Scolaris Content Display Scolaris Content Display

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Forest plot of comparison: 1 Analysis of Overall Survival, outcome: 1.1 OS ‐ all ‐ same recruitment period between the 2 arms (HD9).
Figures and Tables -
Figure 2

Forest plot of comparison: 1 Analysis of Overall Survival, outcome: 1.1 OS ‐ all ‐ same recruitment period between the 2 arms (HD9).

Forest plot of comparison: 2 Analysis of Progression Free Survival, outcome: 2.1 PFS ‐ all ‐ same recruitment period between the 2 arms (HD9).
Figures and Tables -
Figure 3

Forest plot of comparison: 2 Analysis of Progression Free Survival, outcome: 2.1 PFS ‐ all ‐ same recruitment period between the 2 arms (HD9).

Forest plot of comparison: 3 Analysis of complete response (CR) rate, outcome: 3.1 CR.
Figures and Tables -
Figure 4

Forest plot of comparison: 3 Analysis of complete response (CR) rate, outcome: 3.1 CR.

Comparison 1 Analysis overall survival, Outcome 1 OS ‐ all ‐ same recruitment period between the 2 arms (HD9).
Figures and Tables -
Analysis 1.1

Comparison 1 Analysis overall survival, Outcome 1 OS ‐ all ‐ same recruitment period between the 2 arms (HD9).

Comparison 1 Analysis overall survival, Outcome 2 OS subgrouped by stage of disease.
Figures and Tables -
Analysis 1.2

Comparison 1 Analysis overall survival, Outcome 2 OS subgrouped by stage of disease.

Comparison 1 Analysis overall survival, Outcome 3 OS subgrouped by treatment.
Figures and Tables -
Analysis 1.3

Comparison 1 Analysis overall survival, Outcome 3 OS subgrouped by treatment.

Comparison 1 Analysis overall survival, Outcome 4 OS subgrouped by number of cycles of escalated BEACOPP.
Figures and Tables -
Analysis 1.4

Comparison 1 Analysis overall survival, Outcome 4 OS subgrouped by number of cycles of escalated BEACOPP.

Comparison 1 Analysis overall survival, Outcome 5 OS subgrouped by length of follow‐up.
Figures and Tables -
Analysis 1.5

Comparison 1 Analysis overall survival, Outcome 5 OS subgrouped by length of follow‐up.

Comparison 1 Analysis overall survival, Outcome 6 OS subgrouped by publication form.
Figures and Tables -
Analysis 1.6

Comparison 1 Analysis overall survival, Outcome 6 OS subgrouped by publication form.

Comparison 1 Analysis overall survival, Outcome 7 OS subgrouped by type of results.
Figures and Tables -
Analysis 1.7

Comparison 1 Analysis overall survival, Outcome 7 OS subgrouped by type of results.

Comparison 1 Analysis overall survival, Outcome 8 OS ‐ all recruited patients (HD9) with potential risk of bias due to different time periods of recruitment.
Figures and Tables -
Analysis 1.8

Comparison 1 Analysis overall survival, Outcome 8 OS ‐ all recruited patients (HD9) with potential risk of bias due to different time periods of recruitment.

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 1 PFS ‐ all ‐ same recruitment period between the 2 arms (HD9).
Figures and Tables -
Analysis 2.1

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 1 PFS ‐ all ‐ same recruitment period between the 2 arms (HD9).

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 2 PFS subgrouped by stage of disease.
Figures and Tables -
Analysis 2.2

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 2 PFS subgrouped by stage of disease.

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 3 PFS subgrouped by treatment.
Figures and Tables -
Analysis 2.3

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 3 PFS subgrouped by treatment.

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 4 PFS subgrouped by number of cycles of escalated BEACOPP.
Figures and Tables -
Analysis 2.4

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 4 PFS subgrouped by number of cycles of escalated BEACOPP.

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 5 PFS subgrouped by length of follow‐up.
Figures and Tables -
Analysis 2.5

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 5 PFS subgrouped by length of follow‐up.

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 6 PFS subgrouped by publication form.
Figures and Tables -
Analysis 2.6

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 6 PFS subgrouped by publication form.

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 7 PFS subgrouped by type of results.
Figures and Tables -
Analysis 2.7

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 7 PFS subgrouped by type of results.

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 8 PFS ‐ all recruited patients (HD9) with potential risk of bias due to different time periods of recruitment.
Figures and Tables -
Analysis 2.8

Comparison 2 Analysis of progression‐free survival (PFS), Outcome 8 PFS ‐ all recruited patients (HD9) with potential risk of bias due to different time periods of recruitment.

Comparison 3 Analysis of complete response (CR) rate, Outcome 1 CR.
Figures and Tables -
Analysis 3.1

Comparison 3 Analysis of complete response (CR) rate, Outcome 1 CR.

Comparison 3 Analysis of complete response (CR) rate, Outcome 2 CR subgrouped by treatment.
Figures and Tables -
Analysis 3.2

Comparison 3 Analysis of complete response (CR) rate, Outcome 2 CR subgrouped by treatment.

Comparison 3 Analysis of complete response (CR) rate, Outcome 3 CR subgrouped by number of cycles of escalated BEACOPP.
Figures and Tables -
Analysis 3.3

Comparison 3 Analysis of complete response (CR) rate, Outcome 3 CR subgrouped by number of cycles of escalated BEACOPP.

