Effects of azoles on human acute myelogenous leukemia blasts and T lymphocytes derived from acute leukemia patients with chemotherapy-induced cytopenia

The effects of azoles (fluconazole, ketoconazole, miconazole, itraconazole) on human acute myelogenous leukemia (AML) blasts and T lymphocytes were st udied in vitro. All the azoles altered spontaneous proliferation, cytokine- dependent proliferation and constitutive cytokine secretion by native AML b lasts for a subset of patients, and all the drugs then had divergent effect s. All four drugs also affected the responsiveness (cytokine-dependent and mitogen-stimulated proliferation, cytokine release) of clonogenic CD4(+) an d CD8(+) T cells derived from acute leukemia patients with chemotherapy-ind uced cytopenia. However, the T cell effects were also divergent and depende nt on differences between various azoles, AML accessory cells and mitogenic activation signals. These drug effects may have a clinical relevance in ac ute leukemia patients receiving intensive chemotherapy together with azoles as prophylaxis or treatment for fungal infections: (i) effects on AML blas ts may influence their susceptibility to drug-induced apoptosis; and (ii) e ffects on T cells may alter effector functions that mediate additional anti leukemic effects in patients receiving intensive chemotherapy. (C) 2001 Els evier Science B.V. All rights reserved.