Abstract

Thalassemia is a genetic mutation of the α- or β-globin chains that lead to defective erythropoiesis. This study aimed to collect evidences from all published studies that investigated the clinical effectiveness of calcium channel blockers (CCBs) in conjunction with chelation therapy for reducing iron overload in patients with thalassemia. A systematic search was conducted in PubMed, Institute for Scientific Information (ISI) Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and Virtual Health Library. Original studies reporting the use of CCBs in patients with thalassemia were included for meta-analysis. A total of five randomized studies including 210 patients were included with a follow-up period of 3-12 months. There was no significant difference between amlodipine and control groups in increasing the heart T2* magnetic resonance imaging (MRI) [mean difference (MD) 95% confidence interval (95% CI) = -1.9 (-4.4 to 0.5), p = 0.119] or reducing the liver iron concentration [MD 95% CI = -0.046 (-0.325 to 0.2), p = 0.746]. Although there were no serious adverse events reported in the included trials, further studies are recommended to strengthen our findings.

Abstract

Allogenic red blood cell transfusions exert a potential detrimental effect on the survival when delivered to cancer patients undergoing surgery with curative intent. We performed a systematic review and meta-analysis to assess the association between perioperative allogenic red blood cell transfusions and risk of death as well as relapse after surgery for localized solid tumors. PubMed, the Cochrane Library, and EMBASE were searched from inception to March 2019 for studies reporting the outcome of patients receiving transfusions during radical surgery for non-metastatic cancer. Risk of death and relapse were pooled to provide an adjusted hazard ratio with a 95% confidence interval [hazard ratio (HR) (95% confidence interval {CI})]. Mortality and relapse associated with perioperative transfusion due to cancer surgery were evaluated among participants (n = 123 studies). Overall, RBC transfusions were associated with an increased risk of death [HR = 1.50 (95% CI 1.42-1.57), p < 0.01] and relapse [HR = 1.36 (95% CI 1.26-1.46), p < 0.01]. The survival was reduced even in cancer at early stages [HR = 1.45 (1.36-1.55), p < 0.01]. In cancer patients undergoing surgery, red blood cell transfusions reduced the survival and increased the risk of relapse. Transfusions based on patients' blood management policy should be performed by applying a more restrictive policy, and the planned preoperative administration of iron, if necessary, should be pursued.

Abstract

BACKGROUND AND OBJECTIVES Iron overload in thalassaemia is a crucial prognostic factor and a major cause of death due to heart failure or arrhythmia. Therefore, previous research has recommended amlodipine as an auxiliary treatment to current chelating agents for reducing iron overload in thalassaemia patients. MATERIALS AND METHODS A systematic review and meta-analysis of the results of three randomized clinical trials evaluating the use of amlodipine in thalassaemia patients through 12 databases were carried out. RESULTS Our final cohort included 130 patients. Insignificant difference in decreasing liver iron concentrations was found between amlodipine and control groups {weighted mean difference = -0·2, [95% confidence interval = (-0·55-0·15), P = 0·26]}. As regards serum ferritin, our analysis also showed no significant difference in serum ferritin between amlodipine and control groups {weighted mean difference [95% confidence interval = -0·16 (-0·51-0·19), P = 0·36]}. Similarly, there was insignificant difference in cardiac T2* between amlodipine and control groups {weighted mean difference [95% confidence interval = 0·34 (-0·01-0·69), P = 0·06]}. CONCLUSIONS Despite the growing evidence supporting the role of amlodipine in reducing iron overload in thalassaemia patients, our meta-analysis did not find that evidence collectively significant. The results of our simulation suggest that when more data are available, a meta-analysis with more randomized clinical trials could provide more conclusive insights.

Abstract

BACKGROUND Despite common use in clinical practice, the impact of blood transfusions on prognosis among patients with lung cancer remains unclear. The purpose of the current study is to perform an updated systematic review and meta-analysis to evaluate the influence of blood transfusions on survival outcomes of lung cancer patients. METHODS We searched PubMed, Embase, Cochrane Library, and Ovid MEDLINE for publications illustrating the association between blood transfusions and prognosis among people with lung cancer from inception to November 2019. Overall survival (OS) and disease-free survival (DFS) were the outcomes of interest. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using the random-effects model. Study heterogeneity was evaluated with the I(2) test. Publication bias was explored via funnel plot and trim-and-fill analyses. RESULTS We included 23 cohort studies with 12,175 patients (3,027 cases and 9,148 controls) for meta-analysis. Among these records, 22 studies investigated the effect of perioperative transfusions, while one examined that of transfusions during chemotherapy. Two studies suggested the possible dose-dependent effect in accordance with the number of transfused units. In pooled analyses, blood transfusions deleteriously influenced both OS (HR=1.35, 95% CI: 1.14-1.61, P<0.001, I(2)=0%) and DFS (HR=1.46, 95% CI: 1.15-1.86, P=0.001, I(2)=0%) of people with lung cancer. No evidence of significant publication bias was detected in funnel plot and trim-and-fill analyses (OS: HR=1.26, 95% CI: 1.07-1.49, P=0.006; DFS: HR=1.35, 95% CI: 1.08-1.69, P=0.008). CONCLUSIONS Blood transfusions were associated with decreased survival of patients with lung cancer.

