White blood cell transfusions may be helpful for patients with very low granulocyte cell counts who are at greater risk of serious infections and death

Stanworth S, Massey E, Hyde C, Brunskill SJ, Navarette C, Lucas G, Marks D, Paulus U

Published Online:

August 8, 2010

Granulocytes are key cells for fighting infections. Patients whose granulocyte count is very low due to disease or the adverse effects from drug treatments, are at risk of serious infections which can cause death. White blood cells can be used to help fight infections in patients with very low counts. This review of randomised trials found that, although the number of patients involved in the studies was low, granulocyte infusions of more than a million cells may reduce the number of patients dying. However, these published studies all had limitations and were undertaken over 25 years ago. More research by larger and adequately sized trials is needed to evaluate effectiveness and define the optimal schedules of infusion.

Abstract (click to read)

Background:

Transfusions of granulocytes have a long history of usage in clinical practice to support and treat severe infection in high risk groups of patients with neutropenia or neutrophil dysfunction. However, there is considerable current variability in therapeutic granulocyte transfusion practice, and uncertainty about the beneficial effect of transfusions given as an adjunct to antibiotics on mortality.

Objectives:

To determine the effectiveness of granulocyte transfusions compared to no granulocyte transfusions for treating infections in patients with neutropenia or disorders of neutrophil function in reducing mortality.

Search strategy:

Randomised controlled trials (RCTs) were searched for in the Cochrane Central Register of Controlled Trials (CENTRAL) in Issue 2, 2009. Searching was also undertaken on the OVID versions of MEDLINE and EMBASE using an RCT search filter strategy up to May 2009. In this minor update the following databases have also been searched CINAHL, LILACS, KoreaMed, IndMed, PakMediNet, Current Controlled Trials (mRCT), ClinicalTrials.gov and WHO International Clinical trials Registry Platform (ICTRP) up to May 2009.

Selection criteria:

RCTs involving transfusions of granulocytes, given therapeutically, to patients with neutropenia or disorders of neutrophil dysfunction.

Data collection and analysis:

Two reviewers completed data extraction independently. Relative risk (RR) with 95% confidence intervals (CI) using the random effects model were reported for dichotomous outcomes. Pre-specified subgroup analyses were done and reported eg granulocyte dose.

Main results:

Eight parallel RCTs were included with 310 total analysed patient episodes. Different policies were applied for the schedule of transfusion, method of granulocyte procurement and process of donor selection including leucocyte compatibility. Each study used different criteria for neutropenia (range < 0.1 to < 1.0 x 109/L) and definition of infection requiring treatment.

For mortality, which was extracted from six trials, the summary RR = 0.64 in favour of transfusion (95% CI 0.33, 1.26), but with evidence of significant statistical heterogeneity (Chi-square 11.3 and I2 = 56%). The data for the combined RR for mortality for the four studies transfusing higher granulocyte doses greater than 1x1010 indicated a significant summary RR= 0.37 (95% CI 0.17, 0.82); Chi-square 3.9, I2 23%. Data on rates of reversal of infection could be extracted from four studies, and the combined RR was 0.94 (95% CI 0.71, 1.26), again with evidence of heterogeneity. In addition to the observed clinical diversity between all studies, uncertainty about the quantitative and qualitative analyses for these studies is compounded by methodological deficiencies. The searches were updated in May 2009 identified one small additional RCT and an ongoing trial, both of which will be included in a full update when data is available.

Authors' conclusions:

Currently, there is inconclusive evidence from RCTs to support or refute the generalised use of granulocyte transfusion therapy in the most common neutropenic patient populations, that is caused by myeloablative chemotherapy with or without haematopoietic stem cell support. Contemporary well designed prospective trials are required to evaluate the efficacy of this intervention in these patient populations and to establish definitively whether it has clinical benefit. In such studies, average numbers of collected granulocytes for adults should be (at least) greater than 1x1010.

This record should be cited as:

Stanworth S, Massey E, Hyde C, Brunskill SJ, Navarette C, Lucas G, Marks D, Paulus U. Granulocyte transfusions for treating infections in patients with neutropenia or neutrophil dysfunction. Cochrane Database of Systematic Reviews 2005, Issue 3. Art. No.: CD005339. DOI: 10.1002/14651858.CD005339

Assessed as up to date:

June 30, 2010

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Primary Review Group:

Gynaecological Cancer Group

Health topics:

Cancer > Generic cancer care > Infections in neutropenic patients

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Independent high-quality evidence for health care decision making

White blood cell transfusions may be helpful for patients with very low granulocyte cell counts who are at greater risk of serious infections and death

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