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Busulfan-induced chronic bone marrow failure: changes in cortical bone,
marrow stromal cells, and adherent cell colonies
PM McManus and L Weiss
This study represented an effort to determine if there were quantitative or
morphological changes in marrow stromal cells in busulfan-induced marrow
failure and to relate these changes to other disturbances in blood and bone
marrow. Mice received four busulfan (BU) injections at two-week intervals
and were killed at various time points up to 40 weeks after the first
injection. Evaluation techniques included complete blood counts, in vitro
assay of short-term adherent cell colonies per femur (STACC per femur) and
colony-forming unit- culture (CFU-C) per femur, light microscopy of
sternebral marrow and spleen, and electron microscopy (EM) of sternebral
marrow taken at 40 weeks. STACC per femur were acutely reduced to 25% of
control, but recovered to 76% by 40 weeks. CFU-C per femur dropped to below
10% of control and never recovered. Histologically, we found that
hypoplasia of acutely affected marrow was associated with heightened
endosteum and cortical bone thickening. In the chronic phase of BU injury,
bones became osteoporotic, and the frequency of adipocytes and mast cells
rose. BU-affected spleens generally had enhanced erythropoiesis. No stromal
cell changes in 40-week marrow were discernible by EM. We concluded that
there were morphological changes in BU marrow stroma specifically involving
endosteum, bone, adipocytes, and mast cells. Also, there was quantitative
depression in stromal cells measured by the STACC assay, but this improved
substantially with time, unlike damage to hematopoietic stem cells measured
by the CFU-C.
Volume 64,
Issue 5,
pp. 1036-1041,
11/01/1984
Copyright © 1984 by The American Society of Hematology
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