Delayed immune tolerance intentionally achieved years after 2-haplotype matched kidney transplantation

In transplant-naïve patients, intentional immune tolerance has been achieved by combining kidney transplantation with donor stem cell infusion within 2 weeks of the kidney transplant operation. Yet, many patients with a preexisting transplant also desire the opportunity to be freed from the burdens of chronic immunosuppression. In this series (n = 6), healthy, stable human leukocyte antigen-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 and underwent immunosuppression withdrawal, and none of the patients developed graft-vs-host disease. At the time of publication, 5 patients are immunosuppression free, with 1 patient tolerant for more than 3 years. Of interest, all patients had improved allograft function once removed from immunosuppression. However, 1 patient developed rejection after being off immunosuppression for 15 months, requiring reinitiation of maintenance immunosuppression. Although limited to human leukocyte antigen-matched siblings, we report the first successful series of intentional delayed immune tolerance achieved years after their kidney transplant operation.