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1.
The impact of chelation compliance in health outcome and health related quality of life in thalassaemia patients: a systematic review
Lee, W. J., Mohd Tahir, N. A., Chun, G. Y., Li, S. C.
Health and quality of life outcomes. 2024;22(1):14
Abstract
Understanding consequences of poor chelation compliance is crucial given the enormous burden of post-transfusional iron overload complications. We systematically reviewed iron-chelation therapy (ICT) compliance, and the relationship between compliance with health outcome and health-related quality of life (HRQoL) in thalassaemia patients. Several reviewers performed systematic search strategy of literature through PubMed, Scopus, and EBSCOhost. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed. Of 4917 studies, 20 publications were included. The ICT compliance rate ranges from 20.93 to 75.3%. It also varied per agent, ranging from 48.84 to 85.1% for desferioxamine, 87.2-92.2% for deferiprone and 90-100% for deferasirox. Majority of studies (N = 10/11, 90.91%) demonstrated significantly negative correlation between compliance and serum ferritin, while numerous studies revealed poor ICT compliance linked with increased risk of liver disease (N = 4/7, 57.14%) and cardiac disease (N = 6/8, 75%), endocrinologic morbidity (N = 4/5, 90%), and lower HRQoL (N = 4/6, 66.67%). Inadequate compliance to ICT therapy is common. Higher compliance is correlated with lower serum ferritin, lower risk of complications, and higher HRQoL. These findings should be interpreted with caution given the few numbers of evidence.
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2.
Efficacy and Safety of Combined Deferiprone and Deferasirox in Iron-Overloaded Patients: A Systematic Review
Salem, A., Desai, P., Elgebaly, A.
Cureus. 2023;15(11):e48276
Abstract
Despite the established efficacy of iron chelation therapy in transfusion-induced iron-overloaded patients, there is no universal agreement regarding the choice of an optimal chelating regimen. Deferasirox (DFX) and deferiprone (DFP) are two oral iron chelators, and combination usage demonstrated effectiveness as an alternative to monotherapies in patients with a limited response to monotherapy. The present systematic review aimed to assess the evidence regarding the outcomes of combined DFP and DFX in iron-overloaded patients. An online search was conducted in PubMed, Scopus, Web of Science, and CENTRAL databases. Interventional and observational studies that assessed the outcomes of combined DFP and DFX in iron-overloaded patients were included. Eleven studies (12 reports) were considered in this meta-analysis. The studies included dual iron chelation strategies for a number of diagnoses. Single-arm studies (n =7) showed a reduction of serum ferritin, which reached the level of statistical significance in three studies. Likewise, most studies reported a numerical reduction in liver iron concentration (LIC) and increased cardiac MRI-T2* values after chelating therapy. Alternatively, comparative studies showed no significant difference in post-treatment serum ferritin between DFX plus DFP and DFX/DFP plus deferoxamine (DFO). The adherence to combination therapy was good to average in nearly 66.7-100% of the patients across four studies. One study reported a poor adherence rate. The combined regimen was generally tolerable, with no reported incidence of serious adverse events among the included studies. In conclusion, the DFP and DFX combination is a safe and feasible option for iron overload patients with a limited response to monotherapy.
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3.
Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia
Geneen, L. J., Dorée, C., Estcourt, L. J.
