Purpose: Over the last 12 years we have studied the safety and efficacy of a clinical tolerance induction protocol using hematopoietic cell transplantation in combination with kidney transplantation.
Methods: Twenty-nine patients, 16 men and 13 women, age range 22 to 61 years, have undergone HLA-mismatched (n=10) and matched (n=19) living donor kidney transplantation followed by conditioning with 10 doses of total lymphoid irradiation and 5 doses of antithymocyte globulin. This was followed by infusion of purified donor CD34+ hematopoietic progenitor cells and T cells on day 11 post-kidney transplant.
Results: There have been no grafts lost to rejection and all showed excellent function at last observation, three months to 12 years following transplantation. Median follow-up was 4.1 years. Fifteen of the 29 were withdrawn from immunosuppressive drugs, and the remainder are either undergoing drug tapering or did not meet drug withdrawal criteria that included engraftment of donor hematopoietic cells, and lack of rejection episodes and graft versus host disease. Patients successfully withdrawn from drugs have been followed for up to five years. Two mismatched patients patients had a rejection episode after withdrawal and were returned to maintenance immunosuppressive drug therapy. Five patients required hospital readmission within the first year, one for neutropenic fever, one for ureteral stricture, one for pyleonephritis and 2 for acute rejection. One patient with known coronary artery disease died suddenly during vigorous exercise at 3.5 years after transplantation and 3 years off immunosuppressive drug therapy. Death-censored graft survival is 100%. Unadjusted 10-year graft survival is 96%, versus 60% in our combined conventionally treated HLA-matched and mismatched living donor transplant recipients, and versus 78% in in our conventionally treated HLA-matched recipients.
Conclusion: Transplantation under this protocol showed a low incidence of serious adverse events, and long-term graft survival has been excellent and superior to that in conventionally treated patients, without graft loss to rejection either before or after immunosuppressive drug withdrawal.
To cite this abstract in AMA style:Scandling J, Busque S, Shori A, Dejbakhsh-Jones S, Shizuru J, Lowsky R, Benike C, Engleman E, Strober S. Uniform Long-Term Graft Survival in a Clincial Trial of the Induction of Tolerance to Kidney Transplants [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/uniform-long-term-graft-survival-in-a-clincial-trial-of-the-induction-of-tolerance-to-kidney-transplants/. Accessed October 31, 2020.
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