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Syngeneic and allogeneic bone marrow engraftment after total body
irradiation: dependence on dose, dose rate, and fractionation
JD Down, NJ Tarbell, HD Thames and PM Mauch
Department of Radiobiology, State University of Groningen, The Netherlands.
Murine bone marrow chimera models were used to assess the efficacy of host
total body irradiation (TBI) given at different doses, dose rates, and
fractionation schemes in providing for engraftment of syngeneic and
allogeneic bone marrow. B6-Hbbd congenic and LP mice, respectively, were
used as donors (10(7) bone marrow cells) for syngeneic and allogenic (H-2
compatible) transplantation in standard B6 recipients. Stable marrow
chimerism was determined from host and donor stem cell- derived hemoglobin
phenotypes (Hbbs and Hbbd) on gel electrophoresis at 3 months
posttransplant. Partial engraftment of syngeneic marrow was seen at single
doses as low as 2 Gy, with the donor component increasing steadily with
increasing TBI dose to a level of 100% at 7 Gy. Immunologic resistance of
the host appeared to prevent allogeneic engraftment until 5.5 Gy. A very
steep radiation dose response was then observed so that the level of
chimerism with 6 Gy and above became comparable with syngeneic engraftment.
Low dose rate (5 cGy minute-1) and fractionated TBI required higher total
doses for equivalent engraftment (radiation dose-sparing) in both syngeneic
and allogenic bone marrow transplantation. This displacement in the
dose-response curve on fractionation was seen with interfraction intervals
of 3 and 6 hours. A further dose-sparing effect was observed on extending
the interval to 18 and 24 hours, but only for allogeneic transplantation,
and may therefore be related to recovery of immune-mediated graft
resistance. The involvement of multiple target cell populations in
determining allogenic engraftment rendered the application of the
linear-quadratic model for radiation cell survival problematic in this
case. The recovery in dose when low dose rate and 6-hour interfraction
intervals were applied in either syngeneic or allogeneic BMT is consistent
with appreciable sub-lethal damage repair in the primitive self-renewing
stem cell population of the host marrow. These results contrast with the
poor repair capacity of the 11-day spleen colony- forming units (CFUs)
population after fractionated irradiation and support the notion that
ablation of early stem cells in the pre-CFUs compartment is essential for
long-term marrow engraftment.
Volume 77,
Issue 3,
pp. 661-669,
02/01/1991
Copyright © 1991 by The American Society of Hematology
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