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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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Editor's Choice
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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Overview of current progress and challenges in diagnosis, and management of pediatric sickle cell disease in Democratic Republic of the Congo
Kasai ET, Alworong'a Opara JP, Ntokamunda Kadima J, Kalenga M, Batina Agasa S, Marini Djang'eing'a R, Boemer F
Hematology (Amsterdam, Netherlands). 2022;27(1):132-140
Abstract
OBJECTIVES Sickle cell disease (SCD) encompasses health complications, primarily affecting the hematologic system and leading to high death rates in childhood. As a rule, the World Health Organisation (WHO) stepwise gold-standard about the strategies for prevention, diagnosis, and treatment of SCD must be multidimensional. This overview aimed to highlight current advances and challenges linked to strategic issues, diagnosis, the prevalence, and treatment of pediatric cases in Sub-Saharan Africa, particularly the Democratic Republic of the Congo. METHODS We searched data on Google Scholar, Medline, PubMed, Science Direct, Scopus, and ResearchGate. RESULTS The laboratory diagnosis of SCD has progressed from conventional electrophoresis to rapid point-of-care tests that allows early neonate screening. HemoTypeSC(TM) is an affordable test for neonatal screening in DRC. The pediatric SCD prevalence in Sub-Saharan Africa lay within 1-7.7% of homozygous(SS) and 15-40% of the heterozygous(AS) forms of SCD, depending on the method used and the ethnic population tested. Various supportive management protocols for comorbidities and complications exist, but they are not standardized in the Region. CONCLUSION Notwithstanding some progress accomplished, the disease is still challenging in Sub-Saharan Africa due to limited early diagnostic testing and a lack of specific medications. There is a need for harmonizing therapeutic protocols and conducting controlled valid clinical trials.
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Patient-reported outcomes in autosomal inherited bleeding disorders: A systematic literature review
van Hoorn ES, Houwing ME, Al Arashi W, Leebeek FWG, Hazelzet JA, Gouw SC, Schutgens REG, Schols SEM, Lingsma HF, Cnossen MH
Haemophilia : the official journal of the World Federation of Hemophilia. 2022
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Abstract
AIM: Currently, it is unknown which patient-reported outcomes are important for patients with autosomal inherited bleeding disorders. Therefore, the purpose of this study is to systematically review the available literature assessing patient-reported outcomes and their measurement methods in autosomal inherited bleeding disorders. METHODS The Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trails and Google Scholar databases were searched from inception until 14 August 2020. Studies on patient-reported outcomes in patients with von Willebrand disease, inherited platelet function disorders and coagulation factor deficiencies were included. RESULTS Twenty-one articles met the inclusion criteria. Three studies were assessed as having poor quality, and therefore a high risk of bias. Nineteen studies had fair quality rating. Different measurements methods were used, ranging from predefined to self-developed questionnaires. The majority of included studies focused on von Willebrand disease. Patients with von Willebrand disease reported lower health-related quality of life compared to the general population. Overall, this trend was especially visible in the following domains: vitality, physical and social functioning and pain. Women with inherited bleeding disorders scored lower on health-related quality of life compared to men, especially women with heavy menstrual bleeding. Patients with joint bleeds or heavy menstrual bleeding reported an increased level of pain. CONCLUSION Patients with autosomal inherited bleeding disorders report lower health related quality of life, especially those with joint bleeds or heavy menstrual bleeding. Numerous measurement methods are used in patients with autosomal inherited bleeding disorders, highlighting the need for studies using established, standardized measurement methods.
