title: High-dose chemotherapy with autologous stem cell support in first-line treatment of aggressive non-Hodgkin lymphoma - results of a comprehensive meta-analysis.
abstract: BACKGROUND
  Randomized controlled trials (RCTs) reported conflicting results on the impact of high-dose chemotherapy (HDCT) and autologous stem cell transplantation in the first-line treatment of patients with aggressive non-Hodgkin lymphoma (NHL).
  
  
  METHODS
  We performed a systematic meta-analysis to assess the efficacy HDCT compared to conventional chemotherapy in aggressive NHL patients with regard to complete response (CR), overall survival (OS), event-free survival (EFS), toxicity, and impact of the age-adjusted International Prognostic Index (aaIPI) risk factors. We searched the Cochrane Library, MEDLINE and other databases (1/1990 to 1/2005). Hazard ratio (HR), relative risks (RR) and 95% confidence intervals (CIs) were calculated using the fixed effect model.
  
  
  RESULTS
  Fifteen RCTs including 2728 patients were identified. HDCT improved CR when compared to conventional chemotherapy (RR 1.11, CI 1.04-1.18). Overall, there was no evidence for HDCT to improve OS (HR 1.05, 95% CI 0.92-1.19) or EFS (HR 0.92, 95% CI 0.80-1.05) when compared with conventional chemotherapy. However, subgroup analysis indicated OS differences (p=0.032) between good (HR 1.46, 95% CI 1.02-2.09) and poor risk (HR 0.95, 95% CI 0.81-1.11) patients. Conflicting results were reported for poor risk patients, where some studies reported improved and others reduced OS and EFS after HDCT.
  
  
  CONCLUSIONS
  There was no evidence that HDCT improved OS and EFS in good risk NHL patients. The evidence for poor risk patients is inconclusive. HDCT should not be further investigated in good risk patients with aggressive NHL but high quality studies in poor risk patients are warranted.
authors.affiliation: Department of Internal Medicine I, University of Cologne, Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Greb
authors.forename: Julia
authors.initials: J
authors.lastname: Bohlius
authors.forename: Sven
authors.initials: S
authors.lastname: Trelle
authors.forename: Daniel
authors.initials: D
authors.lastname: Schiefer
authors.forename: Carmino A
authors.initials: CA
authors.lastname: De Souza
authors.forename: Christian
authors.initials: C
authors.lastname: Gisselbrecht
authors.forename: Tanin
authors.initials: T
authors.lastname: Intragumtornchai
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kaiser
authors.forename: Hanneke C
authors.initials: HC
authors.lastname: Kluin-Nelemans
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martelli
authors.forename: Noel Jean
authors.initials: NJ
authors.lastname: Milpied
authors.forename: Gino
authors.initials: G
authors.lastname: Santini
authors.forename: Leo F
authors.initials: LF
authors.lastname: Verdonck
authors.forename: Umberto
authors.initials: U
authors.lastname: Vitolo
authors.forename: Guido
authors.initials: G
authors.lastname: Schwarzer
authors.forename: Andreas
authors.initials: A
authors.lastname: Engert
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D014182:Transplantation, Autologous
chemical_list: D000970:Antineoplastic Agents