Vogler 1977.

Methods	Parallel RCT (December 1973 to April 1976) (multi‐centre, 4 centres)
Participants	Inclusion criteria: had a suitable donor, culture proven infection, absolute neutrophil count < 0.3 x 109/L, failure to improve after at least 72 hours of appropriate antibiotic therapy, which was defined as organisms sensitive in vitro to antibiotics being administered Exclusion criteria: Patients with refractory underlying disease, the attending physician believed that further antileukaemic therapy would be of no benefit and that granulocyte transfusions would not be indicated N = 32 patients, 30 included in the analysis (2 patients died on day of randomisation not included in analysis) Age range 2 to 78 years. Average 35 years in granulocyte transfusion group and 45 years in control group. There were 3 children (< 15 years) in the granulocyte transfusion group and 2 children in the control group. Arm 1 (Granulocyte transfusions): N = 17 included in the analysis, Acute myeloid leukaemia = 12, Acute lymphocytic leukaemia = 2, Other = 3 Arm 2 (Control): N = 13, Acute myeloid leukaemia = 10, Acute lymphocytic leukaemia = 2, Other = 1 Type of treatment participants received was not reported.
Interventions	Granulocyte dose: 2.7 x 1010 granulocytes given/day to each patient per dose Granulocyte method of collection: Continuous flow centrifugation Selection of donors: On the basis of ABO compatibility, best HLA match and health of the donor Pre‐medication of donors: initially donors did not receive pre‐medication, subsequently donors were given either hydrocortisone or dexamethasone as pre‐medication 2 hours before the procedure Initiation of granulocyte transfusions: Antibiotics more than 72 hours without response + culture positive infection Frequency of granulocyte transfusions: At least 4 transfusions in an 8‐day period. Daily if possible, but usually omitted at weekends. Termination of granulocyte transfusions: After 8 days of treatment.
Outcomes	Primary Outcome(s): Not reported Secondary Outcome(s): Response to infection at 21 days Adverse events
Definition(s) of infection	Complete resolution of infectious episode: all evidence of infection must clear within the 21‐day period. Measurable parameters included resolution of infection, conversion of cultures to negative, and healing of involved sites Partial resolution: less than complete clearing but definite clinical improvement in more than one measurable parameter for the 21‐day period No change: no measurable effect of granulocyte transfusions, or antibiotics, or both in patients surviving 21 days Worse: obvious progression of infection or death attributable to infection during the study period
Definition of neutropenia	Neutrophil count < 0.3 x 109/L
Co‐interventions	Therapeutic antibiotics: All patients were given combination antibiotics, most were given carbenicillin, cephalothin and gentamicin G‐CSF: G‐CSF not licensed by the Food and Drug Administration (FDA) until 1991. Therapeutic antifungals: Not reported
Notes	Randomised: when patients had failed to improve after at least 72 hours of appropriate antibiotic therapy. Patients were stratified according to duration of infection (less than 5 days, 5 to 10 days, and more than 10 days) and type of infection (Pseudomonas or non‐Pseudomonas) Trial registration: none identified Sources of funding: Grant No. CA 14864 and Grant No. CA 16255 from the National Institutes of Health. Conflicts of Interest: Not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of sequence generation not reported.
Allocation concealment (selection bias)	Unclear risk	Patients were randomly assigned by sealed cards. It was not reported whether envelopes were opaque
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	It was not reported whether participants or clinical personnel were blinded to the intervention
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	It was not reported whether outcome assessors were blinded to the intervention
Incomplete outcome data (attrition bias) All outcomes	Low risk	Patients were followed up for at least 22 days. The median survival was 7.7 days in the control group and 22.5 days in the granulocyte transfusion group.
Selective reporting (reporting bias)	Unclear risk	No protocol was available to assess whether any pre‐specified outcomes were not reported
Other bias	Unclear risk	There was an imbalance in the number of participants in each study arm (13 in the control arm versus 17 in the intervention arm). The average age was younger in the granulocyte transfusion arm (35 years, range 2 to 75 versus 45 years, range 7 to 78). Pre‐medication to donors (steroids) was started part way through the study.