Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support.
Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support.
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DOI：
10.1002/14651858.cd011305.pub2
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发表时间：
2017-01-27
期刊：
影响因子：
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通讯作者：
Murphy MF
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作者：
Estcourt LJ;Malouf R;Trivella M;Fergusson DA;Hopewell S;Murphy MF
许多被诊断患有血液系统恶性肿瘤的人患有贫血，红细胞（RBC）输血在其治疗中起着至关重要的支持作用。不同的策略已经发展为红细胞输注。限制性输血策略旨在维持较低的血红蛋白水平（通常在70 g/L至90 g/L之间），并在血红蛋白低于70 g/L时触发输血)，而自由输血策略旨在维持较高的血红蛋白（通常在100 g/L至120 g/L之间，当血红蛋白低于100 g/L时有输血阈值）。在接受手术或已入住重症监护室的患者中，限制性输血策略已被证明是安全的，在某些情况下比自由输血策略更安全。然而，目前尚不清楚它对血液恶性肿瘤患者是否安全。目的：确定限制性与自由红细胞输注策略对接受强化化疗或放疗，或两者兼有，伴或不伴造血干细胞移植（HSCT）的血液系统恶性肿瘤患者的有效性和安全性。我们在MEDLINE（自1946年起）、Embase（自1974年起）、CINAHL（自1982年起）、Cochrane中央对照试验登记（Central） （Cochrane图书馆2016年第6期）和其他10个数据库（包括4个试验登记）中检索了随机对照试验（rct）和非随机试验（NRS），至2016年6月15日。我们还检索了灰色文献，并联系了输血方面的专家进行额外的试验。对语文、日期或出版状况没有限制。我们纳入了随机对照试验和前瞻性NRS，对患有恶性血液病或接受造血干细胞移植的儿童或成人的限制性和自由红细胞输血策略进行了评估。我们采用Cochrane期望的标准方法程序。我们确定了6项符合纳入本综述的研究；5项随机对照试验和1项NRS。3项完成的rct（156名受试者），1项完成的NRS（84名受试者）和2项正在进行的rct。我们确定了另一个等待分类的RCT。完成的研究于1997年至2015年期间进行，平均随访时间为31天至2年。一项研究包括接受造血干细胞移植的儿童（6名参与者），另外三项研究仅包括成人：218名接受化疗的急性白血病患者，16名接受造血干细胞移植的血液恶性肿瘤患者。限制策略从70 g/L到90 g/L不等。自由策略也从80 g/L到120 g/L不等。根据GRADE评分方法，纳入的研究的总体质量在不同的结果中非常低到低。纳入的研究中没有一项在所有“偏倚风险”领域都没有偏倚。其中一项随机对照试验在只招募了6名儿童后，出于安全考虑提前终止，自由组的所有3名参与者都出现了静脉闭塞性疾病（VOD）。限制性红细胞输血政策可能对以下因素影响不大或没有影响：100天内死亡的受试者人数(两项试验，95名受试者（RR: 0.25, 95% CI 0.02至2.69，低质量证据）；发生出血的受试者人数（两项研究，149名受试者；RR:0.93, 95% CI 0.73至1.18，低质量证据），或临床显著出血的受试者人数（两项研究，149名受试者，RR: 1.03, 95% CI 0.75至1.43，低质量证据）；需要输血的受试者人数（3项试验，155名受试者：RR: 0.97, 95% CI 0.90 ~ 1.05，低质量证据）；或住院时间(限制中位数为35.5天（四分位数间距（IQR）： 31.2至43.8）；自由36天（IQR: 29.2 - 44），低质量证据)。我们不确定限制性红细胞输血策略是否会降低生活质量(一项试验，89名参与者，疲劳评分：限制性中位数4.8 (IQR 4至5.2)；自由中位数为4.5 (IQR为3.6 - 5)（极低质量证据）；或降低发生任何严重感染的风险（一项研究，89名参与者，RR: 1.23, 95% CI 0.74至2.04，证据质量非常低）。限制性的红细胞输血政策可能会减少每位参与者的红细胞输注次数（两项试验，95名参与者；平均差异(MD) -3.58, 95% CI -5.66至-1.49，低质量证据）。我们不确定限制性红细胞输血策略是否：降低100天内死亡风险（一项研究，84名受试者，限制性1例死亡；自由1例死亡；极低质量证据）；降低临床显著出血的风险（一项研究，84名受试者，限制性3名；自由8名；极低质量证据）；或减少红细胞输注次数（根据年龄、性别和急性髓性白血病类型进行校正，几何平均值为1.25；95% CI为1.07至1.47——研究作者进行的数据分析）有出血的受试者人数；严重感染;或者住院时间。没有研究发现：输血不良反应；动脉或静脉血栓栓塞事件；重症监护住院时间；或者再次入院。这篇综述的结果基于四项研究和240名参与者。有低质量的证据表明，限制性红细胞输血政策减少了每位参与者的红细胞输血次数。有低质量的证据表明，限制性红细胞输血政策对30至100天死亡率、出血或住院时间的影响很小或没有影响。这一证据主要基于正在接受化疗的急性白血病成人患者。尽管这两项正在进行的研究（530名参与者）将于2018年1月完成，并将为患有血液系统恶性肿瘤的成人提供更多信息，但我们将无法回答本综述的主要结局。如果我们假设100天内的死亡率为3%，我们需要1492名参与者有80%的机会检测到，在5%的水平上同样显著，全因死亡率从3%增加到6%。需要对儿童进行进一步的随机对照试验。
Many people diagnosed with haematological malignancies experience anaemia, and red blood cell (RBC) transfusion plays an essential supportive role in their management. Different strategies have been developed for RBC transfusions. A restrictive transfusion strategy seeks to maintain a lower haemoglobin level (usually between 70 g/L to 90 g/L) with a trigger for transfusion when the haemoglobin drops below 70 g/L), whereas a liberal transfusion strategy aims to maintain a higher haemoglobin (usually between 100 g/L to 120 g/L, with a threshold for transfusion when haemoglobin drops below 100 g/L). In people undergoing surgery or who have been admitted to intensive care a restrictive transfusion strategy has been shown to be safe and in some cases safer than a liberal transfusion strategy. However, it is not known whether it is safe in people with haematological malignancies. To determine the efficacy and safety of restrictive versus liberal RBC transfusion strategies for people diagnosed with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without a haematopoietic stem cell transplant (HSCT). We searched for randomised controlled trials (RCTs) and non-randomised trials (NRS) in MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 6), and 10 other databases (including four trial registries) to 15 June 2016. We also searched grey literature and contacted experts in transfusion for additional trials. There was no restriction on language, date or publication status. We included RCTs and prospective NRS that evaluated a restrictive compared with a liberal RBC transfusion strategy in children or adults with malignant haematological disorders or undergoing HSCT. We