Liver transplant-associated graft-versus-host disease

Smith, Douglas M.; Agura, Edward; Netto, George J.; Collins, Robert H.; Levy, Marlon F.; Goldstein, Robert M.; Christensen, Laura; Baker, Judy; Altrabulsi, Basel; Osowski, Lori D.; McCormack, Jeffrey M.; Fichtel, Lisa; Dawson, D. Brian; Domiati‐Saad, Rana; Stone, Marvin J.; Klintmalm, Göran B.

doi:10.1097/00007890-200301150-00022

Cited by 170 publications

(141 citation statements)

References 29 publications

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“…The intestine possesses the largest mass of lymphoid tissue of any solid organ in the human body [15]. Not surprisingly, therefore, intestinal transplantation is reported to have a higher rate of GVH disease (GVHD, 5.6%-9.1%) [16][17][18] than a transplant of any other organ type, including liver (1-2%) [19,20]. Since GVHD in transplant recipients is associated with a very high mortality rate (up to 85%) [18] and intestinal transplant recipients have a high rate of GVHD, this may explain why ABO-compatible transplants have a lower graft survival than identical transplants.…”

Section: Discussionmentioning

confidence: 99%

“…O donor to A recipient) with a large quantity of lymphoid tissue, the transplant may contain enough of the recipient's antigen-specific immune cells that will mount GVH immune responses against mismatched recipient's antigens. These antigens include not only ABO blood type antigens, but also HLA antigens, which are all expressed on the surface of platelets [18][19][20][21]. Either GVH HLA-or ABO-specific antibodies will bind to platelets or other blood cells of recipient origin at the site of activation of coagulation, which further enhances the formation of blood clots and results in graft failure.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Is ABO-Compatible but Non-Identical Intestinal Transplant Comparable to ABO-Identical Transplant? An Analysis of the UNOS Registry

Cai¹

2015

SOJI

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SOJ ImmunologyOpen Access Research Article survival in the heart [1,2], lung [3,4], and liver [5] transplants. However, careful investigation of these studies demonstrates that ABO-compatible transplants have lower graft survival than identical transplants in some of these studies, though the differences do not reach statistical significance. Koukoutisis [6] and Bjoro [7] reported that ABO-compatible liver transplant recipients actually have significantly lower graft and patient survival than ABO-identical transplant patients.Compared to other organ transplantation, intestinal transplantation remains the least frequently performed transplantation. There are more than 40 US centers performing intestinal transplants and case numbers in recent years were only around 100 per year in the US, with most centers performing fewer than 10 transplants per year [8]. With limited intestinal transplant cases, it is very difficult or it may take a long time for a single center to provide convincing evidence to show whether ABO-compatible and identical transplants have comparable graft outcome, especially long-term outcome. Our recent analysis demonstrated that during 1990-2013, 9.7% of US intestinal recipients received transplants from ABO-compatible donors. More importantly, we found there was a very significant increasing trend of ABO-compatible intestinal transplants in recent years (from 4% to 16%). These findings make it urgent to know whether it is safe to perform ABO-compatible intestinal transplantation and what we should do to minimize the potential risk if the ABO-compatible transplant is associated with graft failure. By analyzing US national registry data, we show the current status of ABO-compatible intestinal transplantation in the US and its detrimental effects on short-and long-term intestinal allograft outcomes. We also discuss the potential mechanisms of graft-versus-host reaction-induced graft injury and corresponding strategies. Materials and Methods Study populationBetween 1/1/1990 and 6/27/2013, a total of 2,287 US intestinal transplants were reported to the Organ Procurement Absract ABO-compatible intestinal transplants have been more frequently performed in the US in recent years (from 4% to 16%). However, they have not been clearly shown to have comparable short-and long-term graft outcome compared to ABO-identical transplants.The US national registry database was analyzed to show the current status of ABO-compatible intestinal transplantation and to determine its effect on acute rejection and long-term graft survival.Blood type A, B, and AB patients received 11%, 26%, and 62% of ABO-compatible intestinal transplants, respectively. ABO-compatible transplant recipients experienced a higher rate of acute rejection than ABO-identical patients (77% vs. 64%, p < 0.0001). In addition, they had a significantly lower 10-year graft survival rate than ABO-identical transplant recipients (27% vs. 35%, p = 0.020). Acute rejection was the cause of graft failure in 42% of ABO-compatible and 25% of ABOidentical pat...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Is ABO-Compatible but Non-Identical Intestinal Transplant Comparable to ABO-Identical Transplant? An Analysis of the UNOS Registry

