Donor specific HLA antibody desensitization: Efficacy and experience at a single intestinal transplant center.
Hugo Kaneku1, Laura J. Wozniak2, Robert S. Venick2, Paul I. Terasaki3, Ronald W. Busuttil1, Sue V. McDiarmid2, Douglas G. Farmer1
1Surgery/Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States; 2Pediatric Gastroenterology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States; 3Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
Introduction: Donor-specific HLA antibody (DSA) is increasingly recognized as a risk factor for allograft rejection after intestinal transplantation (ITx). Removal of circulating DSA may benefit patients by reducing this risk. The aim of this study was to review our experience with desensitization.
Methods: An IRB approved prospective ITx database revealed that from 1991-2012, 104 patients underwent 127 ITx. DSA monitoring and treatment was instituted on a case-by-case basis in 2009. Any recipient with DSA+ was included in this analysis. Treatments used in these patients included: basiliximab, anti-thymocyte globulin (ATG), intravenous immunoglobulin (IVIG), plasmapheresis, rituximab, and bortezomib.
Results: There were 6 pts with DSA+ (67% Caucasian adults, 50% female, median age 31, and median follow-up 273 days). DSA was identified pre-ITx (3), at ITx (2), and late post-ITx (1). All pts are alive with a functioning graft currently. ITx types were: isolated intestinal transplant (33%), liver-intestine (33%), and multivisceral (33%). 67% of pts showed DSA against both class I and II; 33% showed DSA only against class II. The median MFI of the highest post-ITx class I DSA was 4585 and 6132 for class II DSA. The most common agent used to treat DSA was IVIG, which was used 9 times in 6 pts(2 to 12 doses/pt), followed by basiliximab in 6, ATG in 4, plasmapheresis in 3, rituximab in 3 and bortezomib in only 1. When only therapies using single agents were considered, IVIG showed to be the most effective treatment, with a mean MFI reduction of 68%, followed by plasmapheresis with a mean reduction of 39%. When multiple agents were evaluated, combinations including ATG and IVIG showed the largest MFI reduction (27% and 5%, respectively). Basiliximab showed a MFI reduction of 50% but because it was almost always used as induction agent at ITx, its efficacy in reducing DSA could be masked by antibody absorption due to the implantation of the allograft. Rituximab was always used in combination with other agents and it was the only agent associated with a MFI increase after its use (mean increase of 5%). Class I DSA showed a better response to treatment independent of the agent used as showed by a reduction of 44% compared to 33% for class II DSA. Serial ITx biopsies have been performed in all pts. 3 have not had evidence of acute rejection (ACR). 1 pt had early/reversible ACR; 1 had severe/atypical liver and intestinal ACR; 1 has no evidence of ACRbut has suspected chronic rejection.
Conclusions: DSA is thought to represent a major obstacle to successful ITx although data is limited. Due to this concern, we have initiated therapies aimed at reducing DSA. Therapies with IVIG alone or combinations including plasmapheresis and ATG may result in a more significant reduction of DSA and this may lower the risk of allograft rejection. With this early experience, rejection has been limited and more followup is needed.