Lethal graft-versus-host disease: modification with allogeneic cultured
donor cells
P Mauch, JM Lipton, B Hamilton, J Obbagy, M Kudisch, D Nathan and S Hellman
The use of the bone marrow culture technique was studied as a means to
prepare donor marrow for bone marrow transplantation to avoid lethal
graft-versus-host disease (GVHD). Preliminary experiments demonstrated the
rapid loss of theta-positive cells in such cultures, so that theta-
positive cells were not detected after 6 days. Initial experiments in
C3H/HeJ (H-2k, Hbbd) recipients prepared with 900 rad demonstrated improved
survival when 3-day cultured C57BL/6 (H-2b, Hbbs) donor cells were used in
place of hind limb marrow for transplantation. However, hemoglobin typing
of recipient animals revealed only short-term donor engraftment, with
competitive repopulation of recipient marrow occurring. Subsequent
experiments were done in 1,200-rad prepared recipients, with long-term
donor engraftment demonstrated. The majority of 1,200-rad prepared animals
receiving cultured allogeneic cells died of GVHD, but animals receiving
28-day cultured cells had an improved 90- day survival and a delay in GVHD
development over animals receiving hind limb marrow or marrow from shorter
times in culture. In addition, animals receiving anti-theta-treated, 3-day
nonadherent cells had an improved survival (44%) over animals receiving
anti-theta-treated hind limb marrow (20%). These experiments demonstrate
modest benefit for the use of cultured cells in bone marrow transplantation
across major H-2 histocompatibility complex differences.
Volume 63,
Issue 5,
pp. 1112-1119,
05/01/1984
Copyright © 1984 by The American Society of Hematology
