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.