Granulocyte transfusions for treating infections in people with neutropenia or neutrophil dysfunction

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 ...

Bacterial Pneumonia in Patients with Cancer

“…Both classes demonstrate efficacy in reducing the duration of neutropenia, though a less favorable side-effect profile of GM-CSF limits its use primarily to post-HSCT immune reconstitution [135, 136]. While evidence suggests colony-stimulating factors may be safely used to prevent some bacterial pneumonias in cancer populations [137], they are not generally recommended as a treatment of established bacterial infections. Current guidelines recommend administration of G-CSF if the risk of developing febrile neutropenia is greater than 20% based on patient-specific risk factors [136].…”

“…While this strategy holds promise, it remains investigational and interpretation of the associated studies is challenging due to heterogeneity of the populations and protocols [138]. However, some authors argue that severely ill neutropenic patients may benefit from granulocyte transfusion [137]. …”

An International Registry of Granulocyte Transfusions

“…Potential efficacy including a dose-dependent effect has been raised by systematic reviews / meta-analyses, but the most recent Cochrane reviews find no overall evidence of a benefit and point to considerable uncertainty [17,18,19,20]. These reviews draw on many randomised studies conducted over a long period aimed at trying to establish effectiveness of granulocyte transfusions.…”

“…As for the review of prophylactic trials, 10 RCTs met the inclusion criteria, for a total of 587 participants. Some studies were conducted over 30 years ago (N = 8) [20]. Unfortunately, 3 studies re-randomised participants, and therefore quantitative analysis could not be performed to include these trials.…”

Granulocyte transfusions: A concise review for practitioners

“…The conclusions were that there is low quality evidence suggesting GTX may work for prophylaxis [1] and that there is not enough evidence to decide on treatment efficacy [2]. These systematic reviews include, for methodological reasons, only 12 and 10 papers, respectively.…”