Chemotherapy plus Rituximab versus chemotherapy alone for B‐cell non‐Hodgkin's lymphoma

Holger Schulz; Julia Bohlius; Nicole Skoetz; Sven Trelle; Thilo Kober; Marcel Reiser; Martin Dreyling; Michael Herold; Guido Schwarzer; Michael Hallek; Andreas Engert

doi:10.1002/14651858.CD003805.pub2

Quimioterapia más rituximab versus quimioterapia sola para el linfoma no Hodgkin de células B

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Referencias de los estudios excluidos de esta revisión

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Referencias de los estudios en curso

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Groupe d’Etudes de Lymphomes de L’Adulte HOVON—Dutch Haemato‐Oncology Association German Low Grade Lymphoma Study Group OSHO Australasian Leukaemia and Lymphoma Group (ALLG) Institute of Cancer Research, United Kingdom. Advanced. Advanced follicular lymphoma evaluating the benefit of maintenance therapy with rituximab (MabThera) after induction of response with chemotherapy plus rituximab in comparison with no maintenance therapy. Ongoing clinical trial. Available at: clinicaltrials.gov NCT00140582.

Combination Chemotherapy Plus Filgrastim With or Without Rituximab in Treating Older Patients With Non‐Hodgkin's Lymphoma. Ongoing studyJanuary 2002.

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Schulz H, Bohlius J, Trelle S, Skoetz N, Reiser M, Kober T, et al. Immunochemotherapy With Rituximab and Overall Survival in Patients With Indolent or Mantle Cell Lymphoma: A Systematic Review and Meta‐analysis. Journalof National Cnacer Institute 2007;99:706‐14.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

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estudios en curso

Forstpointner 2004

Methods	Randomised Blind: No Withdrawls: Yes ITT: yes Placebo:No Funding: Deutsche Krebshilfe
Participants	Relapsed or refractory indolent and mantle cell lymphoma
Interventions	4 x R‐FCM vs 4 x FCM
Outcomes	Overall survival Progression free survival Complete Response Partial Response Toxicity
Notes	Second randomisation for maintenance 4xRituximab month 3 and months 9 vs observation
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Herold 2004

Methods	Randomised Blind: No Withdrawls: No ITT: yes Placebo:No Funding: pharmaceutical
Participants	Untreated indolent and mantle cell lymphoma
Interventions	6 x R‐MCP vs 6 x MCP
Outcomes	Overall survival Progression free survival Event free survival Complete Response Partial Response Toxicity
Notes	Interferon maintenance therapy for follicular lymphoma
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Hiddemann 2005

Methods	Randomised Blind: No Withdrawls: No ITT: Deutsche Krebshilfe Placebo:No Funding: pharmaceutical
Participants	Untreated indolent and mantle cell lymphoma
Interventions	6‐8 R‐CHOP vs 6‐8 CHOP
Outcomes	Overall survival Time to treatment failure Complete Response Partial Response Toxicity
Notes	Second randomisation for patients < 60 years for PBSCT vs Interferon maintenance and for patients > 60 years intensive interferon vs standard maintenance patients in CR after 4 cycles received only 6 cycles of therapy whereas all others received 8 cycles. Progressive disease were taken off study after 4 at any time
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Lenz 2005

Methods	Randomised Blind: No Withdrawls: Yes ITT: yes Placebo:No Funding: Deutsche Krebshilfe pharmaceutical
Participants	Untreated mantle cell lymphoma
Interventions	6 x R‐CHOP vs 6 x CHOP
Outcomes	Overall survival Progression free survival Time to treatment failure Complete Response Partial Response Toxicity
Notes	Second randomisation for patients < 65 years for PBSCT vs Interferon maintenance plus 2 cycles of conventional chemotherapy and all patients > 65 years received interferon standard maintenance therapy
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Marcus 2005

Methods	Randomised Blind: No Withdrawls: Yes ITT: yes Placebo:No Funding: pharmaceutical
Participants	Untreated indolent lymphoma
Interventions	8 x R‐CVP vs 8 x CVP
Outcomes	Overall survival Progression free survival Duration of response Complete Response Partial Response
Notes	Restaging were done after 4 cycles and patients with stable disease were taken off study
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Rivas‐Vera 2005

Methods	Randomised Blind: No Withdrawls: Yes ITT: yes Placebo:No Funding: not applicable
Participants	Untreated indolent lymphoma
Interventions	R‐CNOP vs CNOP vs R
Outcomes	Overall survival Time to progressionOverall survival Time to progression Complete Response Partial Response Toxicity
Notes	subgroups of indolent lymphoma are not specified. Three arm study. Patients with R only are not included in the meta‐analysis
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

van Oers 2006

Methods	Randomised Blind: No Withdrawls: Yes ITT: yes Placebo:No Funding:
Participants	Relapsed or refractory indolent lymphoma
Interventions	6 x R‐CHOP vs 6 x CHOP
Outcomes	Overall survival Time to progression Complete Response Partial Response Toxicity
Notes	Second randomisation for maintenance therapy with rituximab every 2 month until 2 years vs observation
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Characteristics of excluded studies [ordered by study ID]

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Study	Reason for exclusion
Byrd JC	Comparison of concurrent vs sequential treatment with rituximab
Cohen 2002	Rituximab Konsolidationtherapy
Czuczman	Non randomised study 6 x Rituximab + 6 x R‐CHOP
Czuczman M	Non randomised study 7 x Rituximab + 6 x Fludarabin
Doelken G	Study focused on rapid clearence of circulating lymphoma cells but had no outcome analysis
Ghielmeni M	Monotherapy R and maintenance rituximab
Gregory S	Konsoldiationtherapy with Rituximab
Hainsworth J	No identical chemotherapy and furthermore rituximab monotherapy as induction followed by R‐CVP or R‐CHOP
Hochster H	rituximab maintenance therapy
Huang J	Non randomised study 6 x R‐CHOP followed by 4 x rituximab every 6 months for 2 years
Jiang Y	Sequential vs concurrent therapy with rituximab 6 x R‐FND vs FND followed by 6 x R
Katakkar S	Non randomised study 6 x Rituximab weekly + CVP and maintenance therapy
Meckenstock G	Standard chemotherapy with rituximab vs high dose therapy with rituximab and no identical chemotherapy in both arms 6 x FMR vs 3 x R‐CHOP 2 x HAM/R and PBSCT
Pettengell	Rituximab maintenance therapy and ongoing trial
Rambaldi A	Treatment outcome was minimal residual disease
Rule S	Non randomised study and ongoing trial
Salles G	No identical chemotherapy schedule. 6 x R‐CHVP vs 12 x CVHP
Solal‐Celigny P	Rituximab monotherapy
Tobinai	Rituximab concurrent vs sequential 6 x R‐CHOP 6 x CHOP 6 x R
Vitolo	Rituximab consolidationtherapy
Witzig	Rituximab mono
Zinzani PL	Konsolidationtherapy with rituximab after 6 x Fludara + Mitoxantrone vs 6 x R‐CHOP.

