a recent systematic analysis showed that in 2011 , 314 ( 296 - 331 ) million children younger than 5 years were mildly , moderately or severely stunted and 258 ( 240 - 274 ) million were mildly , moderately or severely underweight in the developing countries . in iran a study among 752 high school girls in sistan and baluchestan showed prevalence of 16.2% , 8.6% and 1.5% , for underweight , overweight and obesity , respectively . the prevalence of malnutrition among elementary school aged children in tehran varied from 6% to 16% . anthropometric study of elementary school students in shiraz revealed that 16% of them suffer from malnutrition and low body weight . snack should have 300 - 400 kcal energy and could provide 5 - 10 g of protein / day . nowadays , school nutrition programs are running as the national programs , world - wide . national school lunch program in the united states there are also some reports regarding school feeding programs in developing countries . in vietnam , school base program showed an improvement in nutrient intakes . in iran a national free food program ( nffp ) is implemented in elementary schools of deprived areas to cover all poor students . however , this program is not conducted in slums and poor areas of the big cities so many malnourished children with low socio - economic situation are not covered by nffp . although the rate of poverty in areas known as deprived is higher than other areas , many students in deprived areas are not actually poor and can afford food . hence , nutritional value of the nffp is lower than the scientific recommended snacks for this age group . furthermore , lack of variety of food packages has decreased the tendency of children toward nffp . on the other hand , the most important one is ministry of education ( moe ) of iran , which is responsible for selecting and providing the packages for targeted schools . the ministry of health ( moh ) is supervising the health situation of students and their health needs . welfare organizations , along with charities , have the indirect effect on nutritional status of students by financial support of their family . provincial governors have also the role of coordinating and supervising all activities of these organizations . parent - teacher association is a community - based institution that participates in school 's policy such as nffp . in addition to these organizations , nutritional literacy of students , their parents and teachers , is a very important issue , which could affect nutritional status of school age children . therefore , the present study was conducted with the aim of improving the nffp , so that by its resources all poor children will be covered even in big cities . moreover , all food packages were replaced by nutritious and diverse packages that were accessible for non - poor children . according to the aim of this study and multiple factors that could affect the problem , public health advocacy has been chosen as the best strategy to deal with this issue . therefore , the present study determines the effects of nutrition intervention in an advocacy process model on the prevalence of underweight in school aged children in the poor area of shiraz , iran . this interventional study has been carried out between 2009 and 2010 in shiraz , iran . this survey was approved by the research committee of shiraz university of medical sciences . in coordination with education organization of fars province two elementary schools and one middle school in the third region of the urban area of shiraz were selected randomly . in those schools all students ( 2897 , 7 - 13 years old ) were screened based on their body mass index ( bmi ) by nutritionists . according to convenience method all students divided to two groups based on their economic situation ; family revenue and head of household 's job and nutrition situation ; the first group were poor and malnourished students and the other group were well nourished or well - off students . for this report , the children 's height and weight were entered into center for disease control and prevention ( cdc ) to calculate bmi and bmi - for - age z - scores based on cdc for diseases control and prevention and growth standards . the significance of the difference between proportions was calculated using two - tailed z - tests for independent proportions . for implementing the interventions , the advocacy process model weight was to the nearest 0.1 kg on a balance scale ( model # seca scale ) . standing height was measured to the nearest 0.1 cm with a wall - mounted stadiometer . advocacy group formation : this step was started with stakeholder analysis and identifying the stakeholders . the team was formed with representatives of all stakeholders include ; education organization , welfare organization , deputy for health of shiraz university , food and cosmetic product supervisory office and several non - governmental organizations and charities . situation analysis : this was carried out by use of existing data such as formal report of organizations , literature review and focus group with experts . the prevalence of malnutrition and its related factors among students was determined and weaknesses and strengths of the nffp were analyzed . accordingly , three sub - groups were established : research and evaluation , education and justification and executive group . designing the strategies : three strategies were identified ; education and justification campaign , nutritional intervention ( providing nutritious , safe and diverse snacks ) and networking . performing the interventions : interventions that were implementing in selected schools were providing a diverse and nutritious snack package along with nutrition education for both groups while the first group ( poor and malnourished students ) was utilized the package free of charge . education and justification intervention : regarding the literature review and expert opinion , an educational group affiliated with the advocacy team has prepared educational booklets about nutritional information for each level ( degree ) . accordingly , education of these booklets has been integrated into regular education of students and they educated and justified for better nutrition life - style . it leads the educational group to hold several meeting with the student 's parents to justify them about the project and its benefit for their children . after these meetings , parental desire for participation in the project illustrated the effectiveness of the justification meeting with them . for educate fifteen talk show programs in tv and radio , 12 published papers in the local newspaper , have implemented to mobilize the community and gain their support . healthy diet , the importance of breakfast and snack in adolescence , wrong food habits among school age children , role of the family to improve food habit of children were the main topics , in which media campaign has focused on . nutritional intervention : the