Cai¹

2015

SOJI

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“…Although the exact mechanism of GVHD after liver transplant remains unclear, the following risk factors may be important: donor human leukocyte antigen compatibility, 3 recipient age > 65 years, age difference > 40 years between donor and recipient, 2,3 and an immunocompromised state at the time of transplant. 14 Furthermore, CMV infection may induce and influence the severity of GVHD after bone marrow transplant.…”

Section: Discussionmentioning

confidence: 99%

“…However, GVHD after liver transplant, first described in 1988, 1 is very rare (incidence, 0.1% to 1%), 2,3 and usually occurs within the first 6 weeks after transplant. 4 The most common sites of involvement are the skin and gastrointestinal tract, and GVHD after liver transplant is a progressive and fatal disease with mortality > 85% in adults, 5 mostly secondary to overwhelming sepsis or gastrointestinal bleeding.…”

Section: Introductionmentioning

confidence: 99%

Treatment of Liver Transplant Graft-Versus-Host Disease With Antibodies Against Tumor Necrosis Factor-α

Blank

Li²,

Kratt³

et al. 2012

Exp Clin Transplant

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Acute graft-versus-host disease is uncommon after liver transplant. We recently treated a 60-year-old man with liver transplant for hepatocellular carcinoma. After the primary liver transplant graft did not function, revision liver transplant resulted in excellent function. Subsequently, the patient developed watery diarrhea, systemic inflammatory response syndrome, a skin rash on his limbs and trunk, and palmar erythema. Skin biopsy suggested viral exanthems consistent with cytomegalovirus. Despite treatment for cytomegalovirus, intestinal symptoms worsened. Analysis of peripheral blood with fluorescence-activated cell sorting showed a high proportion of T lymphocytes, with 5% to 10% T cells specific to the second donor, suggestive of graft-versus-host disease. Within 48 hours after beginning therapy with antibodies against tumor necrosis factor-α (infliximab), the skin rash disappeared and endoscopy showed slight improvement of the mucosal regeneration. However, despite antifungal prophylaxis with caspofungin, the patient developed angioinvasive pulmonary aspergillosis and multiple organ failure, and he died. In conclusion, typical clinical symptoms of graftversus-host disease after liver transplant may include skin rash and gastrointestinal symptoms, and diagnosis may be confirmed by histologic examination and testing for blood chimerism. A consensus for the treatment of graft-versus-host disease still is lacking, but tumor necrosis factor-α is an encouraging target for therapy to decrease the symptoms of graft-versus-host disease and enable mucosal regeneration.

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“…Neutropenia and thrombocytopenia occurred after the onset of other signs of GVHD. Eleven of the 12 patients died primarily as a result of sepsis [3].…”

Section: Introductionmentioning

confidence: 99%

Partial HLA matching and RH incompatibility resulting in graft versus host reaction and Evans syndrome after liver transplantation

et al. 2008

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We report a case of a 67-year-old male who underwent OLT from a deceased, sex-matched donor. Two months later he developed Evans syndrome and GVHD of the skin. Donor and recipient were matched for HLA-A and -B loci in the direction of rejection but mismatched in the direction of GVHD and fully mismatched for DRB1. These mismatches were permissible for engraftment of donor T-cells but led to GVHD. Chimerism appeared restricted to the T-cell compartment. In this case, partially matched passenger lymphocytes triggered a graft versus host reaction. In addition, alloantibodies caused cytopenias that improved after immunosuppression. HLA typing was critical in confirming this rare diagnosis and elucidating its cause. Recipients of solid organs from donors that are partially matched in the direction of rejection may need to be closely monitored for GVHD. Am. J. Hematol. 83:599-601, 2008. V

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Liver transplant-associated graft-versus-host disease

Cited by 170 publications

References 29 publications

Is ABO-Compatible but Non-Identical Intestinal Transplant Comparable to ABO-Identical Transplant? An Analysis of the UNOS Registry

Is ABO-Compatible but Non-Identical Intestinal Transplant Comparable to ABO-Identical Transplant? An Analysis of the UNOS Registry

Treatment of Liver Transplant Graft-Versus-Host Disease With Antibodies Against Tumor Necrosis Factor-α

Partial HLA matching and RH incompatibility resulting in graft versus host reaction and Evans syndrome after liver transplantation

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