Induction of donor-type chimerism in murine recipients of bone marrow
allografts by different radiation regimens currently used in treatment of
leukemia patients
O Salomon, T Lapidot, A Terenzi, I Lubin, I Rabi and Y Reisner
Department of Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Three radiation protocols currently used in treatment of leukemia patients
before bone marrow transplantation (BMT) were investigated in a murine
model (C57BL/6----C3H/HeJ) for BM allograft rejection. These include (a) a
single dose of total body irradiation (8.5 Gy TBI delivered at a dose rate
of 0.2 Gy/min), (b) fractionated TBI (12 Gy administered in six fractions,
2 Gy twice a day in 3 days, delivered at a dose rate of 0.1 Gy/min, and (c)
hyperfractionated TBI (14.4 Gy administered in 12 fractions, 1.2 Gy three
times a day in 3 days, delivered at a dose rate of 0.1 Gy/min). Donor-type
chimerism 6 to 8 weeks after BMT and hematologic reconstitution on day 12
after BMT found in these groups were compared with results obtained in mice
conditioned with 8 Gy TBI delivered at a dose rate of 0.67 Gy/min,
routinely used in this murine model. The results in both parameters showed
a marked advantage for the single dose 8.5 Gy TBI over all the other
treatments. This advantage was found to be equivalent to three- to fourfold
increment in the BM inoculum when compared with hyperfractionated
radiation, which afforded the least favorable conditions for development of
donor-type chimerism. The fractionated radiation protocol was equivalent in
its efficacy to results obtained in mice irradiated by single-dose 8 Gy
TBI, both of which afforded a smaller but not significant advantage over
the hyperfractionated protocol. This model was also used to test the effect
of radiation dose rate on the development of donor-type chimerism. A
significant enhancement was found after an increase in dose rate from 0.1
to 0.7 Gy/min. Further enhancement could be achieved when the dose rate was
increased to 1.3 Gy/min, but survival at this high dose rate was reduced.
These results demonstrated indirectly that dose rate affects the expression
of host-type pluripotent stem cells, the progeny of which appear 3 to 6
weeks after treatment with 8 Gy TBI delivered at a dose rate of 0.1 Gy/min,
but which are eradicated if radiation is delivered at a dose rate of 1.3
Gy/min.
Volume 76,
Issue 9,
pp. 1872-1878,
11/01/1990
Copyright © 1990 by The American Society of Hematology
