Hematopoietic responses to stress conditions in young dogs compared with elderly dogs

Clinical observations show that older patients do not tolerate high-dose ch emoradiotherapy as well as younger patients, It is unclear whether this is due to age-related differences in their responses to hematopoietic injury o r to differential toxicities to other organs. In the present study, 6 young (0.5 years) and 6 elderly (8 years) dogs were challenged with 7 repeated n onlethal doses of 50 or 100 cGy total body irradiation (TBI) each (total 55 0 cGy), and 21 days of recombinant canine granulocyte-colony stimulating fa ctor (rcG-CSF) after the last TBI dose. Recoveries of absolute neutrophil, platelet, and lymphocyte counts after each TBI dose, responses to rcG-CSF t reatment, and telomere lengths in neutrophils were compared before and afte r the study. No differences were found in recoveries of neutrophils, platel ets, or in responses to rcG-CSF among young and old dogs, in contrast, reco veries were suggestively worse in younger dogs. After rcG-CSF, platelet rec overies were poor in both groups compared with previous platelet recoveries (P < .01), Consequently, 2 old and 3 young dogs were euthanized because of persistent thrombocytopenia and bleeding. At the study's completion, marro w cellularities and peripheral blood counts of the remaining young and elde rly dogs were equivalent. The telomere lengths in both groups were signific antly reduced after the study versus beforehand (P = .03), but the median a ttritions of telomeres were not different. It was concluded that aging does not appear to affect hematopoietic cell recoveries after repeated low-dose TBI, suggesting that poor tolerance of radiochemotherapy regimens in older patients may be due to nonhematopoietic organ toxicities rather than age-r elated changes in hematopoietic stem cells reserves. (C) 2001 by The Americ an Society of Hematology.