in intestinal allografts have led to an evolution of therapies from broad-based immunosuppression to more targeted strategies that hold promise for reducing morbidity from infection, rejection, and GVHD. These should be the focus of further study to facilitate their widespread use.

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“…This has a higher likelihood of anastomotic leak compared to a jejunojejunal anastomosis as would be the case in a liver/intestine transplant. There are likely to be additional immunological advances to this in reducing infections and the risk of graft versus host disease, by preserving the spleen in a liver/intestinal graft [6]. The 2019 international transplant registry report shows 5-year patient survival for liver/intestinal grafts is significantly better than that of full multivisceral grafts (Fig.…”

Section: Advances In Surgical Technique and Managementmentioning

confidence: 99%

Intestinal transplantation: an update

Sharkey¹,

Russell

2023

Current Opinion in Gastroenterology

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Purpose of reviewThe role of intestinal transplant has expanded in recent years and is no longer only considered for patients with no other options remaining. 5 year survival in high-volume centres is over 80% for certain graft types. The aim of this review is to update the audience on the current state of intestinal transplant, with a focus on recent medical and surgical advances. Recent findingsThere has been a greater understanding of the interplay and balance of host and graft immune responses, which may facilitate individualized immunosuppression. Some centres are now performing 'no-stoma' transplants, with preliminary data showing no adverse effects from this strategy and other surgical advances have lessened the physiological insult of the transplant operation. Earlier referrals are encouraged by transplant centres, such that vascular access or liver disease has not progressed too much to increase the technical and physiological challenge of the procedure. SummaryClinicians should consider intestinal transplant as a viable option for patients with intestinal failure, benign unresectable abdominal tumours or acute abdominal catastrophes.

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Graft Versus Host Disease After Intestinal Transplantation: A Single-center Experience

Abstract: Supplemental Digital Content is available in the text.

Cited by 15 publications

References 52 publications

The Microbiome and Metabolomic Profile of the Transplanted Intestine with Long-Term Function

The Microbiome and Metabolomic Profile of the Transplanted Intestine with Long-Term Function

Update on immunosuppressive strategies in intestinal transplantation

Intestinal transplantation: an update

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