Intravenous Iron Supplementation for the Treatment of Chemotherapy-Induced Anemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Journal of clinical medicine. 2022;11(14)
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.
People with chemotherapy induced anaemia enrolled in randomised controlled trials (RCTs), and identified by systematic review (n= 1,015, 8 RCTs).
Intravenous [IV] iron (n= 553).
Oral iron (n= 271), or no iron (n= 191).
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).
A systematic review assessing the under-representation of cancer patients in COVID-19 trials
Acta haematologica. 2022
Background - The new severe acute respiratory syndrome coronavirus 2 have emerged as a global pandemic that threatens thousands around the world. Observational cohort studies have demonstrated that cancer patients have inferior outcomes due to underlying malignancy, treatment-related immunosuppression, or increased comorbidities. We aimed to examine the representation of cancer patients (hematological malignancies and solid tumors) in COVID-19 therapeutic and prophylactic interventional trials. Methods- In this review, all randomized controlled trials (RCTs) published between December 2019 and August 2021 were included. We included only trials evaluating medications that were recommended by NIH guidelines: steroids, Tocilizumab, Remdesivir and REGN-COV2. Results- The search yielded 540 potentially relevant RCTs, 22 of which were considered suitable. All trials included patients with solid cancer and hematological malignancies in the formal reported inclusion criteria. However, only two trials reported the accurate number of cancer patients included. Ten trials excluded neutropenic patients and seven trials excluded thrombocytopenic patients. Eleven trials excluded patients that were treated with any immunosuppression treatment. None of the two trials that included cancer patients reported separate outcomes for this population. Conclusion- Our systematic review shows that cancer patients are under-represented in COVID-19 interventional therapeutic trials, and evidence regarding outcomes are lacking.
Iron supplementation for restless legs syndrome - A systematic review and meta-analysis
European journal of internal medicine. 2019
BACKGROUND Iron supplementation, is recommended for the treatment of restless legs syndrome (RLS). We gathered evidence for the efficacy and safety of iron supplementation for RLS. METHODS A systematic review and meta-analysis of randomized controlled trials that compared iron supplementation versus no iron for patients with RLS was performed. Multiple databases were searched. The primary outcome was the effect of iron on the International Restless Legs Syndrome score (IRLSS) at 4weeks after treatment. For dichotomous data, risk ratios (RR) with 95% confidence intervals (CIs) were estimated and pooled. For continuous data, weighted mean differences (WMD) were calculated. RESULTS Ten trials fulfilled the inclusion criteria. Iron therapy was associated with a significant decrease of the IRLSS of -3.55 [95% CI (-5.41) - (-1.68)] points and an increase in the percentage of patients with improvement of the IRLSS score, RR of 2.16 [95% CI 1.56-2.98]. IV FCM was associated with improvement in both the IRLSS (WMD of -2.79 (95% CI (-4.62) - (-0.96), 4 trials, I(2)=0%) and on the RLS-QOL by WMD of 8.67 (95% CI 1.68-15). Iron was associated with an increased rate of adverse events RR 2.04 (95% CI 1.46-2.85), which were not severe and not associated with increased rate of treatment discontinuation. CONCLUSION Iron supplementation is associated with improvement of the IRLSS score. Our meta-analysis supports the use of iron, oral or IV, as effective therapy for patients with RLS. Further studies should assess subgroups of patients most likely to benefit from iron supplementation.