The Cochrane Database of Systematic Reviews. 2023;3(3):Cd012349
Abstract
BACKGROUND Regularly transfused people with sickle cell disease (SCD) and people with thalassaemia are at risk of iron overload. Iron overload can lead to iron toxicity in vulnerable organs such as the heart, liver and endocrine glands, which can be prevented and treated with iron-chelating agents. The intensive demands and uncomfortable side effects of therapy can have a negative impact on daily activities and wellbeing, which may affect adherence. OBJECTIVES To identify and assess the effectiveness of different types of interventions (psychological and psychosocial, educational, medication interventions, or multi-component interventions) and interventions specific to different age groups, to improve adherence to iron chelation therapy compared to another listed intervention, or standard care in people with SCD or thalassaemia. SEARCH METHODS We searched CENTRAL (Cochrane Library), MEDLINE, PubMed, Embase, CINAHL, PsycINFO, ProQuest Dissertations & Global Theses, Web of Science & Social Sciences Conference Proceedings Indexes and ongoing trial databases (13 December 2021). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register (1 August 2022). SELECTION CRITERIA For trials comparing medications or medication changes, only randomised controlled trials (RCTs) were eligible for inclusion. For studies including psychological and psychosocial interventions, educational interventions, or multi-component interventions, non-randomised studies of interventions (NRSIs), controlled before-after studies, and interrupted time series studies with adherence as a primary outcome were also eligible for inclusion. DATA COLLECTION AND ANALYSIS For this update, two authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using GRADE. MAIN RESULTS We included 19 RCTs and one NRSI published between 1997 and 2021. One trial assessed medication management, one assessed an education intervention (NRSI) and 18 RCTs were of medication interventions. Medications assessed were subcutaneous deferoxamine, and two oral chelating agents, deferiprone and deferasirox. We rated the certainty of evidence as very low to low across all outcomes identified in this review. Four trials measured quality of life (QoL) with validated instruments, but provided no analysable data and reported no difference in QoL. We identified nine comparisons of interest. 1. Deferiprone versus deferoxamine We are uncertain whether or not deferiprone affects adherence to iron chelation therapy (four RCTs, unpooled, very low-certainty evidence), all-cause mortality (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.18 to 1.21; 3 RCTs, 376 participants; very low-certainty evidence), or serious adverse events (SAEs) (RR 1.43, 95% CI 0.83 to 2.46; 1 RCT, 228 participants; very low-certainty evidence). Adherence was reported as "good", "high" or "excellent" by all seven trials, though the data could not be analysed formally: adherence ranged from 69% to 95% (deferiprone, mean 86.6%), and 71% to 93% (deferoxamine, mean 78.8%), based on five trials (474 participants) only. 2. Deferasirox versus deferoxamine We are uncertain whether or not deferasirox affects adherence to iron chelation therapy (three RCTs, unpooled, very low-certainty evidence), although medication adherence was high in all trials. We are uncertain whether or not there is any difference between the drug therapies in serious adverse events (SAEs) (SCD or thalassaemia) or all-cause mortality (thalassaemia). 3. Deferiprone versus deferasirox We are uncertain if there is a difference between oral deferiprone and deferasirox based on a single trial in children (average age 9 to 10 years) with any hereditary haemoglobinopathy in adherence, SAEs and all-cause mortality. 4. Deferasirox film-coated tablet (FCT) versus deferasirox dispersible tablet (DT) One RCT compared deferasirox in different tablet forms. There may be a preference for FCTs, shown through a trend for greater adherence (RR 1.10, 95% CI 0.99 to 1.22; 1 RCT, 88 participants), although medication adherence was high in both groups (FCT 92.9%; DT 85.3%). We are uncertain if there is a benefit in chelation-related AEs with FCTs. We are uncertain if there is a difference in the incidence of SAEs, all-cause mortality or sustained adherence. 5. Deferiprone and deferoxamine combined versus deferiprone alone We are uncertain if there is a difference in adherence, though reporting was usually narrative as triallists report it was "excellent" in both groups (three RCTs, unpooled). We are uncertain if there is a difference in the incidence of SAEs and all-cause mortality. 6. Deferiprone and deferoxamine combined versus deferoxamine alone We are uncertain if there is a difference in adherence (four RCTs), SAEs (none reported in the trial period) and all-cause mortality (no deaths reported in the trial period). There was high adherence in all trials. 7. Deferiprone and deferoxamine combined versus deferiprone and deferasirox combined There may be a difference in favour of deferiprone and deferasirox (combined) in rates of adherence (RR 0.84, 95% CI 0.72 to 0.99) (one RCT), although it was high (> 80%) in both groups. We are uncertain if there is a difference in SAEs, and no deaths were reported in the trial, so we cannot draw conclusions based on these data (one RCT). 8. Medication management versus standard care We are uncertain if there is a difference in QoL (one RCT), and we could not assess adherence due to a lack of reporting in the control group. 9. Education versus standard care One quasi-experimental (NRSI) study could not be analysed due to the severe baseline confounding. AUTHORS' CONCLUSIONS The medication comparisons included in this review had higher than average adherence rates not accounted for by differences in medication administration or side effects, though often follow-up was not good (high dropout over longer trials), with adherence based on a per protocol analysis. Participants may have been selected based on higher adherence to trial medications at baseline. Also, within the clinical trial context, there is increased attention and involvement of clinicians, thus high adherence rates may be an artefact of trial participation. Real-world, pragmatic trials in community and clinic settings are needed that examine both confirmed or unconfirmed adherence strategies that may increase adherence to iron chelation therapy. Due to lack of evidence this review cannot comment on intervention strategies for different age groups.