snack basket of the students was replaced with traditional , nutritious and diverse foods . in general , the new snack package in average has provided 380 kcal energy , 15 g protein along with sufficient calcium and iron . low economic and malnourished children were supported by executive group affiliated with advocacy team and the rest of them prepare their snack by themselves . research and evaluation : in this step , the literacy and anthropometric indices ( bmi ) of students were assessed before and after the interventions . the reference for anthropometric measures was the world health organization / national center for health statistics ( who / nchs ) standards and the cut - offs were - two standard deviations ( sd ) from the mean . each student that was malnourished and poor has been taken into account for free food and nutritious snacks . demographic information , height , weight and knowledge of the students were measured by use of a validated and reliable ( cronbach 's alpha was 0.61 ) questionnaire . this project is granted by shiraz university of medical sciences , charities and welfare organization and education organization of fars province . statistical analyses were performed using the statistical package for the social sciences ( spss ) software , version 17.0 ( spss inc . , the results are expressed as mean sd and proportions as appropriated . in order to determine the effective variables on the malnutrition status paired t test was used to compare the end values with baseline ones in each group . in this project , the who z - score cut - offs used were as follow : using bmi - for - age z - scores ; overweight : > + 1 sd , i.e. , z - score > 1 ( equivalent to bmi 25 kg / m ) , obesity : > + 2 sd ( equivalent to bmi 30 kg / m ) , thinness : < 2 sd and severe thinness : < 3 sd . this interventional study has been carried out between 2009 and 2010 in shiraz , iran . this survey was approved by the research committee of shiraz university of medical sciences . in coordination with education organization of fars province two elementary schools and one middle school in the third region of the urban area of shiraz were selected randomly . in those schools all students ( 2897 , 7 - 13 years old ) were screened based on their body mass index ( bmi ) by nutritionists . according to convenience method all students divided to two groups based on their economic situation ; family revenue and head of household 's job and nutrition situation ; the first group were poor and malnourished students and the other group were well nourished or well - off students . for this report , the children 's height and weight were entered into center for disease control and prevention ( cdc ) to calculate bmi and bmi - for - age z - scores based on cdc for diseases control and prevention and growth standards . the significance of the difference between proportions was calculated using two - tailed z - tests for independent proportions . for implementing the interventions , weight was to the nearest 0.1 kg on a balance scale ( model # seca scale ) . standing height was measured to the nearest 0.1 cm with a wall - mounted stadiometer . advocacy group formation : this step was started with stakeholder analysis and identifying the stakeholders . the team was formed with representatives of all stakeholders include ; education organization , welfare organization , deputy for health of shiraz university , food and cosmetic product supervisory office and several non - governmental organizations and charities . situation analysis : this was carried out by use of existing data such as formal report of organizations , literature review and focus group with experts . the prevalence of malnutrition and its related factors among students was determined and weaknesses and strengths of the nffp were analyzed . accordingly , three sub - groups were established : research and evaluation , education and justification and executive group . designing the strategies : three strategies were identified ; education and justification campaign , nutritional intervention ( providing nutritious , safe and diverse snacks ) and networking . performing the interventions : interventions that were implementing in selected schools were providing a diverse and nutritious snack package along with nutrition education for both groups while the first group ( poor and malnourished students ) was utilized the package free of charge . duration of intervention was 6 months . education and justification intervention : regarding the literature review and expert opinion , an educational group affiliated with the advocacy team has prepared educational booklets about nutritional information for each level ( degree ) . accordingly , education of these booklets has been integrated into regular education of students and they educated and justified for better nutrition life - style . obviously , student 's families had remarkable effect on children 's food habit . it leads the educational group to hold several meeting with the student 's parents to justify them about the project and its benefit for their children . after these meetings , parental desire for participation in the project illustrated the effectiveness of the justification meeting with them . educate fifteen talk show programs in tv and radio , 12 published papers in the local newspaper , have implemented to mobilize the community and gain their support . healthy diet , the importance of breakfast and snack in adolescence , wrong food habits among school age children , role of the family to improve food habit of children were the main topics , in which media campaign has focused on . nutritional intervention : the snack basket of the students was replaced with traditional , nutritious and diverse foods . in general , the new snack package in average has provided 380 kcal energy , 15 g protein along with sufficient calcium and iron . low economic and malnourished children were supported by executive group affiliated with advocacy team and the rest of them prepare their snack by themselves . research and evaluation : in this step , the literacy and anthropometric indices ( bmi ) of students were assessed before and after the interventions . the reference for anthropometric measures was the world health organization / national center for health statistics ( who / nchs ) standards and the cut - offs were - two standard deviations ( sd ) from the mean . each student that was malnourished and poor has been taken into account for free food and nutritious snacks . demographic information , height , weight and knowledge of the students were measured by use of a validated and reliable ( cronbach 's alpha was 0.61 ) questionnaire . this project is granted by shiraz university of medical sciences , charities and welfare organization and education organization of fars province . advocacy group formation : this step was started with stakeholder analysis and identifying the stakeholders . the team was formed with representatives