Classical Tolerance Induction in Renal Transplantation — A Study of 11 Patients

Background

Transplantation biology has accumulated evidence of persistent mixed lymphohematopoietic chimerism (MLHC) after allogeneic hematopoietic stem cell (HSC) grafting, resulting in donor-specific tolerance to alloantigens in solid organ transplantation. We aimed to design a safe, non-toxic, non-myeloablative, high-dose allogeneic HSC transplantation (HSCT) protocol to achieve grafting with persistent low-level MLHC-associated, donor-specific tolerance across major histocompatibility complex barriers in our living related donor (LRD) renal allograft recipients.

Methods

HSC infusion into the portal, marrow and systemic circulation was performed in 11 LRD renal allograft recipients. All patients underwent a tolerance induction protocol (TIP), but two patients also had HSC infusion (n = 1) or donor renal tissue inoculation (n = 1) into the recipient thymus. All patients received low-dose immunosuppressive therapy for a mean of 1 year post-transplantation. Such therapy was discontinued for the following reasons: poor compliance; drug toxicity; and low-level chimerism, as tested across gendermismatched donors by a fluorescent in situ hybridization technique.

Results

All patients had prope tolerance with early, stable allograft function without any episodes of rejection, infection, or graft versus host disease. MLHC could be tested in seven patients, all of whom showed persistent MLHC (average 0.54%) in peripheral blood. All patients had stable allograft function for a mean of 32.6 months after the withdrawal of immunosuppressive therapy, and all had a normal clinical profile as tested by laboratory parameters.

Conclusion

Of 483 patients who underwent TIP using HSCT, weaning of immunosuppressive therapy was implemented in 165 (34.2%), and 11 patients developed successful MLHC-associated donor-specific tolerance.

Key words:  donor-specific transplantation tolerance , hematopoietic stem cell transplantation , mixed lymphohematopoietic chimerism , renal transplantation , tolerance induction protocol

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