SERUM INHIBITORS OF IN VITRO HEMATOPOIESIS AND GRAFT OUTCOME IN BONE MARROW TRANSPLANTATION FOR APLASTIC ANEMIA

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Abstract
The effect of pretransplant serum was studied from patients with severe aplastic anemia (AA) on normal myeloid progenitor cells (CFU-C) to determine whether CFU-C inhibition could predict subsequent bone marrow graft rejection. In a retrospective study of sera from 20 patients that received transplants at UCLA [University of California, Los Angeles, USA] for severe AA, a significant correlation was found between the presence of CFU-C inhibitors and graft outcome (P = 0.005). Analysis of this correlation was complex, because the sera were obtained from patients who received 1 of 4 different conditioning regimens of varying immunosuppressive potency. Studies were undertaken of additional sera from patients conditioned with cyclophosphamide (24 patients) or with cyclophosphamide plus 300 rad of total body irradiation (10 patients). Although CFU-C inhibitors were common in these 2 groups, their presence did not correlate with subsequent graft rejection. The finding in 1 patient that serum inhibitory to allogeneic marrows had no effect on HLA-identical donor marrow, and the demonstration of a significant correlation between CFU-C inhibitory and lymphocytotoxic activity suggested that CFU-C inhibitors might be directed against HLA antigens. Extensive absorption of inhibitory sera with random donor platelets (to remove anti-HLA antibodies) did not remove CFU-C inhibitory activity. It appears that in addition to HLA antigens, human CFU-C probably express non-HLA histocompatibility antigens.