Alavi 1977.

Methods	Parallel RCT (period of enrolment not reported) (number of centres not reported) USA
Participants	Inclusion criteria: Patients with acute leukaemia or blastic phase of chronic myeloid leukaemia if the neutrophil count was < 0.25 x 109/L, and if infection was documented or strongly suspected. The eligibility criteria for children also required culture‐positive microbiology results. Exclusion criteria: No patient was eligible unless he or she was under treatment for acute leukaemia N = 32 patients, 31 included in the analysis Age range 8 to 75 years (Average 38 years) Arm 1 (Granulocyte transfusions): N = 13, 12 included in the analysis, Acute myeloid leukaemia = 8, Acute lymphocytic leukaemia = 3, Other = 1. Arm 2 (Control): N = 19, Acute myeloid leukaemia = 14, Acute lymphocytic leukaemia = 4, Other = 1 Type of treatment participants received for the acute leukaemia was not reported
Interventions	Granulocyte dose: 5 x 1010/day. Average 3.3 x 1010/m2 children; Average 3.2 x 1010/m2 adults Granulocyte method of collection: Filtration leukapheresis Selection of donors: HLA typing results were not used to select prospective donors. Pre‐medication of donors: Hydrocortisone Initiation of granulocyte transfusions: Fever > 38.80C for 1 hour or persistent fever 38.00C for 24 hours Frequency of granulocyte transfusions: Daily Termination of granulocyte transfusions: Until antibiotics discontinued or until the patient was afebrile for 72 hours with negative cultures
Outcomes	Primary Outcome(s): Not reported Secondary Outcome(s): Survival at day 21 Adverse events
Definition(s) of infection	Proven infection: Cultures were positive Probable infection: If there was a clinical source but cultures were negative.
Definition of neutropenia	Neutrophil count <0.25 x 109/L was an inclusion criterion
Co‐interventions	Therapeutic antibiotics: All patients received broad‐spectrum antibiotics, including gentamicin and cephalothin, or a penicillinase‐resistant, semisynthetic penicillin, and most patients also received carbenicillin. Clindamycin was added if a gastrointestinal source of infection seemed likely. 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 were started for presumed or proven infection Trial registration: none identified Sources of funding: Supported by a research grant (CA11630) and research career development awards (A100143 to RKR and AM38345 to RAC) from the National Institutes of Health and by a grant from the Radiation Management Corporation. Dr Schreiber is a Leukemia Scholar of the Leukemia Society of America Conflicts of Interest: Not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomly assigned to control or transfusion groups by means of consecutively numbered cards, randomised by computer. The method of randomisation by the computer was not stated.
Allocation concealment (selection bias)	Unclear risk	The consecutively numbered cards were sealed in an envelope, but it did not state whether the envelopes were opaque.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	The report did not state whether participants were blinded to the intervention. The report did not state whether the clinical personnel or investigators were blinded to the intervention.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	The report did not state whether the outcome assessors were blinded to the participants allocation.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Two febrile episodes were excluded from analysis because of early death before the effects of the transfusions could be analysed: one patient in the transfusion group was excluded for this reason, but the control patient had also contributed to a prior febrile episode. In the transfusion group, one febrile episode was subsequently considered to be due to an allergic reaction and another due to viral infection, and these data were also excluded from the analysis of outcomes, including survival.
Selective reporting (reporting bias)	Unclear risk	The protocol was not available to assess whether any of the pre‐specified outcomes were not reported, or whether additional outcomes that had not been pre‐specified were reported
Other bias	High risk	There was an imbalance between the two arms in the number of participants allocated to each arm (19 vs. 12). There were unit‐of‐analysis issues as patients had more than one episode of fever. In the granulocyte arm there were 22 febrile episodes in 12 patients and in the control arm there were 40 febrile episodes within 19 patients.