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Efficacy of topical hemostatic agents in malignancy-related gastrointestinal bleeding: a systematic review and meta-analysis
Karna R, Deliwala S, Ramgopal B, Mohan BP, Kassab L, Becq A, Dhawan M, Adler DG
Gastrointestinal endoscopy. 2022
Abstract
BACKGROUND AND AIMS Despite advances in endoscopic therapies, malignancy-related gastrointestinal (GI) bleeding remains difficult to manage with high rates of treatment failure and rebleeding. Topical hemostatic agents (THA) are easier to apply to the wide bleeding surface of tumors. We conducted this systematic review and meta-analysis to evaluate the efficacy of THAs in malignancy-related GI bleed. METHODS We conducted a comprehensive search of multiple electronic databases to identify studies reporting on the use of THAs in malignancy-related GI bleeding. The primary outcome was the achievement of hemostasis; secondary outcomes were early rebleeding (≤ 3 days), delayed rebleeding (>3 days), aggregate rebleeding, all-cause mortality, and GI bleed related mortality. A meta-analysis of proportions was done for all outcomes. RESULTS Out of 355 citations, total 16 studies with 530 patients were included. Primary hemostasis was achieved in 94.1% (95% CI: 91.5 - 96.0%). Early rebleeding was seen in 13.9% (95% CI: 9.7 - 19.4%) while delayed rebleeding was seen in 11.4% (95% CI: 5.8 - 21.1%). Aggregate rebleeding was seen in 24.2% (95% CI:18.5 - 31.0%). All-cause mortality was 33.1% (95% CI: 23.7 - 44.0%) while GI bleed related mortality occurred in 5.9% (95% CI: 2.2% - 14.8%). CONCLUSIONS THAs are highly effective for achieving primary hemostasis in malignancy-related GI bleeding. It should be considered as an alternative to traditional endotherapy methods in malignancy-related GI bleeds. Future studies should be designed to evaluate its efficacy and safety as a primary method of hemostasis as compared to traditional endotherapy measures.
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Effectiveness of shengxuexiaoban capsules combined with glucocorticoid therapy for immune thrombocytopenia: A meta-analysis
Ding MY, Li B, Yang M, Zhai WS, Song CD, Zhang J, Zhang QY, Li PF, Liu LY
PloS one. 2022;17(9):e0275122
Abstract
OBJECTIVE To evaluate the effectiveness of the Shengxuexiaoban Capsules combined with glucocorticoid therapy for immune thrombocytopenia (ITP). METHODS We collected randomized controlled trials (RCTs) using shengxuexiaoban capsules in combination with glucocorticoid to treat ITP by searching major Chinese and English electronic databases. The outcome indicators were the effective rate, recurrence rate, the number of platelets in the blood, recovery time of platelets, and adverse reactions. We used STATA 16.0 and RevMan 5.3 for meta-analysis and GRADE pro. for evidence quality evaluation. RESULTS A total of 27 RCTs were included in the meta-analysis, and the results showed a significant difference (all p<0.05) in the effective rate, recurrence rate, the number of platelets, and the recovery time of platelets (≥ 100×109) between ITP patients in the control group (who received glucocorticoid therapy alone) and test group (who received glucocorticoid therapy combined with the Shengxuexiaoban Capsules). And that Shengxuexiaoban capsules combined with glucocorticoid therapy were safe. The funnel plot and Egger's test results indicated no obvious publication bias. The GRADE evidence rating showed an intermediate quality of evidence rating for recurrence rate and overall effectiveness. CONCLUSION Glucocorticoid therapy combined with the Shengxuexiaoban Capsules showed more effectiveness in the treatment of ITP. It can improve the effective rate, reduce the recurrence rate, increase the number of platelets and shorten the recovery time of platelets, and has a good safety profile.
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The lived experience of women with a bleeding disorder: A systematic review
Sanigorska A, Chaplin S, Holland M, Khair K, Pollard D
Research and practice in thrombosis and haemostasis. 2022;6(1):e12652
Abstract
BACKGROUND Research studies have described the morbidity associated with inherited bleeding disorders such as hemophilia and von Willebrand disease in women, but their effect on daily living has long been underrecognized. This systematic review sought to document the lived experience of women with a bleeding disorder by assessing research findings on quality of health care, socioeconomic factors, and mental health. METHODS A systematic search was carried out in Web of Science, the Cumulative Index to Nursing and Allied Health Literature, and PubMed on July 31, 2020. References were hand searched. Abstracts of the 2019 and 2020 congresses on bleeding disorders were hand searched. Key journals were screened for relevant studies published after the search date until the analysis was completed on December 7, 2020. RESULTS Of 635 potentially eligible publications, 27 published since 1998 were selected for review. Most studies were of moderate to high quality but meta-analysis of quantitative studies was not possible due to difference in outcomes and assessment.Women with a bleeding disorder experience obstacles to accessing care, difficulties living with their disorder, interference with schooling and work, and poor mental health. Diagnostic delay and lack of recognition of symptoms mean treatment and support may not be available. Where comparisons with controls were made, women's negative experiences were greater than those of men. CONCLUSIONS Women with bleeding disorders experience major negative impacts of their disorders on daily life and mental well-being. Many of the challenges identified in earlier research are evident in more recent studies.
