Determining the Significant Prognostic Factors for the Recurrence of Pediatric Acute Lymphoblastic Leukemia Using a Competing Risks Approach.

Acute lymphoblastic leukemia (ALL) is the most common cause of cancer-related fatality among children. This study aimed to identify the significant prognostic factors for the incidence of pediatric ALL. This retrospective study, conducted from 2007 to 2016 in the Iranian city of Mashhad, enrolled 417 patients with ALL. The diagnosis was confirmed by Giemsa staining of bone marrow smears. The first recurrence was regarded as the event of interest and non-relapse mortality as the competing event through a three-parameter Gompertz model. The level of statistical significance for univariate and multivariate analyses was set at 0.2 and 0.05, respectively. The first recurrence occurred in 44 (10.6%) survivors. Disease-free survival and 5-year overall survival rates were 85.9% and 74%, correspondingly. The five-year incidence rate for the first recurrence was 11.5% in the presence of non-relapse mortality. Briefly, the characteristics of the Gompertz model conferred more effective prognostic factors. Age above 10 years (P=0.010), involvement of the central nervous system (P=0.050), a high white blood cell count (P=0.020), and tumor lysis syndrome (P=0.010) were the significant prognostic factors for the recurrence and mortality of ALL. Accordingly, careful monitoring in the administration of treatment protocols is suggested to reduce the risk of recurrence and death in these patients.

Effect of Spiritual Care Based on Ghalbe Salim on Anxiety in Adolescent with Cancer.

Cancer is one of the chronic and rare diseases in children that is associated with psychological trauma that can cause fear and anxiety in patients. Considering that spirituality as a solid base may be a strong factor in controlling the tense conditions, this study aimed to investigate the effect of true heart spiritual care on cancer anxiety in Mashhad. This is a case-control study on 40 children referred to Dr. Sheikh Mashhad Children's Therapeutic Center in 2017. Sampling was done randomly in two groups of test and control. The experimental group received the training program in five sessions in 4 weeks. The data were collected using a demographic questionnaire and Marx children's anxiety scale and entered into spssv.20 software. There was no difference the score of anxiety before intervention in any of the dimensions of anxiety and the general dimension of anxiety in the case and control (P < 0.01). However, the mean of anxiety score in the SC group before and after intervention was significantly (75.25 ± 15.2) (44.55 ± 7.62), respectively. So that 50% of the posttest changes are due to the effect of the intervention. Regarding the effect of SC on reducing cancer anxiety, it is recommended that therapists, counselors and clinical psychologists use the spiritual care education method to reduce anxiety.

Rhenium-188 radiosynovectomy for chronic haemophilic synovitis: Evaluation of its safety and efficacy in haemophilic patients.

INTRODUCTION: Radiocolloids labelled with less costly and more accessible radionuclides such as rhenium-188 are of interest to developing countries compared with those labelled with rhenium-186 and yttrium-90. AIM: This study was aimed to evaluate the efficacy and safety of radiosynovectomy using rhenium-188 in patients with chronic haemophilic synovitis and recurrent hemarthrosis. METHODS: In this quasi-experimental prospective study, 20 haemophilic patients were evaluated at preinjection, and at 1, 3, 6 and 12 months after injection. Magnetic resonance imaging (MRI) was done to measure synovial thickness and to calculate Denver score. Joint radiographs were taken to measure the Pettersson score. The Gilbert questionnaire, Functional Independence Score in Hemophilia (FISH) and visual analogue scale (VAS) for pain were completed, and the number of bleeding episodes and factor consumption were recorded at each follow-up visit. RESULTS: The number of bleeding episodes, the amount of factor consumption per month, VAS pain scores and synovial thickness decreased significantly over time (P < .05). Gilbert and FISH scores showed significant improvement (P < .001). However, Pettersson score and Denver score showed no significant changes after injection. Minor complications including temporary pain and swelling occurred in 20% of patients, and no major complication was observed after rhenium-188 injection. CONCLUSION: Our results indicated high clinical impact, efficacy, safety and low invasion of rhenium-188 in radiosynovectomy of haemophilic patients. Considering the availability and relatively low cost of rhenium-188 in developing countries, this can be a good treatment option for haemophilic patients with recurrent hemarthrosis, particularly when the synovial hypertrophy is not massive yet.