of all stakeholders include ; education organization , welfare organization , deputy for health of shiraz university , food and cosmetic product supervisory office and several non - governmental organizations and charities . situation analysis : this was carried out by use of existing data such as formal report of organizations , literature review and focus group with experts . the prevalence of malnutrition and its related factors among students was determined and weaknesses and strengths of the nffp were analyzed . accordingly , three sub - groups were established : research and evaluation , education and justification and executive group . designing the strategies : three strategies were identified ; education and justification campaign , nutritional intervention ( providing nutritious , safe and diverse snacks ) and networking . performing the interventions : interventions that were implementing in selected schools were providing a diverse and nutritious snack package along with nutrition education for both groups while the first group ( poor and malnourished students ) was utilized the package free of charge . education and justification intervention : regarding the literature review and expert opinion , an educational group affiliated with the advocacy team has prepared educational booklets about nutritional information for each level ( degree ) . accordingly , education of these booklets has been integrated into regular education of students and they educated and justified for better nutrition life - style . obviously , student 's families had remarkable effect on children 's food habit . it leads the educational group to hold several meeting with the student 's parents to justify them about the project and its benefit for their children . after these meetings , parental desire for participation in the project illustrated the effectiveness of the justification meeting with them . educate fifteen talk show programs in tv and radio , 12 published papers in the local newspaper , have implemented to mobilize the community and gain their support . healthy diet , the importance of breakfast and snack in adolescence , wrong food habits among school age children , role of the family to improve food habit of children were the main topics , in which media campaign has focused on . nutritional intervention : the snack basket of the students was replaced with traditional , nutritious and diverse foods . in general , the new snack package in average has provided 380 kcal energy , 15 g protein along with sufficient calcium and iron . low economic and malnourished children were supported by executive group affiliated with advocacy team and the rest of them prepare their snack by themselves . research and evaluation : in this step , the literacy and anthropometric indices ( bmi ) of students were assessed before and after the interventions . the reference for anthropometric measures was the world health organization / national center for health statistics ( who / nchs ) standards and the cut - offs were - two standard deviations ( sd ) from the mean . each student that was malnourished and poor has been taken into account for free food and nutritious snacks . demographic information , height , weight and knowledge of the students were measured by use of a validated and reliable ( cronbach 's alpha was 0.61 ) questionnaire . this project is granted by shiraz university of medical sciences , charities and welfare organization and education organization of fars province . statistical analyses were performed using the statistical package for the social sciences ( spss ) software , version 17.0 ( spss inc . , chicago , il , usa ) . the results are expressed as mean sd and proportions as appropriated . in order to determine the effective variables on the malnutrition status paired t test was used to compare the end values with baseline ones in each group . two - sided p < 0.05 was considered to be statistically significant . in this project , the who z - score cut - offs used were as follow : using bmi - for - age z - scores ; overweight : > + 1 sd , i.e. , z - score > 1 ( equivalent to bmi 25 kg / m ) , obesity : > + 2 sd ( equivalent to bmi 30 kg / m ) , thinness : < 2 sd and severe thinness : < 3 sd . study population contains 2897 children ; 70.8% were primary school students and 29.2% were secondary school students . 2336 ( 80.5% ) out of total students were well - off and 561 children ( 19.5% ) were indigent . 19.5% of subjects were in case group ( n = 561 ) and 80.5% were in the control group ( n = 2336 ) . the mean of age in welfare group was 10.0 2.3 and 10.5 2.5 in non - welfare group . demographic characteristics of school aged children in shiraz , iran table 2 shows the frequency of subjects in different categories of bmi for age in non - welfare and welfare groups of school aged children separately among boys and girls before and after a nutrition intervention based on advocacy process model in shiraz , iran . the frequency of subjects with bmi lower than < 2 sd decreased significantly after intervention among non - welfare girls ( p < 0.01 ) . however , there were no significant decreases in the frequency of subjects with bmi lower than < 2 sd boys . when we assess the effect of intervention in total population without separating by sex groups , we found no significant change in this population [ table 3 ] . bmi for age for iranian students aged 7 - 14 years based on gender according to who growth standards 2007 bmi for age for iranian students aged 7 - 14 years according to who growth standards 2007 in non - welfare and welfare groups of total population table 4 has shown the prevalence of normal bmi , mild , moderate and severe malnutrition in non - welfare and welfare groups of school aged children separately among boys and girls before and after a nutrition intervention based on advocacy process model . according to this table there were no significant differences in the prevalence of mild , moderate and severe malnutrition among girls and boys . table 4 also shows the mean of all anthropometric indices changed significantly after intervention both among girls and boys . the pre- and post - test education assessment in both groups showed that the student 's average knowledge score has been significantly increased from 12.5 3.2 to 16.8 4.3 ( p < 0.0001 ) . bmi , height and weight in non - welfare and welfare groups of school aged children separately in males and females before and after a nutrition intervention based on advocacy process model in shiraz , iran according to study 's finding the odds ratio ( or ) of sever thinness and thinness in non - welfare compared with welfare is 3.5 ( or = 3.5 , confidence interval [ ci ] = 2.5 - 3.9 , p < 0.001 ) . furthermore , the finding showed or of overweight and obesity in welfare compared to non - welfare is 19.3 ( or = 19.3 , ci = 2.5 - 3.9 , p = 0.04 ) . the result of this community intervention study revealed that nutrition intervention based on