Comparison 3 Analysis of complete response (CR) rate, Outcome 4 CR subgrouped by length of follow‐up.
Figures and Tables -
Analysis 3.4

Comparison 3 Analysis of complete response (CR) rate, Outcome 4 CR subgrouped by length of follow‐up.

Comparison 3 Analysis of complete response (CR) rate, Outcome 5 CR subgrouped by publication form.
Figures and Tables -
Analysis 3.5

Comparison 3 Analysis of complete response (CR) rate, Outcome 5 CR subgrouped by publication form.

Comparison 4 Analysis of freedom from first progression, Outcome 1 Freedom from first progression.
Figures and Tables -
Analysis 4.1

Comparison 4 Analysis of freedom from first progression, Outcome 1 Freedom from first progression.

Comparison 5 Analysis of treatment‐related mortality, Outcome 1 Treatment‐related mortality.
Figures and Tables -
Analysis 5.1

Comparison 5 Analysis of treatment‐related mortality, Outcome 1 Treatment‐related mortality.

Comparison 6 Analysis of secondary malignancies, Outcome 1 Secondary malignancies.
Figures and Tables -
Analysis 6.1

Comparison 6 Analysis of secondary malignancies, Outcome 1 Secondary malignancies.

Comparison 6 Analysis of secondary malignancies, Outcome 2 Secondary malignancies subgrouped by stage of disease.
Figures and Tables -
Analysis 6.2

Comparison 6 Analysis of secondary malignancies, Outcome 2 Secondary malignancies subgrouped by stage of disease.

Comparison 6 Analysis of secondary malignancies, Outcome 3 Subgrouped by treatment.
Figures and Tables -
Analysis 6.3

Comparison 6 Analysis of secondary malignancies, Outcome 3 Subgrouped by treatment.

Comparison 6 Analysis of secondary malignancies, Outcome 4 Subgrouped by number of cycles of escalated BEACOPP.
Figures and Tables -
Analysis 6.4

Comparison 6 Analysis of secondary malignancies, Outcome 4 Subgrouped by number of cycles of escalated BEACOPP.

Comparison 6 Analysis of secondary malignancies, Outcome 5 Subgrouped by length of follow‐up.
Figures and Tables -
Analysis 6.5

Comparison 6 Analysis of secondary malignancies, Outcome 5 Subgrouped by length of follow‐up.

Comparison 6 Analysis of secondary malignancies, Outcome 6 Subgrouped by publication form.
Figures and Tables -
Analysis 6.6

Comparison 6 Analysis of secondary malignancies, Outcome 6 Subgrouped by publication form.

Comparison 6 Analysis of secondary malignancies, Outcome 7 Subgrouped by type of results.
Figures and Tables -
Analysis 6.7

Comparison 6 Analysis of secondary malignancies, Outcome 7 Subgrouped by type of results.

Comparison 7 Analysis of AML or MDS, Outcome 1 AML or MDS.
Figures and Tables -
Analysis 7.1

Comparison 7 Analysis of AML or MDS, Outcome 1 AML or MDS.

Comparison 8 Analysis of fertility, Outcome 1 Secondary amenorrhoea.
Figures and Tables -
Analysis 8.1

Comparison 8 Analysis of fertility, Outcome 1 Secondary amenorrhoea.

Comparison 9 Analysis of anaemia, Outcome 1 Anaemia.
Figures and Tables -
Analysis 9.1

Comparison 9 Analysis of anaemia, Outcome 1 Anaemia.

Comparison 9 Analysis of anaemia, Outcome 2 Subgrouped by stage of disease.
Figures and Tables -
Analysis 9.2

Comparison 9 Analysis of anaemia, Outcome 2 Subgrouped by stage of disease.

Comparison 9 Analysis of anaemia, Outcome 3 Subgrouped by treatment.
Figures and Tables -
Analysis 9.3

Comparison 9 Analysis of anaemia, Outcome 3 Subgrouped by treatment.

Comparison 9 Analysis of anaemia, Outcome 4 Subgrouped by number of cycles of escalated BEACOPP.
Figures and Tables -
Analysis 9.4

Comparison 9 Analysis of anaemia, Outcome 4 Subgrouped by number of cycles of escalated BEACOPP.

Comparison 9 Analysis of anaemia, Outcome 5 Subgrouped by length of follow‐up.
Figures and Tables -
Analysis 9.5

Comparison 9 Analysis of anaemia, Outcome 5 Subgrouped by length of follow‐up.

Comparison 9 Analysis of anaemia, Outcome 6 Subgrouped by publication form.
Figures and Tables -
Analysis 9.6

Comparison 9 Analysis of anaemia, Outcome 6 Subgrouped by publication form.

Comparison 9 Analysis of anaemia, Outcome 7 Subgrouped by type of results.
Figures and Tables -
Analysis 9.7

Comparison 9 Analysis of anaemia, Outcome 7 Subgrouped by type of results.

Comparison 10 Analysis of infection, Outcome 1 Infection.
Figures and Tables -
Analysis 10.1

Comparison 10 Analysis of infection, Outcome 1 Infection.

Comparison 10 Analysis of infection, Outcome 2 Subgrouped by stage of disease.
Figures and Tables -
Analysis 10.2

Comparison 10 Analysis of infection, Outcome 2 Subgrouped by stage of disease.

Comparison 10 Analysis of infection, Outcome 3 Subgrouped by treatment.
Figures and Tables -
Analysis 10.3

Comparison 10 Analysis of infection, Outcome 3 Subgrouped by treatment.

