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R Storb, RF Raff, FR Appelbaum, FW Schuening, BM Sandmaier, TC Graham and ED Thomas
Division of Clinical Research, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104.
In view of reported attempts at marrow grafting after nuclear accidents
with a broad range of radiation exposures, the present study explored the
total-body irradiation (TBI) conditions needed for engraftment in a canine
model by using marrow from DLA-identical littermates. Previous studies have
shown that such grafts are consistently successful when recipients are
exposed to 920 cGy of TBI delivered at a rate of 7 cGy/min from opposing
dual cobalt sources. The present TBI doses were all in the lethal range.
Five dogs were administered 450 cGy; seven dogs, 600 cGy; five dogs, 700
cGy; and five dogs, 800 cGy of TBI administered at 7 cGy/min. They received
a median of 3.3 x 10(8) marrow cells/kg intravenously after completion of
radiation. Results showed transient allogeneic marrow engraftment in all
dogs administered the lowest dose of TBI studied (450 cGy). Importantly,
transient grafts permitted four of five dogs to live long enough for
autologous marrow recovery to occur. At increasing radiation doses, 600,
700, and 800 cGy, the risk of graft failure lessened, with 3 of 7, 2 of 5,
and 1 of 5 dogs, respectively, showing graft rejection. Fewer dogs survived
with autologous marrow recovery, and more showed sustained allogeneic
engraftment (4 of 7, 3 of 5, and 4 of 5 dogs, respectively). We conclude
that DLA-identical littermate marrow grafts are beneficial in the setting
of otherwise lethal radiation exposures, with most dogs either experiencing
sustained allogeneic engraftment or surviving with autologous marrow
recovery due to the extended support provided by a transient allogeneic
graft.
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| Copyright © 1988 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||