HLA identical non-chimeric and HLA disparate chimeric renal transplant tolerance.

HLA identical non-chimeric and HLA disparate chimeric renal transplant tolerance. Clin Transpl. 2013;:145-56 Authors: Leventhal JR, Mathew JM, Ildstad S, Salomon DR, Kurian SM, Suthanthiran M, Tambur A, Friedewald J, Gallon L, Charette J, Levitsky J, Kanwar Y, Abecassis M, Miller J Abstract In this chapter, we describe studies on non-chimeric human leukocyte antigen (HLA) identical tolerance and chimeric HLA disparate tolerance brought about by infusions of hematopoietic stem cells from the renal donor (DHSC). In our HLA identical series, 4 DHSC infusions were administered during the first 9 months posttransplant in a highly immunoregulatory environment using alemtuzumab induction and rapid conversion from early tacrolimus to mycophenolate and sirolimus. This resulted in the generation of recipient T regulatory cells accompanied by genomic indicators, but only transient chimerism. Seven of the first 12 recipients have been immunosuppression-free between 1 1/2 - 4 years with transplant biopsies free of rejection one year after immunosuppression withdrawal. The HLAdisparate group was treated by non-myeloablative conditioning consisting of: 200cGy whole body irradiation; fludarabine; cyclophosphamide; and, perioperative infusion of a product termed FCRx that contained DHSC, T cells, and a unique fraction of bone marrow derived CD8+TCR-alphabeta-negative cells. Five of the first 8 subjects became 100% chimeric in the peripheral blood and...
Source: Clinical Transplants - Category: Transplant Surgery Tags: Clin Transpl Source Type: research