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No difference in myocardial iron concentration and serum ferritin with deferasirox and deferiprone in pediatric patients with hemoglobinopathies: A systematic review and meta-analysis
Saleem A, Waqar E, Shuja SH, Naeem U, Moeed A, Rais H, Ahmed J
Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine. 2022
Abstract
OBJECTIVES Iron overload is a common complication experienced by transfusion-dependent children with hemoglobin disorders. Chelators such as deferasirox (DFX) and deferiprone (DFP) are effective in overcoming this problem. We conducted this systematic review and meta-analysis to evaluate the effectiveness of DFX compared to DFP in treating iron overload amongst pediatric patients with hemoglobin disorders. MATERIAL AND METHODS PubMed and Cochrane Central were searched from their inception until Dec 21 2021, for randomized clinical trials (RCTs) and observational studies, which assessed the efficacy of DFX compared to DFP in the treatment of inherited hemoglobin disorders. The outcomes of interest included myocardial iron concentration (MRI T2*) at the end of the trial and change in mean serum ferritin (SF) levels at the 6 and 12 months mark. Weighted mean differences (WMDs) with their corresponding 95% confidence intervals (CIs) were calculated for continuous outcomes using random effects model. RESULTS A total of 5 studies comprising 607 children were included. The results of our analysis revealed no significant difference between DFX and DFP in MRI T2* at the end of treatment (WMD: -0.92;95% CI[-3.35,1.52]; p=0.46; I(2)=0). Moreover, there has been no significant difference noted in SF levels at both 6 months (WMD: 97.31; 95% CI[-236.16,430.77]; p=0.57; I(2)=0) and 12 months (WMD: 46.99; 95% CI[-191.42,285.40]; p=0.70; I(2)=0) respectively. CONCLUSION Our analysis shows no significant difference between the efficacy of DFX and DFP in the management of iron overload in children with inherited blood disorders. Future large-scale clinical trials are required to further validate our results.
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The impact of red blood cell transfusion on mortality and treatment efficacy in patients treated with radiation: A systematic review
Deschner M, Vasanthamohan L, Zayed S, Lazo-Langner A, Palma D, D'Souza D, Omar Gilani S, Gabriel Boldt R, Solh Z
Clinical and translational radiation oncology. 2022;33:23-29
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Editor's Choice
Abstract
INTRODUCTION Packed red blood cell (RBC) transfusion is frequently used in patients undergoing radiotherapy (RT) because retrospective data suggest that anemic patients may respond sub-optimally to RT. No high-quality evidence currently exists to guide transfusion practices and establish hemoglobin (Hb) transfusion thresholds for this patient population, and practice varies significantly across centers. This systematic review investigated whether maintaining higher Hb via transfusion in radiation oncology patients leads to improved outcomes. METHODS We performed a literature search of studies comparing RBC transfusion thresholds in radiation oncology patients. Included studies assessed patients receiving RT for malignancy of any diagnosis or stage. Excluded studies did not evaluate Hb or transfusion as an intervention or outcome. The primary outcome was overall survival. Secondary outcomes included locoregional control, number of transfusions and adverse events. RESULTS One study met inclusion criteria. The study pooled results from two randomized controlled trials that stratified anemic patients with head and neck squamous cell carcinoma to RBC transfusion versus no transfusion. The study found no significant differences in overall survival or locoregional control after five years, despite increased Hb levels in the transfused group. We conducted a narrative review by extracting data from 10 non-comparative studies involving transfusion in patients receiving RT. Results demonstrated no consistent conclusions regarding whether transfusions improve or worsen outcomes. CONCLUSIONS There is a lack of data on the effects of RBC transfusion on outcomes in patients undergoing RT. Well-designed prospective studies are needed in this area.
PICO Summary
Population
Patients undergoing radiotherapy (11 studies).
Intervention
Red blood cell transfusion.
