The superoxide dismutase content in erythrocytes predicts short-term toxicity of high-dose cyclophosphamide

Patients receiving high-dose cyclophosphamide as a conditioning regimen for peripheral stem cell collection are subjected over a short period of time to significant exposure to reactive oxygen species (ROS). All these patient s undergo profound leucopenia. Various other short-term toxicities are obse rved in a fraction of the patients, including febrile aplasia requiring hos pitalization, thrombocytopenia and mucositis. Although stem cell collection is feasible in the majority of patients stimulated with haematopoietic gro wth factors, in some instances, graft collection cannot be performed becaus e of insufficient concentrations of stem cells in peripheral blood. There i s currently no predictive assay to determine which patients treated with hi gh-dose cyclophosphamide have a high risk of febrile aplasia or will succes sfully undergo cytaphereses for stem cell collection. In order to identify such predictive factors, we analysed the level of expression before treatme nt of various ROS detoxification mechanisms in the peripheral blood of 37 p atients receiving high-dose cyclophosphamide for lymphoproliferative diseas es. Various parameters involved in the metabolism of ROS were measured in p lasma and/or erythrocytes, including superoxide dismutase, glutathione, glu tathione peroxidase, glutathione reductase and malondialdehyde. High levels of erythrocyte superoxide dismutase before cyclophosphamide therapy were c orrelated with an increased risk of hospitalization for febrile aplasia (65 % vs. 29%, P = 0.013). High superoxide dismutase and low erythrocyte glutat hione reductase were associated with lower CD34 yields. These data suggest that components of the ROS detoxification system modulate the degree of sho rt-term toxicity of cyclophosphamide and could be used as predictive marker s in individual patients.