High-dose chemotherapy followed by autologous stem cell transplantation as first-line therapy in aggressive non-Hodgkin's lymphoma: a meta-analysis.
OBJECTIVE
High-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) has proven to be superior to conventional chemotherapy in patients with chemosensitive relapse of aggressive non-Hodgkin's lymphoma (NHL). Therefore, HDT/ASCT was evaluated as part of first-line therapy. Several trials generated conflicting results. This meta-analysis summarizes the available evidence from all suitable studies.


METHODS
Prospective, randomized trials with HDT/ASCT as first-line therapy of aggressive lymphoma were included in this meta-analysis. The primary outcome was overall mortality. Statistical analysis applied the odds ratio (OR) and a fixed effects model.


RESULTS
Eleven trials with 2228 patients were eligible for meta-analysis. Overall mortality was comparable in the HDT/ASCT and in control arms (OR=0.97, 95% CI: 0.69;1.36, p=0.9), with statistically significant heterogeneity between the trials. To resolve this, we tried to identify variables that could explain this heterogeneity. Among a range of methodological, patient- or treatment-related factors, subgroups formed by the proportion of bulky disease in treated patients, the type of therapy prior to HDT/ASCT, the drop-out rate from the HDT/ASCT arm, and the presence of high or high-intermediate risk IPI showed significant benefit for any of the treatment modalities. However, such post-hoc subgroup analysis may be considerably influenced by random or systemic biases.


CONCLUSIONS
Overall, the analysis of published evidence reveals very heterogeneous results and no overall survival benefit. Therefore, HDT/ASCT cannot be recommended as standard first line treatment for patients with aggressive NHL. However, the exploratory analyses presented here may help to design new trials for this treatment modality.
Strehl
John
J
Medizinische Klinik und Poliklinik I der Rheinischen Friedrich-Wilhelms-Universität Bonn, Germany.
Mey
Ulrich
U
Glasmacher
Axel
A
Djulbegovic
Benjamin
B
Mayr
Christine
C
Gorschlüter
Marcus
M
Ziske
Carsten
C
Schmidt-Wolf
Ingo G H
IG
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D016896:Treatment Outcome