DELAYING TRANSPLANTATION AFTER TOTAL BODY IRRADIATION IS A SIMPLE AND EFFECTIVE WAY TO REDUCE ACUTE GRAFT-VERSUS-HOST DISEASE MORTALITY AFTER MAJOR H2 INCOMPATIBLE TRANSPLANTATION1

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Abstract
We have previously reported that delaying histoincompatible transplantation after total body irradiation (TBI) conditioning markedly decreased the mortality of acute graft-versus-host disease (GVHD) in severe combined immunodeficiency mice. However, it was not clear whether the delayed transplantation would affect the final engraftment and acute GVHD mortality in normal hosts. BALB/c mice (H2d) were lethally irradiated with 8.5 Gy TBI and transplanted with C57BL/6 (H2d) bone marrow plus spleen cells on the same day (TBI+day 0) or 4 days after TBI conditioning (TBI+day 4). We again demonstrated that delaying transplantation by 4 days after TBI conditioning markedly reduced acute GVHD mortality in normal hosts after major histoincompatible transplantation. The survival rates were 66% in TBI+day 4 vs. 0% in TBI+day 0 allogeneic transplanted animals by day +60 (P. This 2- to 3-month early mixed chimerism in TBI+day 4 transplanted animals might be related to lower levels of tumor necrosis factor-α and IL-6 both of which have been shown to stimulate lymphohematopoiesis and was associated with lower acute GVHD mortality. The data again demonstrated in immunologically normal BALB/c mice that delaying allogeneic transplantation after TBI is a simple and effective way to reduce acute GVHD mortality, achieve satisfactory engraftment and significantly increase overall survival.

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