2017 - CIRTA

1- Rejection of the Intestine Allograft

15.10 - Donor specific antibodies in primary liver-free visceral allograft recipients; anti-B cell therapy, immunologic monitoring, and outcome measures

Presenter: Masato, Fujiki, Cleveland, United States
Authors: Masato Fujiki, Mohammed Osman, Aiwen Zhang, Koji Hashimoto, Ajai Khanna, Guilherme Costa, Kareem Abu-Elmagd

Donor specific antibodies in primary liver-free visceral allograft recipients; anti-B cell therapy, immunologic monitoring, and outcome measures

Masato Fujiki1, Mohammed Osman1, Aiwen Zhang2, Koji Hashimoto1, Ajai Khanna1, Guilherme Costa1, Kareem Abu-Elmagd1.

1Center of Gut Rehabilitation and Transplantation, Cleveland Clinic, Cleveland, OH, United States; 2Allogen Laboratories, Cleveland Clinic, Cleveland, OH, United States

Introduction: Pre-formed donor specific antibody (DSA) especially with persistent level after transplant has a significant impact on rejection and longevity of visceral allograft. We sought a strategy to alleviate the burden of persistent DSA to liver-free visceral allografts using anti-B cell therapy and prospective DSA monitoring.

Methods: Virtual cross-match was utilized to perform transplantation with no preformed DSA. However, in patients with PRA of 98-100%, presence of preformed DSA was nearly inevitable. We used anti-B cell induction in primary adult recipients of liver-free visceral allografts with strong preformed DSA (>4000 MFI). Anti-B cell therapy consisted of pretreatment with IVIG, alemtuzumab and bortezomib, and post-transplant treatment with bortezomib or rituximab. Maintenance immunosuppression was tacrolimus based. Prospective DSA monitoring was performed with Luminex single-antigen assay. 

Results: From 2012-2016, 44 adult patients underwent primary liver-free visceral transplants with a mean age of 37±17 years. Thirty-two (73%) patients with median PRA of 0%(0-49%) received suitable allografts with no preformed DSA (group 1). Twelve patients with median PRA of 100% (39-100%) received visceral transplantation with median of 3.5 (range; 1-6) preformed DSA. Of them, 8 patients were treated with anti-B cell therapy (group 2). The remaining 4 patients did not receive anti-B cell therapy because of weak DSA (<4000 MFI) in 2, history of lymphoma in 1, and expected extensiveness of transplant surgery in 1 patient.

With anti-B cell therapy, 5 (42%) of 11 strong preformed DSAs harbored 6 months following transplantation with reduced MFI, but no additional treatment was performed for persistent DSA.

De-novo DSA was detected in 8 (29%) patients in group1 and 4 (57%) patients in group 2. Three detections were at time of acute cellular rejection. All but one de-novo DSA disappeared within 1 month.

Despite of persistent preformed DSA in group 2, cumulative rejection rate, and rejection-related graft loss rate was comparable between the groups. Suboptimal graft survival of group 2 was due to graft loss from surgical complication and fungal infection.

Conclusions: With anti-B cell induction, persistent pre-formed DSA did not increase the rejection rate in primary liver-free visceral allograft recipients. However, improvement of graft survival in these patients remains a challenge.


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