advocacy program had been successful to reduce the prevalence of underweight among poor girls . this study shows determinant factor of nutritional status of school age children was their socio - economic level . according to our knowledge , this is the first study , which determines the effect of a community intervention based on advocacy process on the malnutrition indices in a big city ( shiraz ) in iran . the other program in iran ( nffp ) is specified to deprived area and is not conducted in big cities . allocating millions of dollars to nffp by government , selecting the malnourished students through an active screening system at primary and middle schools , paying attention of policy makers to student 's nutrition have provided the opportunity to combat the problem . however , negligence of under - poverty line , providing poor snacks in terms of nutritional value and lack of variety are the main defects of this program . advocacy by definition is a blending of science , ethics and politics for comprehensive approaching health issues . by using advocacy program in california among the high school students for improving their nutrition and physical activity angeles unified school district participants emphasized on nutrition classes for families as well as students in addition to other interventions . in the present study another study revealed that evaluability assessment gave stakeholders the opportunity to reflect on the project and its implementation issues . it seems that in iran , free food program among the students not only is needed in deprived areas , but also it should be performed in big cities such as shiraz . at baseline , no significant difference was founded among wealthy students between the pre- and post - nutritional status intervention . in contrast , the numbers of students who have malnutrition decreased from 44% to 39.4% , which was identified as a significant among impecunious girls students . there was also a significant increase in the proportion of children with bmi that was normal for age ( 2 to + 1 sd ) most of the published community interventions showed better results among females compared with males . this difference in the impact of nutritional interventions between male and female might be related to the different age of puberty in the female population compared to the male population . in the age range of the present study female although , there is no nffp in big cities of iran , there are some programs for improving the nutritional status such as providing free milk in schools . a recent publication has shown that school feeding programs focus on milk supplementation had beneficial effects on the physical function and school performances specifically among girls in iran . the results of the mentioned study showed an improvement in the weight of children , psychological test 's scores and the grade - point average following this school feeding program . the intervention in the present study had focused on the snack intake in the school time . there are some reports regarding the nutrition transition in iran , which shows the importance of nutrition intervention to provide more healthy eating dietary habits among welfare groups of adolescents . hence , nutrition intervention especially in the form of nutrition education is needed in big cities and among welfare children and adolescents . although a study among iranian adolescents showed that dietary behavior of adolescents does not accord to their knowledge , which emphasize on the necessity of community intervention programs . a recent study regarding the major dietary pattern among iranian children showed the presence of four major dietary patterns , in which fast food pattern and sweet pattern as two major dietary patterns can be mentioned among iranian children . in advocacy program audience 's analysis accordingly , one of the prominent strategies in this study was working with media and was meeting with parent - teacher association that both of them were secondary target audiences . we also took into account policy makers in different levels , from national to local as primary audiences . advocacy team had several meetings with management and planning organization at national level and education organization of the fars province as well as principal of the targeted schools . providing nutritious snacks need contribution of private sector such as food industries or factories , but their benefits should be warranted . another choice was community involvement ; which can be achieved by female health volunteers who are working with the health system . advocacy team by using the support of charities and female health volunteers could establish a local factory that produced student 's snacks based on the new definition . however , there are some challenges on the way of expanding this program . mass production of the proposed snacks according to different desires and cultures and getting involvement of food industries with respect to marketing issues is one of those challenges . moreover , providing a supportive environment in order to change the food habits of the students and their parents among the wide range of the population require a sustainable and continuous inter - sector collaboration . although in a limited number of schools , in our study , interventions and advocacy program was successful , expanding this model to another areas around the country depends on convincing the policy makers at national level . in this regard , advocacy team should prepare evidenced based profile and transitional planning to convince the policy makers for improving the rule and regulation of nffp . the same as this study in other studies have also emphasized that there must be efforts to strengthen the capacity within the schools to deal with the nutritional problems either overweight , obesity or malnutrition by using of educational and nutritional intervention . assessing the dietary adherence is very important in nutrition intervention among population . as this population was children and adolescents we had a limitation in the blood sample collection to assess the subject 's dietary adherence . furthermore , this intervention was only focused on the intake of snack in school time and we did not have comprehensive information on the dietary intake of children and adolescents after school all over the day . the investigators propose further investigation in different areas of the country based on socio - cultural differences in order to make necessary modification and adapt this model to other areas . regarding the nutritional needs of the school age children , provision of a good platform for implementing and expanding this efficient model to the whole country based upon the socio - economic situation of each region is advisable to the moh and the moe . community nutrition intervention based on the advocacy process model is effective on reducing the prevalence of underweight specifically among female school aged children .
