Oxidative burst measurement in patients treated with cytostatics: influence of G-CSF and role as a prognostic factor

The ability to generate reactive oxygen species, the so-called oxidative bu rst, is essential for neutrophils to kill infectious micro-organisms. Flow cytometry was used to study oxidative burst prior to, during, and after cyt ostatic therapy. Seven patients were treated according to the DexaBEAM regi men with 12 cycles monitored. Four patients were treated according to the B -NHL regimen in which nine cycles were monitored. Ten healthy volunteers we re chosen as a control group without any treatment. Neutrophils were collec ted from heparinized peripheral blood and were stimulated by phorbol-12-myr istate-13-acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (FMLP), an d Escherichia coli. The oxidative burst was estimated by the amount of nonf luorescent dihydrorhodamine 123 converted to green fluorescent rhodamine 12 3. Measurements were done daily. The FMLP-induced burst was enhanced in pat ients before therapy as compared with the control group, whereas PMA-induce d burst was decreased slightly. E. coli-, FMLP-, and PMA-induced oxidative burst decreased in both groups during cytostatic therapy. E. coli-induced b urst increased again within 2 days of G-CSF treatment in vivo. FMLP-induced burst increased in the B-NHL group but decreased in the DexaBEAM group. In patients who have recovered from leukopenia the oxidative burst is still p artly suppressed. PMA-induced oxidative burst measured at the start of ther apy correlates with infectious complications. Thus, PMA-induced burst may b e used as a simple method for evaluating the individual risk of infections during therapy. The results demonstrate the modulating effect of cytostatic drugs on the oxidative burst and may explain why some patients suffer from severe bacterial infections although the total number of granulocytes is n ormal.