Abstract

Background

Despite modern antimicrobials and supportive therapy bacterial and fungal infections are still major complications in people with prolonged disease‐related or treatment‐related neutropenia. 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. This is an update of a Cochrane review first published in 2005.

Objectives

To determine the effectiveness and safety of granulocyte transfusions compared to no granulocyte transfusions as adjuncts to antimicrobials for treating infections in people with neutropenia or disorders of neutrophil function aimed at reducing mortality and other adverse outcomes related to infection.

Search methods

We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 2). MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 11 February 2016.

Selection criteria

RCTs comparing people with neutropenia or disorders of neutrophil dysfunction receiving granulocyte transfusions to treat infection with a control group receiving no granulocyte transfusions. Neonates are the subject of another Cochrane review and were excluded from this review. There was no restriction by outcomes examined, language or publication status.

Data collection and analysis

We used standard methodological procedures expected by the Cochrane Collaboration.

Main results

We identified 10 trials that met the inclusion criteria with a total of 587 participants. We also identified another ongoing trial. These trials were conducted between 1975 and 2015. None of the studies included people with neutrophil dysfunction. The studies differed in the type of infections they included. Six studies included both children and adults, however data were not reported separately for children and adults. The two newest studies gave granulocyte colony stimulating factor (G‐CSF) to donors; both were stopped early due to lack of recruitment. Three studies re‐randomised participants and therefore quantitative analysis was unable to be performed.

Overall the quality of the evidence was very low to low across different outcomes according to GRADE methodology. This was due to many of the studies being at high risk of bias, and many of the outcomes being imprecise.

There may be no difference in all‐cause mortality over 30 days between participants receiving therapeutic granulocyte transfusions and those that did not (six studies; 321 participants; RR 0.75, 95% CI 0.54 to 1.04; very low‐quality evidence). There were no differences between the granulocyte dose subgroups (< 1 x 10¹⁰ per day versus ≥ 1 x 10¹⁰ per day) (test for subgroup differences P = 0.39). There was a difference in all‐cause mortality between the studies based on the age of the study (published before 2000 versus published 2000 or later) (test for subgroup differences P = 0.03). There was no difference in all‐cause mortality between participants receiving granulocyte transfusions and those that did not in the newest study (one study; 111 participants; RR 1.10, 95% CI 0.70 to 1.73, low‐quality evidence). There may be a reduction in all‐cause mortality in participants receiving granulocyte transfusions compared to those that did not in studies published before the year 2000 (five studies; 210 participants; RR 0.53, 95% CI 0.33 to 0.85; low‐quality evidence).

There may be no difference in clinical reversal of concurrent infection between participants receiving therapeutic granulocyte transfusions and those that did not (five studies; 286 participants; RR 0.98, 95% CI 0.81 to 1.19; low‐quality evidence).

There is insufficient evidence to determine whether there is a difference in pulmonary serious adverse events (1 study; 24 participants; RR 0.85, 95% CI 0.38 to 1.88; very low‐quality evidence).

None of the studies reported number of days on therapeutic antibiotics, number of adverse events requiring discontinuation of treatment, or quality of life.

Six studies reported their funding sources and all were funded by governments or charities.

Authors' conclusions

In people who are neutropenic due to myelosuppressive chemotherapy or a haematopoietic stem cell transplant, there is insufficient evidence to determine whether granulocyte transfusions affect all‐cause mortality. To be able to detect a decrease in all‐cause mortality from 35% to 30% would require a study containing at least 2748 participants (80% power, 5% significance). There is low‐grade evidence that therapeutic granulocyte transfusions may not increase the number of participants with clinical resolution of an infection.

Author(s)

Lise J Estcourt, Simon J Stanworth, Sally Hopewell, Carolyn Doree, Marialena Trivella, Edwin Massey

Abstract

Plain language summary

Transfusions of white blood cells to treat infections in people with low white blood cell counts or white blood cells that do not function properly

Review question

We evaluated the evidence about whether white blood cell transfusions (also called granulocyte transfusions) given to treat infections are safe and reduce the risk of death or severe outcomes due to infection. Our target population was people with a very low white count (neutropenia) or white cells that did not function properly (neutrophil dysfunction).

Background

Functioning white blood cells are important for fighting life‐threatening bacterial and fungal infections. For many years some hospital physicians have given white blood cell transfusions to people with infections who have a low white blood count. The demand for white blood cells 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 white blood cell numbers in the donor's blood and the collection of a larger dose of white blood cells than was previously possible.

Study Characteristics

The evidence is current to February 2016. In this update we identified 10 completed trials that compared giving white blood cell transfusions to treat infection compared to not giving white blood cells to treat infection. One additional trial has not yet been completed. The 10 trials containing a total of 587 participants were conducted between 1975 and 2015. The studies differed in the type of infections they included. Data from three trials were not included in the analyses because participants were included within the trial more than once. Six trials included both children and adults, but results were not reported separately for children and adults. The two newest trials gave G‐CSF to donors, both were stopped early due to lack of recruitment. Six studies reported their funding sources and all were funded by governments or charities.

Key results

Giving white blood cell transfusions to treat infection may not affect the risk of death or the number of people who recover from an infection.

It is unknown whether white blood cell transfusions increase the risk of having a serious adverse event.

None of the studies reported whether white blood cell transfusions reduced the number of days participants were on therapeutic antibiotics, or whether white blood cell transfusions had an effect on participants' quality of life.

Quality of the Evidence

The evidence for most of the findings are of low or very low quality. This was because the total number of participants included in this review was too small to detect a difference in this review's primary outcome. We calculated that a study would need at least 2748 participants to be able to detect a decrease in the risk of death from 35 people out of 100 to 30 people out of 100 (five additional lives saved per 100 people treated). Also participants and their doctors were likely to know which study arm they had been allocated to in all of the studies.

Author(s)

Lise J Estcourt, Simon J Stanworth, Sally Hopewell, Carolyn Doree, Marialena Trivella, Edwin Massey

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

There is insufficient evidence from randomised controlled trials (RCTs) to support or refute the use of granulocyte transfusion therapy in patients with neutropenia and severe infection to reduce mortality. None of the trials in this review specifically evaluated patients with congenital disorders of neutrophil function or production, although many clinicians might consider this as accepted practice to manage severe infection. None of the studies in this review assessed the use of granulocytes derived from whole blood donations. In keeping with the conclusions from the systematic review of the use of prophylactic granulocyte transfusions, the use of granulocyte transfusions should still be regarded as investigational and should ideally be conducted in the context of ongoing prospective trials designed to answer the question of effectiveness.

Implications for research 

Contemporary well‐designed prospective trials of sufficient power are required to evaluate the efficacy of granulocyte transfusions, in order to establish definitively whether it has clinical benefit or not with regards to reduction in mortality. The one ongoing trial is too small (100 participants) to be able to answer this review's primary outcome.

Side effects need to be evaluated not only for the transfused recipient but also with respect to donors.

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