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Background Langerhans cell histiocytosis (LCH) is a rare disease that originates from the uncontrolled proliferation and accumulation of bone marrow-derived immature myeloid dendritic cells. Dendritic cells are a type of histiocyte that play an important role in the human immune system and are found in the bone, skin, stomach, eyes, intestines, and lungs. Objective This systematic review aimed to collect and report published case reports of rare bone disease caused by LCH to avoid misdiagnoses or delays in diagnosis. Methods We systematically searched Scopus, PubMed, Embase, and Web of Sciences from August 1, 2000 to December 31, 2019. Studies reporting cases of LCH with rare bone involvement were included. Results We identified 60 articles including 64 cases. Of the identified cases, 31 (48.4%) involved children, and 33 (51.6%) involved adults. Additionally, 46.9% (30 individuals) were from Asian countries. The mean age of the children was 7.6 ± 4.3 years and that of the adults was 36 ± 12 years. The findings indicated that unifocal bone involvements were the most prevalent form of the disease (68.7%), and, overall, the skull and chest wall were the most commonly affected bones in both adults and children. The spine and long bones were the second most commonly affected bones in children, and the spine and jaw were the second most commonly affected bones in adults. Pain and swelling were the most frequent presenting signs among the investigated cases, and loss of consciousness, myelopathy, nerve palsy, visual loss, torticollis and clicking sounds were rare signs. Osteolytic lesions were the most frequent radiologic feature (62.5%), and intracranial hemorrhage, fluid–fluid level, dura and intracranial extension and pathologic fractures were rare radiological features. Total excision, curettage and observation in the unifocal group of patients and systemic chemotherapy in the other groups (i.e., multifocal and multisystem) were the most frequent management approaches. The recovery rates of the unifocal and multifocal groups were 77.3% and 81.8%, respectively, while that of the multisystem group was 55.5%. The rates of recurrence and mortality in the multisystem group were 11% and were higher than those in the other groups. Conclusions LCH is a rare disease that can affect any organ in the human body. However, bone is the most commonly involved organ, and rare bone involvements may be the first or only symptom of the disease due to the rarity of such lesions; a lack of familiarity with them may result in misdiagnosis or delayed diagnosis.

Children with hemophilia are an enhanced risk of modifiable cardiovascular and metabolic abnormalities. There is currently no nutritional guideline to prevent or manage cardiometabolic risk factors in these patients. Therefore, the present study sought to investigate the effect of the Dietary Approaches to Stop Hypertension (DASH) diet on cardiovascular and metabolic risk factors among children with hemophilia. In this parallel randomized clinical trial, 40 children (all male) with hemophilia were randomly allocated to the DASH group (n = 20) or control group (n = 20) for 10 weeks. The intervention group received the DASH diet (50%–55% of energy from carbohydrate, 27%–30% of energy from fat and 16%–18% energy from protein), and the control group received nutritional recommendations based on healthy eating practices. Systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood sugar (FBS), triglyceride (TG), total cholesterol (TC), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) were measured at the beginning and end of the study. Serum vitamin C was measured as a biomarker of compliance with the DASH diet. Study was registered at IRCT.ir (IRCT20130903014551N6). A significant increase in serum vitamin C in the DASH diet group was observed compared to the control group (p = .001), indicating good compliance with the DASH diet. There was a significant reduction in SBP (−0.48 mmHg), DBP (−0.48 mmHg), FBS (−5.86 mg/dl), TC (−16.07 mg/dl), TG (−17.21 mg/dl), and LDL‐C (−9.79 mg/dl), and a significant increase in HDL‐C (3.39 mg/dl), in the DASH diet group compared with the control group. Adherence to the DASH diet in children with hemophilia yielded beneficial effects in blood pressure, lipid profiles, and FBS., Forty adolescents with hemophilia were assigned to the DASH group or control group. After 10 weeks, beneficial changes were observed in blood pressure, lipid profile, and FBS among adolescents in the DASH group.

