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Granulocyte Transfusions for Preventing Infections in Patients with Neutropenia or Neutrophil Dysfunction

Authors <> Massey Edwin, Paulus Ulrike, Doree Carolyn, Stanworth Simon

Review Group <> Cochrane Gynaecological Cancer Group

Abstract <> 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 strategy

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.

Implications <> The review has identified a reduction in mortality due to infection and fewer infective episodes in patients receiving a dose of at least 1 x 1010 granulocytes. It would however be premature to conclude that the use of granulocytes as prophylaxis in patients with neutropenia would improve outcomes and prove cost-effective. Supportive therapy in this setting has changed since most of the reviewed studies were performed. None of the trials in this review specifically evaluated patients with congenital disorders of neutrophil function or production. In keeping with the conclusions from the systematic review of the use of granulocyte transfusions for therapeutic indications, the use of granulocyte transfusions should still be regarded as investigational and should ideally be conducted in the context of on-going prospective trials designed to answer the question of effectiveness.

Citation <> Massey E, Paulus U, Doree C, Stanworth S. Granulocyte transfusions for preventing infections in patients with neutropenia or neutrophil dysfunction. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD005341. DOI: 10.1002/14651858.CD005341.pub2.