Efficacy of granulocyte transfusions for neutropenia-related infections: Retrospective analysis of predictive factors

Background: The transfusion of G-CSF-primed granulocytes (GTX) might represent an important treatment option for neutropenia-related infections unresponsive to conventional antimicrobial therapies and to recombinant hematopoietic growth factors. However, few studies to date have identified the factors that can predict clinical outcome and the patient populations who are likely to benefit most from GTX. The primary endpoint of the present retrospective study was to evaluate the efficacy of GTX in 22 patients with hematological malignancies who developed neutropenia-related bacterial and fungal infections that were unresponsive to appropriate antimicrobial therapies. Methods: Peripheral blood granulocytes mere collected by continuous-flow leukapheresis from HLA-identical siblings after priming with G-CSF. The response to GTX was classified as 'favorable' if clinical symptoms and signs of infection resolved or 'unfavorable' if clinical symptoms and signs of infection were unchanged or worsened. Control of infection at Day 30 after the enrollment in the GTX program was considered as the outcome variable in multiple regression analysis. Results: Two patients died of infection before receiving the granulocyte concentrates. Bacterial infections (monomicrobial or mixed bacteremias) were documented in 11 patients, whereas fungal infections (fungemia or focal fungal infections) were diagnosed in seven patients. In two patients, no infecting agent could be isolated (clinical infection). Control of infection at Day 30 after the first GTX was achieved in 10 out of 20 assessable patients. Overall, 54% of patients with bacterial infections had a favorable response, compared with 57% of patients with fungal infections. No differences in terms of survival mere found when comparing patients with bacterial and those with fungal infections at a median follow-up of 90 days from the first GTX. In univariate analysis, disease status before GTX, e.g., complete or partial remission, and spontaneous recovery of the neutrophil count were significantly associated with control of infection. When multivariate regression models were formed, the recovery of 0.5 x 109/L PMN was the only parameter that significantly and independently correlated with a favorable response to GTX. Discussion: GTX can be used to successfully treat bacterial as well as fungal infections in severely neutropenic patients when administered early after the onset of febrile neutropenia in patients with remission of the underlying disease and who are likely to recover marrow function.