	
background : the present study was carried out to assess the effects of community nutrition intervention based on advocacy approach on malnutrition status among school - aged children in shiraz , iran.materials and methods : this case - control nutritional intervention has been done between 2008 and 2009 on 2897 primary and secondary school boys and girls ( 7 - 13 years old ) based on advocacy approach in shiraz , iran . the project provided nutritious snacks in public schools over a 2-year period along with advocacy oriented actions in order to implement and promote nutritional intervention . for evaluation of effectiveness of the intervention growth monitoring indices of pre- and post - intervention were statistically compared.results:the frequency of subjects with body mass index lower than 5% decreased significantly after intervention among girls ( p = 0.02 ) . however , there were no significant changes among boys or total population . the mean of all anthropometric indices changed significantly after intervention both among girls and boys as well as in total population . the pre- and post - test education assessment in both groups showed that the student 's average knowledge score has been significantly increased from 12.5 3.2 to 16.8 4.3 ( p < 0.0001).conclusion : this study demonstrates the potential success and scalability of school feeding programs in iran . community nutrition intervention based on the advocacy process model is effective on reducing the prevalence of underweight specifically among female school aged children .
	
INTRODUCTION MATERIALS AND METHODS Participants Instruments Procedure First step Second step Third step Forth step Interventions Fifth step (assessment) Data analysis RESULTS DISCUSSION CONCLUSION
it occurs in more than 50% of patients and may reach 90% in certain types of cancers , especially in patients undergoing chemotherapy and/or radiation therapy.1 anemia is defined as an inadequate circulating level of hemoglobin ( hb ) ( hb < 12 g / dl ) and may arise as a result of the underlying disease , bleeding , poor nutrition , chemotherapy , or radiation therapy . preliminary studies suggest that survival and loco - regional control after radiation therapy , especially in head and neck cancers , may be compromised by anemia.24 anemia often worsens symptoms such as fatigue , weakness , and dyspnea , and thus may have a negative effect on quality of life ( qol ) and performance status in patients with cancer . thus , to improve physical functioning , qol , and prognosis in patients with cancer , it would be reasonable to take a proactive approach in identifying populations who need treatment for cancer - associated anemia ( caa ) and provide timely management . blood transfusion is an effective way to replace depleted hb within a short period , but the effect is , unfortunately , temporary and can cause serious adverse risks and increased mortality . in randomized clinical trials in patients with caa , erythropoiesis - stimulating agents ( esas ) produced significant increases in hb level , decreased transfusion requirements , and improved qol.57 however , 30%50% of patients do not respond to such agents . in addition , the use of esas often causes concern about severe adverse reactions.6,8 in several studies , esas were found to shorten overall survival time , or time to tumor progression in patients whose hb level reached more than 12 g / dl . these studies included patients with different primary cancers , such as breast , lung , head and neck , cervix , and lymphomas.911 the lack of response to erythropoietin stimulation in patients with cancer is partly attributed to the functional iron deficiency state , in which the high rate of erythropoiesis exceeds the delivery of usable iron , despite adequate iron stores.12 absolute iron deficiency , in contrast , occurs when iron delivery is impaired because iron stores are depleted ( serum ferritin , < 100 ng / ml ; transferring saturation , < 20%).13 hepcidin , a peptide hormone produced by the liver , is up - regulated in chronic inflammatory states including cancer . hepcidin inhibits iron transport across cell membranes , thus decreasing the accessibility of stored iron and gastrointestinal absorption of dietary iron , leading to an increased frequency of iron - restricted erythropoiesis.1416 many randomized trials examined the role of intravenous ( iv ) iron in addition to esas in the treatment of anemia in patients with cancer . many of these studies showed improvement in esa response , time to maximal response , reduction in esa dose , and improvement in qol parameters ( when measured ) in favor of the combination over esas alone . the observed benefit was independent of baseline iron parameters.1721 one study found a 36% reduction in the number of patients transfused.21 this pilot study assessed the efficacy and feasibility of iv iron monotherapy in patients with cancer who have anemia and who are undergoing treatment with chemotherapy and/or radiation therapy without the use of esas . patients received the study treatment for 12 weeks followed by a 4-week follow - up period . eligible patients were at least 18 years old , about to start a cycle of chemotherapy and/or radiation therapy within 1 week of inclusion , and had a nonmyeloid malignancy , hb levels of 11.0 g / dl or less , a life expectancy of more than 24 weeks , and an eastern cooperative oncology group performance status