Induction of donor-type chimerism in murine recipients of bone marrow allografts by different radiation regimens currently used in treatment of leukemia patients
- 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.
- OSTI ID:
- 6320300
- Journal Information:
- Blood (Journal of Hematology); (USA), Vol. 76:9; ISSN 0006-4971
- Country of Publication:
- United States
- Language:
- English
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BONE MARROW CELLS
TRANSPLANTS
IMMUNITY
RADIOINDUCTION
BIOLOGICAL MODELS
EXPERIMENTAL NEOPLASMS
FRACTIONATED IRRADIATION
LEUKEMIA
LYMPHOCYTES
MICE
RADIATION CHIMERAS
SURVIVAL TIME
WHOLE-BODY IRRADIATION
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CHIMERAS
CONNECTIVE TISSUE CELLS
DISEASES
EXTERNAL IRRADIATION
HEMIC DISEASES
IMMUNE SYSTEM DISEASES
IRRADIATION
LEUKOCYTES
MAMMALS
MATERIALS
MOSAICISM
NEOPLASMS
RODENTS
SOMATIC CELLS
VERTEBRATES
560152* - Radiation Effects on Animals- Animals