Cohen syndrome is an autosomal recessive disorder with the primary symptoms of mental deficiency, progressive retinopathy, hypotonia, microcephaly, obesity of midchildhood onset, intermittent neutropenia, and dysmorphic facial features. The syndrome has high phenotypic heterogeneity and is caused by loss-of-function mutations in the VPS13B gene. Here, we introduce a novel homozygous nonsense mutation (c.8698G > T, p.E2900X) in the VPS13B gene in an 11-year-old Iranian boy with major symptoms of Cohen syndrome. He also had mild anemia accompanied by positive antiphospholipid antibodies, the latter has never been previously reported in Cohen syndrome.

Background: Acute kidney injury (AKI) is defined as a failure in renal function leading to insufficiency of fluid and electrolyte homeostasis. Thus, sensitive biomarkers of renal tubular injury are needed to detect AKI earlier. In this study, urinary beta 2-microglobulin (β2-MG) and urinary N-acetyl-β-D-glucosaminidase (NAG) were evaluated for AKI prognosis/diagnosis in pediatric patients suffering different cancers prescribed with Ifosfamide, Ifosfamide plus Carboplatin, and Ifosfamide plus Cisplatin. Materials and Methods: In this prospective study done in Isfahan, Iran, urinary β2-MG, urinary NAG, blood urea nitrogen (BUN), and serum and urinary creatinine (Cr) were measured in 40 pediatric cancer patients less than 16 years old in three age groups during 61 courses of chemotherapy on day 0, three and six after the treatment. Results: Using ANOVA and t-test, the mean levels of urinary β2-MG (p= 0.001), urinary β2-MG/Cr (p= 0.003) and urinary NAG/Cr (p= 0.001), before and on day six of the treatment were statistically significant (p< 0.05). Also, the mean levels of BUN (p= 0.01), urinary β2-MG (p= 0.001), β2-MG/Cr (p= 0.001) and NAG/Cr (p= 0.004) based on the gender groups, the mean levels of urinary NAG (p=0.001), NAG/Cr (p= 0.001) and β2-MG/Cr (p= 0.008) based on three age groups, and the mean levels of serum Cr (p= 0.047), urinary β2-MG (p= 0.005), β2-MG/Cr (p= 0.032) and NAG/Cr (p= 0.032) based on the Ifosfamide dosage were statistically significant during the time of the treatment. Conclusion: Urinary β2-MG, urinary β2-MG/Cr, and urinary NAG/Cr are more significant biomarkers than serum Cr in earlier diagnosis and treatment of AKI in cancer patients. However, urinary NAG should be further studied to prove its reliability for AKI prognosis/diagnosis. It is suggested that urinary NAG can be used along with other renal biomarkers such as urinary β2-MG, kidney injury molecule-1(KIM-1), or interleukin-18 (IL-18) for AKI prognosis/diagnosis.

Background: Malignant disorder with B or T stem cell basis leads to development and continuation of acute lymphoblastic leukemia (ALL) due to aggregation of blast cells in bone marrow. The environmental, genetic, and demographic factors may influence the disease relapse. The objective of this study was to assess the relation between end of induction minimal residual disease and different risk factors in patients with ALL. Materials and Methods: This analytic-descriptive study consisted of 91 patients with ALL who referred to Seyed Alshohada Hospital, Isfahan, Iran. The mean age of the patients was 4.91 3.07 years old. The patients were assessed in terms of demographic characteristics, socioeconomic status, and treatment protocol. Their treatment began with Prednisolon, Dexamethason, Vincristine, L-Asparginase (L.APS) or (PEG-ASP), and Anthracycline for 28 days. Then, the end of induction minimal residual disease was assessed in each patient. For data analysis, Spierman, Mann Whitney, and Kruskal wallis tests were applied. Results: The monthly income level of the patients' families were poor, and we found a significant correlation between monthly income level of the patients' families and the incidence of minimal residual disease (P=0.03). None of the studied factors, including age, the mean of white blood cell count in the first complete blood count, hemoglobin level, platelet level, gender, central nervous system, mediastinal mass, splenomegaly, hepatomegaly, translocation, parents' education, and parents' occupation and response to corticosteroid treatment that might have had not any impacts on the studied disease(p>0.05). Conclusion: In this study, it was found that assessing the effect of risk factors on the minimal residual disease in patients with leukemia could be a good solution for detecting and eliminating risk factors and increasing the relapse time.

