DLA-IDENTICAL BONE-MARROW GRAFTS AFTER LOW-DOSE TOTAL-BODY IRRADIATION - THE EFFECT OF CANINE RECOMBINANT HEMATOPOIETIC GROWTH-FACTORS

Previous studies found that bone marrow (BM) allografts from DLA-ident ical littermates resulted in survival of two thirds of recipient dogs after otherwise lethal doses of 450 to 600 cGy of total body irradiati on (TBI) because of successful allografts or autologous recovery after rejection of the allografts. The current study asked whether survival could be further improved by treating allograft recipients with recom binant canine granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), or G-CSF/SCF. Of 21 dogs, 14 (67%) receiving allografts but no growth factors survived, 10 with successful allografts (includ ing 5 mixed chimeras) and 4 with autologous recovery; whereas 7 animal s died, 5 from infections during BM aplasia and 2 from acute graft-ver sus-host disease. By comparison, 30 of 34 dogs (88%) receiving hema; t opoietic growth factors in addition to the BM graft survived, 17 with successful allografts (including 10 mixed chimeras) and 13 with autolo gous recovery; whereas 4 died, all with infection related to BM aplasi a after rejection of the allograft. Survival was similar for recipient s of G-CSF, SCF, or the combination of G-CSF and SCF. Logistic regress ion analyses, which accounted for possible effects of TBI dose, showed a trend for improved survival in dogs receiving growth factors (P = . 09), no change in allogeneic engraftment (P = .74), and a slight incre ase in autologous recovery (P = .22). In agreement with previous data, we found that grafts of BM from DLA-identical littermates improved su rvival of recipient dogs exposed to low but otherwise lethal doses of TBI. A further improvement in survival could be achieved by additional treatment with G-CSF, SCF, or G-CSF/SCF. Results suggest that treatme nt by hematopoietic growth factors along with BM grafts should be cons idered for victims of radiation accidents. (C) 1994 by The American So ciety of Hematology.