A Narrative Review of Pain in Pediatric Oncology: The Opioid Option.

Opioid therapy is the mainstay for managing pain in pediatric oncology. This narrative review describes the current literature regarding opioids for pediatric cancer pain. The review explores the multifaceted landscape of opioid utilization in this population, including the role of opioids in certain clinical circumstances, modalities of opioid delivery, unique opioids, outpatient and at-home pain management strategies, and other key concepts such as breakthrough pain. This review highlights the importance of individualized dosing and multimodal approaches to enhance efficacy and minimize adverse effects. Drawing from a wide range of evidence, this review offers insights to optimize pediatric oncology pain management.

Demographic Influences on Adult HPV Vaccination: Results from a Cross-Sectional Survey in Tennessee.

HPV is the most prevalent sexually transmitted infection in the U.S., with more than 80% of all Americans contracting it by age 45. Effective vaccines for HPV exist and were recently approved for adults aged 27-45 years, though uptake remains low in all age groups, particularly in Tennessee where 1089 cancers were attributed to HPV in 2020. Between 29 June and 17 August 2023, we conducted a cross-sectional survey to gain insights about the barriers and facilitators of HPV in 2011 adults aged 18 to 45 years in Tennessee. We developed our survey based on previous instruments to understand predictors of HPV vaccination in adults. Using descriptive statistics and bivariate and logistic regression analyses, we found higher vaccination rates in females, participants aged 18-38 years, participants with a high school education or higher, Hispanic or Latine individuals, and participants identifying as moderate or liberal. These insights highlight the need for public health interventions that consider demographic differences to successfully increase vaccination rates and reduce HPV-associated cancer risk.

Views of the Pharmacists' Role in HPV Vaccinations: A Qualitative Study in Tennessee.

The Human Papillomavirus (HPV) is a frequently occurring sexually transmitted infection in adults and is associated with various cancers that can affect both males and females. Recently, the Advisory Committee on Immunization Practices (ACIP) expanded its recommendations for the HPV vaccine to include patients aged 27-45 years with shared clinical decision-making. A commonly reported obstacle to receiving the HPV vaccine among adults is a lack of healthcare provider recommendations. Considering the suboptimal HPV vaccine coverage figures and noting that the vast majority of hesitancy research has been conducted among children and adolescents, limited research is available on the adult perception of HPV vaccination in pharmacies. This study focuses on understanding adults' opinions and perceptions regarding the role of pharmacists in the uptake of the HPV vaccine and awareness of its availability in the pharmacy setting. METHODS: After receiving approval from the Institutional Review Board (IRB), the qualitative study was initiated using virtual focus groups (FGs). Concepts from the Transtheoretical Model, the Health Belief Model, and the Social Cognitive Theory guided the study design. The corpus of data was collected in 2021 and 2022 by two researchers, and a third party transcribed the FGs to avoid any biases. The data were analyzed using Braun and Clarke's Thematic Analysis. RESULTS: Out of 35 subjects that participated in six FGDs, most identified as female, with ages ranging from 18 to 45 years. The following four themes emerged: (1) HPV vaccine awareness; (2) stigmas leading to reduced education and vaccination rates; (3) education preferences; (4) follow-up in vaccination series reminders and preferences. CONCLUSION: Participants' views of the HPV vaccine and the ability to receive the vaccine in a pharmacy are influenced by a myriad of factors. Common factors include improved awareness, preferences for educational modalities, avoiding stigmas associated with HPV vaccination, combating gender-focused biases, and preferences for the location of vaccination. These barriers provide opportunities for pharmacists to promote and enhance vaccine uptake.

Perspectives Associated with Human Papillomavirus Vaccination in Adults: A Qualitative Study.

BACKGROUND: In the last several decades, vaccine hesitancy has become a significant global public health concern. The human papillomavirus (HPV) vaccine has been on the United States of America (USA) market since 2006, with extended approval up to age 45 granted in 2018. To date, there is limited research evaluating barriers and facilitators related to HPV vaccine initiation among adults and the influence of the COVID-19 pandemic on individuals' vaccine-related behaviors. This study's main objective was to characterize the contributing factors that could promote or inhibit HPV vaccine uptake for adults. METHODS: A qualitative approach consisting of focus group discussions (FGDs) was used for this study. The FGD guide was informed by concepts from the Transtheoretical Model, Health Belief Model, and Social Cognitive Theory. All virtual FGDs were led by two researchers, who recorded audio for data collection. The data were transcribed by a third party, and the transcripts were imported into Dedoose® software and analyzed using the six steps recommended by thematic analysis. RESULTS: A total of 35 individuals participated in 6 focus groups over a 6-month period. Thematic analysis revealed four themes: (1) Intrinsic motivators for HPV vaccination, (2) Extrinsic motivators for HPV vaccination, (3) Vaccine promotion strategies, and (4) Impact of COVID-19 Pandemic on vaccine hesitancy. CONCLUSION: Both intrinsic and extrinsic factors play a role in influencing HPV vaccine uptake, and such considerations can guide efforts to improve the odds of HPV vaccination in working-age adults.

