背景:估计1/4到1/2的被诊断为血液系统恶性肿瘤的患者会出现贫血。红细胞(RBC)输血治疗贫血有不同的策略。限制性输血策略允许较低的血红蛋白(Hb)水平,而自由输血策略旨在维持较高的Hb。最有效和最安全的策略是未知的。
目的:为了确定限制性和自由红细胞输注策略对诊断为血液系统恶性肿瘤的患者进行强化化疗或放疗的有效性和安全性,或者两者兼而有之,有或没有造血干细胞移植(HSCT)。
方法:我们搜索了MEDLINE(从1946年开始)的随机对照试验(RCT)和非随机研究(NRS),Embase(自1974年起),CINAHL(自1982年起),Cochrane中央受控试验登记册(CENTRAL)(Cochrane图书馆2023,第2期),和其他八个数据库(包括三个试验登记处)至2023年3月21日。我们还搜索了灰色文献,并联系输血专家进行了其他试验。没有语言,日期或发布状态限制。
方法:我们纳入了RCT和前瞻性NRS,评估了接受强化化疗或放疗的患有恶性血液病的儿童或成人限制性与自由红细胞输注策略,或者两者兼而有之,有或没有HSCT。
方法:两位作者独立筛选参考文献,潜在相关研究的全文报告,从研究中提取数据,并评估了偏差的风险。与第三位评论作者讨论并解决了任何分歧。二分类结果以风险比(RR)和95%置信区间(CI)表示。叙事综合用于异质结果测量。使用ReviewManagerWeb对数据进行元分析。感兴趣的主要结果包括:31至100天的全因死亡率,生活质量,有任何出血的参与者的数量,有临床显著出血的参与者数量,严重感染,住院时间(天)和0至3个月再次入院。使用GRADE评估证据的确定性。
结果:9项研究符合资格;8项RCT和1项NRS。从六个完成的RCT(n=560)和一个完成的NRS(n=84)中纳入了64名参与者,正在进行的两项RCTs包括294名参与者(260名成人和34名儿科参与者)。只有一个完成的RCT包括接受HSCT的儿童(n=6);其他五个RCT仅包括成年人:239例接受化疗的急性白血病和315例接受HSCT(166例同种异体和149例自体)。限制性输血阈值为70g/L至80g/L,自由策略为80g/L至120g/L。由于过早终止的儿科试验提供的证据有限,仅在包括成年人在内的试验中报告了效果,以减少间接性。来自RCT的证据总的来说,与自由输血策略相比,使用限制性输血策略在31至100天内死亡的参与者数量可能几乎没有差异,但证据非常不确定(三项研究;451名参与者;RR1.00,95%CI0.27~3.70,P=0.99;非常低的确定性证据).与自由输血策略相比,使用限制性输血策略在0至3个月时的生活质量可能几乎没有差异。但证据非常不确定(3项研究;431名参与者;由于异质性而无法完成分析;极不确定的证据).与自由输血策略相比,使用限制性输血策略在0至3个月时发生任何出血的参与者数量可能几乎没有差异(三项研究;448名参与者;RR0.91,95%CI0.78至1.06,P=0.22;低确定性证据)。与自由输血策略相比,使用限制性输血策略在0至3个月时发生临床显着出血的参与者数量可能几乎没有差异(四项研究;511名参与者;RR:0.94,95%CI0.74至1.19,P=0.60;低确定性证据)。与自由输血策略相比,使用限制性输血策略在0至3个月时经历严重感染的参与者数量可能几乎没有差异(三项研究,451名参与者;RR:1.20,95%CI0.93至1.55,P=0.17;低确定性证据)。与自由策略相比,限制性输血策略可能在0至3个月的住院时间上几乎没有差异(两项研究;388名参与者;由于报告的异质性而无法完成分析;中度确定性证据)。与自由输血策略相比,使用限制性输血策略再入院可能几乎没有差异(一项研究,299名参与者;RR:0.89,95%CI0.52至1.50;P=0.65;低确定性证据)。来自NRS的证据该证据非常不确定限制性红细胞输血策略是否可以降低100天内的死亡风险(一项研究,84名与会者,限制性1例死亡;自由1例死亡;非常低的确定性证据);或降低临床显著出血的风险(一项研究,84名与会者,限制性3;自由主义8;非常低的确定性证据)。没有NRS报告其他符合条件的结果。
结论:本综述的结果基于7项研究和644名参与者。鉴于纳入的研究相对较少,明确的结论是具有挑战性的,参加人数少,干预和结果报告的异质性,和证据的总体确定性。为了提高限制性红细胞输注策略对临床结局的真实影响的确定性,需要严格设计和执行的研究。证据主要基于两个人群:接受强化化疗的急性白血病成人和需要HSCT的血液系统恶性肿瘤成人。尽管在之前的审查结果中增加了来自三个RCT的405名参与者,仍然没有足够的证据来回答这篇综述的主要结果。如果我们假设100天内的死亡率为3%,我们需要1492名参与者才能有80%的机会被发现,在5%的显著性水平上,全因死亡率从3%增加到6%。总体上需要进一步的RCT,特别是在儿童中。
An estimated one-quarter to one-half of people diagnosed with haematological malignancies experience anaemia. There are different strategies for red blood cell (RBC) transfusions to treat anaemia. A restrictive transfusion strategy permits a lower haemoglobin (Hb) level whereas a liberal transfusion strategy aims to maintain a higher Hb. The most effective and safest strategy is unknown.