Objective To evaluate the repercussions of recent changes to the cut-offs used in the first screening step of the pre-marital screening programme for thalassaemia prevention in Iran. Methods The profiles of 984 subjects referred to a genetic laboratory, and the tests of 242 parents of children with thalassaemia major were assessed for red blood cell (RBC) indices, haemoglobin (Hb) A2 levels and results of Hb electrophoresis. Results Of 407 suspected thalassaemia minor (STM) cases, 18 proved positive for thalassaemia minor on molecular analysis (18/407, confidence interval 2.6–6.9%). If the revised screening cut-offs had been used to determine who would undergo molecular analysis, two of these cases would not have been identified. Only 4.4% of suspected cases with lower than normal RBC indices (mean corpuscular volume Conclusion The thalassaemia major prevention programme is performed in two separate steps. One step involves the screening of subjects and identification of β-thalassaemia minor, suspected cases for thalassaemia minor (STM), and normal subject groups. The other step concerns the identification of thalassaemia minor in the STM group. Changing the cut-offs at the first screening step does not result in significant improvement from an economic view, and is associated with significant risk at the second screening step.

No previous studies were found to examine the effect of soy as a whole food on patients with leukemia. The present randomized controlled clinical trial studied the effect of soy nut on children with B-cell acute lymphoblastic leukemia (ALL) who were in the maintenance phase of chemotherapy. The eligible patients were randomized to receive 30 g/day soy or cowpea nut powder for 12 weeks. Dietary intake, physical activity, anthropometric measurements, complete blood count, serum albumin, serum highly sensitive C-reactive protein (hs-CRP), and Tumor necrosis factor alpha (TNF-α) as well as chemotherapy side effects were assessed at the start and the end of the study. In total 29 and 27 children completed the study (aged 6.34 ± 2.44 and 5.85 ± 2.35 years) in soy and cowpea nut groups, respectively. The total energy and protein intake, and physical activity as well as body weight, body mass index, number of red blood cells, hemoglobin and hematocrit levels, and fatigue were significantly improved in the soy nut group compared to patients who consumed cowpea nut (P 0.05). Soy nut intake might improve the nutritional status, anemia, and fatigue in children with ALL. Studies targeting blood cell fractions and disease recurrence are highly recommended.

A child’s cancer not only affects the child in question, but also their family members and even closes relatives and friends. The nature of this disease is such that, while imposing a high level of care workload on the family, it also affects various family aspects including personal, familial, and social interactions and relationships, as well as family functioning. This study aims to describe family interactions in childhood leukemia. This study was an exploratory descriptive study, conducted on 58 participants (40 family members and 18 members of the health team), with purposeful sampling and semi-structured interviews—63 personal interviews and four group interviews—in the research context of the Cancer Hospital in Isfahan, 2016–2017. Data analysis in this study was carried out with qualitative content analysis using the Graneheim method. In the data analysis, four main categories and 13 subcategories were revealed. The first category, changes in roles, included the subcategories of super caregiver mother, supportive super father, role shift, self and others’ forgetfulness, and confusion in roles and tasks; the second category, changes in interpersonal relationships, included the subcategories of changes in spousal relationships, changes in parent-child relationships, and changes in relationships between children; the third category, changes in social interactions, included the subcategories of changes in relationships with relatives, changes in relationships with peers, changes in relationships with the therapy team, and changes in interaction with supportive social networks; and the fourth category, changes in relationship with God, included the subcategories of spiritual bond and spiritual illness. Regarding the findings of this study, it is expected that health system policymakers in the country, while striving to strengthen the positive aspect of changes in family relationships and interactions, will develop and execute operational, comprehensive, and society-based plans in order to eliminate the barriers and problems of relationships within the family, as well as in relation to the larger community, taking into consideration the family’s cultural and social beliefs.

