title: Autologous stem cell transplantation in follicular lymphoma: a systematic review and meta-analysis.
abstract: BACKGROUND
  The impact of high-dose therapy and autologous stem cell transplantation (ASCT) vs conventional-dose chemotherapy in the initial management of adults with advanced follicular lymphoma (FL) on overall survival remains uncertain. We performed a systematic review of the randomized clinical trials addressing this question.
  
  
  METHODS
  We searched MEDLINE, EMBASE, CENTRAL, American Society of Hematology, American Society of Clinical Oncology, BIOSIS, PAPERSFIRST, PROCEEDINGS, clinical trials registries, and bibliographies of relevant studies for randomized clinical trials comparing myeloablative chemotherapy with ASCT to any chemotherapy in adults with untreated advanced FL. We performed a meta-analysis using random effects models to estimate overall survival, event-free survival, and risks of adverse outcomes. Statistical heterogeneity was calculated by using the I(2) statistic.
  
  
  RESULTS
  Seven trials proved eligible, four of which provided data from 941 patients that could be included in a meta-analysis and three of which remain unpublished. In two of the trials, patients in both arms received rituximab during the induction treatment. Moderate quality evidence from the three trials that reported overall survival (n = 701 patients) suggests that ASCT did not result in improved overall survival (hazard ratio of death = 0.99, 95% confidence interval [CI] = 0.73 to 1.33). Low-quality evidence from the four trials of 941 patients suggests improvement in event-free survival in favor of ASCT (hazard ratio of death = 0.54, 95% CI = 0.36 to 0.82) with substantial heterogeneity (I(2) = 80%). Adverse outcomes of treatment-related mortality, myelodysplastic syndrome, acute myeloid leukemia, and solid tumors were not different between the two arms (relative risk [RR] of treatment-related mortality = 1.04, 95% CI = 0.29 to 3.70; RR of myelodysplastic syndrome/acute myeloid leukemia = 2.19, 95% CI = 0.45 to 10.55; I(2) = 48%; and RR of solid tumors = 1.30, 95% CI = 0.33 to 5.08). The absolute risk of death from treatment was 14 per 1000 patients for those who received chemotherapy and 15 per 1000 for those who received ASCT (range = 4-52).
  
  
  CONCLUSIONS
  Available evidence suggests that high-dose therapy and ASCT as part of FL initial treatment does not improve overall survival. Future trials of ASCT in the context of current chemoimmunotherapy approaches to FL are needed.
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Murtadha
authors.initials: M
authors.lastname: Al Khabori
authors.forename: John R
authors.initials: JR
authors.lastname: de Almeida
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Guyatt
authors.forename: John
authors.initials: J
authors.lastname: Kuruvilla
authors.forename: Michael
authors.initials: M
authors.lastname: Crump
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015986:Confounding Factors, Epidemiologic; D018572:Disease-Free Survival; D019317:Evidence-Based Medicine; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D000069283:Rituximab; D015983:Selection Bias; D033581:Stem Cell Transplantation / Q000401:mortality; D016019:Survival Analysis; D014182:Transplantation, Autologous; D017211:Treatment Failure
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab