DONOR BONE MARROW, CHIMERISM, AND KIDNEY TRANSPLANTATION.

Abstract

422 The role of post-operative specific donor bone marrow cell (DBMC) infusion in solid organ transplantation and the consequent DBMC chimerism established in the recipient has been controversial. We have continued to follow 58 recipients of cadaver donor kidneys transplanted between September 1994 and July 1997 (actuarial followup between 6 and 40 months) who received DBMC, compared with 177 controls given equivalent immunosuppression (consisting of OKT3 induction, tacrolimus, mycophenolate mofetil, and methylprednisolone), but no DBMC. Patient and graft survival in the DBMC-infused group at 40 months was 93% and 93% vs. 96% and 92% in the controls. There were 7/58 biopsy-proven acute rejection episodes (AR) in the DBMC-infused group and 38/177 in the controls (p=.114). There were 1/58 patients with biopsy-proven chronic rejection in the DBMC-infused group vs. 32/177 in the controls (p=.002). Dosaging of tacrolimus and methylprednisolone at 2-years was 0.14±3.9 mg/kg and 0.08±0.04 mg/kg, respectively (n=18), vs. 0.14±0.08 mg/kg and 0.09±0.03 mg/kg, respectively, in the controls (n=29)(p=N.S.). Tacrolimus trough levels were 8.72±3.4 ng/ml in the DBMC-infused group vs. 10.14±3.9 ng/ml in the controls (p=N.S.). PCR-Flow assays of bone marrow aspirates of DBMC-infused recipients were performed sequentially (n=29). In patients who did not have previous AR there was an increase between 1- and 2-years post-operatively in donor total, CD3+, and CD34+ (gated) lymphoid cells from 0.54±0.11, 0.20±0.06, and 0.22±0.05, respectively, to 0.93±0.19, 0.43±0.10, and 0.35±0.07. That is, there was a virtual two-fold increase in PCR-Flow quantitative chimerism. In the DBMC-infused group, early AR was associated with a five-fold decrease in chimerism in bone marrow aspirates at 2-years compared with those patients who did not have AR. In the peripheral blood, donor PCR-Flow chimerism values had decreased between 1-year and 2-years, so that they were an order of magnitude lower in the blood than in the bone marrow. Although other compartments have not been studied as yet, chimeric bone marrow of DBMC-infused recipients appeared to have greater in vitro autoregulatory effects than did marrow of the controls at 2-years post-operatively (i.e., in lymphoproliferative responses to viral protein antigens) (p=<0.05). These clinical and ex vivo observations lend support to the proposal that DBMC infusions and consequent chimerism are a cause of immunoregulation favoring kidney transplant survival.