Comparison 10 Analysis of infection, Outcome 4 Subgrouped by number of cycles of escalated BEACOPP.
Figures and Tables -
Analysis 10.4

Comparison 10 Analysis of infection, Outcome 4 Subgrouped by number of cycles of escalated BEACOPP.

Comparison 10 Analysis of infection, Outcome 5 Subgrouped by length of follow‐up.
Figures and Tables -
Analysis 10.5

Comparison 10 Analysis of infection, Outcome 5 Subgrouped by length of follow‐up.

Comparison 10 Analysis of infection, Outcome 6 Subgrouped by publication form.
Figures and Tables -
Analysis 10.6

Comparison 10 Analysis of infection, Outcome 6 Subgrouped by publication form.

Comparison 10 Analysis of infection, Outcome 7 Subgrouped by type of results.
Figures and Tables -
Analysis 10.7

Comparison 10 Analysis of infection, Outcome 7 Subgrouped by type of results.

Comparison 11 Analysis of leucopenia, Outcome 1 Leucopenia.
Figures and Tables -
Analysis 11.1

Comparison 11 Analysis of leucopenia, Outcome 1 Leucopenia.

Comparison 11 Analysis of leucopenia, Outcome 2 Subgrouped by stage of disease.
Figures and Tables -
Analysis 11.2

Comparison 11 Analysis of leucopenia, Outcome 2 Subgrouped by stage of disease.

Comparison 11 Analysis of leucopenia, Outcome 3 Subgrouped by treatment.
Figures and Tables -
Analysis 11.3

Comparison 11 Analysis of leucopenia, Outcome 3 Subgrouped by treatment.

Comparison 11 Analysis of leucopenia, Outcome 4 Subgrouped by number of cycles of escalated BEACOPP.
Figures and Tables -
Analysis 11.4

Comparison 11 Analysis of leucopenia, Outcome 4 Subgrouped by number of cycles of escalated BEACOPP.

Comparison 11 Analysis of leucopenia, Outcome 5 Subgrouped by length of follow‐up.
Figures and Tables -
Analysis 11.5

Comparison 11 Analysis of leucopenia, Outcome 5 Subgrouped by length of follow‐up.

Comparison 11 Analysis of leucopenia, Outcome 6 Subgrouped by publication form.
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Analysis 11.6

Comparison 11 Analysis of leucopenia, Outcome 6 Subgrouped by publication form.

Comparison 11 Analysis of leucopenia, Outcome 7 Subgrouped by type of results.
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Analysis 11.7

Comparison 11 Analysis of leucopenia, Outcome 7 Subgrouped by type of results.

Comparison 12 Analysis of neutropenia, Outcome 1 Neutropenia.
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Analysis 12.1

Comparison 12 Analysis of neutropenia, Outcome 1 Neutropenia.

Comparison 13 Analysis of thrombocytopenia, Outcome 1 Thrombocytopenia.
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Analysis 13.1

Comparison 13 Analysis of thrombocytopenia, Outcome 1 Thrombocytopenia.

Comparison 13 Analysis of thrombocytopenia, Outcome 2 Subgrouped by stage of disease.
Figures and Tables -
Analysis 13.2

Comparison 13 Analysis of thrombocytopenia, Outcome 2 Subgrouped by stage of disease.

Comparison 13 Analysis of thrombocytopenia, Outcome 3 Subgrouped by treatment.
Figures and Tables -
Analysis 13.3

Comparison 13 Analysis of thrombocytopenia, Outcome 3 Subgrouped by treatment.

Comparison 13 Analysis of thrombocytopenia, Outcome 4 Subgrouped by number of cycles of escalated BEACOPP.
Figures and Tables -
Analysis 13.4

Comparison 13 Analysis of thrombocytopenia, Outcome 4 Subgrouped by number of cycles of escalated BEACOPP.

Comparison 13 Analysis of thrombocytopenia, Outcome 5 Subgrouped by length of follow‐up.
Figures and Tables -
Analysis 13.5

Comparison 13 Analysis of thrombocytopenia, Outcome 5 Subgrouped by length of follow‐up.

Comparison 13 Analysis of thrombocytopenia, Outcome 6 Subgrouped by publication form.
Figures and Tables -
Analysis 13.6

Comparison 13 Analysis of thrombocytopenia, Outcome 6 Subgrouped by publication form.

Comparison 13 Analysis of thrombocytopenia, Outcome 7 Subgrouped by type of results.
Figures and Tables -
Analysis 13.7

Comparison 13 Analysis of thrombocytopenia, Outcome 7 Subgrouped by type of results.

Comparison 14 Analysis of alopecia, Outcome 1 Alopecia.
Figures and Tables -
Analysis 14.1

Comparison 14 Analysis of alopecia, Outcome 1 Alopecia.

Comparison 14 Analysis of alopecia, Outcome 2 Subgrouped by stage of disease.
Figures and Tables -
Analysis 14.2

Comparison 14 Analysis of alopecia, Outcome 2 Subgrouped by stage of disease.

Comparison 14 Analysis of alopecia, Outcome 3 Subgrouped by treatment.
Figures and Tables -
Analysis 14.3

Comparison 14 Analysis of alopecia, Outcome 3 Subgrouped by treatment.

Comparison 14 Analysis of alopecia, Outcome 4 Subgrouped by number of cycles of escalated BEACOPP.
Figures and Tables -
Analysis 14.4

Comparison 14 Analysis of alopecia, Outcome 4 Subgrouped by number of cycles of escalated BEACOPP.