Characteristics of ongoing studies [ordered by study ID]

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GELA Study

Trial name or title
Methods
Participants
Interventions
Outcomes
Starting date
Contact information
Notes

Sonneveld

Trial name or title	Combination Chemotherapy Plus Filgrastim With or Without Rituximab in Treating Older Patients With Non‐Hodgkin's Lymphoma
Methods
Participants	Adult Diffuse Large Cell Lymphoma Adult Non‐Hodgkin's Lymphoma Grade 3 Follicular Lymphoma Mantle Cell Lymphoma
Interventions	Compare the efficacy of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), and filgrastim (G‐CSF) with or without rituximab on event‐free survival of elderly patients with intermediate or high‐risk non‐Hodgkin's lymphoma.
Outcomes	Compare the complete remission rate, overall survival, and disease‐free survival of patients treated with these regimens. Compare the toxicity of these regimens in these patients
Starting date	January 2002
Contact information	Sponsored by: Commissie Voor Klinisch Toegepast Onderzoek Information provided by: National Cancer Institute (NCI) ClinicalTrials.gov Identifier: NCT00028717
Notes

Data and analyses

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Comparison 1. Overall survival

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall survival Total group Show forest plot	7	1943	Peto Odds Ratio (95% CI)	0.65 [0.54, 0.78]
Open in figure viewer Analysis 1.1 Comparison 1 Overall survival, Outcome 1 Overall survival Total group.
2 Overall survival FL vs MCL Show forest plot	6	1740	Peto Odds Ratio (95% CI)	0.63 [0.51, 0.77]
Open in figure viewer Analysis 1.2 Comparison 1 Overall survival, Outcome 2 Overall survival FL vs MCL.
2.1 Follicular lymphoma	5	1480	Peto Odds Ratio (95% CI)	0.63 [0.51, 0.79]
2.2 Mantlecell lymphoma	3	260	Peto Odds Ratio (95% CI)	0.60 [0.37, 0.98]
3 Sensitivity: attrition bias Show forest plot	7	1943	Peto Odds Ratio (95% CI)	0.65 [0.54, 0.78]
Open in figure viewer Analysis 1.3 Comparison 1 Overall survival, Outcome 3 Sensitivity: attrition bias.
3.1 Less than 10% excluded from analysis	5	1694	Peto Odds Ratio (95% CI)	0.68 [0.55, 0.83]
3.2 More than 10% excluded from analysis	2	249	Peto Odds Ratio (95% CI)	0.50 [0.30, 0.83]
4 Overall survival_Doxorubicin vs Mitoxantrone Show forest plot	6	1622	Peto Odds Ratio (95% CI)	0.64 [0.52, 0.79]
Open in figure viewer Analysis 1.4 Comparison 1 Overall survival, Outcome 4 Overall survival_Doxorubicin vs Mitoxantrone.
4.1 Doxorubicin based regimen	3	1015	Peto Odds Ratio (95% CI)	0.70 [0.54, 0.91]
4.2 Mitoxantrone based regimen	3	607	Peto Odds Ratio (95% CI)	0.56 [0.40, 0.77]
5 Overall survival untreated vs treated patients Show forest plot	7	1943	Peto Odds Ratio (95% CI)	0.65 [0.54, 0.78]
Open in figure viewer Analysis 1.5 Comparison 1 Overall survival, Outcome 5 Overall survival untreated vs treated patients.
5.1 Untreated patients	5	1350	Peto Odds Ratio (95% CI)	0.66 [0.52, 0.84]
5.2 Treated patients	2	593	Peto Odds Ratio (95% CI)	0.63 [0.46, 0.86]
6 Overall survival_Anthracylin vs no‐Anthracylin treatment Show forest plot	7	1943	Peto Odds Ratio (95% CI)	0.65 [0.54, 0.78]
Open in figure viewer Analysis 1.6 Comparison 1 Overall survival, Outcome 6 Overall survival_Anthracylin vs no‐Anthracylin treatment.
6.1 Anthracyclin based regimen	6	1622	Peto Odds Ratio (95% CI)	0.64 [0.52, 0.79]
6.2 No anthracylin based regimen	1	321	Peto Odds Ratio (95% CI)	0.70 [0.40, 1.23]
7 Overall survival_Full Text vs Abstract Publication Show forest plot	7	1943	Peto Odds Ratio (95% CI)	0.65 [0.54, 0.78]
Open in figure viewer Analysis 1.7 Comparison 1 Overall survival, Outcome 7 Overall survival_Full Text vs Abstract Publication.
7.1 Full‐text	5	1464	Peto Odds Ratio (95% CI)	0.65 [0.52, 0.81]
7.2 Abstract Form	2	479	Peto Odds Ratio (95% CI)	0.64 [0.43, 0.94]
8 Overall survival_Alloc. concealment Show forest plot	7	1943	Peto Odds Ratio (95% CI)	0.65 [0.54, 0.78]
Open in figure viewer Analysis 1.8 Comparison 1 Overall survival, Outcome 8 Overall survival_Alloc. concealment.
8.1 Adaequate	6	1822	Peto Odds Ratio (95% CI)	0.64 [0.53, 0.78]
8.2 Not adaequate	1	121	Peto Odds Ratio (95% CI)	0.96 [0.32, 2.91]
9 Overall Survival _with or without second randomisation Show forest plot	7	1943	Peto Odds Ratio (95% CI)	0.65 [0.54, 0.78]
Open in figure viewer Analysis 1.9 Comparison 1 Overall survival, Outcome 9 Overall Survival _with or without second randomisation.
9.1 No second randomisation	3	800	Peto Odds Ratio (95% CI)	0.66 [0.48, 0.91]
9.2 Second randomisation	4	1143	Peto Odds Ratio (95% CI)	0.64 [0.51, 0.81]