of 02 . patients were also required to have a serum ferritin level of 100 ng / ml or higher or transferrin saturation ( tsat ) levels of 15% or higher and to have received no esas or iv iron therapy within 30 days and no oral iron therapy ( 27 mg / day or more ) within 7 days before enrollment . patients were excluded for leukoerythroblastic features on blood film , hemolysis , gastrointestinal bleeding , folate or vitamin b12 deficiency , elevated serum ferritin ( 900 ng / ml ) or transferrin saturation ( tsat ) ( 35% ) levels , pregnancy or lactation , liver dysfunction ( grade 2 or higher based on national cancer institute common toxicity criteria ) , renal dysfunction ( serum creatinine levels 2.0 mg / dl ) , active infection requiring systemic antibiotics , personal or family history of hemochromatosis , comorbidities precluding study participation , hypersensitivity to iv iron , red blood cell transfusion within the last 2 weeks , or any investigational agent within 30 days before enrollment . patients were not allowed to take any vitamin , mineral , or herbal supplements containing 27 mg or more of iron per day or 100 mg vitamin c per day during the study or follow - up period . blood transfusions were permitted at the primary physician s discretion if hb levels decreased to 8 g / dl or less , and such patients were considered treatment failures . written informed consent was provided by all patients before study participation , and the protocol and supporting documents were approved by the institutional review board of king hussein cancer center . the study was conducted in accordance with the declaration of helsinki and good clinical practice as contained in the us code of federal regulations that governs the protection of human subjects and the obligations of clinical investigators . patients received 200 mg ferric hydroxide sucrose diluted in 100 ml normal saline and infused over the course of 1 hour weekly for a total of 12 weeks . the first dose was given during the first clinic visit ( 4 days from the initiation of chemotherapy or radiation therapy ) . tsat was monitored , as protocol mandated withholding iron therapy when tsat levels were higher than 50% . at the first clinic visit ( week 1 ; baseline ) , a blood sample was obtained for laboratory assessments before the study treatment was started . patients attended weekly clinic visits for treatment and assessment ; and returned for follow - up visits at week 14 which included a complete physical examination . complete blood count and tsat were done every 3 weeks , and again 2 weeks after last treatment ( week 14 ) . complete laboratory assessment ( hb , serum ferritin , reticulocyte count , transferrin , tsat , serum iron , total iron binding capacity , red cell indices , white blood cell count with differential , platelet count , and serum chemistries ) were done at week 1 and at week 14 ( end of study ) . adverse events were assessed at each clinic visit until study completion or withdrawal , and during the 30 days after the last study treatment . hb test results were presented as mean , median , and range through all 12 weeks . comparison between means of hb level were made between the baseline hb and hb levels in the following weeks , using t - test . a significance criterion of p < 0.05 was used in the analysis . all analyses were performed using sas version 9.1 ( sas institute inc , cary , nc , usa ) . patients received the study treatment for 12 weeks followed by a 4-week follow - up period . eligible patients were at least 18 years old , about to start a cycle of chemotherapy and/or radiation therapy within 1 week of inclusion , and had a nonmyeloid malignancy , hb levels of 11.0 g / dl or less , a life expectancy of more than 24 weeks , and an eastern cooperative oncology group performance status of 02 . patients were also required to have a serum ferritin level of 100 ng / ml or higher or transferrin saturation ( tsat ) levels of 15% or higher and to have received no esas or iv iron therapy within 30 days and no oral iron therapy ( 27 mg / day or more ) within 7 days before enrollment . patients were excluded for leukoerythroblastic features on blood film , hemolysis , gastrointestinal bleeding , folate or vitamin b12 deficiency , elevated serum ferritin ( 900 ng / ml ) or transferrin saturation ( tsat ) ( 35% ) levels , pregnancy or lactation , liver dysfunction ( grade 2 or higher based on national cancer institute common toxicity criteria ) , renal dysfunction ( serum creatinine levels 2.0 mg / dl ) , active infection requiring systemic antibiotics , personal or family history of hemochromatosis , comorbidities precluding study participation , hypersensitivity to iv iron , red blood cell transfusion within the last 2 weeks , or any investigational agent within 30 days before enrollment . patients were not allowed to take any vitamin , mineral , or herbal supplements containing 27 mg or more of iron per day or 100 mg vitamin c per day during the study or follow - up period . blood transfusions were permitted at the primary physician s discretion if hb levels decreased to 8 g / dl or less , and such patients were considered treatment failures . written informed consent was provided by all patients before study participation , and the protocol and supporting documents were approved by the institutional review board of king hussein cancer center . the study was conducted in accordance with the