Delayed immune tolerance intentionally achieved years after two-haplotype matched kidney transplantation

In transplant naïve patients, intentional immune tolerance has been achieved by combining kidney transplantation jointly with donor stem cell infusion within two weeks of the kidney transplant operation. Yet, many patients with a pre-existing transplant also desire the opportunity to be freed from the burdens of chronic immunosuppression. In this series (n=6) healthy, stable HLA matched kidney transplant recipients intentionally underwent nonmyeloablative conditioning and hematopoietic stem cell transplantation from their previous donor to achieve tolerance. All participants achieved engraftment and durable mixed donor chimerism, immunosuppression withdrawal, and none of the patients developed graft versus host disease. At the time of publication five patients are immunosuppression-free, with one patient tolerant for over 3 years. Of interest, all patients had improved allograft function once removed from immunosuppression. However, one patient developed rejection after being off immunosuppression for 15 months, requiring reinitiation of maintenance immunosuppression. While limited to HLA matched siblings, we report the first successful series of intentional delayed immune tolerance achieved years after their kidney transplant operation.