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4.
Red Blood Cell Alloimmunizations in Thalassaemia Patients With Regular Transfusion in China: a Systematic Review and Meta-Analysis
Zhang X, Li Y, Yan B, Li X, Gui S, Sun A
Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine. 2023
Abstract
OBJECTIVE The development of red blood cell alloimmunization intensifies transfusion complication in thalassaemia patients. The purpose of this paper is to evaluate the existing evidence on the prevalence of erythrocyte alloimmunization in China by meta-analysis. We systematically searched cross-sectional studies regarding the alloimmunization of thalassaemia patients with regular blood transfusion in China from year 2000 to May 2021 in the Cochrane library, PubMed, EMBASE, Web of Science, and Chinese databases including CNKI, Wanfang Data, Vip and CBM. Data extraction and quality evaluation of the included studies were performed. Meta-analysis was performed using the DerSimonian and Laird random-effects models with inverse variance weighting. The presence of publication bias was tested by Egger's test, and the methodological quality of each included article was evaluated by the criteria specific to prevalence studies. RESULTS A total of 1874 patients and 263 alloantibodies from 11 studies were identified and included in the meta-analysis. The proportion of alloantibodies against antigens belonging to the Rh, MNSs and Kidd systems were as high as 70.3%, 17.9%, and 6.5%, respectively. Meta-analysis showed that the overall prevalence of alloimmunization among transfusion-dependent thalassaemia patients in China is 11.4% (95%CI: 7.2%∼16.3%). CONCLUSIONS The characteristics of red blood cell alloimmunization among thalassaemia patients with regular transfusion in China differ greatly from those in other countries. Therefore, transfusion strategies shall be actively adapted in line with thalassaemia patients in China to minimize the risk of alloimmunization.
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5.
Does perioperative allogeneic blood transfusion worsen the prognosis of patients with hepatocellular carcinoma? A meta-analysis of propensity score-matched studies
Hu, L., Li, Z., Qiao, Y., Wang, A.
Frontiers in oncology. 2023;13:1230882
Abstract
BACKGROUND Allogeneic blood transfusion is required in a part of liver resection. The effect of allogeneic blood transfusion on the prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. To investigate whether perioperative allogeneic blood transfusion (PBT) affects the long-term prognosis of patients with HCC, we conducted a meta-analysis that included only propensity score-matched (PSM) studies. METHODS The Cochrane Library, Embase, PubMed, and Web of Science databases were systematically searched to identify PSM studies that compared the long-term outcomes of allogeneic blood transfusion in resected HCC patients. Overall survival (OS) and recurrence-free survival (RFS) rates were calculated. RESULTS This meta-analysis included 9 PSM studies with 12 datasets involving 2476 patients. Lower OS and RFS in HCC patients receiving allogeneic blood transfusion were observed than those in patients not receiving blood transfusion (OS: hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.10-1.64; p < 0.01; RFS: HR, 1.29; 95% CI, 1.07-1.56; p < 0.01). Subgroup analysis revealed that among patients with BCLC A HCC, those receiving allogeneic blood transfusion had lower OS and RFS (OS: HR, 2.27; 95% CI, 1.61-3.21; RFS: HR, 2.11; 95% CI, 1.30-3.41). OS and RFS were similar in both groups of patients with BCLC B and C HCC. CONCLUSION The receipt of perioperative allogeneic blood transfusion is associated with a decrease in OS and RFS. These results seem to be reliable for patients in BCLC stage A. But more high-quality research is needed to confirm this conclusion.