Intravenous versus oral iron supplementation for the treatment of anemia in CKD: an updated systematic review and meta-analysis
American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2016;68((5):):677-690
BACKGROUND Iron supplementation is crucial for the treatment of anemia of chronic kidney disease (CKD). Although intravenous (IV) iron is preferred for patients with CKD receiving dialysis (CKD stage 5D), the method of iron replacement for patients with CKD stages 3 to 5 is controversial. STUDY DESIGN Systematic review and meta-analysis. A search was performed until October 2015 of MEDLINE, Cochrane Library, conference proceedings in nephrology, and reference lists of included trials. SETTING & POPULATION Patients with CKD stages 3 to 5 or 5D. SELECTION CRITERIA FOR STUDIES All randomized controlled trials, regardless of publication status or language. INTERVENTION IV versus oral iron supplementation. OUTCOMES The primary outcome was defined as percentage of patients reaching an elevation in hemoglobin (Hb) concentration > 1g/dL. Secondary end points included percentage of patients who reached Hb levels > 11g/dL, absolute Hb concentration, change in Hb concentration, transferrin saturation, ferritin levels, erythropoiesis-stimulating agents and blood transfusion requirement, and quality of life. Safety analysis included all-cause mortality and serious and all adverse events. RESULTS 24 trials were identified, 13 including 2,369 patients with CKD stages 3 to 5 and 11 including 818 patients with CKD stage 5D. Patients treated with IV iron were more likely to reach an Hb response > 1g/dL (risk ratios [RRs] of 1.61 [95% CI, 1.39-1.87] for CKD stages 3-5 and 2.14 [95% CI, 1.68-2.72] for CKD stage 5D). Safety analysis showed similar rates of mortality and serious and any adverse effects. IV iron replacement was associated with higher risk for hypotension (RR, 3.71; 95% CI, 1.74-7.94) and fewer gastrointestinal adverse events (RR, 0.43; 95% CI, 0.28-0.67). LIMITATIONS Significant heterogeneity between trials; follow-up was usually limited to 3 months. CONCLUSIONS Our results agree with current recommendations for IV iron replacement for patients with CKD stage 5D and support increased use of IV iron for patients with CKD stages 3 to 5.
Intravenous iron supplementation for the treatment of chemotherapy-induced anaemia - systematic review and meta-analysis of randomised controlled trials
Acta Oncologica. 2013;52((1):):18-29.
Abstract Background: Current guidelines are inconclusive regarding intravenous (IV) iron for treatment of chemotherapy-induced anaemia (CIA). Material and methods: Systematic review and meta-analysis of randomised controlled trials comparing IV iron with no iron or oral iron for treatment of chemotherapy induced anaemia (CIA). Primary outcomes: haematopoietic response and red blood cell (RBC) transfusion requirements. For dichotomous data, relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. For continuous data, weighted mean differences were calculated. Results: Eleven trials included 1681 patients, the majority examining the addition of IV iron to erythropoiesis stimulating agents (ESA) (1562 patients, 92.9%). IV iron significantly increased haematopoietic response rate [RR 1.28 (95% CI 1.125-1.45), seven trials with ESA] and decreased the rate of blood transfusions both in trials with ESA [RR 0.76 (95% CI 0.61-0.95), seven trials] and without ESA [RR 0.52 (95% CI 0.34-0.80)]. The increase in haematopoietic response rate correlated with total IV iron dose, regardless of baseline iron status. Mortality and safety profile was comparable between groups. Conclusions: IV iron added to ESA results in an increase in haematopoietic response and reduction in the need for RBC transfusions, with no difference in mortality or adverse events.
Intravenous iron supplementation for the treatment of cancer-related anemia - systematic review and meta-analysis
Blood. 2010;116((21):): Abstract No. 4249.
Immunoglobulin prophylaxis in hematopoietic stem cell transplantation: systematic review and meta-analysis
Journal of Clinical Oncology. 2009;27((5):):770-81.
PURPOSE Because the role of immunoglobulins (IVIG) prophylaxis in patients undergoing hematopoietic stem-cell transplantation (HSCT) has not been established in terms of survival and infection prevention, we conducted a meta-analysis evaluating these issues. METHODS Systematic review and meta-analysis of randomized-controlled trials comparing prophylaxis with polyvalent IVIG or cytomegalovirus (CMV)-IVIG and control or another preparation or dose. PUBMED, Cochrane Library, LILACS, and conference proceedings were searched. Two reviewers appraised the quality of trials and extracted data. Relative risks (RRs) with 95% CIs were estimated and pooled. RESULTS Thirty trials including 4,223 patients undergoing bone marrow transplantation (BMT) were included. There was no difference in all-cause mortality when polyvalent IVIG or CMV-IVIG was compared to control (RR, 0.99; 95% CI, 0.88 to 1.12; and RR, 0.86; 95% CI, 0.63 to 1.16, respectively). There was no difference in clinically documented infections when polyvalent IVIG was compared with control (RR, 1.00; 95% CI, 0.90 to 1.10; five trials). CMV infections were not significantly reduced with either polyvalent IVIG or CMV-IVIG. Interstitial pneumonitis was reduced with polyvalent IVIG in older studies but not in the more recent ones, nor in studies assessing CMV-IVIG. Polyvalent IVIG increased the risk for veno-occlusive disease (RR, 2.73; (95% CI, 1.11 to 6.71). Graft-versus-host disease was not affected. CONCLUSION Because there is no advantage in terms of survival or infection prevention, IVIG does not have a role in HSCT.
