Operational tolerance after pediatric composite liver‐pancreas‐intestine transplantation following severe graft‐versus‐host disease

Abstract

Background While operational tolerance has been previously described in isolated intestinal transplant, reports of this phenomenon in combined liver‐intestine transplant are lacking. Case Description We detail a unique case of a patient who received a composite allograft including liver, pancreas, and small bowel due to short gut syndrome secondary to gastroschisis complicated by volvulus. The indication for transplantation was permanent dependence on total parenteral nutrition, end‐stage liver disease, recurrent sepsis, and persistent stomal variceal hemorrhage. The patient developed severe graft‐versus‐host disease with grade 3 skin involvement, ophthalmic, and pulmonary involvement with 53% donor T‐cell chimerism. She required aggressive therapy including high‐dose methylprednisolone, rituximab, cyclophosphamide, and alemtuzumab. Due to infection concerns following depletion of her lymphocytes, immunosuppression was discontinued with close surveillance of her allograft. Nearly 10 years later, the patient has continued off all immunosuppression without evidence of rejection or graft dysfunction and demonstrates immunocompetence with normal functional immune assays and development of appropriate live vaccination titers. Conclusion This report of operational tolerance following pediatric composite liver‐pancreas‐intestine transplantation provides evidence that the complex immunologic balance in intestinal transplantation may on rare occasions favor immunosuppression reduction or even discontinuation. Future trials of immunosuppression minimization in this population may be warranted.

Operational tolerance after intestine re‐transplantation in childhood and immunological correlates. Case report and review

“…Table 2 summarizes the salient features and the variable path to operational tolerance in the three IT recipients from three centers. 1,2 Immunosuppression withdrawal after primary IT occurred following treatment of severe GVHD despite detectable DSA in both previous reports. In contrast, the recipient at our center achieved tolerance after a liver-inclusive multivisceral allograft, after loss of the primary intestine allograft due to refractory rejection.…”

“…1,9 Similarly, serologic responses to vaccine targets or EBV and CMV were also intact. 2 Interestingly, DSA, a hallmark of donor-specific humoral response were present in both previously reported tolerant IT recipients. 1,2 This finding contrasts with previous studies in operationally tolerant liver recipients in whom DSA were absent.…”

“…2 Interestingly, DSA, a hallmark of donor-specific humoral response were present in both previously reported tolerant IT recipients. 1,2 This finding contrasts with previous studies in operationally tolerant liver recipients in whom DSA were absent. 13 A key difference maybe the higher sensitivity for detection of DSA with single HLA antigen-coated beads in the more recent versions of the DSA assays than the earlier study in liver recipients.…”

“…Cellular immune responses to common post‐transplant infections such as EBV and CMV were intact 1,9 . Similarly, serologic responses to vaccine targets or EBV and CMV were also intact 2 . Interestingly, DSA, a hallmark of donor‐specific humoral response were present in both previously reported tolerant IT recipients 1,2 .…”

“…Table 2 summarizes the salient features and the variable path to operational tolerance in the three IT recipients from three centers 1,2 . Immunosuppression withdrawal after primary IT occurred following treatment of severe GVHD despite detectable DSA in both previous reports.…”