Open in table viewer

Comparison 2. Disease Control

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 FFS Total group Show forest plot	7	1913	Peto Odds Ratio (95% CI)	0.62 [0.55, 0.71]
Open in figure viewer Analysis 2.1 Comparison 2 Disease Control, Outcome 1 FFS Total group.
2 FFS_FL vs MCL Show forest plot	5	1537	Peto Odds Ratio (95% CI)	0.58 [0.50, 0.67]
Open in figure viewer Analysis 2.2 Comparison 2 Disease Control, Outcome 2 FFS_FL vs MCL.
2.1 Follicular lymphoma	4	1415	Peto Odds Ratio (95% CI)	0.58 [0.50, 0.68]
2.2 Mantlecell lymphoma	1	122	Peto Odds Ratio (95% CI)	0.54 [0.33, 0.88]
3 FFS_Sensitivity: attrition bias Show forest plot	7	1913	Peto Odds Ratio (95% CI)	0.62 [0.55, 0.71]
Open in figure viewer Analysis 2.3 Comparison 2 Disease Control, Outcome 3 FFS_Sensitivity: attrition bias.
3.1 Less than 10% excluded from analysis	5	1694	Peto Odds Ratio (95% CI)	0.60 [0.52, 0.69]
3.2 More than 10% excluded from analysis	2	219	Peto Odds Ratio (95% CI)	0.76 [0.55, 1.06]
4 Disease control_Doxorubicin vs Mitoxantrone Show forest plot	6	1592	Peto Odds Ratio (95% CI)	0.62 [0.54, 0.72]
Open in figure viewer Analysis 2.4 Comparison 2 Disease Control, Outcome 4 Disease control_Doxorubicin vs Mitoxantrone.
4.1 Doxorubicin based regimen	3	1015	Peto Odds Ratio (95% CI)	0.60 [0.49, 0.72]
4.2 Mitoxantrone based regimen	3	577	Peto Odds Ratio (95% CI)	0.66 [0.53, 0.84]
5 Disease control_untreated vs treated patients Show forest plot	7	1913	Peto Odds Ratio (95% CI)	0.62 [0.55, 0.71]
Open in figure viewer Analysis 2.5 Comparison 2 Disease Control, Outcome 5 Disease control_untreated vs treated patients.
5.1 Untreated patients	5	1320	Peto Odds Ratio (95% CI)	0.61 [0.52, 0.72]
5.2 Treated patients	2	593	Peto Odds Ratio (95% CI)	0.65 [0.52, 0.80]
6 Disease control_Anthracylin vs no‐Anthracylin treatment Show forest plot	7	1913	Peto Odds Ratio (95% CI)	0.62 [0.55, 0.71]
Open in figure viewer Analysis 2.6 Comparison 2 Disease Control, Outcome 6 Disease control_Anthracylin vs no‐Anthracylin treatment.
6.1 Anthracyclin based regimen	6	1592	Peto Odds Ratio (95% CI)	0.62 [0.54, 0.72]
6.2 No anthracylin based regimen	1	321	Peto Odds Ratio (95% CI)	0.62 [0.47, 0.83]
7 Disease control_Full text vs abstract publication Show forest plot	7	1913	Peto Odds Ratio (95% CI)	0.62 [0.55, 0.71]
Open in figure viewer Analysis 2.7 Comparison 2 Disease Control, Outcome 7 Disease control_Full text vs abstract publication.
7.1 Full ‐Text	5	1464	Peto Odds Ratio (95% CI)	0.61 [0.52, 0.71]
7.2 Abstract form	2	449	Peto Odds Ratio (95% CI)	0.68 [0.52, 0.89]
8 FFS_Sensitivity: Alloc. concealment Show forest plot	7	1913	Peto Odds Ratio (95% CI)	0.62 [0.55, 0.71]
Open in figure viewer Analysis 2.8 Comparison 2 Disease Control, Outcome 8 FFS_Sensitivity: Alloc. concealment.
8.1 Allocation concealment adaequate	6	1822	Peto Odds Ratio (95% CI)	0.60 [0.53, 0.69]
8.2 Not adaequate	1	91	Peto Odds Ratio (95% CI)	0.98 [0.59, 1.61]
9 FFS_Endpoints according to start of measurement Show forest plot	6	1785	Peto Odds Ratio (95% CI)	0.62 [0.55, 0.72]
Open in figure viewer Analysis 2.9 Comparison 2 Disease Control, Outcome 9 FFS_Endpoints according to start of measurement.
9.1 Start of treatment	5	1427	Peto Odds Ratio (95% CI)	0.63 [0.54, 0.74]
9.2 End of treatment	1	358	Peto Odds Ratio (95% CI)	0.59 [0.43, 0.81]
10 FFS_Endpoints TTP, EFS, TTF, PFS Show forest plot	6		Peto Odds Ratio (95% CI)	Subtotals only
Open in figure viewer Analysis 2.10 Comparison 2 Disease Control, Outcome 10 FFS_Endpoints TTP, EFS, TTF, PFS.
10.1 Time to progression	2	412	Peto Odds Ratio (95% CI)	0.69 [0.54, 0.89]
10.2 Progression free survival	2	587	Peto Odds Ratio (95% CI)	0.63 [0.51, 0.78]
10.3 Time to treatment failure	2	550	Peto Odds Ratio (95% CI)	0.51 [0.37, 0.70]
10.4 Event free survival	1	201	Peto Odds Ratio (95% CI)	0.41 [0.26, 0.64]

