Blood, Vol. 94 No. 9 (November 1), 1999:
pp. 3234-3241
Engraftment Kinetics After Nonmyeloablative Allogeneic Peripheral
Blood Stem Cell Transplantation: Full Donor T-Cell Chimerism
Precedes Alloimmune Responses
R. Childs,
E. Clave,
N. Contentin,
D. Jayasekera,
N. Hensel,
S. Leitman,
E.J. Read,
C. Carter,
E. Bahceci,
N.S. Young, and
A.J. Barrett
From the Hematology Branch, National Heart, Lung, and Blood
Institute, National Institutes of Health, Bethesda, MD.
Nonmyeloablative allogeneic stem cell transplantation has recently
been explored as a safer alternative to conventional high-dose transplant regimens. Although a high incidence of mixed chimerism after
nonmyeloablative procedures has been reported, the exact kinetics of
engrafting donor cells in specific cellular lineages has yet to be
defined. We investigated lineage-specific chimerism in 15 patients
receiving an allogeneic peripheral blood stem cell (PBSC) transplant
from an HLA-identical (n = 14) or a 5/6 antigen-matched sibling donor
after a preparative regimen of cyclophosphamide and fludarabine. Donor
chimerism was assessed weekly in T lymphocytes and myeloid cells by
polymerase chain reaction (PCR) of minisatellite regions. Eight
patients survived between 121 to 409 days after transplant. Ten of 14 patients surviving more than 30 days (71.4%) had delayed disease
regression consistent with a graft-versus-malignancy (GVM) effect. One
patient rejected the transplant with subsequent recovery of autologous
hematopoiesis. Hematological recovery was rapid (median, 11 days to
500 neutrophils/µL) and was initially predominantly recipient in origin. Donor myeloid chimerism gradually supplanted recipient hematopoiesis and became fully 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
donor lymphocyte infusion. Full donor T-cell engraftment preceded donor
myeloid engraftment, acute graft-versus-host disease, and disease
regression, consistent with a requirement for 100% donor T-cell
chimerism for full expression of the alloresponse. These results
emphasize the importance of lineage-specific chimerism analysis to
successfully manipulate engraftment after nonmyeloablative allogeneic
PBSC transplantation.
