title: Granulopoiesis-stimulating factors in the prevention for adverse effects in the therapeutic treatment of malignant lymphoma.
abstract: BACKGROUND
  Granulopoiesis-stimulating factors (G-CSF and GM-CSF) are being used to prevent febrile neutropenia and infections in the treatment of patients with malignant lymphoma. The question 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 required.
  
  
  OBJECTIVE
  To undertake a systematic review in patients with malignant lymphoma to determine the effectiveness of G-CSF and GM-CSF to prevent neutropenia, febrile neutropenia, infection, improve quality of life, adherence to the treatment protocol, tumour response, freedom from treatment failure (FFTF), overall survival (OS) and to assess adverse events of G-CSF and GM-CSF.
  
  
  METHODS
  Medline, Embase, CancerLit, the Cochrane Library and smaller databases, Internet-databases of ongoing trials, conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology were searched. We included full-text and abstract publications as well as unpublished data.
  
  
  METHODS
  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 in this review. Both study arms had to receive identical chemotherapy and supportive care.
  
  
  METHODS
  Eligibility and quality assessment, data extraction and analysis were done in duplicate. All authors were contacted to obtain missing data.
  
  
  RESULTS
  We included 11 eligible studies with 1434 randomised patients. Compared with no prophylaxis, G-/GM-CSF significantly reduced the relative risk for severe neutropenia (RR 0.64 [95% CI 0.55-0.75]), febrile neutropenia (RR 0.74 [95% CI 0.62-0.89]) and infection (RR 0.74 [95% CI 0.64-0.85]). There was no evidence for G-/GM-CSF to decrease the number of patients who required iv antibiotics (RR 0.82 [95%CI 0.57-1.18]), to reduce infection related mortality (RR 2.07 [95% CI 0.81-5.34]), or to improve complete tumour response (RR 1.06 [95% CI 0.96-1.16]), FFTF (HR 1.22 [95% CI 0.83-1.80]) and OS (HR 0.98 [95% CI 0.81-1.18]). None of the studies evaluated quality of life parameters.
  
  
  CONCLUSIONS
  G-CSF and GM-CSF, when given prophylactically in patients with malignant lymphoma undergoing conventional chemotherapy, reduce the risk of neutropenia, febrile neutropenia and infection. However, based on the currently available randomised trials in this clinical setting, there is no evidence for G-/GM-CSF to provide a significant advantage in terms of complete tumour response, FFTF and OS.
authors.affiliation: Department I of Internal Medicine, University of Cologne, Kerpener Str. 15, Cologne, Germany, 50924. julia.bohlius@medizin.uni-koeln.de
authors.forename: J
authors.initials: J
authors.lastname: Bohlius
authors.forename: M
authors.initials: M
authors.lastname: Reiser
authors.forename: G
authors.initials: G
authors.lastname: Schwarzer
authors.forename: A
authors.initials: A
authors.lastname: Engert
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor