Spleen Transplant in Solid Organ Transplantation

Spleen Transplant as an Immunomodulatory Strategy in Solid Organ Transplantation

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.

Study Overview

• Status: Withdrawn
• Conditions: Kidney Transplant Rejection; Positive FCXM (T or B Cell Positive); Positive CDC Cross-Match (B Cell Positive); Kidney/Pancreas Transplant Rejection
• Intervention / Treatment: Procedure: Spleen Transplantation/Removal

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.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subjects must give written informed consent, and
• Subject is ≥ 18 years of age, and
• Subject is eligible for a kidney or simulateous kidney pancreas transplant, and
• Subjects are highly sensitized (cPRA 98-100%), and
• Subjects have a positive T flow crossmatch

Exclusion Criteria:

• Severe cardiac disease not amenable to intervention
• Clinical significant systemic infection within 30 days prior to transplant
• Life expectancy < 1 Year
• Positive pregnancy test performed < 1 week prior to enrollment or intention to plan a pregnancy in the following year
• Current drug or alcohol abuse
• Uncontrolled, severe psychiatric illness
• Combined transplantation of kidney and other organs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: highly sensitized patients with either a positive FCXM, or positive CDC cross-match; highly sensitized patients that receive a donor offer and have either a positive FCXM (T or B cell positive) or positive CDC cross-match (B cell positive); a positive CDC cross-match (T cell positive) remains a contraindication at this time.	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).
No Intervention: historical cohort of highly sensitized patients with a positive FCXM, or positive CDC cross-match; The control group, as comparison, will be an historical cohort of highly sensitized patients with positive flow (B and T) or positive B standard crossmatch, which received kidney transplant alone or simultaneous kidney and pancreas transplant and followed our standard protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of successful spleen transplantations/removals that can overcome the immunological barrier of positive T flow crossmatch and allow better results in kidney transplant recipients with high cPRA compared to the standard treatment.	Rate of successful spleen transplantations/removals that can overcome the immunological barrier of positive T flow crossmatch and allow better results in kidney transplant recipients with high cPRA compared to the standard treatment.	3 years
Rate of graft success	Rate of graft will be monitored and compared with a cohort of highly sensitized patient and positive T flow crossmatch, treated with our standard protocol.	3 years
Rate of patient survival	Rate of patient survival will be monitored and compared with a cohort of highly sensitized patient and positive T flow crossmatch, treated with our standard protocol.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of T flow crossmatch that becomes negative	Rate of T flow crossmatch that becomes negative, leading to less rejections and consequent improved kidney function.	3 years

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Investigators: Principal Investigator: Ivo Tzvetanov, MD, University of Illinois at Chicago

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2021
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: March 30, 2021
• First Submitted That Met QC Criteria: March 30, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 2021-0286 (Other Identifier: M D Anderson Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No sharing of IPD will be included at this time. We do plan to report our final results after deidentification.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No