Higby 1975.

Methods	Parallel RCT (period of enrolment not reported) (number of centres not reported) USA
Participants	Inclusion criteria: Patients with haematological malignancies, neutrophil count < 0.5 x 109/L, clinical evidence of infection and fever > 38oC. Exclusion criteria: Not reported N = 36 9 patients aged > 45 years. Minimum age 15 years Arm 1 (Granulocyte transfusions): N = 17 (Acute myeloid leukaemia = 11). 1/17 patients aged > 45 years Arm 2 (Control): N = 19, (Acute myeloid leukaemia =12). 8/19 patients aged > 45 years Patients were receiving chemotherapy for acute leukaemia. 6 patients in each arm were being treated with remission induction chemotherapy.
Interventions	Granulocyte dose: 2.2 x 1010/m2 (range 1.11 to 5) Granulocyte method of collection: Filtration leukapheresis Selection of donors: HLA typing results were not used to select prospective donors. Pre‐medication of donors: Dexamethasone immediately prior to collection (i.e. not priming) Initiation of granulocyte transfusions: Neutropenia < 0.5x109/L + fever >380C + antibiotics more than 2 days (i.e. 48‐hour period to assess response to antibiotics) + clinical evidence of infection (organism or focus) Frequency of granulocyte transfusions: Daily over 4 consecutive days Termination of granulocyte transfusions: After 4 consecutive days
Outcomes	Primary Outcome(s): Not reported Secondary Outcome(s): Survival at day 20 Remission rates Adverse events
Definition(s) of infection	Clinical evidence of infection was not defined, but culture‐positive results were not required as mandatory prior to randomisation (although positive cultures were documented subsequently in 32 patients).
Definition of neutropenia	neutrophil count < 0.5 x 109/L
Co‐interventions	Therapeutic antibiotics: type of antibiotics not specified G‐CSF: G‐CSF not licensed by the Food and Drug Administration (FDA) until 1991. Therapeutic antifungals: Not reported
Notes	Randomised: Patients were not randomised until antibiotics had been given for two or more days and were judged clinically ineffective as evidenced by persistent fever and clinical deterioration Trial registration: none identified Sources of funding: Supported by research grants (CA‐5834 and CA‐10044) from the National Cancer Institute Conflicts of Interest: Not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Patients qualifying for this study were placed in the study group or the control group by drawing an assignment card from a prearranged deck. Method of sequence generation for the prearranged deck were not reported.
Allocation concealment (selection bias)	Unclear risk	Cards in prearranged deck were enclosed in sealed envelopes. It was not reported whether the 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	There was no loss to follow up at day 20.
Selective reporting (reporting bias)	Unclear risk	The protocol was not available to assess whether all pre‐specified outcomes were reported
Other bias	High risk	There was imbalance between the two groups in the baseline characteristics of the patients. 16/17 patients were aged under 45 years of age in the granulocyte transfusion arm, whereas 11/19 patients were aged under 45 years of age in the control arm.