used the standard methodological procedures expected by Cochrane. We identified six studies eligible for inclusion in this review; five RCTs and one NRS. Three completed RCTs (156 participants), one completed NRS (84 participants), and two ongoing RCTs. We identified one additional RCT awaiting classification. The completed studies were conducted between 1997 and 2015 and had a mean follow-up from 31 days to 2 years. One study included children receiving a HSCT (six participants), the other three studies only included adults: 218 participants with acute leukaemia receiving chemotherapy, and 16 with a haematological malignancy receiving a HSCT. The restrictive strategies varied from 70 g/L to 90 g/L. The liberal strategies also varied from 80 g/L to 120 g/L. Based on the GRADE rating methodology the overall quality of the included studies was very low to low across different outcomes. None of the included studies were free from bias for all ’Risk of bias’ domains. One of the three RCTs was discontinued early for safety concerns after recruiting only six children, all three participants in the liberal group developed veno-occlusive disease (VOD). A restrictive RBC transfusion policy may make little or no difference to: the number of participants who died within 100 days (two trials, 95 participants (RR: 0.25, 95% CI 0.02 to 2.69, low-quality evidence); the number of participants who experienced any bleeding (two studies, 149 participants; RR:0.93, 95% CI 0.73 to 1.18, low-quality evidence), or clinically significant bleeding (two studies, 149 participants, RR: 1.03, 95% CI 0.75 to 1.43, low-quality evidence); the number of participants who required RBC transfusions (three trials; 155 participants: RR: 0.97, 95% CI 0.90 to 1.05, low-quality evidence); or the length of hospital stay (restrictive median 35.5 days (interquartile range (IQR): 31.2 to 43.8); liberal 36 days (IQR: 29.2 to 44), low-quality evidence). We are uncertain whether the restrictive RBC transfusion strategy: decreases quality of life (one trial, 89 participants, fatigue score: restrictive median 4.8 (IQR 4 to 5.2); liberal median 4.5 (IQR 3.6 to 5) (very low-quality evidence); or reduces the risk of developing any serious infection (one study, 89 participants, RR: 1.23, 95% CI 0.74 to 2.04, very low-quality evidence). A restrictive RBC transfusion policy may reduce the number of RBC transfusions per participant (two trials; 95 participants; mean difference (MD) -3.58, 95% CI -5.66 to -1.49, low-quality evidence). We are uncertain whether the restrictive RBC transfusion strategy: reduces the risk of death within 100 days (one study, 84 participants, restrictive 1 death; liberal 1 death; very low-quality evidence); decreases the risk of clinically significant bleeding (one study, 84 participants, restrictive 3; liberal 8; very low-quality evidence); or decreases the number of RBC transfusions (adjusted for age, sex and acute myeloid leukaemia type geometric mean 1.25; 95% CI 1.07 to 1.47 - data analysis performed by the study authors) No NRS were found that looked at: quality of life; number of participants with any bleeding; serious infection; or length of hospital stay. No studies were found that looked at: adverse transfusion reactions; arterial or venous thromboembolic events; length of intensive care admission; or readmission to hospital. Findings from this review were based on four studies and 240 participants. There is low-quality evidence that a restrictive RBC transfusion policy reduces the number of RBC transfusions per participant. There is low-quality evidence that a restrictive RBC transfusion policy has little or no effect on: mortality at 30 to 100 days, bleeding, or hospital stay. This evidence is mainly based on adults with acute leukaemia who are having chemotherapy. Although, the two ongoing studies (530 participants) are due to be completed by January 2018 and will provide additional information for adults with haematological malignancies, we will not be able to answer this review’s primary outcome. If we assume a mortality rate of 3% within 100 days we would need 1492 participants to have a 80% chance of detecting, as significant at the 5% level, an increase in all-cause mortality from 3% to 6%. Further RCTs are required in children.