declaration of helsinki and good clinical practice as contained in the us code of federal regulations that governs the protection of human subjects and the obligations of clinical investigators . patients received 200 mg ferric hydroxide sucrose diluted in 100 ml normal saline and infused over the course of 1 hour weekly for a total of 12 weeks . the first dose was given during the first clinic visit ( 4 days from the initiation of chemotherapy or radiation therapy ) . tsat was monitored , as protocol mandated withholding iron therapy when tsat levels were higher than 50% . at the first clinic visit ( week 1 ; baseline ) , a blood sample was obtained for laboratory assessments before the study treatment was started . patients attended weekly clinic visits for treatment and assessment ; and returned for follow - up visits at week 14 which included a complete physical examination . complete blood count and tsat were done every 3 weeks , and again 2 weeks after last treatment ( week 14 ) . complete laboratory assessment ( hb , serum ferritin , reticulocyte count , transferrin , tsat , serum iron , total iron binding capacity , red cell indices , white blood cell count with differential , platelet count , and serum chemistries ) were done at week 1 and at week 14 ( end of study ) . adverse events were assessed at each clinic visit until study completion or withdrawal , and during the 30 days after the last study treatment . hb test results were presented as mean , median , and range through all 12 weeks . comparison between means of hb level were made between the baseline hb and hb levels in the following weeks , using t - test . a significance criterion of p < 0.05 was used in the analysis . all analyses were performed using sas version 9.1 ( sas institute inc , cary , nc , usa ) . twenty - five patients ( 17 women and 8 men ) were eligible , consented , and included in the study ; their mean age ( standard deviation , [ sd ] ) was 56 years ( 13.0 years ) . chemotherapy varied according to the primary cancer and included anthracycline , platinum , taxanes , cyclophosphamide , high - dose ifosfamide , vincristine , vinblastine , bleomycin , and others . many of the included patients had their chemotherapy treatment as second- or third - line therapy . patients characteristics , including age , primary tumor , and active anticancer treatment are summarized in table 1 . one patient died during the study from his tumor ( after week 2 ) , and five patients withdrew from the study because of inconvenience ( three after week 3 , and two after week 4 ) . nineteen ( 76.0% ) patients completed a minimum of three treatments , 15 ( 60.0% ) completed nine treatments , and 14 ( 56.0% ) completed all twelve planned weekly treatments . as seen in table 2 , the mean hb level of the 25 patients at baseline was 9.6 g / dl ( median , 9.9 g / dl ; range , 6.9 g / dl10.9 g / dl ) . for the 15 patients who completed at least nine treatments , the mean change in their hb level was 1.7 g / dl ( median , 1.1 g / dl ; range , 1.9 g / dl to 3.2 g / dl ) . for the 14 patients who completed the whole treatment period ( 12 weeks ) , the mean hb level change was 2.1 g / dl ( median , 1.3 g / dl ; range , 0.2 g / dl to 4.6 g / dl ; p = 0.0007 ) . eight ( 42.1% ) of the 19 patients who completed at least three iron infusions had a more than 1 g / dl increase in their hb level . hemoglobin level changes for the 14 patients who completed twelve iron infusions are shown in figure 1 . no iv iron - related adverse events were reported among patients during the study or the follow - up period . tsat was monitored during the study period , and no patients had tsat levels increase to more than 50% . the highest ferritin level among patients who completed at least nine iv iron treatments was 1,170 ng / ml ; the mean level at the end of study period for the whole group was 379 ng / ml . five ( 20.0% ) patients received blood transfusions and were considered treatment failures ( three after week 3 , transfused at hb levels of 6.9 g / dl , 7.8 g / dl , and 5.4 g / dl ; one after week 4 , transfused at an hb level of 8.2 g / dl ; and one after week 9 , transfused at an hb level of 7.2 g / dl ) . low hb levels are associated with diminished qol and possibly decreased overall survival.2 successful treatment of anemia has undeniable benefits for patients , often yielding dramatic symptomatic improvement . although the role of esas is well - established in treating caa , big concerns were recently raised about the negative effect of esas on survival in some patients with cancer.911 concerns about the risk for thromboembolism in patients with cancer with higher hb levels who are receiving esa were also addressed in many trials.22,23 in addition , the possible immunosuppressive effects of blood product transfusions that may have relevance to neoplasia progression were addressed before.24 , 25 in our pilot study , we tested the feasibility of using iron supplementation alone to treat anemia in patients with cancer who are undergoing chemotherapy without the use of esas or blood transfusion , which could be a valid alternative , especially for patients with curable cancers . oral iron is easier to administer and relatively inexpensive , but low patient adherence , poor enteral absorption , and poor tolerance because of a wide range of troublesome gastrointestinal adverse effects limit its overall effectiveness.26 anemia of chronic