Comparison 14 Analysis of alopecia, Outcome 5 Subgrouped by length of follow‐up.
Figures and Tables -
Analysis 14.5

Comparison 14 Analysis of alopecia, Outcome 5 Subgrouped by length of follow‐up.

Comparison 14 Analysis of alopecia, Outcome 6 Subgrouped by publication form.
Figures and Tables -
Analysis 14.6

Comparison 14 Analysis of alopecia, Outcome 6 Subgrouped by publication form.

Comparison 14 Analysis of alopecia, Outcome 7 Subgrouped by type of results.
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Analysis 14.7

Comparison 14 Analysis of alopecia, Outcome 7 Subgrouped by type of results.

Comparison 15 Analysis of constipation, Outcome 1 Constipation.
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Analysis 15.1

Comparison 15 Analysis of constipation, Outcome 1 Constipation.

Comparison 16 Analysis of mucositis, Outcome 1 Mucositis.
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Analysis 16.1

Comparison 16 Analysis of mucositis, Outcome 1 Mucositis.

Comparison 17 Analysis of nausea/vomiting, Outcome 1 Nausea/vomiting.
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Analysis 17.1

Comparison 17 Analysis of nausea/vomiting, Outcome 1 Nausea/vomiting.

Comparison 18 Analysis of neurologic, Outcome 1 Neurologic.
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Analysis 18.1

Comparison 18 Analysis of neurologic, Outcome 1 Neurologic.

Comparison 19 Analysis of pain, Outcome 1 Pain.
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Analysis 19.1

Comparison 19 Analysis of pain, Outcome 1 Pain.

Comparison 20 Analysis of respiratory, Outcome 1 Respiratory.
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Analysis 20.1

Comparison 20 Analysis of respiratory, Outcome 1 Respiratory.

Comparison 21 Analysis of skin, Outcome 1 Skin.
Figures and Tables -
Analysis 21.1

Comparison 21 Analysis of skin, Outcome 1 Skin.

Chemotherapy including escalated BEACOPP compared with chemotherapy including ABVD for patients with early unfavourable or advanced stage Hodgkin lymphoma

Patient or population: patients with early unfavourable or advanced stage Hodgkin lymphoma

Intervention: chemotherapy including escalated BEACOPP

Comparison: chemotherapy including ABVD

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

ABVD

escalated BEACOPP

OS

Low risk population1

HR 0.80 [0.59 to 1.09]

2586
(4 studies)

+++O
moderate4

100 deaths per 1000

81 per 1000
(60 to 108)

High risk population2

250 deaths per 1000

206 per 1000
(156 to 269)

PFS

Low risk population3

HR 0.53 [0.44 to 0.64]

2586
(4 studies)

+++O
moderate5

100 progressions or relapses per 1000

54 per 1000
(45 to 65)

High risk population2

330 progressions or relapses per 1000

191 per 1000
(162 to 226)

CR rate

High risk population2

RR 1.11 [1.06 to 1.16]

1245
(3 studies)

++++
high

831 complete responses per 1000

922 per 1000
(881 to 964)

Adverse events WHO grade III or IV

See comment

See comment

See comment

2547
(3 studies)

+++O6
moderate

Escalated BEACOPP regimens cause more haematological toxicities, infections, alopecia, mucositis and pain. No differences were found for constipation, nausea, neurologic toxicity.

Incidence of secondary malignancies

Low risk population2

RR 0.95 (0.61 to 1.48)

2547
(3 studies)

++OO
low7

As most of the trials had a median observation of less than 10 years, sufficient long term information on secondary malignancies cannot be expected.

2 per 1000

2 per 1000 (2 to 2)

High risk population2

44 per 1000

42 per 1000
(25 to 65)

Incidence of infertility

375 per 1000

514 per 1000

(311 to 847)

RR 1.37 [0.83 to 2.26]

106
(1 study)

+OOO
very low8

The subset of only 106 out of 608 eligible women of the HD9 were available for analyses regarding infertility. Reasons for availability are unknown and might have introduced bias in the results.

Treatment related mortality

See comment

See comment

RR 5.05 (0.25 to 103.87)

197
(1 study)

+OOO
very low9

No participant died in the control group and 2 died in the intervention group of the only study that reported this outcome.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk Ratio; HR: Hazard Ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1The risk for the "low risk population" (i.e. patients with early unfavourable HL) was taken from the GHSG HD8 trial, because the HD14 trial did not provide sufficient information regarding the control risk.

2The risk for the "high risk population" (i.e. patients with advanced stage of HL) was approximately the risk of the GHSG HD9 trial.

3The risk for the "low risk population" (i.e. patients with early unfavourable HL) was taken from the GHSG HD14 trial.

4 The median follow‐up varied between the trials. Longer follow‐ups and the inclusion of the EORTC 20012 trial will lead to a more precise estimate of the effect. This uncertainty causes the downgrading here.

5The definition of how to assess progression of disease varied between the trials. These heterogeneous definitions lead to an imprecise estimate of the effect that causes the downgrading here.

6So far two of the four trials reported results regarding adverse effects. The inclusion of further trials might lead to a more precise estimate of the effect. This uncertainty causes the downgrading here.

7 So far two of the four trials reported results regarding secondary malignancies. Furthermore, as most of the trials had a median observation of less than 10 years, sufficient long term information on secondary malignancies cannot be expected. The inclusion of further trials and results of longer follow‐up might lead to a more precise estimate of the effect. This uncertainty causes the downgrading here.

