Bone Marrow Transplantation in the Busulfan-Treated Rat

Lewis rats were given graded doses of cyclophosphamide (CY) alone or in combination with graded doses of busulfan (BU), rabbit anti-rat thymocyte serum, or BU plus rabbit anti-rat thymocyte serum, and transplanted with bone marrow from syngeneic or allogeneic Ag-B-incompatible ACI donors. Another group of Lewis rats was given a standard dose of CY plus graded doses of BU followed by infusion of graded numbers of ACI marrow cells. The animals were followed for mortality and clinical and histological evidence of graft-versus-host disease (GVHD). Chimerism was indirectly assessed by donor allotyping and skin graft survival. Furthermore, the peripheral lymphocytes of the transplanted animals were typed with strain-specific cytotoxic alloantisera. After conditioning with CY alone, a direct relation between the dose of CY, evidence of engraftment, and appearance of GVHD was observed. Adding antithymocyte serum to the conditioning regimen reduced the incidence of GVHD but did not increase the fraction of chimeras or completeness of engraftment. Adding BU to the conditioning regimen increased the fraction of chimeras displaying earlier and more complete engraftment but also increased the incidence of GVHD. Adding BU also permitted a reduction in the critical number of donor cells required to establish engraftment. The data stress the importance of a myelosuppressive “space making” principle in addition to an immunosuppressive principle for successful bone marrow transplantation.