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Lymphohematopoietic Engraftment in Minimally Myeloablated Hosts
F.M. Stewart,
S. Zhong,
J. Wuu,
C.-c. Hsieh,
S.K. Nilsson, and
P.J. Quesenberry
From the Cancer Center and Division of Hematology-Oncology,
University of Massachusetts Medical Center, Worcester, MA.
The concept that myeloablation to open space was a prerequisite for
marrow stem cell engraftment has been challenged by studies showing
high rates of engraftment in nonmyeloablated mice (Stewart et al,
Blood 81:2566, 1993; Quesenberry et al, Blood Cells
20:97, 1994; Brecher et al, Blood Cells 5:237, 1979; Saxe et
al, Exp Hematol 12:277, 1984; and Wu et al, Exp Hematol
21:251, 1993). However, relatively large numbers of marrow
cells were necessary to achieve high long-term donor percentages. We
have demonstrated, using a BALB/c male/female marrow transplant model
and detecting male DNA in host tissues by Southern blot or fluorescent
in situ hybridization, that exposure to doses of irradiation that cause minimal myeloablation (50 to 100 cGy) leads to very high levels of
donor chimerism, such that relatively small numbers of marrow cells (10 to 40 million) can give donor chimerism in the 40% to 100% range.
Studies of radiation sensitivity of long-term engrafting cells have
shown that 100 cGy, although not myelotoxic, is stem cell toxic, and
indicate that the final host:donor ratios are determined by competition
between host and donor stem cells. These data indicate that low levels
of irradiation should be an effective approach to nontoxic marrow
transplantation in gene therapy or in attempts to create allochimerism
to treat such diseases as cancer, sickle cell anemia, or thalassemia.
Blood, Vol. 91 No. 10 (May 15), 1998:
pp. 3681-3687
© 1998 by The American Society of Hematology.

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