Abstract

Background and aim: We conducted a systematic review to apprise the efficacy of silymarin in conjunction with standard iron chelators on iron overload for transfusion-dependent β-thalassemia (TDT) patients.Methods: We searched PubMed, Web of Science, Scopus, Sciencedirect, the Cochrane Library (the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials (CENTRAL) to 1 May 2020. All randomized controlled trials (RCTs) studies comparing the effect of iron chelators alone versus silymarin plus standard routine treatment on iron burden amid TDT were included in this review. Primary outcomes comprised serum ferritin level (ng/mL), liver iron concentration (LIC Fe/kg dry weight), and total iron binding capacity (TIBC mcg/dL)Results: Combination therapy of silymarin and iron chelators showed a significant improvement in serum ferritin level in TDT patients, compared to nonsilymarin users [eight studies, n = 477]; weighted mean difference (WMD) -1.79, 95% confidence interval [CI] -2.86 to -0.72, I(2) 96.1%; P = 0.001. Concurrent treatment with silymarin failed to significantly decrease LIC in TDT patients [two studies, n = 106]; WMD 0.74, 95% CI -1.62 to 3.10, I(2) 96.6%; P = 0.54.Conclusion: There is no evidence of the effectiveness of adding silymarin to standard iron chelators to reduce iron load in TDT.

Abstract

Myelodysplastic syndromes (MDS) are a group of malignant hematologic diseases characterized by ineffective hematopoiesis, which may lead to chronic anemia and transfusion dependency, with up to 30% of patients progressing to acute myeloid leukemia (AML). Studies suggest transfusion dependency may impact overall survival (OS); however, there is a lack of evidence concerning the association between transfusion status (TS) and OS in patients with MDS who become transfusion independent (TI) after treatment. In addition, the holistic impact of TS on other clinical, economic, and humanistic outcomes has not been well understood. We conducted a systematic literature review (SLR) to understand this impact. Ten studies were included and showed consistent decrease in OS in transfusion dependent (TD) compared with TI patients. These findings were confirmed by a meta-analysis (MA) reporting better OS prognosis for TI patients. A second SLR was conducted to understand the association between TS and other clinical, economic, and humanistic outcomes. Twenty-eight studies were included and showed better prognosis for other outcomes, including AML progression and leukemia-free survival for TI patients. Risk of AML progression and cumulative non-leukemic death assessed by the MA showed a trend toward worse prognosis and higher risk of AML progression for TD patients. Lower healthcare resource utilization, better quality of life, and reduced non-leukemic death for TI patients were observed. Studies not eligible for MA also showed better clinical, economic and humanistic outcomes for TI patients. These findings contribute to understanding the association between transfusion dependence and OS among other outcomes in patients with MDS.

Abstract

The negative impact of perioperative blood transfusion on survival outcomes has been reported in several cancer types. The purpose of the present study is to summarize existing evidence in ovarian cancer patients. We searched the Medline, Scopus, http://clinicaltrials.gov/ EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases for observational and randomized trials that assessed the impact of perioperative blood transfusion on the disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients that undergone debulking surgery were selected for inclusion. The methodological quality of the included studies was assessed by using the Newcastle-Ottawa Scale. Statistical meta-analysis was performed with the RevMan 5.3 software using the Der-Simonian Laird random effects model. Seven studies were identified which included 2341 ovarian cancer patients. Meta-analyses that were based on univariate and multivariate reporting revealed that perioperative blood transfusion had a significant negative impact on the patient`s OS rates (OR 1.78, 95 %CI 1.16, 2.74 and OR 1.31, 95 %CI 1.00, 1.71 respectively). Disease free survival rates were also influenced according to the results of the univariate analysis (OR 1.58, 95 %CI 1.14, 2.19), however, the effect was not significant in the multivariate analysis. The analysis that was based on propensity score matched populations did not reveal differences among transfused and non-transfused. Concluding, the findings of our meta-analysis suggest that transfusion of blood products during the perioperative period is not an independent factor that may affect survival outcomes of ovarian cancer patients. Nevertheless, it should be noted that patients that receive transfusion have several potential confounders that may affect their survival outcomes.

