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

Abstract

The ability to generate reactive oxygen species, the so-called oxidative burst, is essential for neutrophils to kill infectious micro-organisms. Flow cytometry was used to study oxidative burst prior to, during, and after cytostatic therapy. Seven patients were treated according to the DexaBEAM regimen with 12 cycles monitored. Four patients were treated according to the B-NHL regimen in which nine cycles were monitored. Ten healthy volunteers were chosen as a control group without any treatment. Neutrophils were collected from heparinized peripheral blood and were stimulated by phorbol-12-myristate-13-acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (FMLP), and Escherichia coli. The oxidative burst was estimated by the amount of nonfluorescent dihydrorhodamine 123 converted to green fluorescent rhodamine 123. Measurements were done daily. The FMLP-induced burst was enhanced in patients before therapy as compared with the control group, whereas PMA-induced burst was decreased slightly. E. coli-, FMLP-, and PMA-induced oxidative burst decreased in both groups during cytostatic therapy. E. coli-induced burst 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 partly suppressed. PMA-induced oxidative burst measured at the start of therapy correlates with infectious complications. Thus, PMA-induced burst may be 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 normal.

Evaluation of immunomodulatory effect of recombinant human granulocyte‐macrophage colony‐stimulating factor on polymorphonuclear cell from dogs with cancer in vitro

“…With rhGM‐CSF stimulation, the percentage of PMNs performing phagocytosis and oxidative burst was similar to that in control dogs, indicating rhGM‐CSF reversed cancer‐induced impaired phagocytic and killing ability. The similar decreased function of phagocytic and oxidative burst has been reported from human studies and in people, is correlated with increased risk of treatment‐related complications . The defective phagocytic function in PMNs from dogs with cancer may result from dysregulation of cell surface receptors, such as TLRs involved in recognition and response of foreign pathogens.…”

Reconstitution and functional analyses of neutrophils and distinct subsets of monocytes after allogeneic stem cell transplantation

“…In contrast to allogeneic PBSCT, there are some reports of functional recovery on the innate immune system especially in patients who received allogeneic BMT or autologous PBSCT (Volk et al 2000;Dayyani et al 2004). In detail, Krause and colleagues reported on a rapid numeral engraftment of neutrophils and monocytes after autologous PBSCT that were associated with an impaired ability to secrete proinflammatory cytokines (Krause et al 2003).…”

Distinct reconstitution of neutrophil functions after allogeneic peripheral blood stem cell transplantation

“…The functional capacity of this innate immune system is of special importance in patients who received myelotoxic chemotherapy or who underwent autologous or even allogeneic BMT or PBSCT (Volk et al 2000;Dayyani et al 2003;Krause et al 2003).…”