Iron is an intracellular element whose accumulation in the body is associated with tissue damage. This study examines the effect of iron on pediatric acute lymphoblastic leukemia (ALL) and its “response to treatment.” At the end of the first year of treatment, bone marrow iron store (BMIS) was evaluated in children with ALL and the relationship between iron store and minimal residual disease was investigated. Moreover, the 3-year disease-free survival (3-DFS) of patients was determined. Patients’ BMIS were compared with that of subjects with normal bone marrow. The study examined 93 children, including 78 Pre-B and 15 T-cell ALL patients. BMIS did not differ between the children with ALL and those with no evidence of cancer. BMIS was increased in 26.6% of patients at the end of the first year of treatment. Drug resistance and BM relapses were more prevalent in cases with high BMIS in both Pre-B and T-cell groups. Bone marrow iron store is not considered a risk factor for childhood ALL. However, high levels of BMIS are associated with poor response to treatment and the risk of relapse. Bone marrow iron store control during treatment can therefore help achieve better outcomes and improve the chances of recovery.

Despite advances in treatment, children with acute lymphoblastic leukemia (ALL) still experience drug resistance and relapse. Several gene mutations are involved in the onset of this disease and resistance to therapy. The present study examines the incidence of IKZF1, CDKN2A/B, PAX5, EBF1, ETV6, BTG1, RB1, JAK2, and Xp22.33 gene deletions/duplications associated with pediatric ALL in Iran and investigates the possible effect of these mutations on drug resistance. Three-year disease-free survival (3DFS) was evaluated for children diagnosed with Philadelphia negative precursor-B-cell ALL hospitalized at Sayed-al-Shohada Hospital, Isfahan-Iran, from January 2009 until December 2012. DNA was extracted from bone marrow slides, and ALL correlated gene deletions and duplications were measured using Multiplex Ligation-dependent Probe Amplification (MLPA) method. The correlation between gene mutations and 3DFS was then assessed. Among the nine aforementioned investigated genes, 63% of samples showed at least one gene mutation. At least two concomitant genomic mutations were observed in 42% of samples. Pax5 deletion was the most prevalent gene mutation observed in 45% of cases, and showed significant negative impact on response to treatment. CDKN2A/B (9p21.3) gene deletion, and ETV6 (12p13.2) gene duplication also demonstrated negative effect on patient survival and contributed to a worse prognosis if concomitant with Pax5 gene deletion. ALL patients with one of the gene deletions including Pax5 and CDKN2A/B (9p21.3) or ETV6 (12p13.2) gene duplication are classified as high-risk patients and need more intensified protocols of treatment to improve their chance of survival.

Acute leukemia is the most common cancer in children and involves several factors that contribute to the development of multidrug resistance and treatment failure. According to our recent studies, the BAALC gene is identified to have high mRNA expression levels in childhood acute lymphoblastic leukemia (ALL) and those with multidrug resistance. Several polymorphisms are associated with the expression of this gene. To date, there has been no study on the rs62527607 [GT] single nucleotide polymorphism (SNP) of BAALC gene and its link with childhood acute lymphoblastic and myeloid leukemia (AML). The purpose of this study is to evaluate the prevalence of this polymorphism in pediatric acute leukemia, as well as its relationship with prognosis. DNA samples were extracted from bone marrow slides of 129 children with ALL and 16 children with AML. The rs62527607 [GT] SNP was evaluated using mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based analysis. The association between the SNP alleles and patient disease-free survival was then assessed. The prevalence of the T-allele of rs62527607 [GT] SNP in childhood T-ALL and pre-B-ALL was 28.3% and 11.2%, respectively. In the pre-B-ALL patients, 3 year disease free survival was associated with the GG genotype. Results showed a robust association between the rs62527607 SNP and the risk of relapse in ALL, but not AML, patients. T-ALL patients with the GT genotype had an 8.75 fold higher risk of relapse. The current study demonstrates a significant association between the genotype GT and the polymorphic allele G424T, and introduces this SNP as a negative prognostic factor in children with ALL.