A Comprehensive Review of Vaping Use in Pediatric Patients and Recent Changes in Regulatory Laws.

The use of electronic cigarettes (e-cigarettes), also known as vapes, by adolescents and young adults has dramatically increased over the past several years. E-cigarettes continue to be the most used form of tobacco among youth. As a result of this concerning trend, policies at both the state and federal levels have been implemented to limit availability in this population. Additionally, the coronavirus disease 2019 (COVID-19) pandemic has had some positive and negative effects on the youth vaping epidemic with adolescent consumers reporting limited access to retail sites during the stay-at-home executive orders, but easier access with online purchasing because age verification was often not required. Complications resulting from vaping have been reported and include e-cigarette or vaping product use-associated lung injury (EVALI) and thrombotic events. Data suggest that the use of vaping devices can lead to both short- and long-term respiratory morbidity in the pediatric population. This review serves to provide a comprehensive examination of vaping use in pediatric patients and recent changes in regulatory laws to equip pharmacists with the knowledge to be aware of the different devices and products available, ask their pediatric patients regularly about use, and counsel and educate on the potential harmful effects.

Pexidartinib treatment in Alexander disease model mice reduces macrophage numbers and increases glial fibrillary acidic protein levels, yet has minimal impact on other disease phenotypes.

BACKGROUND: Alexander disease (AxD) is a rare neurodegenerative disorder that is caused by dominant mutations in the gene encoding glial fibrillary acidic protein (GFAP), an intermediate filament that is primarily expressed by astrocytes. In AxD, mutant GFAP in combination with increased GFAP expression result in astrocyte dysfunction and the accumulation of Rosenthal fibers. A neuroinflammatory environment consisting primarily of macrophage lineage cells has been observed in AxD patients and mouse models. METHODS: To examine if macrophage lineage cells could serve as a therapeutic target in AxD, GFAP knock-in mutant AxD model mice were treated with a colony-stimulating factor 1 receptor (CSF1R) inhibitor, pexidartinib. The effects of pexidartinib treatment on disease phenotypes were assessed. RESULTS: In AxD model mice, pexidartinib administration depleted macrophages in the CNS and caused elevation of GFAP transcript and protein levels with minimal impacts on other phenotypes including body weight, stress response activation, chemokine/cytokine expression, and T cell infiltration. CONCLUSIONS: Together, these results highlight the complicated role that macrophages can play in neurological diseases and do not support the use of pexidartinib as a therapy for AxD.

Mutations in GFAP Disrupt the Distribution and Function of Organelles in Human Astrocytes.

How mutations in glial fibrillary acidic protein (GFAP) cause Alexander disease (AxD) remains elusive. We generated iPSCs from two AxD patients and corrected the GFAP mutations to examine the effects of mutant GFAP on human astrocytes. AxD astrocytes displayed GFAP aggregates, recapitulating the pathological hallmark of AxD. RNA sequencing implicated the endoplasmic reticulum, vesicle regulation, and cellular metabolism. Corroborating this analysis, we observed enlarged and heterogeneous morphology coupled with perinuclear localization of endoplasmic reticulum and lysosomes in AxD astrocytes. Functionally, AxD astrocytes showed impaired extracellular ATP release, which is responsible for attenuated calcium wave propagation. These results reveal that AxD-causing mutations in GFAP disrupt intracellular vesicle regulation and impair astrocyte secretion, resulting in astrocyte dysfunction and AxD pathogenesis.

Characterization of Tolerance in Children during Fentanyl Continuous Infusions.

