Presented at:
2005 American Transplant Congress, Seattle, WA, May 2005.
Combined kidney and bone marrow transplantation for induction of mixed chimerism and renal allograft tolerance in HLA matched and mismatched recipients
Kawai T, Sachs DH, Spitzer T, Tolkoff-Rubin N, Delmonico F, Saidman S, Shaffer J, Williams W, Dey B, McAfee S, Ko D, Hertl M, Goes N, Wong W, Fishman JA, Colvin RB, Sykes M, Cosimi B.
University of Miami, Miami, FL
BACKGROUND: We developed a clinically applicable non-myeloablative preparative regimen for induction of mixed hematopoietic chimerism and renal allograft tolerance, which has now been administered to nine subjects with end stage renal disease (ESRD).
METHODS: Six subjects with ESRD secondary to multiple myeloma received combined kidney and bone marrow transplantation (CKBMT) from HLA identical siblings. The preparative regimen consisted of cyclophosphamide (60mg/kg/d x 2), thymic irradiation, equine anti-thymocyte globulin (ATG) and cyclosporine. Three ESRD subjects without underlying malignancy received CKBMT from HLA haplotype mismatched donors. For these individuals, ATG was replaced by anti-CD2 monoclonal antibody.
RESULTS: All six subjects with myeloma developed mixed chimerism. Five of these patients have shown no rejection of their renal allografts for up to 6 years. One patient showed evidence of rejection requiring resumption of immunosuppression at 3 months and two required minimum immunosuppression for chronic GVHD. Three of the six patients have achieved a sustained complete remission of their myeloma. All three recipients of HLA mismatched CKBMT developed transient chimerism. Immunosuppressants were successfully discontinued in two, despite suspected earlier rejection in one. Renal allograft function and protocol biopsies plus in-vitro assay results have been consistent with an immunologically tolerant state in these two individual. The third subject developed early irreversible humoral rejection and required retransplantation with conventional immunosuppression.
CONCLUSIONS: Renal allograft tolerance has been induced successfully in HLA matched and mismatched recipients by CKBMT after a non-myeloablative conditioning regimen. We are now entering patients into a revised protocol to address the humoral rejection observed.