title: Acute myeloid leukemia or myelodysplastic syndrome in randomized controlled clinical trials of cancer chemotherapy with granulocyte colony-stimulating factor: a systematic review.
abstract: OBJECTIVE
  To evaluate the risk of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and overall mortality in patients receiving chemotherapy with or without granulocyte colony-stimulating factor (G-CSF), a systematic review of randomized controlled trials (RCTs) was conducted.
  
  
  METHODS
  Electronic databases searched through October 2008 identified 3,794 articles for initial screening. Eligibility included solid tumor or lymphoma patients randomly assigned to chemotherapy with or without G-CSF support, > or = 2 years of follow-up, and reporting AML/MDS or all second malignancies. Dual blinded data extraction was performed. Relative risk (RR) and absolute risk (AR) estimates +/- 95% CIs were calculated by the Mantel-Haenszel method.
  
  
  RESULTS
  In the 25 eligible RCTs, 6,058 and 6,746 patients were randomly assigned to receive chemotherapy with and without initial G-CSF support, respectively. At mean and median follow-up across studies of 60 and 53 months, respectively, AML/MDS was reported in 22 control patients and 43 G-CSF-treated patients, with an estimated RR of 1.92 (95% CI, 1.19 to 3.07; P = .007) and AR increase of 0.41% (95% CI, 0.10% to 0.72%; P = .009). Deaths were reported in 1,845 patients randomly assigned to G-CSF and in 2,099 controls, for estimates of RR and AR decrease of 0.897 (95% CI, 0.857 to 0.938; P < .001) and 3.40% (95% CI, 2.01% to 4.80%; P < .001), respectively. Greater RR reduction for mortality was seen for both larger studies (P = .05) and greater chemotherapy dose-intensity (P = .012).
  
  
  CONCLUSIONS
  Delivered chemotherapy dose-intensity and risk of AML/MDS are increased but all-cause mortality is decreased in patients receiving chemotherapy with G-CSF support. Greater reductions in mortality were observed with greater chemotherapy dose-intensity.
authors.affiliation: Duke University and Duke Comprehensive Cancer Center, 2424 Erwin Rd, Ste 205, Durham, NC 27705, USA. Gary.Lyman@Duke.edu
authors.forename: Gary H
authors.initials: GH
authors.lastname: Lyman
authors.forename: David C
authors.initials: DC
authors.lastname: Dale
authors.forename: Debra A
authors.initials: DA
authors.lastname: Wolff
authors.forename: Eva
authors.initials: E
authors.lastname: Culakova
authors.forename: Marek S
authors.initials: MS
authors.lastname: Poniewierski
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Kuderer
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Crawford
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D015201:Meta-Analysis as Topic; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor