Testing G-CSF responsiveness predicts the individual susceptibility to infection and consecutive treatment in recipients of high-dose chemotherapy

Abstract

The individual risk of infection and requirements for medical treatment after high-dose chemotherapy have been unpredictable. In this prospective, multicenter, open-label study we investigated the potential of granulocyte colony-stimulating factor (G-CSF) responsiveness as a predictor. A total of 168 patients with multiple myeloma or lymphoma received a single dose of subcutaneous G-CSF (lenograstim, 263 g) after high-dose chemotherapy. Highly variable leukocyte peaks were measured and grouped as low (quartile 1; leukocytes 100-10 100/L), medium (quartile 2; leukocytes > 10 100-18 300/L), and high (quartiles 3/4; leukocytes > 18 300-44 800/L). G-CSF responsiveness (low vs medium vs high) was inversely correlated with febrile neutropenia (77% vs 60% vs 48%; P ‫؍‬ .0037); the rate of infection, including fever of unknown origin (91% vs 67% vs 54%; P < .0001); days with intravenous antibiotics (9 vs 6 vs 5; P < .0001); and antifungal therapy (P ‫؍‬ .042). In multivariate analysis, G-CSF responsiveness remained the only factor significantly associated with infection (P ‫؍‬ .016). In addition, G-CSF responsiveness was inversely correlated with grade 3/4 oral mucositis (67% vs 33% vs 23%; P < .0001). G-CSF responsiveness appears as a signature of the myeloid marrow reserve predicting defense against neutropenic infection after intensive chemotherapy. This study is registered at http://www.clinicaltrials. gov as NCT01085058. (Blood. 2011;117(7): 2121-2128)

Prevention and Treatment of Cancer-Related Infections

“…G-CSF responsiveness showed a significant inverse correlation with incidences of febrile neutropenia and infections (ie, higher responsiveness associated with lower infection rates), and was shown to be the only independent predictor of infections based on multivariate analysis. 68 The spectrum of pathogens to which allogeneic HSCT recipients are most susceptible follows a timeline corresponding to the predominant immune defects. In the first month after HSCT (preengraftment period), neutropenia and breakdown of mucocutaneous barrier constitute the principal host defense defect, which predisposes patients to bacterial and fungal infections.…”

“…[65][66][67] Recently, a multicenter prospective study evaluated the potential role of granulocyte colony-stimulating factor (G-CSF) responsiveness in predicting the occurrence of infections in patients with hematologic malignancies undergoing high-dose therapy and autologous HSCT. 68 Responsiveness to G-CSF was determined by the administration of a single dose of G-CSF after completion of high-dose therapy (but before HSCT), and measuring the induced leukocyte peak 12 to 14 hours after the G-CSF dose. G-CSF responsiveness showed a significant inverse correlation with incidences of febrile neutropenia and infections (ie, higher responsiveness associated with lower infection rates), and was shown to be the only independent predictor of infections based on multivariate analysis.…”

Clinical significance of pre‐transplant circulating CD3+CD4+CD161+ cell frequency on the occurrence of neutropenic infections after allogeneic stem cell transplantation

“…Documentation of infection was distinguished for microbially and clinically defined infections and fevers of unknown origin as proposed by the Immunocompromised Host Society . Pre‐specified bacteremia, pneumonia, enterocolitis, urinary tract infection, infectious stomatitis, catheter infection, viral infection, fungal infection, and others were documented based on the infection type and/or location …”

Haematological support, fatigue and elderly patients

“…108 Furthermore, responsiveness to G-CSF prior to leucopenia has recently been found to predict defence against infection in high-dose chemotherapy patients. 109 In a prospective, multicentre, open-label study of 168 patients in Germany aged 18-70 years with multiple myeloma or lymphoma, G-CSF responsiveness was significantly correlated with reduced rates of FN and infection, and a reduced requirement for antibiotic or antifungal therapy. As a result, a test dose of G-CSF applied prior to cyclical chemotherapy may provide a basis for dose adjustments or the use of prophylactic G-CSF in future studies.…”