Background: Conflicting data exists on iron metabolism in adults with beta thalassemia minor (BTM). The purpose of this study was to evaluate the serum ferritin (SF) levels in Iranian adults with BTM in order to determine the iron status in these subjects. Methods: Eighty four (41 males, 43 females) Iranian adults with BTM and 102 (55 males, 47 females) healthy subjects as a control group were enrolled in the study. SF level was measured by immunoradiometric assay (IRMA). Results: The mean SF concentration in the BTM group was 101.84 ± 8.5 μg/L, which was higher than the mean SF in non-BTM subjects (67.98 ± 5.4 μg/L, p = 0.001). Comparing SF concentrations between BTM males and males in the control group showed that the SF level was significantly higher in BTM males (150.57 ± 75.13 μg/L vs. 96.66 ± 56.79 μg/L, p < 0.001). Similar data was found for females (55.38 ± 47.94 μg/L in the BTM group vs. 34.42 ± 25.72 μg/L in the non-BTM group, p = 0.01). Conclusion: This study showed that BTM may play a role in improving iron status in females with BTM. However in males, BTM can lead to iron overload. Therefore, we suggest determining the levels of SF in subjects with BTM, especially in males, to avoid harmful effects of iron overload in early stages of the disorder.

BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the mRNA expression levels of BAALC and MRD1 were measured in bone marrow samples of 28 new diagnosed childhood ALL patients and 13 children without cancer. Minimal residual disease (MRD) was measured one year after the initiation of the chemotherapy using the RT-qPCR method. The high level expression of BAALC had a significant association with the pre-B-ALL subtype, leukocytosis and positive MRD after one year of treatment in leukemic patients. In addition, a positive correlation between BAALC and MDR1 mRNA expression was shown in this group. In conclusion, to the best of our knowledge, the increase of BAALC expression as a poor prognostic factor for childhood ALL is shown for the first time. Additionally, the correlation between BAALC and MDR1 in mRNA expression levels can aid for an improved understanding of the mechanism through which BAALC may function in ALL and multidrug resistance.

Background: Quality of life (QOL) of children with cancer reduces right from the diagnosis of disease and the start of treatment. Computer games in medicine are utilized to interact with patients and to improve their health-related behaviors. This study aimed to investigate the effect of an interactive computer game on the QOL of children undergoing chemotherapy. Materials and Methods: In this clinical trial, 64 children with cancer aged between 8 and12 years were selected through convenience sampling and randomly assigned to experimental or control group. The experimental group played a computer game for 3 hours a week for 4 consecutive weeks and the control group only received routine care. The data collection tool was the Pediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Module Child self-report designed for children aged between 8 to 12 years. Data were analyzed using descriptive and inferential statistics in SPSS software. Results: Before intervention, there was no significant difference between the two groups in terms of mean total QOL score (p = 0.87). However, immediately after the intervention (p = 0.02) and 1 month after the intervention (p < 0.001), the overall mean QOL score was significantly higher in the intervention group than the control group. Conclusions: Based on the findings, computer games seem to be effective as a tool in influencing health-related behavior and improving the QOL of children undergoing chemotherapy. Therefore, according to the findings of this study, computer games can be used to improve the QOL of children undergoing chemotherapy.