Open in table viewer

Comparison 3. Overall Response

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall Response Total Group Show forest plot	7	1914	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [1.16, 1.27]
Open in figure viewer Analysis 3.1 Comparison 3 Overall Response, Outcome 1 Overall Response Total Group.
2 Overall Response FL vs MCL Show forest plot	7	1830	Risk Ratio (M‐H, Fixed, 95% CI)	1.19 [1.14, 1.24]
Open in figure viewer Analysis 3.2 Comparison 3 Overall Response, Outcome 2 Overall Response FL vs MCL.
2.1 follicular	6	1570	Risk Ratio (M‐H, Fixed, 95% CI)	1.19 [1.13, 1.24]
2.2 Mantle cell	3	260	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [1.05, 1.42]
3 Sensitivity: attrition bias Show forest plot	7	1914	Odds Ratio (M‐H, Fixed, 95% CI)	2.76 [2.17, 3.51]
Open in figure viewer Analysis 3.3 Comparison 3 Overall Response, Outcome 3 Sensitivity: attrition bias.
3.1 Less than 10% excluded from analysis	5	1693	Odds Ratio (M‐H, Fixed, 95% CI)	2.88 [2.22, 3.74]
3.2 More than 10% excluded from analysis	2	221	Odds Ratio (M‐H, Fixed, 95% CI)	2.10 [1.10, 4.01]
4 Overall Response_Doxorubicin vs Mitoxantrone Show forest plot	6	1593	Odds Ratio (M‐H, Fixed, 95% CI)	2.63 [1.99, 3.46]
Open in figure viewer Analysis 3.4 Comparison 3 Overall Response, Outcome 4 Overall Response_Doxorubicin vs Mitoxantrone.
4.1 Doxorubicin based regimen	3	1014	Odds Ratio (M‐H, Fixed, 95% CI)	2.58 [1.76, 3.76]
4.2 Mitoxantrone based regimen	3	579	Odds Ratio (M‐H, Fixed, 95% CI)	2.69 [1.80, 4.03]
5 Overall Response_untreated vs treated patients Show forest plot	7	1914	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [1.16, 1.27]
Open in figure viewer Analysis 3.5 Comparison 3 Overall Response, Outcome 5 Overall Response_untreated vs treated patients.
5.1 Untreated patients	5	1319	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [1.15, 1.28]
5.2 Treated patients	2	595	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [1.10, 1.32]
6 Overall response_Anthracyclin vs no‐Anthracyclin treatment Show forest plot	7	1914	Odds Ratio (M‐H, Fixed, 95% CI)	2.76 [2.17, 3.51]
Open in figure viewer Analysis 3.6 Comparison 3 Overall Response, Outcome 6 Overall response_Anthracyclin vs no‐Anthracyclin treatment.
6.1 Anthracyclin based regimen	6	1593	Odds Ratio (M‐H, Fixed, 95% CI)	2.63 [1.99, 3.46]
6.2 No Anthracyclin based regimen	1	321	Odds Ratio (M‐H, Fixed, 95% CI)	3.24 [1.96, 5.35]
7 Overall Response_Full text vs Abstract publication Show forest plot	7	1914	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [1.16, 1.27]
Open in figure viewer Analysis 3.7 Comparison 3 Overall Response, Outcome 7 Overall Response_Full text vs Abstract publication.
7.1 Full Text	5	1465	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [1.14, 1.26]
7.2 Abstract form	2	449	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [1.12, 1.38]
8 Overall Response Allocation concealment Show forest plot	7	1914	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [1.16, 1.27]
Open in figure viewer Analysis 3.8 Comparison 3 Overall Response, Outcome 8 Overall Response Allocation concealment.
8.1 Adaequate	6	1823	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [1.16, 1.28]
8.2 Not adaequate	1	91	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.90, 1.23]

Open in table viewer

Comparison 4. Complete Response

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Complete Response Total Group Show forest plot	7	1914	Risk Ratio (M‐H, Fixed, 95% CI)	2.03 [1.71, 2.40]
Open in figure viewer Analysis 4.1 Comparison 4 Complete Response, Outcome 1 Complete Response Total Group.
2 Complete Response FL vs MCL Show forest plot	6	2043	Risk Ratio (M‐H, Fixed, 95% CI)	2.26 [1.89, 2.71]
Open in figure viewer Analysis 4.2 Comparison 4 Complete Response, Outcome 2 Complete Response FL vs MCL.
2.1 Follicula lymphoma	5	1701	Risk Ratio (M‐H, Fixed, 95% CI)	2.16 [1.77, 2.63]
2.2 Mantle cell lymphoma	3	342	Risk Ratio (M‐H, Fixed, 95% CI)	2.90 [1.80, 4.67]
3 Complete Response_Doxorubicine vs Mitoxantrone Show forest plot	6	1593	Risk Ratio (M‐H, Fixed, 95% CI)	1.85 [1.55, 2.21]
Open in figure viewer Analysis 4.3 Comparison 4 Complete Response, Outcome 3 Complete Response_Doxorubicine vs Mitoxantrone.
3.1 Mitixantrone based regimen	3	579	Risk Ratio (M‐H, Fixed, 95% CI)	2.02 [1.58, 2.59]
3.2 Doxorubicine based regimen	3	1014	Risk Ratio (M‐H, Fixed, 95% CI)	1.71 [1.33, 2.21]
4 Complete Response_anthracycline vs no anthracyclin treatment Show forest plot	7	1914	Risk Ratio (M‐H, Fixed, 95% CI)	2.03 [1.71, 2.40]
Open in figure viewer Analysis 4.4 Comparison 4 Complete Response, Outcome 4 Complete Response_anthracycline vs no anthracyclin treatment.
4.1 Anthracyclin based regimen	6	1593	Risk Ratio (M‐H, Fixed, 95% CI)	1.85 [1.55, 2.21]
4.2 No Anthracyclin based regimen	1	321	Risk Ratio (M‐H, Fixed, 95% CI)	4.01 [2.22, 7.25]
5 Complete Response _untreated vs treated patients Show forest plot	7	1914	Risk Ratio (M‐H, Fixed, 95% CI)	2.03 [1.71, 2.40]
Open in figure viewer Analysis 4.5 Comparison 4 Complete Response, Outcome 5 Complete Response _untreated vs treated patients.
5.1 Complete remission untreated patients	5	1319	Risk Ratio (M‐H, Fixed, 95% CI)	2.03 [1.66, 2.48]
5.2 Complete remission_treated patients	2	595	Risk Ratio (M‐H, Fixed, 95% CI)	2.01 [1.45, 2.77]

