Dataset Information

Tacrolimus to Belatacept Conversion Following Hand Transplantation: A Case Report.

ABSTRACT: Vascularized composite allotransplantation (VCA) has emerged as a viable limb replacement strategy for selected patients with upper limb amputation. However, allograft rejection has been seen in essentially all reported VCA recipients indicating a requirement for substantial immunosuppressive therapy. Calcineurin inhibitors have served as the centerpiece agent in all reported cases, and CNI-associated complications associated with the broad therapeutic effects and side effects of calcineurin inhibitors have been similarly common. Recently, belatacept has been approved as a calcineurin inhibitor replacement in kidney transplantation, but to date, its use in VCA has not been reported. Herein, we report on the case of a hand transplant recipient who developed recurrent acute rejection with alloantibody formation and concomitant calcineurin inhibitor nephrotoxicity, all of which resolved upon conversion from a maintenance regimen of tacrolimus, mycophenolate mofetil and steroids to belatacept and sirolimus. This case indicates that belatacept may be a reasonable maintenance immunosuppressive alternative for use in VCA, providing sufficient prophylaxis from rejection with a reduced side effect profile, the latter being particularly relevant for nonlife threatening conditions typically treated by VCA.

SUBMITTER: Cendales L

PROVIDER: S-EPMC4836872 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tacrolimus to Belatacept Conversion Following Hand Transplantation: A Case Report.

Cendales L L Bray R R Gebel H H Brewster L L Elbein R R Farthing D D Song M M Parker D D Stillman A A Pearson T T Kirk A D AD

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20150313 8

Vascularized composite allotransplantation (VCA) has emerged as a viable limb replacement strategy for selected patients with upper limb amputation. However, allograft rejection has been seen in essentially all reported VCA recipients indicating a requirement for substantial immunosuppressive therapy. Calcineurin inhibitors have served as the centerpiece agent in all reported cases, and CNI-associated complications associated with the broad therapeutic effects and side effects of calcineurin inh ...[more]

PMID: 25773260

Similar Datasets

Project description:BackgroundRecent advancements in molecularly targeted chemotherapy for stage IV colorectal cancer have enabled the possibility of complete resection in primary colorectal cancer, which often involves distant liver or lung metastases, by aggressive surgical resection followed by multi-combination chemotherapy.Case descriptionA 73-year-old man treated previously for hyperuricemia, hypertension, and a dissecting abdominal aortic aneurysm was referred to us after an incidental finding of multiple liver masses on abdominal ultrasound during follow-up for the aneurysm. A detailed examination by contrast-enhanced computed tomography revealed a ring-enhancing mass larger than 5 cm in diameter in segment 3 of the liver and more than 6 low-density areas with total diameter of 1 to 2 cm in both lobes. A barium enema examination revealed a Borrmann type 2 lesion covering two-thirds of the circumference of the colon, with a 5-cm major axis in the rectosigmoid colon. Biopsy revealed a well-differentiated adenocarcinoma. The patient was diagnosed with stage IV rectal cancer. Because there was no intestinal obstruction, we administered 9 cycles of bevacizumab with capecitabine and oxaliplatin as chemotherapy. Subsequent diagnostic imaging revealed the metastatic lesions in liver segment 3 had reduced to 2 low-density areas with a diameter of 8 mm, and the other hepatic metastases had disappeared; the main tumor had flattened and shrunk. Therefore, we used hand-assisted laparoscopic surgery (HALS) to perform anterior resection of the rectosigmoid colon and partial resection of liver segment 3 as conversion therapy. The patient was discharged 10 days after surgery. The rectal lesion was a well-differentiated adenocarcinoma with a depth of invasion of p-MP and a spread of L0, V0, and pN0. The partial hepatectomy did not indicate viable cancer cells; only necrotic, lysed tissue was observed. Postoperative chemotherapy involved 4 cycles of bevacizumab with capecitabine and oxaliplatin. At more than 42 months postoperatively, no metastasis or recurrence has been observed.ConclusionsThis rare case demonstrates that conversion surgery can be a viable option following systemic chemotherapy in patients with advanced colon cancer and H3 liver metastases.

Project description:BackgroundCostimulatory blockade provides new therapeutic opportunities for ensuring the long-term survival of kidney grafts. The adoption of the novel immunosuppressant Belatacept has been limited, partly due to concerns regarding higher rates and grades of acute rejection in clinical trials. In this study, we hypothesized that a combined therapy, Belatacept combined with BTLA overexpression, may effectively attenuate acute rejection after kidney transplantation.Materials and methodsThe rat kidney transplantation model was used to investigate graft rejection in single and combined therapy. Graft function was analyzed by detecting serum creatinine. Pathological staining was used to observe histological changes in grafts. The expression of T cells was observed by immunohistochemistry and flow cytometry. In vitro, we constructed an antigen-stimulated immune response by mixed lymphocyte culture, treated with or without Belatacept and BTLA-overexpression adenovirus, to observe the proliferation of receptor cells and the expression of cytokines. In addition, western blot and qRT-PCR analyses were performed to evaluate the expression of CTLA-4 and BTLA at various time points during the immune response.ResultsIn rat models, combined therapy reduced the serum creatinine levels and prolonged graft survival compared to single therapy and control groups. Mixed acute rejection was shown in the allogeneic group and inhibited by combination treatment. Belatacept reduced the production of DSA and the deposition of C4d in grafts. Belatacept combined with BTLA overexpression downregulated the secretion of IL-2 and IFN-γ, as well as increasing IL-4 and IL-10 expression. We also found that Belatacept combined with BTLA overexpression inhibited the proliferation of spleen lymphocytes. The duration of the elevated expression levels of CTLA-4 and BTLA differentially affected the immune response.ConclusionBelatacept combined with BTLA overexpression attenuated acute rejection after kidney transplantation and prolonged kidney graft survival, which suggests a new approach for the optimization of early immunosuppression after kidney transplantation.

Dataset Information

Tacrolimus to Belatacept Conversion Following Hand Transplantation: A Case Report.

Publications

Tacrolimus to Belatacept Conversion Following Hand Transplantation: A Case Report.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets