Prediction of marrow graft rejection by the lymphocyte-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity assays.

We previously reported on 26 patients with severe aplastic anemia who were studied using the lymphocyte-mediated cytotoxicity (LMC) and antibody-dependent cell-mediated cytotoxicity (ADCC) assays. Eighty-one additional patients have now been studied. Overall, lymphocytes of 47% of the patients in LMC and sera of 30% in ADCC were reactive against the lymphocytes of HLA-identical siblings. LMC reactivity was more frequent in patients studied less than 1 month after diagnosis, but the frequency of ADCC reactivity was unrelated to time after diagnosis. In patients receiving the basic cyclophosphamide (CY) regimen, LMC results correlated with rejection in patients receiving transplants greater than or equal to 1 month after diagnosis but not in patients receiving transplants less than 1 month after diagnosis. Reactivity in ADCC correlated with graft rejection regardless of the time between diagnosis and study. No correlation between results of either assay and graft outcome was found in patients who received conditioning regimens aimed at abrogating rejection including total body irradiation or addition of donor buffy coat cells to the marrow inoculum. The finding of reactivity in the LMC assay early after diagnosis and in 8 or 15 untransfused patients indicates that mechanisms in addition to transfusion-induced sensitization must be involved in LMC reactivity. This LMC reactivity may be an epiphenomenon secondary to the stem cell defect of aplastic anemia. Alternatively, this LMC reactivity may be involved in the etiology of aplastic anemia.