Prevalence of ß-Thalassemia Mutations among Northeastern Iranian Population and their Impacts on Hematological Indices and Application of Prenatal Diagnosis, a Seven-Years Study.

BACKGROUND AND OBJECTIVE: ß-thalassemia results from a diverse range of mutations inside the hemoglobin subunit ß (HBB) gene. In a study of ß-thalassemia carriers and some of their at-risk fetuses in the Khorasan province of Iran, we aimed to recognize the most common mutations in the region. We also investigated a possible link between these mutations and some of the relevant hematological indices. METHODS: Amplification-refractory mutation system-PCR (ARMS-PCR) was used to detect the typical HBB mutations among 1593 individuals, suspected of having a mutated HBB allele from March/2011 to January/2018. Sanger sequencing of HBB had been performed, where ARMS-PCR was uninformative. In some cases, reverse dot blot was utilized. Analysis of variance was used to compare parametric variables. RESULTS: Among 1273 ß-thalassemia carriers, the prevalence of the mutations were reported as follows: IVS-I-5 (42.03%), IVS-II-1 (11.23%), codons 8/9 (4.79%), codon 44 (4.56%), codon 15 (3.53%), Los Angeles (2.91%), codon 5 (2.75%), IVS-I-110 (2.51%), -88 (2.20%) and other mutations were less than 2% of all of the reported mutations. 644 conceptions were subjected to prenatal diagnosis, using chorionic villus sampling. 118 cases were reported as normal. 352 cases were detected as carriers. 174 cases were diagnosed as affected. There was a significant difference in mean corpuscular volume and hemoglobin A2 levels between the nine most commonly reported mutation types (p<0.001). CONCLUSION: This study makes a reliable guide for ß-thalassemia diagnosis in the region. The possibility of a correlation between HBB mutations and hematological indices opens a gate of future investigations.

Prevention of Chemotherapy-Induced Nephrotoxicity in Children with Cancer.

Children with cancer treated with cytotoxic drugs are frequently at risk of developing renal dysfunction. The cytotoxic drugs that are widely used for cancer treatment in children are cisplatin (CPL), ifosfamide (IFO), carboplatin, and methotrexate (MTX). Mechanisms of anticancer drug-induced renal disorders are different and include acute kidney injury (AKI), tubulointerstitial disease, vascular damage, hemolytic uremic syndrome (HUS), and intrarenal obstruction. CPL nephrotoxicity is dose-related and is often demonstrated with hypomagnesemia, hypokalemia, and impaired renal function with rising serum creatinine and blood urea nitrogen levels. CPL, mitomycin C, and gemcitabine treatment cause vascular injury and HUS. High-dose IFO, streptozocin, and azacitidine cause renal tubular dysfunction manifested by Fanconi syndrome, rickets, and osteomalacia. AKI is a common adverse effect of MTX, interferon-alpha, and nitrosourea compound treatment. These strategies to reduce the cytotoxic drug-induced nephrotoxicity should include adequate hydration, forced diuresis, and urinary alkalization. Amifostine, sodium thiosulfate, and diethyldithiocarbamate provide protection against CPL-induced renal toxicity.

Acute Lymphoblastic Leukemia Following Nasopharyngeal Carcinoma: Report of an Unusual Case.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is a rare malignancy in children. Nasal obstruction, otitis media with effusion, pain in the ear, hearing problems, and unusual neck mass are among the signs and symptoms of this malignancy. CASE REPORT: We report the case of a 13-year-old girl with NPC who later developed acute lymphoblastic leukemia (ALL) through the course of her disease. To our knowledge, this is the first report of ALL following childhood nasopharyngeal carcinoma in the English-language literature. CONCLUSION: Reports of secondary malignancies at the site of radiotherapy for NPC exist, but this is the first report of ALL following NPC.

