High-dose chemotherapy with autologous stem cell support in first-line treatment of aggressive non-Hodgkin lymphoma - results of a comprehensive meta-analysis.
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.
Greb
Alexander
A
Department of Internal Medicine I, University of Cologne, Cologne, Germany.
Bohlius
Julia
J
Trelle
Sven
S
Schiefer
Daniel
D
De Souza
Carmino A
CA
Gisselbrecht
Christian
C
Intragumtornchai
Tanin
T
Kaiser
Ulrich
U
Kluin-Nelemans
Hanneke C
HC
Martelli
Maurizio
M
Milpied
Noel Jean
NJ
Santini
Gino
G
Verdonck
Leo F
LF
Vitolo
Umberto
U
Schwarzer
Guido
G
Engert
Andreas
A
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
D000970:Antineoplastic Agents