Open in table viewer

Comparison 5. Toxicity Grade 3/4

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Adverse events (number of patients) Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 5.1 Comparison 5 Toxicity Grade 3/4, Outcome 1 Adverse events (number of patients).
1.1 Infection	4	1267	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.74, 1.48]
1.2 Fever	2	481	Risk Ratio (M‐H, Fixed, 95% CI)	3.79 [1.47, 9.78]
1.3 Leukocytopenia	2	681	Risk Ratio (M‐H, Fixed, 95% CI)	1.31 [1.11, 1.55]
1.4 Thrombocytopenia	4	1267	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.76, 1.72]
1.5 Granulocytopenia	3	907	Risk Ratio (M‐H, Fixed, 95% CI)	1.18 [1.00, 1.38]

Figure 1

Forest plot of comparison: 1 Overall survival, outcome: 1.1 Overall survival Total group.

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Figure 2

Forest plot of comparison: 1 Overall survival, outcome: 1.5 Overall survival untreated vs treated patients.

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Figure 3

Forest plot of comparison: 1 Overall survival, outcome: 1.8 Overall survival_Alloc. concealment.

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Figure 4

Forest plot of comparison: 1 Overall survival, outcome: 1.3 Sensitivity: attrition bias.

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Figure 5

Forest plot of comparison: 1 Overall survival, outcome: 1.7 Overall survival_Full Text vs Abstract Publication.

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Figure 6

Forest plot of comparison: 1 Overall survival, outcome: 1.2 Overall survival FL vs MCL.

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Figure 7

Forest plot of comparison: 2 Disease Control, outcome: 2.1 FFS Total group.

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Figure 8

Forest plot of comparison: 2 Disease Control, outcome: 2.9 FFS_Endpoints according to start of measurement.

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Figure 9

Forest plot of comparison: 2 Disease Control, outcome: 2.2 FFS_FL vs MCL.

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Figure 10

Forest plot of comparison: 3 Overall Response, outcome: 3.1 Overall Response Total Group.

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Figure 11

Forest plot of comparison: 4 Complete Response, outcome: 4.1 Complete Response Total Group.

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Figure 12

Forest plot of comparison: 3 Overall Response, outcome: 3.2 Overall Response FL vs MCL.

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Figure 13

Forest plot of comparison: 4 Complete Response, outcome: 4.2 Complete Response FL vs MCL.

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Figure 14

Forest plot of comparison: 5 Toxicity Grade 3/4, outcome: 5.1 Adverse events (number of patients).

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Analysis 1.1

Comparison 1 Overall survival, Outcome 1 Overall survival Total group.

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Analysis 1.2

Comparison 1 Overall survival, Outcome 2 Overall survival FL vs MCL.

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Analysis 1.3

Comparison 1 Overall survival, Outcome 3 Sensitivity: attrition bias.

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Analysis 1.4

Comparison 1 Overall survival, Outcome 4 Overall survival_Doxorubicin vs Mitoxantrone.

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Analysis 1.5

Comparison 1 Overall survival, Outcome 5 Overall survival untreated vs treated patients.

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Analysis 1.6

Comparison 1 Overall survival, Outcome 6 Overall survival_Anthracylin vs no‐Anthracylin treatment.

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Analysis 1.7

Comparison 1 Overall survival, Outcome 7 Overall survival_Full Text vs Abstract Publication.

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Analysis 1.8

Comparison 1 Overall survival, Outcome 8 Overall survival_Alloc. concealment.

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Analysis 1.9

Comparison 1 Overall survival, Outcome 9 Overall Survival _with or without second randomisation.

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Analysis 2.1

Comparison 2 Disease Control, Outcome 1 FFS Total group.

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Analysis 2.2

Comparison 2 Disease Control, Outcome 2 FFS_FL vs MCL.

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Analysis 2.3

Comparison 2 Disease Control, Outcome 3 FFS_Sensitivity: attrition bias.

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Analysis 2.4

Comparison 2 Disease Control, Outcome 4 Disease control_Doxorubicin vs Mitoxantrone.

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Analysis 2.5

Comparison 2 Disease Control, Outcome 5 Disease control_untreated vs treated patients.

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Analysis 2.6

Comparison 2 Disease Control, Outcome 6 Disease control_Anthracylin vs no‐Anthracylin treatment.

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Analysis 2.7

Comparison 2 Disease Control, Outcome 7 Disease control_Full text vs abstract publication.

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Analysis 2.8

Comparison 2 Disease Control, Outcome 8 FFS_Sensitivity: Alloc. concealment.

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Analysis 2.9

Comparison 2 Disease Control, Outcome 9 FFS_Endpoints according to start of measurement.

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Analysis 2.10

Comparison 2 Disease Control, Outcome 10 FFS_Endpoints TTP, EFS, TTF, PFS.

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Analysis 3.1

Comparison 3 Overall Response, Outcome 1 Overall Response Total Group.

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Analysis 3.2

Comparison 3 Overall Response, Outcome 2 Overall Response FL vs MCL.

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Analysis 3.3

Comparison 3 Overall Response, Outcome 3 Sensitivity: attrition bias.

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Analysis 3.4

Comparison 3 Overall Response, Outcome 4 Overall Response_Doxorubicin vs Mitoxantrone.

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Analysis 3.5

Comparison 3 Overall Response, Outcome 5 Overall Response_untreated vs treated patients.

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Analysis 3.6

Comparison 3 Overall Response, Outcome 6 Overall response_Anthracyclin vs no‐Anthracyclin treatment.

