Infections after experimental cadaver bone marrow transplantation in beagle dogs. Transplantations with and without selective gastrointestinal decontamination.

Experimental transplantations of cadaver bone marrow (BMT) in beagle dogs were performed to evaluate the problems and potentials in a preclinical setting. The effectiveness of selective decontamination of the gut (SD) and gnotobiotic surveillance in preventing infections during longer aplastic periods was investigated. Three groups of dogs were compared. Group A: controls. Group B: dogs with BMT, without SD and irregular gnotobiotic surveillance. Group C: dogs with BMT, with SD and regular gnotobiotic surveillance. The intestinal colonization of normal healthy beagles shows similarities as well as dissimilarities to the human intestinal microflora. Aerobic potentially pathogenic organisms do not colonize the gut of healthy beagles under our keeping conditions. SD resulted in a significant decrease in infections with Escherichia coli and Plesiomonas. Infections with anaerobes, as well as bacterial infections of the respiratory tract were, however, not prevented. The intestinal colonization in dogs of group C with Clostridium difficile is another obvious effect of SD. The infections encountered during the study indicate the importance of the "take" for the clinical significance and outcome of intestinal colonization with potentially pathogenic organisms. In order to reduce the drug burden of BMT patients, we consider the elimination of routine SD after BMT not to be superior to gnotobiotic surveillance and germ-specific short term decontamination.

Immune transfer studies in canine allogeneic marrow graft donor-recipient pairs.

Transfer of immunity occurring with bone marrow grafting was studied using the dog as a preclinical model. Allogeneic bone marrow transplantation (BMT) was performed between DLA-identical beagle litter-mates. The donors were immunized with tetanus toxoid (TT) or sheep red blood cells (SRBC), and their humoral response was monitored by hemagglutination. The recipients of bone marrow from TT-immunized donors showed a marked increase of antibody titer one week posttransplantation, while in the recipients of marrow from SRBC immunized donors the antibody titers were considerably lower. Within the following 60 days the antibody titers in both groups diminished gradually to pregrafting levels. Control experiments in which cell-free plasma from donors immunized with TT and SRBC respectively was transfused indicated that the initial rise of specific antibody titers after marrow grafting is likely to be due to a passive transfer of humoral immunity. A single challenge of these marrow graft recipients with the respective antigen 15-18 weeks posttransplantation led to a secondary type of humoral immune response. In addition, it could be demonstrated that transfer of memory against TT or SRBC was independent from the actual antibody titer and the time of vaccination of the donor. One dog was immunized with TT after serving as marrow donor. When the donor had shown an antibody response, a peripheral blood leukocytes (PBL) transfusion was given to his chimera. Subsequent challenge of the latter resulted in a secondary type of specific antibody response. This indicates that specific cellular-bound immunological memory can be transferred after BMT from the donor to his allogeneic bone marrow chimera by transfusion of peripheral blood leukocytes. The data presented may be of importance in clinical BMT to protect patients during the phase of reduced immune reactivity by transfer of memory cells from histocompatible immunized donors.