Intervention Review

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

  1. Simon Stanworth2,
  2. Edwin Massey1,*,
  3. Chris Hyde3,
  4. Susan J Brunskill4,
  5. Cristina Navarette5,
  6. Geoff Lucas6,
  7. David Marks7,
  8. Ulrike Paulus8

Editorial Group: Cochrane Gynaecological Cancer Group

Published Online: 21 JAN 2009

Assessed as up-to-date: 29 JUN 2010

DOI: 10.1002/14651858.CD005339

Database Title

Additional Information

How to Cite

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.

Author Information

  1. 1

    NHS Blood and Transplant, Bristol, UK

  2. 2

    NHS Blood and Transplant, Haematology/Transfusion Medicine, Oxford, UK

  3. 3

    Peninsula College of Medicine & Dentistry, Peninsula Technology Assessment Group (PenTAG), Exeter, UK

  4. 4

    NHS Blood and Transplant, Systematic Review Initiative, Oxford, Oxon, UK

  5. 5

    National Blood Service, North London Blood Transfusion Centre, London, UK

  6. 6

    National Blood Service, Bristol, UK

  7. 7

    Bristol Royal Hospital for Children, Department of Adult BMT, Bristol, UK

  8. 8

    Department of Haematology, Dept of Haematology, Newport, South Wales, UK

*Edwin Massey, NHS Blood and Transplant, North Bristol Park, Northway, Filton, Bristol, BS34 7QH, UK. edwin.massey@nhsbt.nhs.uk.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 21 JAN 2009

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

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 methods

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.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

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

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.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

以顆粒性白血球輸注治療嗜中性白血球減少症或嗜中性白血球功能不良病人的感染

在臨床實作上，以顆粒性白血球輸注來支持及治療嗜中性白血球減少症或嗜中性白血球功能不良的高風險病人族群之嚴重感染，已有很長一段歷史。然而治療用的顆粒性白血球輸注作為治療的運用，目前仍有很多的變化，而且醫學界對於輸注之有利效果的不確定性，使這種療法在對抗死亡率時，淪為抗生素的附屬品。

目標

本研究的目的是測定以顆粒性白血球輸注，治療嗜中性白血球減少症或嗜中性白血球功能不良病人的感染，而減少其死亡率的效果，同時與未利用顆粒性白血球輸注治療的效果進行比較。

搜尋策略

搜尋Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2009) 藉此找出隨機對照試驗 (RCTs) 。此外還以RCT搜尋篩選策略搜尋MEDLINE及EMBASE (使用OVID介面) ，時間直到2009年5月。在本次小型的更新中還搜尋了下述資料庫：CINAHL、LILACS、 KoreaMed、IndMed、PakMediNet、Current Controlled Trials (mRCT) 、ClinicalTrials.gov及WHO International Clinical trials Registry Platform (ICTRP) 時間直到2009年5月。

選擇標準

這些RCT包含因治療之目的，為嗜中性白血球減少症或嗜中性功能不良疾病的病人進行顆粒性白血球輸注的研究。

資料收集與分析

2位研究回顧者獨立完成了數據摘錄。使用隨機效果模型之相對風險(RR)與95% 信賴區間(CI)，提出二分化結果。我們完成預先指定的子群分析，並提出顆粒性白血球的劑量。

主要結論

我們搜尋到8篇平行化的RCT，一共包含310個完整分析的病人事件。在這些試驗中，輸注時間表、取得顆粒性球的方法及捐贈者的選擇(包括白血球相容性)，都採用了不同的策略。每項研究採用的嗜中性白血球減少症判定標準(範圍從 <0.1至 <1.0 x 109/L)，以及需要治療之感染定義均不同。我們從6項試驗中摘錄了死亡率的數據，總計的RR = 0.64，比較支持輸注治療的效果(95% CI 0.33, 1.26)，但是存在著顯著的統計異質性證據(卡方檢定11.3及I2 = 56%)。4項輸注顆粒性白血球劑量較高(高於1x1010)的研究結果，其合併的死亡率RR = 0.37(95% CI 0.17, 0.82)；卡方檢定3.9，I2 = 23% 。從4項研究摘錄了感染情況逆轉的比率，其合併RR為0.94(95% CI 0.71, 1.26)，同樣又出現了異質性的證據。除了在所有試驗中觀察到的臨床差異之外，對於這些研究之定量及定性分析的不確定性，也因為方法學的差異而增加了。

作者結論

目前，從RCT獲得支持或反對廣泛地使用顆粒性白血球輸注療法治療最常見的嗜中性白血球減少之病人族群的證據，是非決定性的。這些病人發生嗜中性白血球減少的原因，是由於有或無造血幹細胞支持的骨髓殲滅性的化學治療所造成的。目前需要經過縝密設計的前瞻性試驗，來評估這種干預治療對於這些病人族群的效果，並且明確地確認它是否具有臨床的效益。在這樣的研究中，用於治療成人而收集的顆粒性白血球平均數目，應高於(至少)1x1010。

翻譯人

此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。

總結

白血球輸注可能有助於顆粒性白血球數量非常低的病人，他們處於較高的重度感染及死亡的風險中。由於疾病或藥物治療的副作用，造成顆粒性白血球數量非常低的病人，處於可能導致死亡的嚴重感染之風險中。白血球有助於幫助這些顆粒性白血球數量非常低的病人對抗感染。這篇隨機化試驗的回顧發現，雖然試驗所包含的病人數量很少，數量超過一百萬個顆粒性白血球的輸注治療，可以減少病人死亡的數字。然而，這些發表的研究全都存在著限制，而且是在25年多前進行的。還需要更大型且人數更充足的試驗，來評估效果及訂出最理想的輸注時間表。

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