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Genetic polymorphisms influencing deferasirox pharmacokinetics, efficacy, and adverse drug reactions: a systematic review and meta-analysis
Yampayon, K., Anantachoti, P., Chongmelaxme, B., Yodsurang, V.
Frontiers in pharmacology. 2023;14:1069854
Abstract
Objective: Deferasirox is an iron-chelating agent prescribed to patients with iron overload. Due to the interindividual variability of deferasirox responses reported in various populations, this study aims to determine the genetic polymorphisms that influence drug responses. Methods: A systematic search was performed from inception to March 2022 on electronic databases. All studies investigating genetic associations of deferasirox in humans were included, and the outcomes of interest included pharmacokinetics, efficacy, and adverse drug reactions. Fixed- and random-effects model meta-analyses using the ratio of means (ROM) were performed. Results: Seven studies involving 367 participants were included in a meta-analysis. The results showed that subjects carrying the A allele (AG/AA) of ABCC2 rs2273697 had a 1.23-fold increase in deferasirox C(max) (ROM = 1.23; 95% confidence interval [CI]:1.06-1.43; p = 0.007) and a lower Vd (ROM = 0.48; 95% CI: 0.36-0.63; p < 0.00001), compared to those with GG. A significant attenuated area under the curve of deferasirox was observed in the subjects with UGT1A3 rs3806596 AG/GG by 1.28-fold (ROM = 0.78; 95% CI: 0.60-0.99; p = 0.04). In addition, two SNPs of CYP24A1 were also associated with the decreased C(trough): rs2248359 CC (ROM = 0.50; 95% CI: 0.29-0.87; p = 0.01) and rs2585428 GG (ROM = 0.47; 95% CI: 0.35-0.63; p < 0.00001). Only rs2248359 CC was associated with decreased C(min) (ROM = 0.26; 95% CI: 0.08-0.93; p = 0.04), while rs2585428 GG was associated with a shorter half-life (ROM = 0.44; 95% CI: 0.23-0.83; p = 0.01). Conclusion: This research summarizes the current evidence supporting the influence of variations in genes involved with drug transporters, drug-metabolizing enzymes, and vitamin D metabolism on deferasirox responses.
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7.
Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia
Padhani, Z. A., Gangwani, M. K., Sadaf, A., Hasan, B., Colan, S., Alvi, N., Das, J. K.
