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Intravenous Iron Supplementation for the Treatment of Chemotherapy-Induced Anemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Buchrits S, Itzhaki O, Avni T, Raanani P, Gafter-Gvili A
Journal of clinical medicine. 2022;11(14)
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Abstract
BACKGROUND The pathophysiology of cancer-related anemia is multifactorial, including that of chemotherapy-induced anemia (CIA). The guidelines are not consistent in their approach to the use of intravenous (IV) iron in patients with cancer as part of the clinical practice. MATERIALS AND METHODS All randomized controlled trials that compared IV iron with either no iron or iron taken orally for the treatment of CIA were included. We excluded trials if erythropoiesis-stimulating agents (ESAs) were used. The primary outcome was the percentage of patients requiring a red blood cell (RBC) transfusion during the study period. The secondary outcomes included the hematopoietic response (an increase in the Hb level by more than 1 g/dL or an increase above 11 g/dL), the iron parameters and adverse events. For the dichotomous data, risk ratios (RRs) with 95% confidence intervals (Cis) were estimated and pooled. For the continuous data, the mean differences were calculated. A fixed effect model was used, except in the event of significant heterogeneity between the trials (p < 0.10; I(2) > 40%), in which we used a random effects model. RESULTS A total of 8 trials published between January 1990 and July 2021 that randomized 1015 patients fulfilled the inclusion criteria. Of these, 553 patients were randomized to IV iron and were compared with 271 patients randomized to oral iron and 191 to no iron. IV iron decreased the percentage of patients requiring a blood transfusion compared with oral iron (RR 0.72; 95% CI 0.55-0.95) with a number needed to treat of 20 (95% CI 11-100). IV iron increased the hematopoietic response (RR 1.23; 95% CI 1.01-1.5). There was no difference with respect to the risk of adverse events (RR 0.97; 95% CI 0.88-1.07; 8 trials) or severe adverse events (RR 1.09; 95% CI 0.76-1.57; 8 trials). CONCLUSIONS IV iron resulted in a decrease in the need for RBC transfusions, with no difference in adverse events in patients with CIA. IV iron for the treatment of CIA should be considered in clinical practice.
PICO Summary
Population
People with chemotherapy induced anaemia enrolled in randomised controlled trials (RCTs), and identified by systematic review (n= 1,015, 8 RCTs).
Intervention
Intravenous [IV] iron (n= 553).
Comparison
Oral iron (n= 271), or no iron (n= 191).
Outcome
IV iron decreased the percentage of patients requiring a blood transfusion compared with oral iron (Risk ratio [RR] 0.72; 95% confidence interval [CI] 0.55-0.95) with a number needed to treat of 20 (95% CI 11-100). IV iron increased the hematopoietic response (RR 1.23; 95% CI 1.01-1.5). There was no difference with respect to the risk of adverse events (RR 0.97; 95% CI 0.88-1.07; 8 trials) or severe adverse events (RR 1.09; 95% CI 0.76-1.57; 8 trials).
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Comparison of early mortality between leukapheresis and non-leukapheresis in adult acute myeloid leukemia patients with hyperleukocytosis: a systematic review and meta-analysis
Rinaldi I, Sutandyo N, Winston K
Hematology (Amsterdam, Netherlands). 2022;27(1):141-149
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Abstract
OBJECTIVES One of the treatment modalities that can be used for hyperleukocytosis is leukapheresis. However, the result of studies showing the benefit of early mortality through the use of leukapheresis versus no leukapheresis is still inconclusive. Hence, we aimed to conduct a systematic review with meta-analysis to determine the effect of leukapheresis on early mortality in AML patients with hyperleukocytosis. METHODS We conducted a literature search on five databases (PubMed, EBSCOhost, Scopus, Clinicalkey, and JSTOR) up to October 2021 for studies comparing early mortality outcomes between hyperleukocytosis AML patients treated with leukapheresis versus no leukapheresis. Summary odds ratios (OR) and 95% confidence intervals (CI) were calculated using random-effects models. Heterogeneity tests were presented in I(2) value and publication bias was analyzed using a funnel plot. RESULTS Eleven retrospective cohort studies were eligible based on the inclusion and exclusion criteria. Pooled analysis showed that there was no significant difference in early mortality between patients receiving leukapheresis and not receiving leukapheresis in studies using hyperleukocytosis cutoff of 95,000/mm(3) or 100,000/mm(3) (OR: 1.17; 95% CI: 0.74-1.86; p: 0.50; I(2): 0%). Similarly, studies using hyperleukocytosis cutoff of 50,000/mm(3) also showed no benefits of early mortality (OR: 0.67; 95% CI: 0.43-1.05; p: 0.08; I(2): 0%). Most of the studies used had a moderate risk of bias due to being observational studies. Funnel plot showed an indication of publication bias on studies using hyperleukocytosis cutoff of ≥50,000/mm(3). CONCLUSION The use of leukapheresis does not provide early mortality benefit in adult AML patients with hyperleukocytosis.
PICO Summary
Population
Adult acute myeloid leukemia patients (11 studies, n= 1,407).
Intervention
Leukapheresis intervention (n= 1,090).
Comparison
Not receiving leukapheresis (n= 317).
Outcome
Pooled analysis showed that there was no significant difference in early mortality between patients receiving leukapheresis and not receiving leukapheresis in studies using hyperleukocytosis cutoff of 95,000/mm3 or 100,000/mm3. Studies using hyperleukocytosis cutoff of 50,000/mm3 showed no benefits of early mortality.
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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
Estcourt LJ, Malouf R, Trivella M, Fergusson DA, Hopewell S, Murphy MF
The Cochrane Database of Systematic Reviews. 2017;((1)):CD011305.
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Full text
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Abstract
BACKGROUND 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. OBJECTIVES 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). SEARCH METHODS 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. SELECTION CRITERIA 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. DATA COLLECTION AND ANALYSIS We used the standard methodological procedures expected by Cochrane. MAIN RESULTS 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). Evidence from RCTsA 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 m
PICO Summary
Population
Children or adults with malignant haematological disorders treated with intensive chemotherapy or radiotherapy, or both, with or without a haematopoietic stem cell transplant (6 studies).
Intervention
Restrictive red blood cell (RBC) transfusion strategy.
Comparison
Liberal RBC transfusion strategy.
Outcome
Evidence from randomised controlled trials showed that a restrictive RBC transfusion policy may make little or no difference to: the number of participants who died within 100 days (RR: 0.25); the number of participants who experienced any bleeding (RR: 0.93), or clinically significant bleeding (RR: 1.03); the number of participants who required RBC transfusions (RR: 0.97); or the length of hospital stay. It was uncertain whether the restrictive RBC transfusion strategy: decreases quality of life, or reduces the risk of developing any serious infection (RR: 1.23).