Tolerance is a complication of fentanyl continuous infusions (CINs) in critically ill children, but the incidence and time of onset are lacking. The primary objective was to identify the incidence of tolerance. Secondary objectives were to determine the onset time and compare risk factors between children with tolerance versus no tolerance and between children with early (< 24 hours) versus late tolerance. Children aged 0 to 17 years, receiving fentanyl CIN > 3 days from May 1, 2012 to June 30, 2013 were included. Tolerance was defined as a doubling of the fentanyl CIN dose. Descriptive and inferential statistics were performed. A logistic regression model was used to assess the relationship between the development of tolerance and independent variables. A total of 59 CINs were included. Tolerance occurred in 46 CINs (78%), with median time to tolerance of 26 hours (range: 1-160 hours). Early tolerance was identified in 21 CINs (45.7%). Patients with tolerance had higher peak CIN doses (p < 0.001), final CIN doses (p = 0.031), and cumulative exposure (p = 0.017). No significant differences were noted between those with early versus late tolerance. The regression model noted factors associated with the odds of development of tolerance were lower initial fentanyl dose (p = 0.007; odds ratio [OR]: 0.011, 95% confidence interval [CI]: 0.0004-0.29) and higher cumulative exposure (p = 0.009; OR: 1.01, 95% CI: 1.001-1.01). Tolerance developed in 78% of children, and half developed it within 24 hours. Lower initial opioid dose and higher cumulative exposure were independently associated with tolerance.

Vancomycin Dosing and Pharmacokinetics in Postoperative Pediatric Cardiothoracic Surgery Patients.

OBJECTIVES: This study compared vancomycin trough concentrations and pharmacokinetic parameters in pediatric cardiothoracic surgery (CTS) patients versus those in controls receiving 20 mg/kg/dose, intravenously, every 8 hours. METHODS: A retrospective study was conducted in children <18 years of age, following CTS, versus an age-and sex-matched control group. The primary objective was to determine differences in trough concentrations between groups. Secondary objectives included comparisons of pharmacokinetics between groups and development of vancomycin-associated acute kidney injury (AKI), defined as a doubling in serum creatinine from baseline. Also dosing projections were developed to target an area-under-the-curve-to-minimum inhibitory concentration (AUC:MIC) ratio of ≥400. RESULTS: Twenty-seven patients in each group were evaluated. Mean trough concentrations were significantly different between groups (CTS: 18.4 mg/L; control: 8.8 mg/L; p < 0.01). Vancomycin-associated acute kidney injury AKI was significantly higher in the CTS group than in controls (25.9% versus 0%, respectively, p<0.01). There were significant differences in vancomycin elimination rates, with a high degree of variability, but no statistical differences in other parameters. Based on dosing projections, CTS patients would require 21 to 88 mg/kg/day, with a dosage interval determined by the child's glomerular filtration rate to achieve the target AUC:MIC ≥400. CONCLUSIONS: Vancomycin dosage of 20 mg/kg/dose intravenously every 8 hours achieved significantly higher trough concentrations in CTS patients than in controls. Pharmacokinetic parameters were highly variable in CTS patients, indicating more individualization of dosage is needed. A future prospective study is needed to determine whether the revised dosage projections achieve the AUC:MIC target and to determine whether these regimens are associated with less vancomycin-associated AKI.

A multimodal approach to improving human papillomavirus vaccination in a community pharmacy setting.

BACKGROUND: Community pharmacy has become a major access point for several types of vaccinations. Despite the success of vaccination programs like influenza, pneumococcal, and herpes zoster, the rates of human papillomavirus vaccination continue to lag. OBJECTIVES: The primary objective is to describe and report on the impact of a multimodal series of pharmacist-led educational interventions on human papillomavirus vaccination rates in a community pharmacy setting. The primary outcome of this study was change in pharmacist-delivered human papillomavirus vaccination throughout a corresponding 8-week period in 2014 and 2015. METHODS: A single-center, quasi-experimental interrupted time series mixed-methods pilot study was used to investigate a pharmacist-led, multimodal educational intervention approach to improve human papillomavirus vaccination rates in the community. RESULTS: During the 2014 control period, there were no human papillomavirus vaccines dispensed or administered according to the internal prescription dispensing software. In 2015, a total of 10 patients indicated that they were vaccinated, with 9 patients receiving their first dose and 1 patient receiving his or her second dose at the pharmacy. Pharmacist recommendation was the most reported education method for increasing patient awareness of the human papillomavirus vaccine (n = 10). CONCLUSION: This study demonstrates pharmacist designed, educational interventions may impact human papillomavirus vaccination rates in the community. Further community-based research with larger sample sizes is warranted to verify these results. Due to the unique barriers to human papillomavirus vaccination, a multimodal and inter-professional approach such as the one presented here is warranted.

