Model identifies patients at high-risk of infections

A model based on risk factors for infection in fludarabine-based treatments, identifies a group of patients with indolent lymphoid cancer who are likely to have severe complications from treatment, according to a report in Cancer.Fludarabine based combinations with cyclophosphamide and/or mitoxantrone produce response rates of greater than 90% in patients with indolent lymphoid cancer, but one third of patients have severe infections. The risk factors for infections with combination therapy may differ from single agent fludarabine as patients are given lower fludarabine doses, but have increased myelotoxicity and epithelial damage from the other agents. This retrospective study from Melbourne analysed data from 92 patients who were treated with fludarabine and mitoxantrone or cyclophosphamide. Most patients had previous therapy and advanced stage disease.Treatment was associated with infections in 14% of cycles and 38% of patients. This was Grade 3 and above in 6% of cycles and 18% of patients. There was no significant difference between cyclophosphamide and mitoxantrone containing treatment. Univariate analysis identified six risk factors for infections. These were age over 60 years, previous fludarabine treatment, at least three previous therapies, greater than three years from diagnosis to treatment, performance score of at least two and baseline absolute neutrophil count of less than 2x109/L. Standard risk patients were identified as those with no or two risk factors and high-risk patients had three or more risk factors. Per cycle, high-risk patients had statistically more total infections (26% compared to 7%), severe infections (11% compared to 25%), Grade 4 neutropaenia (41% compared to 8%), Grade 4 thrombocytopenia (17% compared to 5%) and infections associated with concurrent Grade 4 neutropenia (15% compared to 1%). The number of infections per cycle was 5% in those with a complete response, 15% for those with a partial response and 35% in those without response (p = 0.0003).The authors considered most of the increased risk was in infections relating to severe neutropenia although other factors were important, and suggested the prophylactic use of granular granulocyte colony-stimulating factor in high-risk patients. The model using six baseline risk factors identified patients who were likely to have severe complications and indicated the population that was most appropriate for studies of prophylaxis or infection risk from other agents such as rituximab. The authors recommended trials targeting these high-risk patients.Reference...