Effects of low-dose total-body irradiation on canine bone marrow function and canine lymphoma

Abstract

Low-dose total-body irradiation, 150 rad given in 10 fractions over 5 weeks, is a useful treatment modality for favorable-prognosis lymphomas. Little is known, however, about the effects of this regimen on normal bone marrow. Six healthy beagle dogs and 5 dogs of various breeds with lymphoma were treated with total-body irradiation. Three of the 5 lymphomatous dogs achieved remissions of limited duration. No changes in hemograms or in bone marrow cellularity (as assessed by needle marrow biopsies) could be detected during or after treatment. Bone marrow progenitor cells were studied weekly during treatment and for 4 weeks thereafter using in vitro growth assays for GM-CFC and M-CFC. These studies demonstrated significant reductions (P less than 0.001) of granulocyte and macrophage progenitor cells with subsequent recovery toward normal pre-irradiation and sham irradiation values. Two additional dogs were injected with sublethal doses of Salmonella typhosa endotoxin 2 weeks after completion of the irradiation regimen. Their bone marrow GM-CFC responses were dramatically blunted compared to nonirradiated controls whereas their peripheral leukocyte responses and serum CSF levels were comparable to nonirradiated controls. These studies suggest that total-body irradiation may induce bone marrow injury that may be clinically significant if patients so treated are further stressed by infections or myelosuppressive drugs.