The Cochrane database of systematic reviews. 2023;11(11):Cd011626
Abstract
BACKGROUND Beta-thalassaemia is an inherited blood disorder that reduces the production of haemoglobin. The most severe form requires recurrent blood transfusions, which can lead to iron overload. Cardiovascular dysfunction caused by iron overload is the leading cause of morbidity and mortality in people with transfusion-dependent beta-thalassaemia. Iron chelation therapy has reduced the severity of systemic iron overload, but removal of iron from the myocardium requires a very proactive preventive strategy. There is evidence that calcium channel blockers may reduce myocardial iron deposition. This is an update of a Cochrane Review first published in 2018. OBJECTIVES To assess the effects of calcium channel blockers plus standard iron chelation therapy, compared with standard iron chelation therapy (alone or with a placebo), on cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. SEARCH METHODS We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books, to 13 January 2022. We also searched ongoing trials databases and the reference lists of relevant articles and reviews. SELECTION CRITERIA We included randomised controlled trials (RCTs) of calcium channel blockers combined with standard chelation therapy versus standard chelation therapy alone or combined with placebo in people with transfusion-dependent beta thalassaemia. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. We used GRADE to assess certainty of evidence. MAIN RESULTS We included six RCTs (five parallel-group trials and one cross-over trial) with 253 participants; there were 126 participants in the amlodipine arms and 127 in the control arms. The certainty of the evidence was low for most outcomes at 12 months; the evidence for liver iron concentration was of moderate certainty, and the evidence for adverse events was of very low certainty. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may have little or no effect on cardiac T2* values at 12 months (mean difference (MD) 1.30 ms, 95% confidence interval (CI) -0.53 to 3.14; 4 trials, 191 participants; low-certainty evidence) and left ventricular ejection fraction (LVEF) at 12 months (MD 0.81%, 95% CI -0.92% to 2.54%; 3 trials, 136 participants; low-certainty evidence). Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may reduce myocardial iron concentration (MIC) after 12 months (MD -0.27 mg/g, 95% CI -0.46 to -0.08; 3 trials, 138 participants; low-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on heart T2*, MIC, or LVEF after six months, but the evidence is very uncertain. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may increase liver T2* values after 12 months (MD 1.48 ms, 95% CI 0.27 to 2.69; 3 trials, 127 participants; low-certainty evidence), but may have little or no effect on serum ferritin at 12 months (MD 0.07 μg/mL, 95% CI -0.20 to 0.35; 4 trials, 187 participants; low-certainty evidence), and probably has little or no effect on liver iron concentration (LIC) after 12 months (MD -0.86 mg/g, 95% CI -4.39 to 2.66; 2 trials, 123 participants; moderate-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on serum ferritin, liver T2* values, or LIC after six months, but the evidence is very uncertain. The included trials did not report any serious adverse events at six or 12 months of intervention. The studies did report mild adverse effects such as oedema, dizziness, mild cutaneous allergy, joint swelling, and mild gastrointestinal symptoms. Amlodipine may be associated with a higher risk of oedema (risk ratio (RR) 5.54, 95% CI 1.24 to 24.76; 4 trials, 167 participants; very low-certainty evidence). We found no difference between the groups in the occurrence of other adverse events, but the evidence was very uncertain. No trials reported mortality, cardiac function assessments other than echocardiographic estimation of LVEF, electrocardiographic abnormalities, quality of life, compliance with treatment, or cost of interventions. AUTHORS' CONCLUSIONS The available evidence suggests that calcium channel blockers may reduce MIC and may increase liver T2* values in people with transfusion-dependent beta thalassaemia. Longer-term multicentre RCTs are needed to assess the efficacy and safety of calcium channel blockers for myocardial iron overload, especially in younger children. Future trials should also investigate the role of baseline MIC in the response to calcium channel blockers, and include a cost-effectiveness analysis.
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8.
HLA Class II regulation of immune response in sickle cell disease patients: Susceptibility to red blood cell alloimmunization (systematic review and meta-analysis)
Wong K, Lai WK, Jackson DE
Vox sanguinis. 2022
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Abstract
BACKGROUND AND OBJECTIVES Sickle cell disease (SCD) patients are commonly treated with red blood cell (RBC) transfusion. Pretransfusion tests commonly involve limited serological antibody testing. RBC alloimmunization to RBC antigens is a frequently encountered complication seen in chronically transfused patients. Genetic factors such as the human leukocyte antigen (HLA) are known to influence and regulate immune responses. HLAs are highly polymorphic and play an essential role in regulating immune responses, including RBC alloimmunization. The aim of this study was to conduct a systematic review and meta-analysis to evaluate the association between HLA Class II allelic polymorphisms with the possible risk of developing RBC alloantibodies. MATERIALS AND METHODS Four databases were systematically searched for relevant studies between the years 2000 and 2021 following the PRISMA guidelines. Four articles met the eligibility and quality criterion, and three alleles, HLA-DRB1*04, HLA-DRB1*15 and HLA-DQB1*03, that were found to be potentially associated with an increased risk in alloantibody formation were included. RESULTS The primary outcome measure was alloimmunization by RBC antigen exposure in multiply transfused SCD patients. The total estimate of alloimmunization of the SCD patients was 2.33 (95% CI, 1.58-3.44), demonstrating susceptibility to RBC alloantibody formation. Heterogeneity between the studies was insignificant, suggesting the differences associated with random sampling errors. The results showed that SCD patients carry an increased risk of producing RBC alloantibodies. CONCLUSION A strategy to prevent RBC alloimmunization is genotyping for genetically susceptible SCD patients receiving multiple transfusions. Early identification of genetic variants that can potentially increase the risk of RBC alloimmunization could aid in the screening process and selection of phenotypically matched RBC units.