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Analysis 3.7

Comparison 3 Overall Response, Outcome 7 Overall Response_Full text vs Abstract publication.

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Analysis 3.8

Comparison 3 Overall Response, Outcome 8 Overall Response Allocation concealment.

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Analysis 4.1

Comparison 4 Complete Response, Outcome 1 Complete Response Total Group.

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Analysis 4.2

Comparison 4 Complete Response, Outcome 2 Complete Response FL vs MCL.

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Analysis 4.3

Comparison 4 Complete Response, Outcome 3 Complete Response_Doxorubicine vs Mitoxantrone.

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Analysis 4.4

Comparison 4 Complete Response, Outcome 4 Complete Response_anthracycline vs no anthracyclin treatment.

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Analysis 4.5

Comparison 4 Complete Response, Outcome 5 Complete Response _untreated vs treated patients.

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Analysis 5.1

Comparison 5 Toxicity Grade 3/4, Outcome 1 Adverse events (number of patients).

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Table 1. Trials included in the Meta‐Analysis

Author	Total Group (N)	FL (N)	MCL (N)	Unspecified lymphoma
Forstpointner 2004	128	65	48	15
Herold 2004	358	201	90	67
Hiddemann 2005	428	428	not included	none
Lenz 2005	122	none	122	none
Marcus 2005	321	321	none	none
Rivas‐Vera 2005	121	not applicable	not applicable	121
van Oers 2006	465	465	none	none
Total amount	1943	1480	260	203

Table 1. Trials included in the Meta‐Analysis

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Table 2. Characteristics of the included studies

Author	Therapy	Previous therapy	Ann Arbor stage	High FLIPI risk	Observation time
Forstpointner 2004	4 x R‐FCM vs 4 x FCM	Yes	III/IV	not applicable	18 months
Herold 2004	8 x R‐MCP vs 8 x MCP	No	III/IV	55%	36 months
Hiddemann 2005	6‐8 x R‐CHOP vs 6 to 8 x CHOP	No	III/IV	45%	36 months
Lenz 2005	6 x R‐CHOP vs 6 x CHOP	No	III/IV	35 % (IPI high and high‐intermediate risk)	18 months
Marcus 2005	8 x R‐CVP vs 8 CVP	No	III/IV	45%	18 months
Rivas‐Vera 2005	6 x R‐CNOP vs 6 x CNOP vs 6 x R	No	III/IV	not applicable	24 months
van Oers 2006	8 x R‐CHOP vs 8 x CHOP	Yes	III/IV	37%	39 months

Table 2. Characteristics of the included studies

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Table 3. Quality assessment of the included studies

Author	ITT‐ Analysis	Allocation concealed	Drop outs	Source of data
Forstpointner 2004	Yes	Yes	13%	Full text
Herold 2004	Yes	Yes	0	Abstract
Hiddemann 2005	Yes	Yes	0	Full text
Lenz 2005	Yes	Yes	5%	Full text
Marcus 2005	Yes	Yes	1%	Full text
Rivas‐Vera 2005	No	No	13%	Abstract
van Oers 2006	Yes	Yes	0	Full text

Table 3. Quality assessment of the included studies

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Comparison 1. Overall survival

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall survival Total group Show forest plot	7	1943	Peto Odds Ratio (95% CI)	0.65 [0.54, 0.78]

2 Overall survival FL vs MCL Show forest plot	6	1740	Peto Odds Ratio (95% CI)	0.63 [0.51, 0.77]

2.1 Follicular lymphoma	5	1480	Peto Odds Ratio (95% CI)	0.63 [0.51, 0.79]
2.2 Mantlecell lymphoma	3	260	Peto Odds Ratio (95% CI)	0.60 [0.37, 0.98]
3 Sensitivity: attrition bias Show forest plot	7	1943	Peto Odds Ratio (95% CI)	0.65 [0.54, 0.78]

3.1 Less than 10% excluded from analysis	5	1694	Peto Odds Ratio (95% CI)	0.68 [0.55, 0.83]
3.2 More than 10% excluded from analysis	2	249	Peto Odds Ratio (95% CI)	0.50 [0.30, 0.83]
4 Overall survival_Doxorubicin vs Mitoxantrone Show forest plot	6	1622	Peto Odds Ratio (95% CI)	0.64 [0.52, 0.79]

4.1 Doxorubicin based regimen	3	1015	Peto Odds Ratio (95% CI)	0.70 [0.54, 0.91]
4.2 Mitoxantrone based regimen	3	607	Peto Odds Ratio (95% CI)	0.56 [0.40, 0.77]
5 Overall survival untreated vs treated patients Show forest plot	7	1943	Peto Odds Ratio (95% CI)	0.65 [0.54, 0.78]

5.1 Untreated patients	5	1350	Peto Odds Ratio (95% CI)	0.66 [0.52, 0.84]
5.2 Treated patients	2	593	Peto Odds Ratio (95% CI)	0.63 [0.46, 0.86]
6 Overall survival_Anthracylin vs no‐Anthracylin treatment Show forest plot	7	1943	Peto Odds Ratio (95% CI)	0.65 [0.54, 0.78]

6.1 Anthracyclin based regimen	6	1622	Peto Odds Ratio (95% CI)	0.64 [0.52, 0.79]
6.2 No anthracylin based regimen	1	321	Peto Odds Ratio (95% CI)	0.70 [0.40, 1.23]
7 Overall survival_Full Text vs Abstract Publication Show forest plot	7	1943	Peto Odds Ratio (95% CI)	0.65 [0.54, 0.78]

7.1 Full‐text	5	1464	Peto Odds Ratio (95% CI)	0.65 [0.52, 0.81]
7.2 Abstract Form	2	479	Peto Odds Ratio (95% CI)	0.64 [0.43, 0.94]
8 Overall survival_Alloc. concealment Show forest plot	7	1943	Peto Odds Ratio (95% CI)	0.65 [0.54, 0.78]

