Clift 1978.

Methods	Parallel RCT (conducted from February 1974 to September 1977). Single centre. Country: USA.
Participants	Inclusion criteria: Adults and children with acute leukaemia and aplastic anaemia undergoing related HLA‐matched allogeneic haematopoietic stem cell transplantation Exclusion criteria: Infection criteria for excluding people from the study was not reported Total randomised N = 86 Total analysed N = 69 Arm 1 (Granulocyte transfusions):randomised = 41, analysed = 29 ; Acute leukaemia = 17, Aplastic anaemia = 12 Arm 2 (Control): randomised = 45, analysed = 40: Acute leukaemia = 27 , Aplastic anaemia = 13
Interventions	Comparison between standard treatment and prophylactic granulocyte transfusions Granulocyte dose: mean 2.22 x 1010 (leucofiltration) 1.57 x 1010 (centrifugation) Granulocyte method of collection: by either continuous flow centrifugation or reversible leukoadhesion to nylon columns Donor premedication: None Initiation of granulocyte transfusions: 1st post‐transplant day neutrophil count ≤ 0.2 x 109/L Frequency of granulocyte transfusions: Daily Termination of granulocyte transfusions: Neutrophil count > 0.2 x 109/L [not clearly stated]
Outcomes	Primary Outcome: The effectiveness of granulocytes in reducing the acquisition of bacterial or fungal infection during the first 21 post‐transplant days Secondary Outcomes: Mortality/survival, fever (days or episodes), infection (days or episodes), antibiotic use, adverse events
Definition of infection	Febrile day ‐ two temperatures greater than 38.3oC in 24 hours. Febrile episode ‐ not defined Proven infection: subdivided in to:‐ Septicaemia ‐ at least one positive blood culture with appropriate symptoms, or two consecutive blood cultures growing the same organism (daily surveillance blood cultures were performed). Local infection ‐ lesions with symptoms or signs of infection and isolation of causative bacterial or fungal organisms.
Definition of neutropenia	Not reported but the 'trigger' neutrophil count was 0.2 x 109/L
Co‐interventions	Prophylactic antibiotics: not reported Therapeutic antibiotics: no restrictions on type of systemic antibiotic treatment given. Therapeutic granulocyte transfusions: participants in the control group were eligible for granulocyte transfusions as clinically indicated for the treatment of established infection.
Notes	Funding Sources: Grants CA18579, CA18029, CA17117 and CA15704 from the National Cancer Institute. Dr Thomas is the recipient of a research career award (AI 02425) from the National Institute for Allergy and Infectious Diseases Conflict of Interests: Not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of sequence generation was not reported
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment was not reported
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	It was not reported whether participants were blinded to the intervention. It was not reported whether clinicians or investigators 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	High risk	Only 40 of the 45 participants randomised to the control group were included in the analysis. Only 29 of the 41 participants randomised to the intervention group were included in the analysis. Five randomised participants were not included in the control group: One patient was not eligible for treatment with the marrow transplantation protocol Three participants could not be evaluated because the decision was made to transplant them elsewhere One patient died of cardiac failure on the 11th day after transplantation. This patient was not receiving antibiotics before the first day but antibiotics were initiated on the second day because of fever without documented infection. There was no autopsy evidence of an infective process Twelve randomised participants were not included in the intervention group: Three participants were withdrawn because the potential granulocyte donors were unacceptable for medical reasons Three participants the granulocyte transfusions were abandoned because of donor complications Three participants the granulocyte transfusions were abandoned because their HLA‐matched granulocyte donors were the only source of effective platelets and granulocyte collections were jeopardising the recipients' platelet support One participant did not receive a transplant in accordance with the protocol One participant died on the 10th post‐transplant day after receiving nine daily granulocyte transfusions One participant reason not given
Selective reporting (reporting bias)	Unclear risk	The protocol was not available to assess whether any pre‐specified outcomes were not reported or outcomes were reported that were not pre‐specified
Other bias	Unclear risk	Although none identified, it is difficult to rule out any significant bias due to insufficient reporting of the study. More control participants had relapsed disease (16/40 compared to 8/29).