Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: Full donor T-cell chimerism precedes alloimmune responses

Nonmyeloablative allogeneic stem cell transplantation has recently been exp lored as a safer alternative to conventional high-dose transplant regimens. Although a high incidence of mixed chimerism after nonmyeloablative proced ures has been reported, the exact kinetics of engrafting donor cells in spe cific cellular lineages has yet to be defined. We investigated lineage-spec ific chimerism in 15 patients receiving an allogeneic peripheral blood stem cell (PBSC) transplant from an HLA-identical (n = 14) or a 5/6 antigen-mat ched sibling donor after a preparative regimen of cyclophosphamide and flud arabine. Donor chimerism was assessed weekly in T lymphocytes and myeloid c ells by polymerase chain reaction (PCR) of minisatellite regions. Eight pat ients survived between 121 to 409 days after transplant. Ten of 14 patients surviving more than 30 days (71.4%) had delayed disease regression consist ent with a graft-versus-malignancy (GVM) effect. One patient rejected the t ransplant with subsequent recovery of autologous hematopoiesis. Hematologic al recovery was rapid (median, 11 days to greater than or equal to 500 neut rophils/mu L) and was initially predominantly recipient In origin. Donor my eloid chimerism gradually supplanted recipient hematopoiesis and became ful ly donor in all survivors by 200 days after transplantation. In contrast, T -cell engraftment was more rapid, with full chimerism in 7 patients by day 30 and in 6 further patients by day 200 after cyclosporine withdrawal and d onor lymphocyte infusion. Full donor T-cell engraftment preceded donor myel oid engraftment, acute graft-versus-host disease, and disease regression, c onsistent with a requirement for 100% donor T-cell chimerism for full expre ssion of the alloresponse. These results emphasize the importance of lineag e-specific chimerism analysis to successfully manipulate engraftment after nonmyeloablative allogeneic PBSC transplantation.