Abstract

β-thalassemia major (TM) is one of the most prevalent inherited hemoglobinopathies in Pakistan. It has one of the highest prevalence of transfusion-dependent TM patients globally, with an estimated greater than 100,000 active cases. Blood transfusions (BT) are essential in the management of severe TM; it is critical to have a safe BT to reduce the risk of transfusion transmissible infections (TTIs). Frequent blood transfusions in these patients increase their risk of acquiring TTIs compared to the general population. We performed a systematic literature search to identify studies related to the TTIs and transfusion-related infections in Pakistan from January 1, 2010, to January 31, 2020. The search was conducted using PubMed and PakMediNet, with initial search retrieved 981 studies. Among these, 166 studies met the inclusion criteria, and only 14 studies met the final criteria for qualitative synthesis. Analysis of 14 studies (n = 3786) showed the seroprevalence of hepatitis B virus (HBV) of 3.13% (0.66% to 7.4%) and hepatitis C virus (HCV) of 26% (5.56% to 68.2%). There were only two studies that reported HIV seroprevalence of 0% and 0.5% (n = 6). The rate of seropositivity for HBV and HCV was directly related to the number of transfusions, higher ferritin levels, and older age groups. There was an increase in the HCV rate with the increasing age of patients. Thalassemia patients, who were older than ten years of age, had an HCV rate of 22% compared to only 8.4% in patients younger than ten years of age. A comparison of HCV in healthy donors vs. thalassemia patients showed a rate of 1.9% vs. 13.1% for TM patients. The majority of the patients were males (51% to 88%). The seroprevalence of TTIs was higher in males than in females (73.4% vs. 26.6%). On average, a single TM patient is exposed to at least 17 different donors annually, requiring 1-2 transfusions every month. Our study highlights that the prevalence of transfusion-transmitted infections, especially HCV, is alarmingly higher (26%) in the TM population than in the general population. There is limited data regarding the prevalence of HIV, syphilis, and malaria in this population. This is mainly due to a fragmented system of blood transfusion, weak regulations, and lower rates of voluntary blood donations. These findings warrant better health measures to improve the blood donation system and specialized care for TM patients.

Abstract

Sickle cell disease (SCD) is the most common monogenic disorder in sub-Saharan Africa (SSA). Blood transfusion to increase the oxygen carrying capacity of blood is vital in the management of many patients with SCD. However, red blood cell (RBC) alloimmunization is a major challenge to transfusions in these patients. Commonly in SSA, pretransfusion tests only involve ABO D grouping and compatibility without RBC antibody testing. Data on the frequency of RBC alloimmunization in patients with SCD in SSA are limited. We performed a systematic review and meta-analysis on available data on alloimmunization in transfused patients with SCD to determine the published prevalence of RBC alloimmunization in SCD patients in SSA. Six databases were systematically searched to identify relevant studies, without year or language restrictions. In all, 249 articles were identified and 15 met our selection criteria. The overall proportion of alloimmunization was 7.4 (95% confidence interval: 5.1-10.0) per 100 transfused patients. Antibodies against E, D, C, and K antigens accounted for almost half of antibody specificities, and antibodies to low- and high-frequency antigens were also common and represented almost 30% (20% to low-frequency antigens and 9% to high-frequency antigens) of specificities. Heterogeneity between studies was moderate, and meta-analysis found region of Africa as the major contributor to the heterogeneity. We also observed inconsistencies across studies in reporting of factors that may influence alloimmunization. This review provides an overview of the extent of the alloimmunization problem in SSA and provides a baseline against which to compare the effect of any interventions to reduce the alloimmunization risk.

Abstract

To systematically evaluate the efficacy and safety of iron chelators for transfusion-dependent patients with MDS. Thirteen cohort studies with 12,990 patients diagnosed with MDS were included in this study. According to m eta-analysis results transfusion-dependent MDS patients with secondary iron overload had a longer (HR = 0.52, 95%CI = 0.43-0.62, P < 0.001). Further subgroup analysis revealed a longer LFS (HR = 0.84, 95%CI = 0.76-0.93, P = 0.001) in MDS patients receiving iron chelators than in MDS patients not receiving iron chelators (HR = 0.52, 95%CI = 0.43-0.62, P < 0.001) and in patients with lower-risk MDS (HR = 0.50, 95%CI = 0.43-0.59, P < 0.001). Subgroup analysis of DFX showed that compared with patients not treated with iron chelators, the group receiving DFX monotherapy had significantly increased OS (HR = 0.43, 95%CI = 0.27-0.69, P < 0.001). In terms of tolerance, meta-analysis of binary variables in CAEs indicated that the occurrence of CAEs was significantly reduced by ICT (RR = 0.64, 95%CI = 0.57-0.71, P < 0.001).