BACKGROUND: Fludarabine induces leukemic cell apoptosis and is highly efficient in chronic lymphocytic leukemia. However, fludarabine therapy causes severe leukopenia. Leukocyte myeloperoxidase (MPO) catalyzes the formation of HOCl, and this is the main microbicidal function in phagocytes. The aim of our study was to evaluate the effect of fludarabine on leukocytes, i.e. their degranulation capacity, MPO activity and HOCl production. METHODS: Peripheral blood leukocytes were incubated for 48 h with fludarabine. Degranulation was measured using a flow-cytometric method. MPO activity and HOCl production were measured spectrophotometrically. RESULTS: The degranulation capacity of fludarabine-treated leukocytes was significantly elevated compared to untreated controls. MPO activity and HOCl production were also increased in parallel. A possible direct activating effect of fludarabine was tested on the MPO activity of HL60 cells. Fludarabine did not affect MPO activity at concentrations ranging from 10 microM to 2 mM. CONCLUSION: Fludarabine had no inhibitory effect on the microbial killing of leukocytes. 2004 S. Karger AG, Basel.
BACKGROUND:Fludarabine induces leukemic cell apoptosis and is highly efficient in chronic lymphocytic leukemia. However, fludarabine therapy causes severe leukopenia. Leukocyte myeloperoxidase (MPO) catalyzes the formation of HOCl, and this is the main microbicidal function in phagocytes. The aim of our study was to evaluate the effect of fludarabine on leukocytes, i.e. their degranulation capacity, MPO activity and HOCl production. METHODS: Peripheral blood leukocytes were incubated for 48 h with fludarabine. Degranulation was measured using a flow-cytometric method. MPO activity and HOCl production were measured spectrophotometrically. RESULTS: The degranulation capacity of fludarabine-treated leukocytes was significantly elevated compared to untreated controls. MPO activity and HOCl production were also increased in parallel. A possible direct activating effect of fludarabine was tested on the MPO activity of HL60 cells. Fludarabine did not affect MPO activity at concentrations ranging from 10 microM to 2 mM. CONCLUSION:Fludarabine had no inhibitory effect on the microbial killing of leukocytes. 2004 S. Karger AG, Basel.