Prophylaxis and treatment recommendations for sinusoidal obstruction syndrome in adult and pediatric patients undergoing hematopoietic stem cell transplant: a review of the literature.

Sinusoidal obstruction syndrome, a complication occurring early after hematopoietic stem cell transplantation, is a concern for clinicians. There are no guidelines to direct clinicians on the optimal way to prevent and treat this disease. Newer data show that defibrotide is a promising drug both for prevention and treatment, although it is not yet FDA approved.

Duration of intrathecal morphine effect in children with idiopathic scoliosis undergoing posterior spinal fusion.

OBJECTIVE: Intrathecal (IT) morphine improves pain control and decreases opioid requirements in children following thoracic and abdominal surgery. However, studies in children report variable durations of analgesia following IT morphine. The purpose of this study is to describe the duration of analgesia in children undergoing surgical correction of idiopathic scoliosis. DESIGN: Retrospective chart review. SETTING: Pediatric hospital within a tertiary care academic medical center. PARTICIPANTS: Forty-four pediatric patients with idiopathic scoliosis who received IT morphine following posterior spinal fusion (PSF). MAIN OUTCOME MEASURE(S): Mean opioid exposure 0-12 hours and 13-24 hours post-IT morphine. RESULTS: Mean opioid exposure was significantly increased during the 13-24-hour compared to the 0-12-hour time period (23.0 ± 12.5 mg parenteral morphine vs 15.9 ± 1.7 mg; p = 0.0006). The only factors significantly associated with morphine exposure during the 0-12-hour period included the median pain score (0-12 hours) (odds ratio [OR], 1.92; 95% confidence interval [CI], 0.033-3.80; p = 0.046) and total acetaminophen dose (OR, 0.003; 95% CI, 0.0008-0.005; p = 0.011). CONCLUSIONS: These data indicate that patients experienced improved analgesia for at least 12 hours following IT morphine. Increased use of adjuvant analgesics such as acetaminophen may reduce opioid requirements following PSF procedures. More studies are needed to investigate the combination of adjuvants and IT morphine to reduce postoperative pain in this population.

External validation of the medication taper complexity score for methadone tapers in children with opioid abstinence syndrome.

BACKGROUND: Methadone is commonly prescribed for children with opioid abstinence syndrome (OAS) as a taper schedule over several days to weeks. The Medication Taper Complexity Score (MTCS) was developed to evaluate outpatient methadone tapers. OBJECTIVE: To further validate the MTCS and determine if it is a reliable tool for clinicians to use to assess the complexity of methadone tapers for OAS. METHODS: An expert panel of pediatric clinical pharmacists was convened. Panel members were provided 9 methadone tapers (ie, "easy," "medium," and "difficult") to determine construct and face validity of the MTCS. The primary objective was to further establish reliability and construct/face validity of the MTCS. The secondary objective was to assess the reliability of the MTCS within and between tapers. Instrument reliability was assessed using a Pearson correlation coefficient; with 0.8 as the minimum acceptable coefficient. Construct (divergent) validity was assessed via a repeated-measures ANOVA analysis (Bonferroni post hoc analyses) of the mean scores provided by panel members. RESULTS: Six panel members were recruited from various geographical locations. Panel members had 18.3 ± 5.5 years of experience, with practice expertise in general pediatrics, hematology/oncology, and the pediatric and neonatal intensive care unit. The MTCS had a reliability coefficient of .9949. There was vivid discrimination between the easy, medium, and difficult tapers; P = .001. The panel recommended minor modifications to the MTCS. CONCLUSIONS: The MTCS was found to be a reliable and valid tool. Overall, the panel felt that the MTCS was easy to use and had potential applications in both practice and research.

Caspase cleavage of GFAP produces an assembly-compromised proteolytic fragment that promotes filament aggregation.