8 So far only 106 patients of the HD9 were analysed regarding infertility. The inclusion of further trials will lead to a more precise estimate of the effect.This uncertainty causes the downgrading here.

9 So far one of the four trials reported results regarding treatment‐related mortality. The inclusion of further trials will lead to a more precise estimate of the effect.This uncertainty causes the downgrading here.

Figures and Tables -
Comparison 1. Analysis overall survival

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 OS ‐ all ‐ same recruitment period between the 2 arms (HD9) Show forest plot

4

2583

Hazard Ratio (Fixed, 95% CI)

0.80 [0.59, 1.09]

2 OS subgrouped by stage of disease Show forest plot

4

2583

Hazard Ratio (Fixed, 95% CI)

0.80 [0.59, 1.09]

2.1 early unfavourable stage

1

1623

Hazard Ratio (Fixed, 95% CI)

1.02 [0.54, 1.91]

2.2 advanced stage

3

960

Hazard Ratio (Fixed, 95% CI)

0.74 [0.52, 1.06]

3 OS subgrouped by treatment Show forest plot

4

2583

Hazard Ratio (Fixed, 95% CI)

0.80 [0.59, 1.09]

3.1 only ABVD regimen

3

2141

Hazard Ratio (Fixed, 95% CI)

1.03 [0.67, 1.59]

3.2 ABVD including regimen

1

442

Hazard Ratio (Fixed, 95% CI)

0.62 [0.40, 0.96]

4 OS subgrouped by number of cycles of escalated BEACOPP Show forest plot

4

2583

Hazard Ratio (Fixed, 95% CI)

0.80 [0.59, 1.09]

4.1 eight cycles of escalated BEACOPP

1

442

Hazard Ratio (Fixed, 95% CI)

0.62 [0.40, 0.96]

4.2 four cycles of escalated BEACOPP

2

518

Hazard Ratio (Fixed, 95% CI)

1.05 [0.58, 1.90]

4.3 two cycles of escalated BEACOPP

1

1623

Hazard Ratio (Fixed, 95% CI)

1.02 [0.54, 1.91]

5 OS subgrouped by length of follow‐up Show forest plot

4

2583

Hazard Ratio (Fixed, 95% CI)

0.80 [0.59, 1.09]

5.1 short term follow‐up (median length up to 5 years)

3

2141

Hazard Ratio (Fixed, 95% CI)

1.03 [0.67, 1.59]

5.2 long term follow‐up (median length 10 years)

1

442

Hazard Ratio (Fixed, 95% CI)

0.62 [0.40, 0.96]

6 OS subgrouped by publication form Show forest plot

4

2583

Hazard Ratio (Fixed, 95% CI)

0.80 [0.59, 1.09]

6.1 full text publication

2

639

Hazard Ratio (Fixed, 95% CI)

0.67 [0.45, 1.01]

6.2 abstract publication

2

1944

Hazard Ratio (Fixed, 95% CI)

1.02 [0.64, 1.65]

7 OS subgrouped by type of results Show forest plot

4

2583

Hazard Ratio (Fixed, 95% CI)

0.80 [0.59, 1.09]

7.1 preliminary results

2

1944

Hazard Ratio (Fixed, 95% CI)

1.02 [0.64, 1.65]

7.2 mature results

2

639

Hazard Ratio (Fixed, 95% CI)

0.67 [0.45, 1.01]

8 OS ‐ all recruited patients (HD9) with potential risk of bias due to different time periods of recruitment Show forest plot

4

Hazard Ratio (Fixed, 95% CI)

0.66 [0.50, 0.88]

Figures and Tables -
Comparison 1. Analysis overall survival
Comparison 2. Analysis of progression‐free survival (PFS)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 PFS ‐ all ‐ same recruitment period between the 2 arms (HD9) Show forest plot

4

2583

Hazard Ratio (Fixed, 95% CI)

0.53 [0.44, 0.64]

2 PFS subgrouped by stage of disease Show forest plot

4

2583

Hazard Ratio (Fixed, 95% CI)

0.53 [0.44, 0.64]

2.1 early unfavourable stage

1

1623

Hazard Ratio (Fixed, 95% CI)

0.49 [0.34, 0.71]

2.2 advanced stage

3

960

Hazard Ratio (Fixed, 95% CI)

0.54 [0.43, 0.67]

3 PFS subgrouped by treatment Show forest plot

4

2583

Hazard Ratio (Fixed, 95% CI)

0.53 [0.44, 0.64]

3.1 only ABVD regimen

3

2141

Hazard Ratio (Fixed, 95% CI)

0.54 [0.43, 0.67]

3.2 ABVD including regimen

1

442

Hazard Ratio (Fixed, 95% CI)

0.50 [0.34, 0.72]

4 PFS subgrouped by number of cycles of escalated BEACOPP Show forest plot

4

2583

Hazard Ratio (Fixed, 95% CI)

0.53 [0.44, 0.64]

4.1 eight cycles of escalated BEACOPP

1

442

Hazard Ratio (Fixed, 95% CI)

0.50 [0.34, 0.72]

4.2 four cycles of escalated BEACOPP

2

518

Hazard Ratio (Fixed, 95% CI)

0.57 [0.43, 0.74]

4.3 two cycles of escalated BEACOPP

1

1623

Hazard Ratio (Fixed, 95% CI)

0.49 [0.34, 0.71]