Multidrug resistance (MDR) is an important cause of treatment failure in acute lymphoblastic leukemia (ALL). The ABC family of membrane transporters is proposed, albeit with controversy, to be involved in this process. The present study aims to investigate the mRNA expression profile of several genes of this family, including ABCA2, ABCA3, ABCB1/MDR1, MRP1/ABCC1, MRP3/ABCC3, ABCG2/BCRP, and the intracellular transporter MVP/LRP, in childhood ALL, and to evaluate their association with response to therapy. Some genes in the present research are being studied for the first time in Iran. Using quantitative real-time PCR, we evaluated 27 children with ALL at diagnosis and 15 children with normal bone marrow. The status of response to therapy was assessed one year after the onset of therapy through investigating the IgH/TCRγ gene rearrangements. Our findings indicate a considerable and direct relationship between mRNA expression levels of ABCA2, ABCA3, MDR1, and MRP1 genes and positive minimal residual disease (MRD) measured after one year of treatment. Statistical analysis revealed that expression of these genes higher than the cutoff point will raise the risk of MRD by 15-, 6.25-, 12-, and 9-fold, respectively. No relationship was found between of MVP/LRP, MRP3 and ABCG2 genes expression and ALL prognoses. Considering the direct and significant relationship between the increased expression of ABCA2, ABCA3, MDR1, and MRP1 genes and positive risk of MRD in children with ALL, evaluating the expression profile of these genes on diagnosis may identify high risk individuals and help plan a more efficient treatment strategy.

Thalassemia is the most widespread recessive disease worldwide (Ryan et al. 2010; Weatherall and Clegg 2001). Beta-thalassemia is characterized by the deficiency or absence of beta globin production. The condition is clinically mild in the healthy carrier that can be easily detected through routine blood testing, but intermediate or severe in the patients who are born with 25 % chance at each pregnancy from parents who are both healthy carriers. Thalassemia carriers are today present worldwide with high frequencies mainly in the endemic countries of Africa, the Middle East, the Indian subcontinent, Southeast Asia, and the Mediterranean region (Fucharoen and Winichagoon 2007; AlHamdan et al. 2007; Sarper et al. 2009). Thalassemia is a common disease in Iran with higher frequencies in the north and south parts of the country (Haddow 2005; Samavat and Modell 2004; Moafi et al. 2010). Thalassemia major leads to serious medical, social, and economic problems for patients and their families, and patient’s care represents a considerable financial burden for the public health budget (Verma et al. 2011; Langlois et al. 2008). After a 5-year pilot screening, the Iranian Ministry of Health approved in 1996 a mandatory national screening protocol for premarital testing. This program included a laboratory strategy to identify and counsel couples at risk providing support and care (Samavat and Modell 2004; Iranian Health 2004). Although compared to other regions, the Isfahan province can be considered an area at moderate prevalence; premarital screening was locally started in 1992 and gradually extended to the entire province by 1997 (Zeinalian et al. 2009). This report presents the results of the premarital screening program applied in the Isfahan province during the last two decades (1992–2010).

Studies have shown that there is a relationship between zinc levels and depression. Thalassemic patients are at risk of zinc deficiency due to various causes including Desferal injection. The aim of this study, therefore, is to investigate hair zinc levels in thalassemic patients and their association with depression. For the purposes of this survey, 50 patients with major thalassemia between 10-20 years old were selected randomly. The patients' hair zinc concentration was compared with a control group of similarly aged healthy individuals. Simultaneously, their psychological status was evaluated with either the "Beck" or "Marya Kovacs" test (according to age) so that the relation between depression and zinc concentration could be assessed. The mean hair zinc concentration in patients was more than the controls (193.96 +/- 92.4 ppm vs 149.6 +/- 72.21 ppm). Zinc deficiency was present in 10% of the patients, and 52% had some degree of depression. There was a reverse correlation between zinc deficiency and blood transfusion rate (p0.05). Also, while there were more incidences of depression among the zinc deficient patients, the difference was not significant. Regarding the high prevalence of depression and insignificant relation to the zinc deficiency in these thalassemic patients, this research suggests the need for further consideration concerning patients' psychological status, the risk factors of zinc deficiency, as well as extended assessment into other causes of depression.