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Blood, 15 March 2002, Vol. 99, No. 6, pp. 2235-2240
TRANSPLANTATION
Addition of a second, different allogeneic graft accelerates
white cell and platelet engraftment after T-cell-depleted bone marrow
transplantation
Benny J. Chen,
Xiuyu Cui, and
Nelson J. Chao
From the Bone Marrow Transplantation Program, Duke
University Medical Center, Durham, NC.
Significant delays in engraftment and lymphoid recovery are the 2 major challenges in cord blood transplantation. The cause for this
delay is presumed to be the low numbers of hematopoietic precursors
found in one unit of cord blood. One approach to increase the stem cell
doses could be to combine cord blood units from different donors
differing at the major histocompatibility complex (MHC). As a first
step toward this goal, the kinetics of hematologic engraftment and
immune reconstitution were compared between 1 unit
(2.5 × 106 cells) of T-cell-depleted bone marrow cells
from a single donor (C57BL/6 [H2b] or SJL/J
[H2s]) and 2 units from different donors (C57BL/6 + SJL/J) after transplantation into lethally irradiated (8.5 Gy) BALB/c
recipients (H2d). Addition of T-cell-depleted bone marrow
from an MHC-mismatched allogeneic donor doubled the white blood counts
compared with recipients of one single unit on days +10 and +14.
Similar effects were also observed on platelets. The beneficial effect
of additional cells on peripheral T-cell counts were first observed on
day +14. Cells both from donors (C57BL/6 and/or SJL/J) and
recipients (BALB/c) contributed to myeloid and lymphoid reconstitution.
The chimeras containing cells from 3 strains of mice were able to mount
a recall immune response. Our data suggest that combining stem cells
from MHC-mismatched allogeneic donors is feasible, that it has
beneficial effects on myeloid engraftment and T-cell phenotypic
recovery, and that the long-term stable mixed chimeras are
immunologically normal following T-cell-depleted bone marrow transplantation.

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