5 PFS subgrouped by length of follow‐up Show forest plot

4

2583

Hazard Ratio (Fixed, 95% CI)

0.53 [0.44, 0.64]

5.1 short term follow‐up (median length up to 5 years)

3

2141

Hazard Ratio (Fixed, 95% CI)

0.54 [0.43, 0.67]

5.2 long term follow‐up (median length 10 years)

1

442

Hazard Ratio (Fixed, 95% CI)

0.50 [0.34, 0.72]

6 PFS subgrouped by publication form Show forest plot

4

2583

Hazard Ratio (Fixed, 95% CI)

0.53 [0.44, 0.64]

6.1 full text publication

2

639

Hazard Ratio (Fixed, 95% CI)

0.51 [0.39, 0.65]

6.2 abstract publication

2

1944

Hazard Ratio (Fixed, 95% CI)

0.56 [0.42, 0.75]

7 PFS subgrouped by type of results Show forest plot

4

2583

Hazard Ratio (Fixed, 95% CI)

0.53 [0.44, 0.64]

7.1 preliminary results

2

1944

Hazard Ratio (Fixed, 95% CI)

0.56 [0.42, 0.75]

7.2 mature results

2

639

Hazard Ratio (Fixed, 95% CI)

0.51 [0.39, 0.65]

8 PFS ‐ all recruited patients (HD9) with potential risk of bias due to different time periods of recruitment Show forest plot

4

Hazard Ratio (Fixed, 95% CI)

0.48 [0.40, 0.58]

Figures and Tables -
Comparison 2. Analysis of progression‐free survival (PFS)
Comparison 3. Analysis of complete response (CR) rate

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 CR Show forest plot

3

1245

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [1.06, 1.16]

2 CR subgrouped by treatment Show forest plot

3

1245

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [1.06, 1.16]

2.1 only ABVD regimen

2

518

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [1.00, 1.16]

2.2 ABVD including regimen

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [1.07, 1.19]

3 CR subgrouped by number of cycles of escalated BEACOPP Show forest plot

3

1245

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [1.06, 1.16]

3.1 eight cycles of escalated BEACOPP

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [1.07, 1.19]

3.2 four cycles of escalated BEACOPP

2

518

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [1.00, 1.16]

4 CR subgrouped by length of follow‐up Show forest plot

3

1245

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [1.06, 1.16]

4.1 short term follow‐up (median length up to 5 years)

2

518

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [1.00, 1.16]

4.2 long term follow‐up (median length 10 years)

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [1.07, 1.19]

5 CR subgrouped by publication form Show forest plot

3

1245

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [1.06, 1.16]

5.1 full text publication

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [1.07, 1.18]

5.2 abstract publication

1

321

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.97, 1.19]

Figures and Tables -
Comparison 3. Analysis of complete response (CR) rate
Comparison 4. Analysis of freedom from first progression

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Freedom from first progression Show forest plot

1

321

Hazard Ratio (Fixed, 95% CI)

0.51 [0.31, 0.85]

Figures and Tables -
Comparison 4. Analysis of freedom from first progression
Comparison 5. Analysis of treatment‐related mortality

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Treatment‐related mortality Show forest plot

1

197

Risk Ratio (M‐H, Fixed, 95% CI)

5.05 [0.25, 103.87]

Figures and Tables -
Comparison 5. Analysis of treatment‐related mortality
Comparison 6. Analysis of secondary malignancies

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Secondary malignancies Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.61, 1.48]

2 Secondary malignancies subgrouped by stage of disease Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.61, 1.48]

2.1 early unfavourable stage

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.44, 1.65]

2.2 advanced stage

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.58, 1.89]

3 Subgrouped by treatment Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.61, 1.48]

3.1 only ABVD regimen

2

1820

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.46, 1.64]

3.2 ABVD including regimen

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.57, 1.92]

4 Subgrouped by number of cycles of escalated BEACOPP Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.61, 1.48]

4.1 eight cycles of escalated BEACOPP

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.57, 1.92]

4.2 four cycles of escalated BEACOPP

1

197

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.06, 15.92]

4.3 two cycles of escalated BEACOPP

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.44, 1.65]

5 Subgrouped by length of follow‐up Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.61, 1.48]

5.1 short term follow‐up (median length up to 5 years)

2

1820

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.46, 1.64]

5.2 long term follow‐up (median length 10 years)

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.57, 1.92]

6 Subgrouped by publication form Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.61, 1.48]

6.1 full text publication

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.58, 1.89]

6.2 abstract publication

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.44, 1.65]

7 Subgrouped by type of results Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.61, 1.48]

7.1 preliminary results

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.44, 1.65]

7.2 mature results

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.58, 1.89]

Figures and Tables -
Comparison 6. Analysis of secondary malignancies
Comparison 7. Analysis of AML or MDS

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 AML or MDS Show forest plot

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

7.84 [1.04, 59.29]

Figures and Tables -
Comparison 7. Analysis of AML or MDS
Comparison 8. Analysis of fertility

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Secondary amenorrhoea Show forest plot

1

106

Risk Ratio (M‐H, Fixed, 95% CI)

1.37 [0.83, 2.26]

Figures and Tables -
Comparison 8. Analysis of fertility
Comparison 9. Analysis of anaemia

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Anaemia Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

10.47 [7.06, 15.54]

2 Subgrouped by stage of disease Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

10.47 [7.06, 15.54]

2.1 early unfavourable stage

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

9.15 [4.43, 18.86]

