LYMPHOHEMATOPOIETIC ENGRAFTMENT IN MINIMALLY MYELOABLATED HOSTS

The concept that myeloablation to open space was a prerequisite for ma rrow 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 W u et al, Exp Hematol 21:251, 1993). However, relatively large numbers of marrow cells were necessary to achieve high long-term donor percent ages. We have demonstrated, using a BALB/c male/female marrow transpla nt model and detecting male DNA in host tissues by Southern blot or fl uorescent in situ hybridization, that exposure to doses of irradiation that cause minimal myeloablation (50 to 100 cGy) leads to very high l evels 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 compet ition between host and donor stem cells. These data indicate that low levels of irradiation should be an effective approach to nontoxic marr ow transplantation in gene therapy or in attempts to create allochimer ism to treat such diseases as cancer, sickle cell anemia, or thalassem ia. (C) 1998 by The American Society of Hematology.