Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of malignant lymphoma.

Abstract

Granulopoiesis-stimulating factors, such as granulocyte-colony-stimulating factor (G-CSF) and granulocyte-macrophage-colony-stimulating factor (GM-CSF), are being used to prevent febrile neutropenia and infection in patients undergoing treatment for malignant lymphoma. The question of whether G-CSF and GM-CSF improve dose intensity, tumour response, and overall survival in this patient population has not been answered yet. Since the results from single studies are inconclusive, a systematic review was undertaken. To determine the effectiveness of G-CSF and GM-CSF in patients with malignant lymphoma with respect to preventing neutropenia, febrile neutropenia and infection; improving quality of life, adherence to treatment protocol, tumour response, freedom from treatment failure (FFTF) and overall survival (OS); and adverse effects. We searched The Cochrane Library, MEDLINE, EMBASE, CancerLit, and other relevant literature databases; internet databases of ongoing trials; and conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology (1980 - 2003). We included full-text and abstract publications as well as unpublished data. Randomised controlled trials comparing prophylaxis with G-CSF or GM-CSF versus placebo/no prophylaxis in adult patients with malignant lymphoma undergoing chemotherapy were included for review. Both study arms had to receive identical chemotherapy and supportive care. Trial eligibility and quality assessment, data extraction and analysis were done in duplicate. Authors were contacted to obtain missing data. We included 12 eligible randomised controlled trials with 1823 patients. Compared with no prophylaxis, both G-CSF and GM-CSF significantly reduced the relative risk (RR) for severe neutropenia (RR 0.67; 95% confidence interval (CI) 0.60 to 0.73), febrile neutropenia (RR 0.74; 95% CI 0.62 to 0.89) and infection (RR 0.74; 95% CI 0.64 to 0.85). There was no evidence that either G-CSF or GM-CSF reduced the number of patients requiring intravenous antibiotics (RR 0.82; 95%CI 0.57 to 1.18); lowered infection related mortality (RR 1.37; 95% CI 0.66 to 2.82); or improved complete tumour response (RR 1.02; 95% CI 0.94 to 1.11), FFTF (hazard ratio 1.11; 95% CI 0.91 to 1.35) and OS (hazard ratio 1.00; 95% CI 0.86 to 1.16). One study evaluated quality of life parameters and found no differences between the treatment groups. G-CSF and GM-CSF, when used as a prophylaxis in patients with malignant lymphoma undergoing conventional chemotherapy, reduce the risk of neutropenia, febrile neutropenia and infection. However, based on the randomised trials currently available, there is no evidence that either G-CSF or GM-CSF provide a significant advantage in terms of complete tumour response, FFTF or OS.