Mannoni 1979.
Methods | Parallel RCT (recruitment period not reported). Number of centres unclear. Country: France | |
Participants |
Inclusion criteria: Adults (>16 years old) with acute myeloid leukaemia receiving standardised chemotherapy inducing profound bone marrow depression Exclusion criteria: "not severely infected", severe infection being defined as pulmonary or perineal localisation or diarrhoea with abdominal distension. Total randomised: N = 44 participants and 50 episodes of aplasia Arm 1 (Granulocyte transfusions): randomised = 20, Acute myeloid leukaemia = 20 (22 separate episodes of aplasia) Arm 2 (Control): randomised = 26* , Acute myeloid leukaemia = 26 (28 separate episodes of aplasia) Acute leukaemia (myeloid) * Six participants may have been re‐randomised but this is not clear in the text. Randomisation occurred at the onset of 50 episodes of aplasia. |
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Interventions | Comparison between standard treatment and prophylactic granulocyte transfusions Granulocyte dose: 2.1 x 1010 (1.3 to 3.7) Granulocyte method of collection: intermittent flow centrifugation Donor premedication: dexamethasone or hydrocortisone Initiation of granulocyte transfusions: Fourth day of chemotherapy Frequency of granulocyte transfusions: Daily Termination of granulocyte transfusions: After approximately 12 days in the absence of fever or infection |
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Outcomes |
Primary Outcome: Not reported Other Outcomes: Mortality/survival, infection (days or episodes), adverse events |
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Definition of infection |
Febrile day ‐ Not reported Febrile episode ‐ temperature elevation alone of 38oC for at least 24 hours excluding febrile reactions to blood products or administration of chemotherapy Minor infection: Bacteraemia alone, with at least 2 positive blood cultures, or local skin or mucocutaneous infection, or in case of diarrhoea without abdominal distension Major infection: Any life‐threatening infection or the associations of septicaemia and local infections were considered as major infections |
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Definition of neutropenia | Neutrophils < 0.5 x 109/L | |
Co‐interventions |
Prophylactic antibiotics: non absorbable antibiotics Therapeutic antibiotics: combination of two systemic antibiotics if the patient was febrile for 24 hours. Therapeutic granulocyte transfusions: given to the control group if participants had a severe infection or in the case of refractoriness to antibiotics in minor infections. |
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Notes |
Funding Sources: Not reported Conflict of Interests: Not reported |
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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 | High risk | It was not reported whether participants were blinded to the intervention. In the intervention group "the number of platelets contaminating the leucocyte transfusions was usually enough to maintain the platelet count" above 20. Therefore clinicians would be able to tell whether patient was receiving prophylactic granulocyte transfusions. |
Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Clinical data were collected and re‐examined by two different persons who had not been in charge of the participants, in order to determine the diagnosis and severity of infection. However it was not reported whether these outcome assessors were blinded to the intervention |
Incomplete outcome data (attrition bias) All outcomes | Unclear risk | It was unclear whether any participants were lost to follow‐up |
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 | High risk | Study funding and any conflicts of interest were not reported. Baseline characteristics of the participants were not reported. It appeared that at least six participants had been re‐randomised, 44 participants and 50 episodes of aplasia. |