IF (intermediate filament) proteins can be cleaved by caspases to generate proapoptotic fragments as shown for desmin. These fragments can also cause filament aggregation. The hypothesis is that disease-causing mutations in IF proteins and their subsequent characteristic histopathological aggregates could involve caspases. GFAP (glial fibrillary acidic protein), a closely related IF protein expressed mainly in astrocytes, is also a putative caspase substrate. Mutations in GFAP cause AxD (Alexander disease). The overexpression of wild-type or mutant GFAP promotes cytoplasmic aggregate formation, with caspase activation and GFAP proteolysis. In this study, we report that GFAP is cleaved specifically by caspase 6 at VELD²²5 in its L12 linker domain in vitro. Caspase cleavage of GFAP at Asp²²5 produces two major cleavage products. While the C-GFAP (C-terminal GFAP) is unable to assemble into filaments, the N-GFAP (N-terminal GFAP) forms filamentous structures that are variable in width and prone to aggregation. The effect of N-GFAP is dominant, thus affecting normal filament assembly in a way that promotes filament aggregation. Transient transfection of N-GFAP into a human astrocytoma cell line induces the formation of cytoplasmic aggregates, which also disrupt the endogenous GFAP networks. In addition, we generated a neo-epitope antibody that recognizes caspase-cleaved but not the intact GFAP. Using this antibody, we demonstrate the presence of the caspase-generated GFAP fragment in transfected cells expressing a disease-causing mutant GFAP and in two mouse models of AxD. These findings suggest that caspase-mediated GFAP proteolysis may be a common event in the context of both the GFAP mutation and excess.

Beneficial effects of Nrf2 overexpression in a mouse model of Alexander disease.

Alexander disease is a fatal neurodegenerative disease caused by dominant mutations in glial fibrillary acidic protein (GFAP). The disease is characterized by protein inclusions called Rosenthal fibers within astrocyte cell bodies and processes, and an antioxidant response mediated by the transcription factor Nrf2. We sought to test whether further elevation of Nrf2 would be beneficial in a mouse model of Alexander disease. Forcing overexpression of Nrf2 in astrocytes of R236H GFAP mutant mice decreased GFAP protein in all brain regions examined (olfactory bulb, hippocampus, cerebral cortex, brainstem, cerebellum, and spinal cord) and decreased Rosenthal fibers in olfactory bulb, hippocampus, corpus callosum, and brainstem. Nrf2 overexpression also restored body weights of R236H mice to near wild-type levels. Nrf2 regulates several genes involved in homeostasis of the antioxidant molecule glutathione, and the neuroprotective effects of Nrf2 in other neurological disorders may reflect restoration of glutathione to normal levels. However, glutathione levels in R236H mice were not decreased. Nrf2 overexpression did not change glutathione levels or ratio of reduced to oxidized glutathione (indicative of oxidative stress) in olfactory bulb, where Nrf2 dramatically reduced GFAP. Depletion of glutathione through knock-out of the GCLM (glutamate-cysteine ligase modifier subunit) also did not affect GFAP levels or body weight of R236H mice. These data suggest that the beneficial effects of Nrf2 are not mediated through glutathione.

Prevention and treatment of oral mucositis in children with cancer.

Oral mucositis affects more than three-fourths of patients undergoing chemotherapy and represents a significant burden to patients and caregivers. Lesions develop as a result of chemotherapeutic agents attacking the rapidly dividing cells of the gastrointestinal tract. Severity can range from mild, painless tissue changes to bleeding ulcerations that prevent oral intake and require narcotic pain relievers. Oral mucositis also leads to an increased risk of infection and can often delay further chemotherapy treatment. A number of assessment scales have been developed to better qualify the symptoms associated with this condition. Few pharmacologic agents have been approved to either prevent the development or alleviate the symptoms of oral mucositis. Current options include the use of antimicrobial mouthwashes, amino acid rinses, and topical healing agents. Palifermin, a keratinocyte growth factor, may be a future option after its use in children is explored. With achievements in other areas of supportive care in patients undergoing chemotherapy, oral mucositis should represent the forefront of new research. This review will provide a comprehensive examination of available options for children who have oral mucositis.

Knockdown of MLC1 in primary astrocytes causes cell vacuolation: a MLC disease cell model.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy, in the majority of cases caused by mutations in the MLC1 gene. MRI from MLC patients shows diffuse cerebral white matter signal abnormality and swelling, with evidence of increased water content. Histopathology in a MLC patient shows vacuolation of myelin, which causes the cerebral white matter swelling. MLC1 protein is expressed in astrocytic processes that are part of blood- and cerebrospinal fluid-brain barriers. We aimed to create an astrocyte cell model of MLC disease. The characterization of rat astrocyte cultures revealed MLC1 localization in cell-cell contacts, which contains other proteins described typically in tight and adherent junctions. MLC1 localization in these contacts was demonstrated to depend on the actin cytoskeleton; it was not altered when disrupting the microtubule or the GFAP networks. In human tissues, MLC1 and the protein Zonula Occludens 1 (ZO-1), which is linked to the actin cytoskeleton, co-localized by EM immunostaining and were specifically co-immunoprecipitated. To create an MLC cell model, knockdown of MLC1 in primary astrocytes was performed. Reduction of MLC1 expression resulted in the appearance of intracellular vacuoles. This vacuolation was reversed by the co-expression of human MLC1. Re-examination of a human brain biopsy from an MLC patient revealed that vacuoles were also consistently present in astrocytic processes. Thus, vacuolation of astrocytes is also a hallmark of MLC disease.

