APLASTIC-ANEMIA - ANALYSIS OF STROMAL CELL-FUNCTION IN LONG-TERM MARROW CULTURES

Marrow samples from 89 patients with aplastic anemia (AA) were evaluat ed for their ability to grow stromal layers in standard long-term marr ow cultures (LTMCs). Results were highly variable: 6.8% failed to grow any stromal cells (group I); 42.5% either failed to grow to confluenc y or appeared to have a decreased number of adipocytes and/or macropha ges (group II); and 52.8% appeared as normal confluent cultures with f ibroblasts, adipocytes, and macrophages (group III). Analyses of patie nt data suggested that group I patients had a longer disease duration and poorer survival (P = .07). Enzyme-linked immunosorbent assay analy sis of cytokine production was performed on 20 of the normal-appearing AA LTMCs and 12 LTMCs established from normal donors. Significant dif ferences between the AA and control groups were apparent for macrophag e inflammatory protein-1 alpha (MIP-1 alpha), interleukin-1 receptor a ntagonist (IL-1ra), granulocyte-macrophage colony-stimulating factor ( GM-CSF), granulocyte colony-stimulating factor (G-CSF), and leukemia-i nhibitory factor (LIF). The most dramatic differences observed were el evated levels of MIP-1 alpha and GM-CSF and decreased levels of IL-1ra , particularly after IL-1 alpha stimulation. In contrast. IL-1 alpha s timulation of AA LTMCs produced levels of IL-6, LIF, and G-CSF compara ble with those of controls. These data suggest that defects exist with in the microenvironment of some AA marrows. Whether the majority of th ese defects are the cause or consequence of aplasia is not clear. Howe ver, we speculate that some of these abnormalities may contribute to t he maintenance of the hypoplastic state and, in extreme cases, prevent engraftment of donor marrow. (C) 1994 by The American Society of Hema tology.