GAMMA-IRRADIATION OF PRETRANSPLANT BLOOD-TRANSFUSIONS FROM UNRELATED DONORS PREVENTS SENSITIZATION TO MINOR HISTOCOMPATIBILITY ANTIGENS ON DOG LEUKOCYTE ANTIGEN-IDENTICAL CANINE MARROW GRAFTS

Pretransplant blood transfusions from a dog leukocyte antigen (DLA)-id entical canine Iittermate marrow donor will sensitize the recipient to non-DLA-linked polymorphic minor histocompatibility antigens, which u niformly results in graft rejection. We observed previously that 2000 cGy gamma-irradiation of marrow donor blood transfusions prevented thi s sensitization and subsequent marrow graft rejection. The purpose of the present study was to determine whether treatment of unrelated bloo d transfusions with gamma-irradiation would also prevent sensitization . conceivably sensitization to minor histocompatibility antigens might be more efficient or potent and thus more difficult to prevent when t hose antigens are seen in the context of disparity for DLA antigens. F urthermore, this model, in which sensitization to DLA-identical Iitter mate marrow is caused by unrelated blood transfusions, is directly rel evant to the clinical circumstances of human marrow transplantation. W e assessed sensitization caused by unrelated blood transfusions by mon itoring graft outcome in recipients transplanted with DLA-identical li ttermate marrow after conditioning with 920 cGy total body irradiation . Two thousand cGy gamma-irradiation of unrelated blood transfusions s ignificantly reduced the incidence of transfusion-induced sensitizatio n of recipients. There was successful marrow engraftment in 15 of 16 ( 94%, P<0.003) of these animals in contrast to the previous study in wh ich only 7 of 16 (44%) animals engrafted after they were transfused wi th unmodified blood on the same schedule. These results suggest that b lood transfusions for use in humans, especially for patients with apla stic anemia, should be gamma-irradiated in order to reduce the inciden ce of marrow graft rejection caused by sensitization to minor histocom patibility antigens.