NCT04827186

Spleen Transplant in Solid Organ Transplantation

Spleen Transplant as an Immunomodulatory Strategy in Solid Organ Transplantation

• Status: Withdrawn
• Phase: N/A
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of Illinois at Chicago · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

Although the notions that kidney transplantation is the treatment of choice for patients with end-stage renal disease and that simultaneous kidney and pancreas transplant is the only treatment able to restore euglycemia in patients with type 1 diabetes and selected patients with type 2 diabetes, are now consolidated, rates of transplantation remain low among potential candidates with high levels of preformed anti-HLA antibodies. Most of the data comes from the experience in kidney transplant but can be easily translated to pancreas transplant. Approximately 30% of patients on the transplant waiting list have evidence of sensitization in the form of alloantibodies, generated from exposure to previous transplants, blood transfusions, pregnancy, or other events. The presence of a panel-reactive antibody level of at least 80% (i.e. a high level of sensitization) creates difficulty in finding matched kidneys from compatible donors, leading to lower rates of transplantation in highly sensitized candidates compared to non-sensitized; the longer waiting times translates in an increased mortality rate. Despite the development of desensitization strategies and the advancement in immunosuppression protocols, it is apparent that transplanting these patients carries an increased risk of acute antibody mediated rejection; 25%-50% of transplants will have an early acute antibody mediated rejection . Most of these rejections can be successfully treated, but a high rate of transplant glomerulopathy and chronic antibody mediated rejection (AMR) leading to accelerated allograft failure is common.

Detailed description

Although the notions that kidney transplantation is the treatment of choice for patients with end-stage renal disease and that simultaneous kidney and pancreas transplant is the only treatment able to restore euglycemia in patients with type 1 diabetes and selected patients with type 2 diabetes, are now consolidated, rates of transplantation remain low among potential candidates with high levels of preformed anti-HLA antibodies. Most of the data comes from the experience in kidney transplant but can be easily translated to pancreas transplant. Approximately 30% of patients on the transplant waiting list have evidence of sensitization in the form of alloantibodies, generated from exposure to previous transplants, blood transfusions, pregnancy, or other events. The presence of a panel-reactive antibody level of at least 80% (i.e. a high level of sensitization) creates difficulty in finding matched kidneys from compatible donors, leading to lower rates of transplantation in highly sensitized candidates compared to non-sensitized; the longer waiting times translates in an increased mortality rate. Despite the development of desensitization strategies and the advancement in immunosuppression protocols, it is apparent that transplanting these patients carries an increased risk of acute antibody mediated rejection; 25%-50% of transplants will have an early acute antibody mediated rejection . Most of these rejections can be successfully treated, but a high rate of transplant glomerulopathy and chronic antibody mediated rejection (AMR) leading to accelerated allograft failure is common. This protocol has been designed to demonstrate the feasibility and efficacy of spleen transplant as a desensitization strategy for highly sensitized patients, potential candidates of kidney or simultaneous kidney pancreas transplant with (positive cross-match by flow cytometry (T or B) or B positive standard cross-match). After obtaining surgical and research consent at a pre-transplant clinic visit, patients will be receiving spleen transplant followed by spleen removal and kidney or simultaneous kidney pancreas transplant. Duration of the subject participation will begin upon consent and will last for one year after the surgery. Incidence of treated acute rejection (humoral or cellulo-mediated) within the first year (defined as biopsy proven or clinically indicated) will be determined. Graft and patient survival will be monitored and compared with a cohort of highly sensitized patients with similar immunological characteristics, treated with our standard protocol. DSA levels and post-transplant cross-match will be determined.

Conditions

• Kidney Transplant Rejection
• Positive FCXM (T or B Cell Positive)
• Positive CDC Cross-Match (B Cell Positive)
• Kidney/Pancreas Transplant Rejection

Interventions

Type	Name	Description
PROCEDURE	Spleen Transplantation/Removal	Spleen transplantation/removal and kidney transplantation alone or simultaneous kidney and pancreas transplantation in highly sensitized patients with either a positive flow cytometry cross-match (FCXM) (T or B cell positive) or a complement-dependent cytotoxicity (CDC) cross-match (B cell positive).

Timeline

• Start date: 2021-03-26
• Primary completion: 2024-04-01
• Completion: 2026-04-01
• First posted: 2021-04-01
• Last updated: 2024-02-13

Locations

1 site across 1 country: United States