Abstract: We identified six studies eligible for inclusion in this review; five RCTs and one NRS. Three completed RCTs (156 participants), one completed NRS (84 participants), and two ongoing RCTs. We identified one additional RCT awaiting classification. The completed studies were conducted between 1997 and 2015 and had a mean follow-up from 31 days to 2 years. One study included children receiving a HSCT (six participants), the other three studies only included adults: 218 participants with acute leukaemia receiving chemotherapy, and 16 with a haematological malignancy receiving a HSCT. The restrictive strategies varied from 70 g/L to 90 g/L. The liberal strategies also varied from 80 g/L to 120 g/L. Based on the GRADE rating methodology the overall quality of the included studies was very low to low across different outcomes. None of the included studies were free from bias for all 'Risk of bias' domains. One of the three RCTs was discontinued early for safety concerns after recruiting only six children, all three participants in the liberal group developed veno-occlusive disease (VOD). Evidence from RCTs A restrictive RBC transfusion policy may make little or no difference to: the number of participants who died within 100 days (two trials, 95 participants (RR: 0.25, 95% CI 0.02 to 2.69, low-quality evidence); the number of participants who experienced any bleeding (two studies, 149 participants; RR:0.93, 95% CI 0.73 to 1.18, low-quality evidence), or clinically significant bleeding (two studies, 149 participants, RR: 1.03, 95% CI 0.75 to 1.43, low-quality evidence); the number of participants who required RBC transfusions (three trials; 155 participants: RR: 0.97, 95% CI 0.90 to 1.05, low-quality evidence); or the length of hospital stay (restrictive median 35.5 days (interquartile range (IQR): 31.2 to 43.8); liberal 36 days (IQR: 29.2 to 44), low-quality evidence). We are uncertain whether the restrictive RBC transfusion strategy: decreases quality of life (one trial, 89 participants, fatigue score: restrictive median 4.8 (IQR 4 to 5.2); liberal median 4.5 (IQR 3.6 to 5) (very low-quality evidence); or reduces the risk of developing any serious infection (one study, 89 participants, RR: 1.23, 95% CI 0.74 to 2.04, very low-quality evidence). A restrictive RBC transfusion policy may reduce the number of RBC transfusions per participant (two trials; 95 participants; mean difference (MD) -3.58, 95% CI -5.66 to -1.49, low-quality evidence). Evidence from NRS We are uncertain whether the restrictive RBC transfusion strategy: reduces the risk of death within 100 days (one study, 84 participants, restrictive 1 death; liberal 1 death; very low-quality evidence); decreases the risk of clinically significant bleeding (one study, 84 participants, restrictive 3; liberal 8; very low-quality evidence); or decreases the number of RBC transfusions (adjusted for age, sex and acute myeloid leukaemia type geometric mean 1.25; 95% CI 1.07 to 1.47 - data analysis performed by the study authors) No NRS were found that looked at: quality of life; number of participants with any bleeding; serious infection; or length of hospital stay. No studies were found that looked at: adverse transfusion reactions; arterial or venous thromboembolic events; length of intensive care admission; or readmission to hospital. Findings from this review were based on four studies and 240 participants. There is low-quality evidence that a restrictive RBC transfusion policy reduces the number of RBC transfusions per participant. There is low-quality evidence that a restrictive RBC transfusion policy has little or no effect on: mortality at 30 to 100 days, bleeding, or hospital stay. This evidence is mainly based on adults with acute leukaemia who are having chemotherapy. Although, the two ongoing studies (530 participants) are due to be completed by January 2018 and will provide additional information for adults with haematological malignancies, we will not be able to answer this review's primary outcome. If we assume a mortality rate of 3% within 100 days we would need 1492 participants to have a 80% chance of detecting, as significant at the 5% level, an increase in all-cause mortality from 3% to 6%. Further RCTs are required in children.

Plain-language summary: We searched for randomised and prospective non-randomised trials. Six studies met our inclusion criteria, four are completed and two are still ongoing. An additional study is awaiting classification. The completed studies were conducted between 1997 and 2015 and included 240 participants. One study included children receiving a stem cell transplant and it was stopped early due to safety concerns (six children), the other three studies only included adults, 218 adults with acute leukaemia receiving chemotherapy, and 16 with a blood cancer receiving a stem cell transplant. Three studies were randomised controlled trials and the fourth was a non-randomised study. The haemoglobin threshold of the restrictive strategies varied across the studies. The sources of funding were reported in all four studies. One study was industry sponsored. The evidence is current to June 2016 and is mainly based on adults with acute leukaemia who are having chemotherapy. A restrictive red blood cell transfusion policy may reduce the number of red blood cell transfusions received by an individual. A restrictive red blood cell transfusion policy may have little or no effect on: whether an individual receives a red blood cell transfusion; death due to any cause; bleeding; or hospital stay. We are uncertain whether a restrictive red blood cell transfusion policy affects quality of life, or the risk of developing a serious infection. No studies were found that looked at: adverse reactions to transfusion; development of blood clots; length of stay in intensive care; or need to be readmitted to hospital. There are two ongoing trials (planning to recruit 530 adults) that are due to be completed by January 2018 and will provide additional information for adults with blood cancers. There are no ongoing trials in children. The overall quality of the evidence was very low to low as the included studies were at considerable risk of bias, the estimates were imprecise, and most of the evidence was only for adults with acute leukaemia.