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 studies (NRS) in MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2023, Issue 2), and eight other databases (including three trial registries) to 21 March 2023. We also searched grey literature and contacted experts in transfusion for additional trials. There were no language, date or publication status restrictions.
We included RCTs and prospective NRS that evaluated restrictive versus liberal RBC transfusion strategies in children or adults with malignant haematological disorders receiving intensive chemotherapy or radiotherapy, or both, with or without HSCT.
Two authors independently screened references, full-text reports of potentially relevant studies, extracted data from the studies, and assessed the risk of bias. Any disagreement was discussed and resolved with a third review author. Dichotomous outcomes were presented as a risk ratio (RR) with a 95% confidence interval (CI). Narrative syntheses were used for heterogeneous outcome measures. Review Manager Web was used to meta-analyse the data. Main outcomes of interest included: all-cause mortality at 31 to 100 days, quality of life, number of participants with any bleeding, number of participants with clinically significant bleeding, serious infections, length of hospital admission (days) and hospital readmission at 0 to 3 months. The certainty of the evidence was assessed using GRADE.
Nine studies met eligibility; eight RCTs and one NRS. Six hundred and forty-four participants were included from six completed RCTs (n = 560) and one completed NRS (n = 84), with two ongoing RCTs consisting of 294 participants (260 adult and 34 paediatric) pending inclusion. Only one completed RCT included children receiving HSCT (n = 6); the other five RCTs only included adults: 239 with acute leukaemia receiving chemotherapy and 315 receiving HSCT (166 allogeneic and 149 autologous). The transfusion threshold ranged from 70 g/L to 80 g/L for restrictive and from 80 g/L to 120 g/L for liberal strategies. Effects were reported in the summary of findings tables only for the trials that included adults to reduce indirectness due to the limited evidence contributed by the prematurely terminated paediatric trial. Evidence from RCTs Overall, there may be little to no difference in the number of participants who die within 31 to 100 days using a restrictive compared to a liberal transfusion strategy, but the evidence is very uncertain (three studies; 451 participants; RR 1.00, 95% CI 0.27 to 3.70, P=0.99; very low-certainty evidence). There may be little to no difference in quality of life at 0 to 3 months using a restrictive compared to a liberal transfusion strategy, but the evidence is very uncertain (three studies; 431 participants; analysis unable to be completed due to heterogeneity; very low-certainty evidence). There may be little to no difference in the number of participants who suffer from any bleeding at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (three studies; 448 participants; RR 0.91, 95% CI 0.78 to 1.06, P = 0.22; low-certainty evidence). There may be little to no difference in the number of participants who suffer from clinically significant bleeding at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (four studies; 511 participants; RR: 0.94, 95% CI 0.74 to 1.19, P = 0.60; low-certainty evidence). There may be little to no difference in the number of participants who experience serious infections at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (three studies, 451 participants; RR: 1.20, 95% CI 0.93 to 1.55, P = 0.17; low-certainty evidence). A restrictive transfusion strategy likely results in little to no difference in the length of hospital admission at 0 to 3 months compared to a liberal strategy (two studies; 388 participants; analysis unable to be completed due to heterogeneity in reporting; moderate-certainty evidence). There may be little to no difference between hospital readmission using a restrictive transfusion strategy compared to a liberal transfusion strategy (one study, 299 participants; RR: 0.89, 95% CI 0.52 to 1.50; P = 0.65; low-certainty evidence). Evidence from NRS The evidence is very uncertain whether a restrictive RBC transfusion strategy: reduces the risk of death within 100 days (one study, 84 participants, restrictive 1 death; liberal 1 death; very low-certainty evidence); or decreases the risk of clinically significant bleeding (one study, 84 participants, restrictive 3; liberal 8; very low-certainty evidence). No NRS reported on the other eligible outcomes.
Findings from this review were based on seven studies and 644 participants. Definite conclusions are challenging given the relatively few included studies, low number of included participants, heterogeneity of intervention and outcome reporting, and overall certainty of evidence. To increase the certainty of the true effect of a restrictive RBC transfusion strategy on clinical outcomes, there is a need for rigorously designed and executed studies. The evidence is largely based on two populations: adults with acute leukaemia receiving intensive chemotherapy and adults with haematologic malignancy requiring HSCT. Despite the addition of 405 participants from three RCTs to the previous review\'s results, there is still insufficient evidence to answer this review\'s primary outcome. If we assume a mortality rate of 3% within 100 days, we would need a total of 1492 participants to have an 80% chance of detecting, at a 5% level of significance, an increase in all-cause mortality from 3% to 6%. Further RCTs are needed overall, particularly in children.