Graft versus host disease after multivisceral transplantation: A UK center experience and update on management

Abstract

Graft versus host disease (GVHD) following transplantation of an intestine-containing graft occurs more frequently than with other solid organ transplants and is known to have a poor outcome. The presentation differs from other solid organ transplants, as the gastrointestinal tract is not involved following intestinal transplant. Diagnosis is based on clinical symptoms arising due to native tissue damage and the detection of donor T lymphocytes in circulating blood (T-cell chimerism). The ideal treatment strategy has not been defined, with advocates for both increased and decreased immunosuppression. We reviewed all cases of GVHD in an adult intestinal transplant center in the United Kingdom and report on management strategies of five cases and methods of detecting T-cell chimerism. The practice in our center has evolved with experience. The first two patients received an increase in immunosuppression, which was only successful in one case. Subsequently, reducing immunosuppression has been more effective. However, patients with bone marrow involvement have a poorer prognosis. We demonstrate successful treatment of GVHD after multivisceral transplant with a reduction in immunosuppression. This should be followed by vigilant graft surveillance and serial monitoring of the level of T-cell chimerism, with reintroduction of immunosuppression at the earliest sign of graft dysfunction.

Extracorporeal photopheresis: A case of graft‐versus‐host‐disease and hemophagocytic lymphohistiocytosis following liver transplantation

“…GVHD was unresponsive to steroids, multiple immunosuppressive agents, biologics, in addition to ECP. In adults, ECP use has been reported in GVHD with good outcomes following multivisceral organ transplantation, 13 liver transplantation, 14 and simultaneous pancreas‐kidney transplantation 15 . Houston et al reported the use of ECP in a 28‐year‐old man on Days 62 and 67 post multivisceral organ transplantation with reduction in chimerism over 9 days; however, the patient died of sepsis on Day 73 16 .…”

Current Advances in Graft-Versus-Host Disease After Intestinal Transplantation

“…Therapeutic targets that warrant further investigation include IL-6, rho-associated coiled-coil-containing protein kinase-2 (ROCK2), Bruton's tyrosine kinase, and colony-stimulating factor 1 receptor (CSF-1R). 82,[89][90][91][92][93] GvHD in ITx poses unique challenges in early detection, diagnosis, and treatment. Diagnosis rests on the combination of clinical and histopathological findings in ≥1 target organ systems including the skin, native intestine, liver, respiratory tract, and bone marrow, among others.…”

“…88 Multiple studies have demonstrated the efficacy of ECP in refractory GvHD after HSCT; however, limited studies have shown the effectiveness of ECP in GvHD after ITx. 77,85,86,89 Merola et al 77 described 2 case reports demonstrating the potential benefits from ECP. Decreased chimerism in both patients, in addition to full recovery in one patient, was described.…”

“…Decreased chimerism in both patients, in addition to full recovery in one patient, was described. 85,86 Sharkey et al 89 described 2 case reports in which ECP was used successfully in adjunct to steroids, and decreased immunosuppression suggesting the possibility of its use in a combined therapeutic approach.…”

Histopathologic and immunophenotypic features of cutaneous solid organ transplant‐associated graft‐vs‐host disease: Comparison with acute hematopoietic cell transplant‐associated graft‐vs‐host disease and cutaneous drug eruption

“…It occurs when immunocompetent lymphocytes from the transplanted organ mount an immune response against host antigens, causing cytotoxic damage to cells. Small bowel and multi‐visceral transplants, which contain a relatively large burden of donor lymphoid tissue, have the highest incidence of GVHD 2,3 . However, it is most commonly seen in the setting of liver transplantation given the higher frequency of this procedure 1,4 .…”