PICO Summary
Population
Sickle cell disease (SCD) patients (4 studies).
Intervention
Systematic review and meta-analysis evaluating the association between human leukocyte antigen (HLA) Class II allelic polymorphisms with the possible risk of developing red blood cell (RBC) alloantibodies.
Comparison
Outcome
Three alleles: HLA-DRB1*04, HLA-DRB1*15 and HLA-DQB1*03, found to be potentially associated with an increased risk in alloantibody formation were included in the systematic review. The primary outcome measure was alloimmunization by RBC antigen exposure in SCD patients receiving multiple transfusions. The total estimate of alloimmunization of the SCD patients was 2.33 (95% CI, 1.58-3.44), demonstrating susceptibility to RBC alloantibody formation. Heterogeneity between the studies was insignificant, suggesting the differences associated with random sampling errors. The results showed that SCD patients carry an increased risk of producing RBC alloantibodies.
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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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Global longitudinal strain for detection of cardiac iron overload in patients with thalassemia: a meta-analysis of observational studies with individual-level participant data
Attar A, Hosseinpour A, Hosseinpour H, Rezaeian N, Abtahi F, Mehdizadeh F, Parsaee M, Akiash N, Behjati M, Meloni A, et al
Cardiovascular ultrasound. 2022;20(1):22
Abstract
BACKGROUND Although cardiac magnetic resonance (CMR) is the most reliable tool for assessment of CIO in patients with thalassemia, it is not always readily available. Recent studies have explored the potential of GLS as an alternative for diagnosis of CIO. We aimed to investigate the efficacy of global longitudinal strain (GLS) for detection of cardiac iron level (CIO). METHODS We searched SCOPUS, MEDLINE, and Embase to identify the studies which used GLS for assessment of CIO. We searched for individual participant data (IPD) in eligible studies to perform ROC curve analysis. CMR with a T2* cut-off value of 20 ms was considered as the gold standard. A meta-analysis was performed and the risk of bias was assessed using the JBI Checklist. RESULTS A total of 14 studies with 789 thalassemia patients (310 and 430 with and without CIO respectively and 49 with undetermined condition) were considered eligible for meta-analysis. IPDs of 405 participants were available. GLS was significantly lower in patients with CIO (-17.5 ± 2.7%) compared to those without CIO (-19.9 ± 2.3%; WMD = 1.6%, 95% CI = [0.76-2.4], p = 0.001, I(2) = 77.1%) and to normal population (-20.61 ± 2.26%; WMD = 2.2%, 95% CI = [0.91-3.5], p = 0.001, I(2) = 83.9%). A GLS < -19.5% could predict CIO with 92.8% sensitivity and 34.63% specificity (AUC = 0.659, 95% CI = [0.6-0.72], p-value < 0.0001). A GLS value < -6% has 100% positive predictive and ≥ -24.5% has 100% negative predictive values for detection of CIO. CONCLUSIONS According to our study, GLS is a strong predictor of CIO and when CMR is not available, it may be a useful screening method for identification of CIO in thalassemia patients.