Comparison
No transfusion.
Outcome
Only one study met the inclusion criteria which pooled results from two randomized controlled trials (DAHANCA 5 and 7). The study found no significant differences in overall survival or locoregional control after five years, despite increased haemoglobin levels in the transfused group (n= 235) vs. no transfused group (n= 230). A narrative review was conducted by extracting data from 10 other non-comparative studies involving transfusion in patients receiving radiotherapy. There were no consistent conclusions from these 10 studies on whether transfusions improve or worsen outcomes.
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Adding caplacizumab to standard of care in thrombotic thrombocytopenic purpura: A systematic review and meta-analysis
Djulbegovic M, Tong J, Xu A, Yang J, Chen Y, Cuker A, Pishko A
Blood advances. 2022
Abstract
Introduction Immune thrombotic thrombocytopenic purpura (iTTP) is an acquired, fatal microangiopathy if untreated. Randomized controlled trials (RCT's) demonstrated faster time-to-response with adding caplacizumab to standard of care (SOC). However, concerns about RCT selection bias and the high cost of caplacizumab warrant examination of all evidence, including real-world observational studies. Methods In this systematic review and meta-analysis, we searched the literature for comparative studies evaluating SOC with or without caplacizumab for the treatment of iTTP. We assessed risk-of-bias using the Cochrane RoB-2 tool (RCT's) and Newcastle-Ottawa Scale (observational studies). The primary efficacy outcome was all-cause mortality, and the primary safety outcome was treatment-emergent bleeding. Secondary outcomes included exacerbation and relapse, refractory iTTP, and time-to-response. Results We included two high-quality RCT's and three observational studies at high-risk-of-bias comprising 632 participants. Compared with SOC, caplacizumab was associated with a non-significant reduction in the RR (0.21 [CI 0.05-1.74]) of death in RCT's and observational studies (RR 0.62 [CI 0.07, 4.41]). Compared with SOC, caplacizumab was associated with an increased risk of bleeding in RCT's (RR 1.37 [CI 1.06, 1.77]). In observational studies, the risk of bleeding was not significantly increased (RR 7.10 [CI 0.90, 56.14]). Addition of caplacizumab was also associated with a significant reduction in refractory iTTP and exacerbation, increased risk of relapse, and shortened response time. Conclusion Frontline addition of caplacizumab does not significantly reduce all-cause mortality compared with SOC alone, although it reduces refractory disease risk, shortens time-to-response, and improves exacerbation rates, at the expense of increased relapse and bleeding risk.
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The Impact of Recombinant Versus Plasma-Derived Factor VIII Concentrates on Inhibitor Development in Previously Untreated Patients With Hemophilia A: A 2021 Update of a Systematic Review and Meta-Analysis
Kohar K, Prayogo SA, Wiyono L
Cureus. 2022;14(6):e26015
Abstract
Hemophilia A, the most common hereditary disorder, is caused by clotting factor deficiency. Challenges encountered in the current treatment of hemophilia A [factor VIII (FVIII) replacement therapy] due to inhibitor development have caused ineffective treatment as well as morbidity and mortality among patients. However, there are no studies comparing the two types of FVIII treatments in terms of inhibitor development rate. Therefore, we conducted this systematic review to devise a better treatment option with a lower risk of inhibitor development. The systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and by searching several databases. Data extraction on study characteristics and outcomes was conducted. Reviewers also conducted a risk of bias assessment on all studies. All eligible studies for quantitative analysis were then processed using RevMan 5.4.1 and the data was extrapolated into cumulative outcomes and expressed in forest and funnel plots. Nine studies were included in the meta-analysis, involving a total of 2,531 hemophilia A patients who were followed up from birth until death. A higher incidence of inhibitor development was found to be associated with recombinant FVIII (rFVIII) [odds ratio (OR)=1.57, 95% confidence interval (CI): 0.95-2.59; hazard ratio (HR)=1.89, 95% CI: 1.15-3.12]. The same trend was also found for high-responding inhibitors (OR=1.38, 95% CI: 0.70-2.70; HR=1.42, 95% CI: 0.84-2.39). rFVIII is associated with a higher risk of overall and high-responding inhibitor development compared to plasma-derived FVIII (pdFVIII).
