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HEMATOPOIESIS
From the Clinical Research Division, Fred Hutchinson
Cancer Research Center; and the Department of Medicine, University of
Washington, Seattle, WA.
Clinical observations show that older patients do not tolerate
high-dose chemoradiotherapy as well as younger patients. It is unclear
whether this is due to age-related differences in their responses to
hematopoietic injury or 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 nonlethal doses of 50 or
100 cGy total body irradiation (TBI) each (total 550 cGy), and 21 days
of recombinant canine granulocyte-colony stimulating factor (rcG-CSF)
after the last TBI dose. Recoveries of absolute neutrophil, platelet,
and lymphocyte counts after each TBI dose, responses to rcG-CSF
treatment, and telomere lengths in neutrophils were compared before and
after the study. No differences were found in recoveries of
neutrophils, platelets, or in responses to rcG-CSF among young and old
dogs. In contrast, recoveries were suggestively worse in younger dogs.
After rcG-CSF, platelet recoveries 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,
marrow cellularities and peripheral blood counts of the remaining young
and elderly dogs were equivalent. The telomere lengths in both groups
were significantly reduced after the study versus beforehand
(P = .03), but the median attritions 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-related changes in hematopoietic stem cells reserves. This article has been cited by other articles:
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| Copyright © 2001 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
