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Granulocyte transfusions for preventing infections in patients with neutropenia or neutrophil dysfunction

  • Review
  • Intervention

Authors


Abstract

Background

Since the late 1990s there has been increasing demand for donated granulocyte transfusions to treat or prevent severe infections in patients who lack their own functional granulocytes. Other than in neonates, no systematic reviews have been performed for over 10 years relating to the efficacy of prophylactic granulocyte transfusions.

Objectives

To determine the effectiveness and safety of granulocyte transfusions compared with a control population not receiving this intervention for preventing mortality due to infection or due to any other cause in patients with neutropenia or disorders of neutrophil function.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 3, 2008, MEDLINE, EMBASE and other specialised databases up to October 2008. We also searched reference lists of articles and contacted experts in the field.

Selection criteria

Randomised controlled trials (RCTs) comparing patients receiving granulocyte transfusions to prevent the development of infection with a control group receiving no granulocyte transfusions. Neonates have been the subject of a recent review and were excluded. There was no restriction by outcomes examined, but this review focuses on mortality, mortality due to infection and adverse events.

Data collection and analysis

Two review authors independently assessed potentially relevant studies for inclusion. Data were extracted by two review authors and the methodological quality was examined. Data were analysed using random and fixed effects models.

Main results

Ten trials met the inclusion criteria. Allocation in all trials was random, with the control arm receiving no prophylactic therapy, except one trial in which the control group received specific prophylactic antibiotics. One study reported biological randomisation based upon the availability of suitably matched, related donors rather than strict randomisation. All trials were conducted over twenty years ago with one exception, a study from 2006 in which donors were pre-medicated with granulocyte colony stimulating factor (G-CSF) resulting in significantly higher mean doses of granulocytes collected for transfusion. Different policies otherwise applied for the schedule for transfusion, method of granulocyte procurement and criteria for defining infection. Combining the results showed a relative risk (RR) for mortality of 0.94 (95% confidence intervals (CI) 0.71 to 1.25). Exclusion of the two trials which reported transfusion of an average number of granulocytes below 1 x 1010 indicated a summary RR for mortality and mortality due to infection of 0.89 (CI 0.64 to 1.24) and 0.36 (0.14 to 0.96) respectively.

Authors' conclusions

Implications for clinical practice: The controlled trials that have been identified raise the possibility that prophylactic granulocyte transfusions at a dose of at least 1 x 1010 may reduce the risk of mortality from infection. Overall mortality was not affected. However, the majority of studies were performed decades ago, and standards of supportive care have advanced considerably. These earlier trials were also based on transfusing lower yields of collected granulocytes than currently recommended. It is difficult to recommend prophylactic granulocyte transfusions outside the setting of ongoing controlled trials, given the resource and cost implications.

Implications for research: Larger trials are needed to establish the validity of the potential benefits raised by this review, in view of the methodological limitations, the small sample sizes and the heterogeneous definitions of infection that were encountered in the included studies.

Plain language summary

Transfusions of white blood cells called granulocytes for preventing infections in patients who lack functioning granulocytes

Functioning white blood cells, in particular granulocytes are important for fighting life-threatening bacterial and fungal infections. For many years, some hospital physicians have been ordering granulocytes for patients who lack white cells as a result of disease and/or treatment which has reduced their number or function.

The demand for granulocytes for transfusion has shown a steady increase since the 1990s mainly as a result of the introduction of a drug called granulocyte colony stimulating factor (G-CSF) which, if given to donors, leads to increased granulocyte numbers in the donor's blood and the collection of a larger dose of granulocytes than was previously possible. Other than in newborn children, no systematic reviews have been performed for over 10 years relating to the efficacy of granulocyte transfusions in preventing the development of infections. This review of patients of all ages other than the newborn was therefore performed to address this

Ten trials met the criteria for analysis. Combining the results of all ten studies showed that there was no significant difference between those receiving granulocytes and those who did not in terms of the numbers who died. When the two trials, which used low doses of granulocytes (less than 1 x 1010) were excluded, patients in the remaining 8 trials (who received more than 1 x 1010 granulocytes per transfusion) were less likely to die of infection than those who did not receive granulocytes transfusions. Overall however, when death from any cause was considered, patients receiving granulocyte transfusion were no less likely to die.

There were difficulties obtaining granulocytes from donor veins. Donors developed shivers and chills. Recipients suffered transfusion reactions including fevers, shortness of breath and fluid in the lungs. One patient was reported to have died as a result of side effects from the transfused white cells.

The review has several limitations. One trial administered high dose antibiotics to the patients who did not receive granulocyte transfusions but did not give these antibiotics to the patients receiving transfusions. Another study relied on “biological” randomization of patients based upon the availability, or not, of donors. All bar one study were performed more than twenty years ago, and two trials used small doses by modern standards.

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