Cell-mediated inhibition of granulopoiesis in vitro in patients with acute myeloid leukemia in remission.

Abstract

We investigated the in vitro granulopoiesis in 11 patients with acute myeloid leukemia (AML) in complete remission 3-80 months after diagnosis (median 8.5 months). 3 of the patients had subnormal levels of bone marrow-derived CFU-GM. 6 of 10 patients tested had defective recloning capacity of d-7 CFU-GM, suggesting a stem cell defect. Most patients (7/11) showed an increased colony growth of bone marrow-derived CFU-GM after T-cell depletion by E-rosetting, while readdition of isolated autologous T cells to T-cell depleted marrow caused a dose-dependent inhibition of colony formation; bone marrow T cells were more effective in this inhibition than peripheral blood T cells. Experiments using cells depleted of either CD4- or CD8-positive cells and CD4/CD8-enriched cell populations showed that both CD4- and CD8-positive cells had the capacity to inhibit colony growth. Long-term culture of bone marrow cells in suspension showed that the production of CFU-GM declined at about the same rate as in normal controls. Our findings suggest that there are persisting stem cell defects in patients with AML in remission and that the cell growth regulatory systems may be altered. These abnormalities could possibly be an effect of residual damage to the hematopoietic system caused by intensive chemotherapy.