Alexander disease mutant glial fibrillary acidic protein compromises glutamate transport in astrocytes.

Alexander disease (AxD) is a leukodystrophy caused by heterozygous mutations in the gene for glial fibrillary acidic protein, an intermediate filament protein expressed by astrocytes. The mutation causes prominent protein aggregates inside astrocytes; there is also loss of myelin and oligodendrocytes and neuronal degeneration. We show that immunohistochemical staining for glutamate transporter 1, the major brain glutamate transporter expressed primarily in astrocytes suggests decreased levels in the hippocampi of infantile AxD patients. A knock-in mouse model of AxD also shows significant reduction of glutamate transporter 1 in the hippocampus. To explore this phenomenon at the cellular level, wild-type and R239C mutant glial fibrillary acidic proteins (the most common mutation) were overexpressed in astrocytes in culture. Western blotting and whole-cell patch clamp recordings demonstrated that the R239C astrocytes exhibited markedly reduced glutamate transporter 1 protein levels; this resulted in attenuated or abolished glutamate-induced inward transporter current. Neurons cocultured with the R239C astrocytes exhibited increased death after glutamate challenge. These results indicate that aberrant astrocytes have decreased glutamate uptake, which may play an important role in the pathogenesis of neuronal and oligodendrocyte injury and death in AxD.

Autophagy induced by Alexander disease-mutant GFAP accumulation is regulated by p38/MAPK and mTOR signaling pathways.

Glial fibrillary acidic protein (GFAP) is the principle intermediate filament (IF) protein in astrocytes. Mutations in the GFAP gene lead to Alexander disease (AxD), a rare, fatal neurological disorder characterized by the presence of abnormal astrocytes that contain GFAP protein aggregates, termed Rosenthal fibers (RFs), and the loss of myelin. All GFAP mutations cause the same histopathological defect, i.e. RFs, though little is known how the mutations affect protein accumulation as well as astrocyte function. In this study, we found that GFAP accumulation induces macroautophagy, a key clearance mechanism for prevention of aggregated proteins. This autophagic response is negatively regulated by mammalian target of rapamycin (mTOR). The activation of p38 MAPK by GFAP accumulation is in part responsible for the down-regulation of phosphorylated-mTOR and the subsequent activation of autophagy. Our study suggests that AxD mutant GFAP accumulation stimulates autophagy, in a manner regulated by p38 MAPK and mTOR signaling pathways. Autophagy, in turn, serves as a mechanism to reduce GFAP levels.

Deferasirox--an oral agent for chronic iron overload.

OBJECTIVE: To review the available literature on the pharmacology, pharmacokinetics, efficacy, toxicology, adverse effects, drug interactions, and dosage guidelines for deferasirox, an oral iron chelator, in Phase III trials. DATA SOURCES: Reviewers searched the following databases for English-language studies: MEDLINE (1966-April 2006), International Pharmaceutical Abstracts (1970-April 2006), and the Cochrane Library Database. Key search terms included iron chelation, chelation, iron overload, deferasirox, and ICL670. STUDY SELECTION AND DATA EXTRACTION: Data on efficacy, toxicology, adverse effects, and pharmacokinetics for deferasirox were obtained from randomized, open-label, blinded clinical trials. Other information was obtained from the manufacturer, including unpublished studies in abstract form as well as available data on deferasirox. DATA SYNTHESIS: Deferasirox is an orally active iron chelator. In clinical trials, deferasirox demonstrated efficacy at dosages of 20 and 30 mg/kg/day in treating iron overload in patients with beta-thalassemia. Deferasirox has been studied in patients older than 2 years and appears to be safe, with the most common adverse effects reported being mild, transient nausea, gastrointestinal disturbances, and rash. There were no reports of serious adverse effects in trials to date. CONCLUSIONS: Deferasirox represents a new approach to the management of chronic iron overload in patients with chronic anemias who require blood transfusions. The available literature suggests that deferasirox is safe and as effective as the current standard of therapy at dosages of 20-30 mg/kg/day for beta-thalassemia. Further studies are needed to confirm its efficacy in other chronic transfusion-requiring diseases.