disease may occur in patients with cancer and is associated with an increase in hepcidin levels , which decreases oral iron absorption and bone marrow iron use , negating any possible effect of regular doses of oral iron.15 iv iron therapy significantly improves response to epoetin alfa when compared with oral iron or no iron in anemic patients with cancer who are receiving chemotherapy.1721 oral iron supplements with esas showed no significant benefit over esas alone in treating caa.21 sodium ferric gluconate and iron sucrose appear to have more favorable safety profiles over iron dextran . a large prospective safety comparison trial failed to show serious anaphylactoid reactions,27 which is confirmed in our study , in which no patients developed reactions and no patients withdrew from the study because of adverse effects . given that the mean hb increase using esas with iv iron in one large controlled trial was 2.4 g / dl,21 the results obtained in our study are clinically significant . these findings should be further confirmed and better assessed in larger studies , in which questions such as the optimal timing of iv iron therapy with respect to chemotherapy and the optimal total dose of iv iron should be determined . the use of iv iron monotherapy was recently reviewed by a group in germany that studied the use of ferric carboxymaltose to replace esa and blood transfusions as a treatment for caa . iron - deficient patients treated with ferric carboxymaltose alone ( n = 233 ) had a median of 1.4 g / dl increase in hemoglobin levels compared with those receiving additional treatment with esas ( n = 46 ; median , 1.6 g / dl ) . our study , however , is peculiar in using iron therapy in a non - iron - deficiency state.28 iron overload after iv iron therapy , with potential concerns about the risk of developing secondary cancers and infection , might be raised . the highest serum ferritin level in the present study in patients who completed at least 9 weeks of iv iron therapy was 1,170 ng / ml . most of the literature addressing cancer and infections in iron - overloaded patients comes from patients with hemochromatosis or patients who are undergoing hemodialysis . published reviews report an increase in hepatocellular carcinoma only in patients with hemochromatosis after they develop cirrhosis.29 similarly data supporting the association between iv iron therapy and higher infection rate are weak and not well - supported.30 in fact , anemia itself is a risk factor for infections in patients receiving hemodialysis.31 a multivariate analysis of associations between iron and mortality in more than 58,000 patients receiving hemodialysis reported no increased death rate from serum ferritin levels as high as 1,200 ng / ml.30 the increasing cost of therapy in patients with cancer is of grave concern , which could be an additional benefit of iv iron over the use of esas in such patients . to further address many of the questions raised , our team is planning a bigger trial for iv iron in patients with cancer who have anemia to confirm the results discussed in this pilot trial . in addition , we will be looking into predictors of response to iv iron , such as serum hepcidin level . iv iron therapy alone is safe and may be effective in improving hb levels in patients with cancer who are undergoing active anticancer therapy . further randomized trials are needed to address many of the questions raised in our pilot study .
	
backgroundanemia in patients with cancer who are undergoing active therapy is commonly encountered and may worsen quality of life in these patients . the effect of blood transfusion is often temporary and may be associated with serious adverse events . erythropoiesis - stimulating agents are not effective in 30%50% of patients and may have a negative effect on overall survival.aimsto assess the efficacy and feasibility of intravenous iron therapy in patients with cancer who have non - iron - deficiency anemia and who are undergoing treatment with chemotherapy without the use of erythropoiesis - stimulating agents.methodsadult patients with solid cancers and non - iron - deficiency anemia were included . ferric sucrose at a dose of 200 mg was given in short intravenous infusions weekly for a total of 12 weeks . hemoglobin level was measured at baseline , every 3 weeks , and 2 weeks after the last iron infusion ( week 14 ) . adverse events related to intravenous iron were prospectively reported.resultsof 25 patients included , 19 ( 76.0% ) completed at least three iron infusions and 14 ( 56.0% ) finished the planned 12 weeks of therapy . the mean hemoglobin level of the 25 patients at baseline was 9.6 g / dl ( median , 9.9 g / dl ; range , 6.9 g / dl 10.9 g / dl ) . the mean change in hemoglobin level for the 15 patients who completed at least 9 treatments was 1.7 g / dl ( median , 1.1 g / dl ; range , 1.9 g / dl to 3.2 g / dl ) ; it reached 2.1 g / dl ( median , 1.3 g / dl ; range , 0.2 g / dl to 4.6 g / dl ; p = 0.0007 ) for the 14 patients who completed all 12 weekly treatments . five ( 20.0% ) patients were transfused and considered as treatment failures . no treatment - related adverse events were reported.conclusionintravenous iron treatment alone is safe and may reduce blood transfusion requirements and improve hemoglobin level in patients with cancer who are undergoing anticancer therapy . further randomized studies are needed to confirm these findings .