2.2 advanced stage

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

10.96 [6.86, 17.51]

3 Subgrouped by treatment Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

10.47 [7.06, 15.54]

3.1 only ABVD regimen

2

1820

Risk Ratio (M‐H, Fixed, 95% CI)

6.87 [3.87, 12.18]

3.2 ABVD including regimen

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

13.27 [7.78, 22.63]

4 Subgrouped by number of cycles of escalated BEACOPP Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

10.47 [7.06, 15.54]

4.1 eight cycles of escalated BEACOPP

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

13.27 [7.78, 22.63]

4.2 four cycles of escalated BEACOPP

1

197

Risk Ratio (M‐H, Fixed, 95% CI)

3.23 [1.23, 8.48]

4.3 two cycles of escalated BEACOPP

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

9.15 [4.43, 18.86]

5 Subgrouped by length of follow‐up Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

10.47 [7.06, 15.54]

5.1 short term follow‐up (median length up to 5 years)

2

1820

Risk Ratio (M‐H, Fixed, 95% CI)

6.87 [3.87, 12.18]

5.2 long term follow‐up (median length 10 years)

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

13.27 [7.78, 22.63]

6 Subgrouped by publication form Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

10.47 [7.06, 15.54]

6.1 full text publication

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

10.96 [6.86, 17.51]

6.2 abstract publication

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

9.15 [4.43, 18.86]

7 Subgrouped by type of results Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

10.47 [7.06, 15.54]

7.1 preliminary results

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

9.15 [4.43, 18.86]

7.2 mature results

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

10.96 [6.86, 17.51]

Figures and Tables -
Comparison 9. Analysis of anaemia
Comparison 10. Analysis of infection

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Infection Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

3.67 [2.57, 5.24]

2 Subgrouped by stage of disease Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

3.67 [2.57, 5.24]

2.1 early unfavourable stage

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

2.14 [1.38, 3.32]

2.2 advanced stage

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

7.13 [3.78, 13.45]

3 Subgrouped by treatment Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

3.67 [2.57, 5.24]

3.1 only ABVD regimen

2

1820

Risk Ratio (M‐H, Fixed, 95% CI)

2.47 [1.63, 3.74]

3.2 ABVD including regimen

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

7.14 [3.53, 14.43]

4 Subgrouped by number of cycles of escalated BEACOPP Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

3.67 [2.57, 5.24]

4.1 eight cycles of escalated BEACOPP

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

7.14 [3.53, 14.43]

4.2 four cycles of escalated BEACOPP

1

197

Risk Ratio (M‐H, Fixed, 95% CI)

7.07 [1.65, 30.30]

4.3 two cycles of escalated BEACOPP

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

2.14 [1.38, 3.32]

5 Subgrouped by length of follow‐up Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

3.67 [2.57, 5.24]

5.1 short term follow‐up (median length up to 5 years)

2

1820

Risk Ratio (M‐H, Fixed, 95% CI)

2.47 [1.63, 3.74]

5.2 long term follow‐up (median length 10 years)

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

7.14 [3.53, 14.43]

6 Subgrouped by publication form Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

3.67 [2.57, 5.24]

6.1 full text publication

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

7.13 [3.78, 13.45]

6.2 abstract publication

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

2.14 [1.38, 3.32]

7 Subgrouped by type of results Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

3.67 [2.57, 5.24]

7.1 preliminary results

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

2.14 [1.38, 3.32]

7.2 mature results

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

7.13 [3.78, 13.45]

Figures and Tables -
Comparison 10. Analysis of infection
Comparison 11. Analysis of leucopenia

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leucopenia Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

2.26 [2.09, 2.44]

2 Subgrouped by stage of disease Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [2.10, 2.45]

2.1 early unfavourable stage

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

3.30 [2.90, 3.74]

2.2 advanced stage

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

1.49 [1.37, 1.62]

3 Subgrouped by treatment Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [2.10, 2.45]

3.1 only ABVD regimen

2

1820

Risk Ratio (M‐H, Fixed, 95% CI)

3.22 [2.86, 3.64]

3.2 ABVD including regimen

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

1.39 [1.28, 1.50]

4 Subgrouped by number of cycles of escalated BEACOPP Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [2.10, 2.45]

4.1 eight cycles of escalated BEACOPP

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

1.39 [1.28, 1.50]

4.2 two cycles of escalated BEACOPP

1

197

Risk Ratio (M‐H, Fixed, 95% CI)

2.57 [1.71, 3.86]

4.3 two cycles of escalated BEACOPP

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

3.30 [2.90, 3.74]

5 Subgrouped by length of follow‐up Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [2.10, 2.45]

5.1 short term follow‐up (median length up to 5 years)

2

1820

Risk Ratio (M‐H, Fixed, 95% CI)

3.22 [2.86, 3.64]

5.2 long term follow‐up (median length 10 years)

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

1.39 [1.28, 1.50]

6 Subgrouped by publication form Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [2.10, 2.45]

6.1 full text publication

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

1.49 [1.37, 1.62]

6.2 abstract publication

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

3.30 [2.90, 3.74]

7 Subgrouped by type of results Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [2.10, 2.45]

7.1 preliminary results

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

3.30 [2.90, 3.74]

7.2 mature results

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

1.49 [1.37, 1.62]

Figures and Tables -
Comparison 11. Analysis of leucopenia
Comparison 12. Analysis of neutropenia

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Neutropenia Show forest plot

1

197

Risk Ratio (M‐H, Fixed, 95% CI)

1.57 [1.13, 2.19]

