Balleari 2006.

Methods	Randomisation: A randomised controlled trial with 2 arms: Erythropoietin (rHEPO) versus rHEPO plus G‐CSF Allocation ratios: 1:1 Recruitment period: From April 2001 to December 2003 Median follow‐up time: 28 months (range 17 to 50) ‐ the study protocol allowed the addition of G‐CSF for patients who did not respond to rHEPO 8 weeks after treatment begin (9 of 15 patients of the rHEPO arm received G‐CSF after 8 weeks)
Participants	Eligibility: Inclusion criteria Low‐risk MDS (IPSS < 1) No previous treatment with haematopoietic growth factors Performance status < 3 (ECOG) Life expectancy of 6 months or greater Age >18 years Hb <10 g/dL or transfusion‐dependent anaemia Patients recruited (N = 30): rHEPO: N = 15 rHEPO plus G‐CSF: N = 15 Mean age: rHEPO: 74.4 (range: 59 to 89 years) rHEPO plus G‐CSF: 73.6 (range: 62 to 87 years) Gender (male, female): rHEPO: 60%, 40% rHEPO plus G‐CSF: 66%, 44% Subtypes of MDS classified by WHO criteria: RA: 4 patients in rHEPO arm; 6 patients in rHEPO plus G‐CSF arm RARS: 3 patients; 2 patients, respectively RCMD: 3 patients; 4 patients, respectively RAEBt: 3 patients; 2 patients, respectively 5q‐syndrome: 2 patients; 1 patients, respectively Platelet transfusion dependency: rHEPO: 6 of 15 patients rHEPO plus G‐CSF: 5 of 15 patients Country Italy (single‐centre study)
Interventions	Arm 1: rHEPO at a dosage of 10,000 IU subcutaneously three times a week, 8 weeks Arm 2: rHEPO at a dosage of 10,000 IU subcutaneously three times a week, 8 weeks G‐CSF at a fixed dose of 300 mg subcutaneously once or twice a week, depending on the baseline neutrophil count (above or below 3×109/L, respectively). The dosage of G‐CSF was reduced to 300 mg once a week if neutrophils increased to more than 10×109/L, duration: 8 weeks The study protocol allowed the addition of G‐CSF for patients who did not respond to rHEPO 8 weeks after treatment begin (9 of 15 patients of the rHEPO arm received G‐CSF after 8 weeks) Additional therapy: Patients usually underwent transfusion when Hb levels fell to 8.0 g/dL, unless a higher transfusion threshold was indicated by other concomitant medical conditions. Throughout the entire duration of the study, patients were supplemented with folate (15 mg/day) and oral iron if ferritin values decreased to < 100 μg/L.
Outcomes	As stated above 9 of 15 patients of the rHEPO arm received G‐CSF after 8 weeks, therefore we only considered results that were assessed at 8 weeks after treatment begin for this review. Primary outcome of the study: Information not provided Outcomes and time points from the study that are considered in the review: reported: Incidence and duration of anaemia Incidence of blood product transfusion Quality of Life not reported: OS PFS Time to progression to AML CR PR Adverse events Incidence and duration of infections Incidence and duration of neutropenia Incidence and duration of antibiotic treatment Hospitalisation
Notes	The publication provided no declaration on authors' conflicts of interest or received funding.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “Patients were randomly divided in a 1:1 fashion“ Comment: The authors did not describe the method used to generate the allocation sequence.
Allocation concealment (selection bias)	Unclear risk	No information provided
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Comment: This was not a placebo‐controlled randomised trial
Blinding of outcome assessment (OS; detection bias)	Unclear risk	OS not reported
Blinding of outcome assessment (secondary outcomes)	Unclear risk	No information provided
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "After the 8th week of treatment, FACT‐An assessment of both baseline and post‐treatment conditions was obtained for 18/30 (60%) patients enrolled in the study (7 in the rHEPO arm and 11 in the rHEPO+G‐CSF arm)."
Selective reporting (reporting bias)	Unclear risk	A protocol of this trial was not registered
Other bias	Unclear risk	No information provided