8.1 Adaequate	6	1822	Peto Odds Ratio (95% CI)	0.64 [0.53, 0.78]
8.2 Not adaequate	1	121	Peto Odds Ratio (95% CI)	0.96 [0.32, 2.91]
9 Overall Survival _with or without second randomisation Show forest plot	7	1943	Peto Odds Ratio (95% CI)	0.65 [0.54, 0.78]

9.1 No second randomisation	3	800	Peto Odds Ratio (95% CI)	0.66 [0.48, 0.91]
9.2 Second randomisation	4	1143	Peto Odds Ratio (95% CI)	0.64 [0.51, 0.81]

Comparison 1. Overall survival

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Comparison 2. Disease Control

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 FFS Total group Show forest plot	7	1913	Peto Odds Ratio (95% CI)	0.62 [0.55, 0.71]

2 FFS_FL vs MCL Show forest plot	5	1537	Peto Odds Ratio (95% CI)	0.58 [0.50, 0.67]

2.1 Follicular lymphoma	4	1415	Peto Odds Ratio (95% CI)	0.58 [0.50, 0.68]
2.2 Mantlecell lymphoma	1	122	Peto Odds Ratio (95% CI)	0.54 [0.33, 0.88]
3 FFS_Sensitivity: attrition bias Show forest plot	7	1913	Peto Odds Ratio (95% CI)	0.62 [0.55, 0.71]

3.1 Less than 10% excluded from analysis	5	1694	Peto Odds Ratio (95% CI)	0.60 [0.52, 0.69]
3.2 More than 10% excluded from analysis	2	219	Peto Odds Ratio (95% CI)	0.76 [0.55, 1.06]
4 Disease control_Doxorubicin vs Mitoxantrone Show forest plot	6	1592	Peto Odds Ratio (95% CI)	0.62 [0.54, 0.72]

4.1 Doxorubicin based regimen	3	1015	Peto Odds Ratio (95% CI)	0.60 [0.49, 0.72]
4.2 Mitoxantrone based regimen	3	577	Peto Odds Ratio (95% CI)	0.66 [0.53, 0.84]
5 Disease control_untreated vs treated patients Show forest plot	7	1913	Peto Odds Ratio (95% CI)	0.62 [0.55, 0.71]

5.1 Untreated patients	5	1320	Peto Odds Ratio (95% CI)	0.61 [0.52, 0.72]
5.2 Treated patients	2	593	Peto Odds Ratio (95% CI)	0.65 [0.52, 0.80]
6 Disease control_Anthracylin vs no‐Anthracylin treatment Show forest plot	7	1913	Peto Odds Ratio (95% CI)	0.62 [0.55, 0.71]

6.1 Anthracyclin based regimen	6	1592	Peto Odds Ratio (95% CI)	0.62 [0.54, 0.72]
6.2 No anthracylin based regimen	1	321	Peto Odds Ratio (95% CI)	0.62 [0.47, 0.83]
7 Disease control_Full text vs abstract publication Show forest plot	7	1913	Peto Odds Ratio (95% CI)	0.62 [0.55, 0.71]

7.1 Full ‐Text	5	1464	Peto Odds Ratio (95% CI)	0.61 [0.52, 0.71]
7.2 Abstract form	2	449	Peto Odds Ratio (95% CI)	0.68 [0.52, 0.89]
8 FFS_Sensitivity: Alloc. concealment Show forest plot	7	1913	Peto Odds Ratio (95% CI)	0.62 [0.55, 0.71]

8.1 Allocation concealment adaequate	6	1822	Peto Odds Ratio (95% CI)	0.60 [0.53, 0.69]
8.2 Not adaequate	1	91	Peto Odds Ratio (95% CI)	0.98 [0.59, 1.61]
9 FFS_Endpoints according to start of measurement Show forest plot	6	1785	Peto Odds Ratio (95% CI)	0.62 [0.55, 0.72]

9.1 Start of treatment	5	1427	Peto Odds Ratio (95% CI)	0.63 [0.54, 0.74]
9.2 End of treatment	1	358	Peto Odds Ratio (95% CI)	0.59 [0.43, 0.81]
10 FFS_Endpoints TTP, EFS, TTF, PFS Show forest plot	6		Peto Odds Ratio (95% CI)	Subtotals only

10.1 Time to progression	2	412	Peto Odds Ratio (95% CI)	0.69 [0.54, 0.89]
10.2 Progression free survival	2	587	Peto Odds Ratio (95% CI)	0.63 [0.51, 0.78]
10.3 Time to treatment failure	2	550	Peto Odds Ratio (95% CI)	0.51 [0.37, 0.70]
10.4 Event free survival	1	201	Peto Odds Ratio (95% CI)	0.41 [0.26, 0.64]

Comparison 2. Disease Control

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Comparison 3. Overall Response

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall Response Total Group Show forest plot	7	1914	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [1.16, 1.27]

2 Overall Response FL vs MCL Show forest plot	7	1830	Risk Ratio (M‐H, Fixed, 95% CI)	1.19 [1.14, 1.24]

2.1 follicular	6	1570	Risk Ratio (M‐H, Fixed, 95% CI)	1.19 [1.13, 1.24]
2.2 Mantle cell	3	260	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [1.05, 1.42]
3 Sensitivity: attrition bias Show forest plot	7	1914	Odds Ratio (M‐H, Fixed, 95% CI)	2.76 [2.17, 3.51]

3.1 Less than 10% excluded from analysis	5	1693	Odds Ratio (M‐H, Fixed, 95% CI)	2.88 [2.22, 3.74]
3.2 More than 10% excluded from analysis	2	221	Odds Ratio (M‐H, Fixed, 95% CI)	2.10 [1.10, 4.01]
4 Overall Response_Doxorubicin vs Mitoxantrone Show forest plot	6	1593	Odds Ratio (M‐H, Fixed, 95% CI)	2.63 [1.99, 3.46]

4.1 Doxorubicin based regimen	3	1014	Odds Ratio (M‐H, Fixed, 95% CI)	2.58 [1.76, 3.76]
4.2 Mitoxantrone based regimen	3	579	Odds Ratio (M‐H, Fixed, 95% CI)	2.69 [1.80, 4.03]
5 Overall Response_untreated vs treated patients Show forest plot	7	1914	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [1.16, 1.27]