Figures and Tables -
Comparison 12. Analysis of neutropenia
Comparison 13. Analysis of thrombocytopenia

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Thrombocytopenia Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

18.73 [12.17, 28.82]

2 Subgrouped by stage of disease Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

18.73 [12.17, 28.82]

2.1 early unfavourable stage

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

179.86 [25.26, 1280.82]

2.2 advanced stage

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

11.53 [7.30, 18.23]

3 Subgrouped by treatment Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

18.73 [12.17, 28.82]

3.1 only ABVD regimen

2

1820

Risk Ratio (M‐H, Fixed, 95% CI)

50.43 [18.84, 134.96]

3.2 ABVD including regimen

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

12.17 [7.42, 19.97]

4 Subgrouped by number of cycles of escalated BEACOPP Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

18.73 [12.17, 28.82]

4.1 eight cycles of escalated BEACOPP

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

12.17 [7.42, 19.97]

4.2 four cycles of escalated BEACOPP

1

197

Risk Ratio (M‐H, Fixed, 95% CI)

7.41 [2.29, 23.95]

4.3 two cycles of escalated BEACOPP

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

179.86 [25.26, 1280.82]

5 Subgrouped by length of follow‐up Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

18.73 [12.17, 28.82]

5.1 short term follow‐up (median length up to 5 years)

2

1820

Risk Ratio (M‐H, Fixed, 95% CI)

50.43 [18.84, 134.96]

5.2 long term follow‐up (median length 10 years)

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

12.17 [7.42, 19.97]

6 Subgrouped by publication form Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

18.73 [12.17, 28.82]

6.1 full text publication

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

11.53 [7.30, 18.23]

6.2 abstract publication

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

179.86 [25.26, 1280.82]

7 Subgrouped by type of results Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

18.73 [12.17, 28.82]

7.1 preliminary results

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

179.86 [25.26, 1280.82]

7.2 mature results

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

11.53 [7.30, 18.23]

Figures and Tables -
Comparison 13. Analysis of thrombocytopenia
Comparison 14. Analysis of alopecia

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Alopecia Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

1.97 [1.77, 2.19]

2 Subgrouped by stage of disease Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

1.97 [1.77, 2.19]

2.1 early unfavourable stage

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

2.00 [1.74, 2.31]

2.2 advanced stage

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

1.93 [1.65, 2.26]

3 Subgrouped by treatment Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

1.97 [1.77, 2.19]

3.1 only ABVD regimen

2

1820

Risk Ratio (M‐H, Fixed, 95% CI)

1.85 [1.62, 2.12]

3.2 ABVD including regimen

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

2.19 [1.85, 2.59]

4 Subgrouped by number of cycles of escalated BEACOPP Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

1.97 [1.77, 2.19]

4.1 eight cycles of escalated BEACOPP

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

2.19 [1.85, 2.59]

4.2 four cycles of escalated BEACOPP

1

197

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.59, 1.40]

4.3 two cycles of escalated BEACOPP

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

2.00 [1.74, 2.31]

5 Subgrouped by length of follow‐up Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

1.97 [1.77, 2.19]

5.1 short term follow‐up (median length up to 5 years)

2

1820

Risk Ratio (M‐H, Fixed, 95% CI)

1.85 [1.62, 2.12]

5.2 long term follow‐up (median length 10 years)

1

727

Risk Ratio (M‐H, Fixed, 95% CI)

2.19 [1.85, 2.59]

6 Subgrouped by publication form Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

1.97 [1.77, 2.19]

6.1 full text publication

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

1.93 [1.65, 2.26]

6.2 abstract publication

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

2.00 [1.74, 2.31]

7 Subgrouped by type of results Show forest plot

3

2547

Risk Ratio (M‐H, Fixed, 95% CI)

1.97 [1.77, 2.19]

7.1 preliminary results

1

1623

Risk Ratio (M‐H, Fixed, 95% CI)

2.00 [1.74, 2.31]

7.2 mature results

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

1.93 [1.65, 2.26]

Figures and Tables -
Comparison 14. Analysis of alopecia
Comparison 15. Analysis of constipation

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Constipation Show forest plot

2

923

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.56, 2.55]

Figures and Tables -
Comparison 15. Analysis of constipation
Comparison 16. Analysis of mucositis

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mucositis Show forest plot

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

6.32 [2.25, 17.75]

Figures and Tables -
Comparison 16. Analysis of mucositis
Comparison 17. Analysis of nausea/vomiting

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Nausea/vomiting Show forest plot

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.71, 1.25]

Figures and Tables -
Comparison 17. Analysis of nausea/vomiting
Comparison 18. Analysis of neurologic

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Neurologic Show forest plot

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.55, 2.35]

Figures and Tables -
Comparison 18. Analysis of neurologic
Comparison 19. Analysis of pain

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Pain Show forest plot

2

924

Risk Ratio (M‐H, Fixed, 95% CI)

4.88 [2.04, 11.66]

Figures and Tables -
Comparison 19. Analysis of pain
Comparison 20. Analysis of respiratory

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Respiratory Show forest plot

1

726

Risk Ratio (M‐H, Fixed, 95% CI)

2.12 [0.80, 5.61]

Figures and Tables -
Comparison 20. Analysis of respiratory
Comparison 21. Analysis of skin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Skin Show forest plot

1

726

Risk Ratio (M‐H, Fixed, 95% CI)

2.60 [0.76, 8.98]

Figures and Tables -
Comparison 21. Analysis of skin