Presented at:
9th Basic Science Symposium of the International Transplantation Society, La Baule , France , June 19-23, 2005.
Comparative chimerism levels in cadaver and living related donor whole bone marrow infused kidney recipients vs. a 2X stem cell-infused recipient treated with alemtuzumab
Garcia-Morales RO, Esquenazi V, Kleiner G, Cirocco RE, Burke GW, Carreno MR, Ciancio G, Kenyon NS, Ricordi C, Tzakis AG, Shariatmadar S, Miller J.
University of Miami, Miami, FL
Introduction: The role of bone marrow-derived cell chimerism in organ transplant recipients is controversial, especially if only small numbers of such cells are present (microchimerism).
Methods: We have followed the persistence of multilineage microchimerism in peripheral blood of cadaver (CAD) and living-related (LRD) kidney transplant recipients who also received perioperative (whole) donor bone marrow cells (DBMC). We compared these up to one year postoperatively with two recipients (NR and RO) who received donor hematopoietic stem cells (DHSC). In contrast with patient NR, patient RO with a (new) alemutuzumab induction protocol, the most recent DHSC recipient, received perioperative DHSC and a DHSC boost at 3 months postoperatively. The following (earlier series) DBMC and (newer) DHSC dosages were administered:
Unmodified donor-specific cadaveric DBMC perioperatively, 7.01±1.9x10 8 cells/kg (N=63); unmodified LRD DBMC perioperatively, 1.8±1.9x10 8 cells/kg (N=47); patient NR, DHSC 1X perioperatively, 6.75x10 6 cells/kg; patient RO, DHSC in two infusions, i.e., perioperatively and boost three months later, 8.6x10 6 cells/kg.
Results: There were markedly higher and sustained levels of (macro)chimerism by PCR-Flow analysis after the boost in the percentages of donor cell subsets (especially of CD34+ stem cells) when the two-dose DHSC alemtuzumab-treated patient RO (rejection-free) was compared with all the rest (also rejection-free). Patient RO had the following donor chimeric cell percentages in peripheral blood at 1-yr: Total lymphoid, 1.6%; CD34+, 9.1%; CD3+, 3.8%. The latter two values were 100X and 30X higher, respectively, than in any previous group. In contrast, non-DBMC-infused recipients transplanted during the same period had no peripheral blood donor cell chimerism.
Conclusion: A new two-dose (boost) stem cell infusion protocol, in conjunction with alemtuzumab induction treatment (with tacrolimus converted to sirolimus and Cellcept® in half-doses, but no steroids), may allow further insight into the ability to reduce immunosuppressive dosing as a result of long-term macrochimerism finally developing.