Reduction of lethal graft-versus-host disease: transplantation of cultured
murine bone marrow across minor histocompatibility differences
P Mauch, JM Lipton, BL Hamilton, J Obbagy, D Nathan and S Hellman
The murine bone marrow culture technique was used to prepare donor marrow
for bone marrow transplantation across minor histocompatibility complex
differences. Previous studies have shown that theta-positive cells are
rapidly lost from such cultures and that transplantation of cultured marrow
across major histocompatibility complex differences results in a delay in
the development of lethal graft-v-host disease (GVHD). In this study, a
total of 1 to 2 X 10(7) nonadherent cells (740 to 1560 CFUs [colony-forming
units]) from three-day-old cultures were used as a source of donor marrow.
Three strain combinations were evaluated; LP/J into C57BL/6; BIO.BR into
CBA/J; and C57BL/6 into LP/J. Donor mice were immunized with recipient
spleen cells prior to culture in order to increase the graft-v-host
response. For LP/J marrow into C57BL/6 mice, 5 X 10(7) donor spleen cells
transplanted along with the marrow were needed to induce lethal GVHD.
However, lethal GVHD was seen without the addition of spleen cells for
BIO.BR into CBA/J and C57BL/6 into LP/J strain combinations. Most animals
receiving fresh marrow were dead of GVHD five weeks after transplantation.
With the use of cultured marrow the three-month survival was 80%, 51%, and
93%, respectively, for LP/J into C57BL/6, BIO.BR into CBA/J, and C57BL/6
into LP/J strain combinations. Long-term donor engraftment in all recipient
animals receiving cultured marrow was confirmed by analyzing hemoglobin
polymorphisms between the strain combinations. These results demonstrate
that in contrast to transplantation across major histocompatibility complex
differences, the use of cultured cells for bone marrow transplantation
across minor histocompatibility complex differences allows for engraftment
while reducing the risk of lethal GVHD.
Volume 66,
Issue 3,
pp. 542-547,
09/01/1985
Copyright © 1985 by The American Society of Hematology
