Allogeneic bone marrow transplantation in irradiated adult rabbits

Abstract

In an effort to produce stable, long-term, complete hematopoietic chimerism in unrelated RLA-matched adult rabbits, the maximum dose of total-body irradiation (TBI) tolerated both with and without autologous marrow support was defined, and it was then determined whether the maximum tolerated dose was sufficiently immunosuppressive and myeloablative to allow engraftment of allogeneic marrow. Forty rabbits received TBI at 4.8 cGy/min at doses from 525-925 cGy. All rabbits receiving 525, 625, 725 and 825 cGy survived without marrow transplantation. At 875 cGy 50% of animals died and at 925 cGy all animals died within 96 hr of TBI. Survival was not changed with autologous marrow support, with all animals receiving 825 cGy surviving, while 50% survived at 875 cGy, and none at 925 cGy. Two RLA-matched, sex and immunoglobulin allotype-mismatched pairs were transplanted following 825 cGy and were given posttransplant cyclosporine. Both recipients survived beyond 200 days posttransplant, with cytogenetic and immunoglobulin allotype evidence of complete, or nearly complete, hematopoietic engraftment. Thus, stable, long-term complete chimerism can be achieved in adult RLA-matched unrelated rabbits prepared by TBI, and this animal model can be used for bone marrow transplantation studies.