Immunoglobulin prophylaxis in chronic lymphocytic leukemia and multiple myeloma: systematic review and meta-analysis
Leukemia & Lymphoma. 2009;50((5):):764-72.
The role of intravenous immunoglobulins (IVIG) prophylaxis in hypogammaglobulinemic patients with lymphoproliferative disorders (LPD) and plasma cell dyscrasias (PCD) has not been established. We performed a systematic review and meta-analysis of randomized-controlled trials comparing prophylaxis with polyvalent IVIG versus control. The primary outcomes were all-cause mortality and major infections. Nine trials, assessing patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), were included. No survival benefit could be demonstrated, RR 1.36 (95% CI 0.58-3.19, two trials), but there was a significant decrease in the occurrence of major infections, RR 0.45 (95% CI 0.27-0.75, three trials) and a significant reduction in clinically documented infections, RR 0.49 (95% CI 0.39-0.61, three trials). Adverse events, usually not requiring discontinuation of IVIG, occurred significantly more with IVIG. On the basis of the available data, IVIG cannot be recommended routinely for patients with CLL or MM with hypogammaglobulinemia and/or recurrent infections and should be considered on individual basis.
Intravenous versus oral iron supplementation for the treatment of anemia in CKD: systematic review and meta-analysis
American Journal of Kidney Diseases. 2008;52((5):):897-906.
BACKGROUND Iron supplementation is essential for the treatment of patients with anemia of chronic kidney disease (CKD). It is not clear which is the best method of iron administration. STUDY DESIGN Systematic review and meta-analysis. A search was performed until January 2008 of MEDLINE, Cochrane Central Register of Controlled Trials, conference proceedings in nephrology, and reference lists of included trials. SETTING & POPULATION Patients with CKD (stages III to V). We included dialysis patients and patients with CKD not on dialysis therapy (hereafter referred to as patients with CKD). SELECTION CRITERIA FOR STUDIES We included all randomized controlled trials regardless of publication status or language. INTERVENTION Intravenous (IV) versus oral iron supplementation. OUTCOMES MEASURES Primary outcomes assessed: absolute hemoglobin (Hb) level or change in Hb level from baseline. We also assessed all-cause mortality, erythropoiesis-stimulating agent requirement, adverse events, ferritin level, and need for renal replacement therapy in patients with CKD. RESULTS 13 trials were identified, 6 including patients with CKD and 7 including dialysis patients. Compared with oral iron, there was a significantly greater Hb level in dialysis patients treated with IV iron (weighted mean difference, 0.83 g/dL; 95% confidence interval, 0.09 to 1.57). Meta-regression showed a positive association between Hb level increase and IV iron dose administered and a negative association with baseline Hb level. For patients with CKD, there was a small but significant difference in Hb level favoring the IV iron group (weighted mean difference, 0. 31 g/dL; 95% confidence interval, 0.09 to 0. 53). Data for all-cause mortality were sparse, and there was no difference in adverse events between the IV- and oral-treated patients. LIMITATIONS There was significant heterogeneity between trials. Follow-up was limited to 2 to 3 months. CONCLUSIONS Our review shows that patients on hemodialysis therapy have better Hb level response when treated with IV iron. For patients with CKD, this effect is small.
Immunoglobulin prophylaxis in hematological malignancies and hematopoietic stem cell transplantation
Cochrane Database of Systematic Reviews. 2008;((4):):CD006501.