5.1 Untreated patients	5	1319	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [1.15, 1.28]
5.2 Treated patients	2	595	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [1.10, 1.32]
6 Overall response_Anthracyclin vs no‐Anthracyclin treatment Show forest plot	7	1914	Odds Ratio (M‐H, Fixed, 95% CI)	2.76 [2.17, 3.51]

6.1 Anthracyclin based regimen	6	1593	Odds Ratio (M‐H, Fixed, 95% CI)	2.63 [1.99, 3.46]
6.2 No Anthracyclin based regimen	1	321	Odds Ratio (M‐H, Fixed, 95% CI)	3.24 [1.96, 5.35]
7 Overall Response_Full text vs Abstract publication Show forest plot	7	1914	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [1.16, 1.27]

7.1 Full Text	5	1465	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [1.14, 1.26]
7.2 Abstract form	2	449	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [1.12, 1.38]
8 Overall Response Allocation concealment Show forest plot	7	1914	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [1.16, 1.27]

8.1 Adaequate	6	1823	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [1.16, 1.28]
8.2 Not adaequate	1	91	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.90, 1.23]

Comparison 3. Overall Response

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Comparison 4. Complete Response

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Complete Response Total Group Show forest plot	7	1914	Risk Ratio (M‐H, Fixed, 95% CI)	2.03 [1.71, 2.40]

2 Complete Response FL vs MCL Show forest plot	6	2043	Risk Ratio (M‐H, Fixed, 95% CI)	2.26 [1.89, 2.71]

2.1 Follicula lymphoma	5	1701	Risk Ratio (M‐H, Fixed, 95% CI)	2.16 [1.77, 2.63]
2.2 Mantle cell lymphoma	3	342	Risk Ratio (M‐H, Fixed, 95% CI)	2.90 [1.80, 4.67]
3 Complete Response_Doxorubicine vs Mitoxantrone Show forest plot	6	1593	Risk Ratio (M‐H, Fixed, 95% CI)	1.85 [1.55, 2.21]

3.1 Mitixantrone based regimen	3	579	Risk Ratio (M‐H, Fixed, 95% CI)	2.02 [1.58, 2.59]
3.2 Doxorubicine based regimen	3	1014	Risk Ratio (M‐H, Fixed, 95% CI)	1.71 [1.33, 2.21]
4 Complete Response_anthracycline vs no anthracyclin treatment Show forest plot	7	1914	Risk Ratio (M‐H, Fixed, 95% CI)	2.03 [1.71, 2.40]

4.1 Anthracyclin based regimen	6	1593	Risk Ratio (M‐H, Fixed, 95% CI)	1.85 [1.55, 2.21]
4.2 No Anthracyclin based regimen	1	321	Risk Ratio (M‐H, Fixed, 95% CI)	4.01 [2.22, 7.25]
5 Complete Response _untreated vs treated patients Show forest plot	7	1914	Risk Ratio (M‐H, Fixed, 95% CI)	2.03 [1.71, 2.40]

5.1 Complete remission untreated patients	5	1319	Risk Ratio (M‐H, Fixed, 95% CI)	2.03 [1.66, 2.48]
5.2 Complete remission_treated patients	2	595	Risk Ratio (M‐H, Fixed, 95% CI)	2.01 [1.45, 2.77]

Comparison 4. Complete Response

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Comparison 5. Toxicity Grade 3/4

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Adverse events (number of patients) Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Infection	4	1267	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.74, 1.48]
1.2 Fever	2	481	Risk Ratio (M‐H, Fixed, 95% CI)	3.79 [1.47, 9.78]
1.3 Leukocytopenia	2	681	Risk Ratio (M‐H, Fixed, 95% CI)	1.31 [1.11, 1.55]
1.4 Thrombocytopenia	4	1267	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.76, 1.72]
1.5 Granulocytopenia	3	907	Risk Ratio (M‐H, Fixed, 95% CI)	1.18 [1.00, 1.38]

Comparison 5. Toxicity Grade 3/4

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Referencias

Referencias de los estudios incluidos en esta revisión

Forstpointner 2004 {published and unpublished data}

Herold 2004 {published and unpublished data}

Hiddemann 2005 {published data only}

Lenz 2005 {published data only}

Marcus 2005 {published data only}

Rivas‐Vera 2005 {published data only}

van Oers 2006 {published data only}

Referencias de los estudios excluidos de esta revisión

Byrd JC {published data only}

Cohen 2002 {published data only}

Czuczman {published data only}

Czuczman M {published data only}

Doelken G {published data only}

Ghielmeni M {published data only}

Gregory S {published data only}

Hainsworth J {published data only}

Hochster H {published data only}

Huang J {published data only}

Jiang Y {published data only}

Katakkar S {published data only}

Meckenstock G {published data only}

Pettengell {published data only}

Rambaldi A {published data only}

Rule S {published data only}

Salles G {published data only}

Solal‐Celigny P {published data only}

Tobinai {published data only}

Vitolo {published data only}

Witzig {published data only}

Zinzani PL {published data only}

Referencias de los estudios en curso

GELA Study {published data only}

Sonneveld {published data only}

Referencias adicionales

Altman 1999

Ardeshna 2003

Barosi 2006

Bonavida 2005

Boye 2003

Brice 1997

Brody 2006

Czuczman 1999

Czuczman 2004

Demidem 1997

Dickersin 1994

Dreyling 2006

Egger 1997

Feugier 2005

Fisher 1993

Gallagher 1986

Habermann 2005

Horning 1993

Ihaka 1996

Imrie 2005

Jazirehi 2005

Jazirehi 2005a

Juni 2001

Kober 2002

Landis 1998

Liu 2006

McLaughlin 1986

McLaughlin 1998

Montoto 2003

Parmar 1998

Rosenberg 1971

Solal‐Celigny 2004

Swenson 2005

Williams 2001

Zinzani 1998

Referencias de otras versiones publicadas de esta revisión

Schulz 2007

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Characteristics of ongoing studies [ordered by study ID]

Data and analyses