Granulocyte transfusions for treating infections in people with neutropenia or neutrophil dysfunction.
Granulocyte transfusions for treating infections in people with neutropenia or neutrophil dysfunction.
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DOI：
10.1002/14651858.cd005339.pub2
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发表时间：
2016-04-29
期刊：
影响因子：
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通讯作者：
Massey E
中科院分区：
文献类型：
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作者：
Estcourt LJ;Stanworth SJ;Hopewell S;Doree C;Trivella M;Massey E
尽管有现代抗菌剂和支持性治疗，细菌和真菌感染仍然是长期疾病相关或治疗相关中性粒细胞减少症患者的主要并发症。在临床实践中，粒细胞输注长期用于支持和治疗嗜中性粒细胞减少或中性粒细胞功能障碍患者的高危人群的严重感染。然而，目前在治疗性粒细胞输注实践中存在相当大的差异，并且不确定输注作为抗生素辅助治疗对死亡率的有益影响。这是对2005年首次发表的Cochrane综述的更新。确定输注粒细胞与不输注粒细胞作为抗微生物药物治疗中性粒细胞减少症或中性粒细胞功能紊乱患者感染的辅助治疗的有效性和安全性，旨在降低死亡率和其他与感染相关的不良后果。我们在Cochrane中央对照试验登记册（Central） （Cochrane图书馆2016年第2期）中检索了随机对照试验（RCTs）。MEDLINE（从1946年开始）、Embase（从1974年开始）、CINAHL（从1937年开始）、输血证据库（从1980年开始）和正在进行的试验数据库（截至2016年2月11日）。比较中性粒细胞减少症或中性粒细胞功能障碍患者接受粒细胞输注治疗感染与不接受粒细胞输注的对照组的随机对照试验。新生儿是另一篇Cochrane综述的主题，并被排除在本综述之外。不受研究结果、语言或出版状况的限制。我们采用Cochrane协作网期望的标准方法程序。我们确定了10项符合纳入标准的试验，共有587名受试者。我们还确定了另一项正在进行的试验。这些试验在1975年至2015年间进行。没有一项研究包括有中性粒细胞功能障碍的人。这些研究所包含的感染类型有所不同。六项研究包括儿童和成人，但没有分别报告儿童和成人的数据。两项最新的研究给捐赠者注射了粒细胞集落刺激因子（G-CSF）；由于招募不足，这两个项目都被提前叫停。三项研究重新随机分配了参与者，因此无法进行定量分析。总体而言，根据GRADE方法，不同结果的证据质量非常低。这是由于许多研究存在很高的偏倚风险，而且许多结果不精确。接受治疗性粒细胞输注的受试者与未接受治疗性粒细胞输注的受试者在30天内的全因死亡率可能没有差异（6项研究；321名受试者；RR 0.75, 95% CI 0.54至1.04；证据质量非常低）。粒细胞剂量亚组之间无差异（< 1 × 1010 /天vs≥1 × 1010 /天）（亚组差异检验P = 0.39）。基于研究年龄的研究（2000年之前发表的与2000年或之后发表的）的全因死亡率存在差异（亚组差异检验P = 0.03）。在最新的研究中，接受粒细胞输注的参与者与未接受粒细胞输注的参与者之间的全因死亡率没有差异（一项研究，111名参与者；RR 1.10, 95% CI 0.70至1.73，低质量证据）。在2000年以前发表的研究中，接受粒细胞输注的受试者与未接受输注的受试者相比，全因死亡率可能降低（5项研究，210名受试者；RR 0.53, 95% CI 0.33 ~ 0.85；低质量证据）。接受治疗性粒细胞输注的受试者与未接受治疗性粒细胞输注的受试者在并发感染的临床逆转方面可能没有差异（5项研究；286名受试者；RR 0.98, 95% CI 0.81至1.19；低质量证据）。没有足够的证据来确定肺部严重不良事件是否存在差异（1项研究，24名受试者；RR 0.85, 95% CI 0.38 - 1.88；证据质量非常低）。没有一项研究报告了治疗性抗生素的天数，需要停止治疗的不良事件的数量，或生活质量。六项研究报告了它们的资金来源，全部由政府或慈善机构资助。在因骨髓抑制化疗或造血干细胞移植而出现中性粒细胞减少的患者中，没有足够的证据来确定粒细胞输注是否会影响全因死亡率。要发现全因死亡率从35%下降到30%，需要至少包含2748名参与者的研究（80%的功效，5%的显著性）。有低级别证据表明，治疗性粒细胞输注可能不会增加感染临床解决的参与者人数。
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. 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. 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. 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. We used standard methodological procedures expected by the Cochrane Collaboration. 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. 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.