. 2016 Apr 29;2016(4):CD005339. doi: 10.1002/14651858.CD005339.pub2

Winston 1982a.

Methods	Parallel RCT (period of enrolment not reported) (Single centre ) USA
Participants	Inclusion criteria: Patients with neutrophil count was < 0.5 x10⁹/L, and a documented infection. Exclusion criteria: Patients with only fever and no documented infections, or patients with fungal or viral infections N = 95 patients randomised and analysed Age range 4 to 81 years. Median 49 years granulocyte transfusion group, 44 years control group. Arm 1 (Granulocyte transfusions): N = 48 included in the analysis, Acute myeloid leukaemia = 30 , Acute lymphocytic leukaemia = 1 , Other = 17. Refractory disease = 13. Arm 2 (Control): N = 47 , Acute myeloid leukaemia = 22 , Acute lymphocytic leukaemia = 10 , Other = 15. Refractory disease = 11. Type of treatment participants received was not reported.
Interventions	Granulocyte dose: 0.5x10¹⁰/day (range 0.1 to 2.7 x 10¹⁰/day) Granulocyte method of collection: Discontinuous flow centrifugation Selection of donors: HLA typing results were not used to select prospective donors, selected on basis of ABO compatibility (related and unrelated donors) Pre‐medication of donors: None Initiation of granulocyte transfusions: Given within 24 hours of a positive blood culture, the appearance of an infiltrate on chest X‐ray, or the initial development of a cellulitis or abscess Frequency of granulocyte transfusions: Daily Termination of granulocyte transfusions: Granulocytes >0.5 x10⁹ Death of the patient Resolution of infection and antimicrobial therapy was stopped despite neutrophil count < 0.5 x10
Outcomes	Primary Outcome(s): Not reported Secondary Outcome(s): Overall survival (and at day 5)  Clinical response rates  Duration of time febrile  Adverse events
Definition(s) of infection	Documented infection: Either blood culture positive for a gram‐positive or gram‐negative organism with clinical features compatible with septicaemia, a lobar or segmental infiltrate on chest X‐ray consistent with bacterial pneumonia, or a localised area of cellulitis or abscess formation involving the skin or other soft tissues. Septic shock: hypotension, tachypnoea, decreased urine output, or altered mental state
Definition of neutropenia	Neutrophil count < 0.5 x10⁹/L
Co‐interventions	Therapeutic antibiotics: Initial antimicrobial therapy in all patients consisted of an aminoglycoside (amikacin or netilmicin) plus an antipseudomonal penicillin (carbenicillin or piperacillin). For patients allergic to penicillin, cefazolin was substituted for penicillin. If a patient had a documented or strongly suspected staphylococcal infection an antistaphylococcal agent was incorporated into the patient's therapy. G‐CSF: G‐CSF not licensed by the Food and Drug Administration (FDA) until 1991. Therapeutic antifungals: Patients who remained febrile for 7 days or had surveillance cultures positive for fungi were eligible to receive amphotericin B. 19 patients in the granulocyte transfusion arm and 14 patients in the control arm received amphotericin B.
Notes	Randomised: Patients were not randomised until antibiotics were started for presumed or proven infection Trial registration: none identified Sources of funding: Grants HB‐62971 from the national Heart, Lung and Blood Institute. CA‐23175 and CA‐15688 from the National Cancer Institute of Allergy and Insfections Diseases. Dr. Gale is a Scholar of the Leukaemia Sociaty of America. Conflicts of Interest: Not reported Other: "The probability of a type 2 error (not obtaining a statistically significant result when there actually is a difference) was computed for the alternative hypothesis using an assumed true odds ratio of 5.57. This odds ratio was based on previously reported data suggesting that infected patients receiving granulocyte transfusions have a response rate of 75% and that patients treated with only antimicrobial therapy have a response rate of 35%. The probability of type 2 error also considered the total number of favourable responses seen in both the transfused and control patients in the present study"
*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	Method of allocation concealment not reported
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	Unclear risk	It was unclear how long patients were followed up for and whether any patients were lost to follow‐up
Selective reporting (reporting bias)	Unclear risk	No protocol was available
Other bias	Unclear risk	Other sources of bias may have been present but this study was not reported in sufficient detail to assess the risk

CMV: cytomegalovirus  G‐CSF: granulocyte colony stimulating factor  HCV: hepatitis C virus  HLA: human leucocyte antigen  HSCT: haematopoietic stem cell transplant  MIU: million international units  po: by mouth  RCT: randomised controlled trial  SD: standard deviation