Autologous bone marrow grafts in dogs treated with lethal doses of cyclophosphamide.
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Biomedical subjects
Publications and source records attributed to R B Epstein.
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Granulocyte transfusions were administered to dogs rendered neutropenic by prior cyclophosphamide treatment. Linear regression analysis established significant direct relationships between numbers of granulocytes infused per kg body weight and blood increment achieved. Migration of granulocytes to cerebrospinal fluid during induced Candida albicans meningitis related to concurrent increments in blood following transfusion. Levels of C. albicans systemic infection were inversely related to numbers of granulocytes administered during a four-day course of therapy. These studies demonstrate the quantitative relationships of granulocyte transfusion therapy to potential therapeutic effects at the tissue level.
Studies were carried out in dogs to detect alloimmunization to granulocytes by indirect immunofluorescence (GIIF) and to determine the significance of cross-matching in selecting donors for immunized recipients. All recipients were rendered neutropenic (less than 500 per microliter) by chemotherapy. Three groups of transfusions were evaluated. Group I consisted of 14 transfusions administered to sensitized dogs that were GIIF-negative with donor cells; Group II, 12 transfusions to the same dogs with GIIF-positive donor cells; Group III, 16 transfusions to nonimmunized control dogs. At 1 hour following transfusion, circulating granulocytes demonstrated increments of 956 +/- 137 per microliter (mean +/- SEM) in Group I dogs compared to 236 +/- 57 per microliter for Group II (p less than 0.001). Group III transfusions yielded increments of 888 +/- 116 per microliter, not significantly different from Group I. GIIF correlated better with transfusion results than granulocyte cytotoxicity or lymphocyte cytotoxicity tests or leukoagglutination cross-matching. Nineteen sera with alloantibodies to granulocytes were produced by random or intrafamilial immunizations with granulocytes. Partial characterization of specificities showed that granulocyte specificities were independent of DLA, and consistent with a genetic system of dominant alleles. It was concluded that a) alloimmunization to granulocytes is detected by the GIIF, b) positive tests predict transfusion effects, and c) a genetic system independent of DLA could be recognized on dog granulocytes.