Assessment of Heart and Liver Iron Overload in Thalassemia Major Patients Using T2* Magnetic Resonance Imaging.

Accumulation of excess iron in heart can lead to cardiac dysfunction, which is the most common cause of death in thalassemia major patients. Biopsy is an invasive procedure and therefore not an ideal option to assess iron load. However, standard/usual non-invasive methods, such as ferritin measurement, have some limitations and the results show poor correlations with iron load. Magnetic Response Imaging (MRI-T2*), as a non-invasive and reliable method for iron load assessment in organs such as liver and heart, can be suggested as a favorable alternative. This cross-sectional study was implemented in Thalassemia and Hemophilia Clinic Center (Sarvar) affiliated with Mashhad University of Medical Sciences, Mashhad, Iran, from 2012 to 2013. After the approval of the research protocol by the local ethic committee, laboratory tests, including CBC and serum ferritin, were carried out, and echocardiography and heart and liver MRI-T2* were performed. All statistical analysis was done through SPSS software (version 11.5), using independent sample t test and Pearson's correlation coefficient test. A P value ≤0.05 was considered to be significant. 88 patients with the mean (±SD) age of 21.2 (±5.6) years, (range 11-37 years) were observed. Iron load was assessed using MRI-T2* with the following results: Out of 88 patients, 48.9 % had mild to severe cardiac siderosis, and 75.2 % had mild to severe liver siderosis. We demonstrated a correlation between liver MRI-T2* and serum ferritin, and heart MRI-T2* and ejection fraction. However, no correlation between liver and heart MRI-T2* was observed. Heart and liver siderosis is a common and serious problem in thalassemia major patients, and MRI-T2* as a sensitive and non-invasive technique can be used for early/timely detection of siderosis and good therapeutic monitoring in these patients.

Prevalence of Pulmonary Hypertension in Patients with Thalassemia Intermedia in 2009: a single center's experience.

BACKGROUND: There are various clinical symptoms of thalassemia intermedia, and they lie roughly between those of major and minor forms of the disease. Patients with thalassemia intermedia occasionally require blood transfusions. This renders them susceptible to pulmonary arterial hypertension (PAH) syndrome, which is one of the most significant complications in patients with thalassemia intermedia. PAH is more common in in thalassemia intermedia than in thalassemia major, and it may cause cardiac complications in patients who are older than 30. The objective of this study was to estimate the prevalence of PAH in thalassemia intermedia patients so that they can be referred expeditiously for treatment, thereby preventing the complications that occur later. METHODS: This cross sectional study was conducted under the supervision of hematology department of Mashhad Medical University. Forty-one patients with thalassemia intermedia were examined at the Sarvar Thalassemia and Hemophilia Clinic of Mashhad. Electrocardiography, chest radiography, and echocardiography tests were performed for all of the patients by the same pediatric cardiologist. The data were processed by SPSS software, version 11.5, and the results were analyzed using chi-squared, Student's t, and Mann-Whitney tests. RESULTS: The mean age of the patients was 21.93±8.34. They had been under pediatric heart specialists' constant examination and treatment since their childhood when they were diagnosed with TI, and continue to receive regular follow-up care. The prevalence of pulmonary hypertension was 24% in our study population. In patients with thalassemia intermedia, the left ventricular (LV) mass indices were about 3-5 times higher than would be expected in a normal population. Patients with higher LV mass indices have a greater risk of developing pulmonary hypertension, and those with serum ferritin levels below 1000 ng/ml are less susceptible to diastolic dysfunction. CONCLUSION: Pulmonary hypertension is common in patients with thalassemia intermedia. Irregular chelation therapy or absence of this treatment might lead to diastolic dysfunction, and serum ferritin levels below 1000 ng/ml could be an important factor in preventing the development of diastolic dysfunction or slowing down its progression.

Childhood Facial Osteo Sarcoma: a Case Report.

Osteosarcoma (OS) is the eighth common cancer of childhood and its incidence is 4 cases in one million in children younger than 14. Facial OS incidence is estimated between 8 and 10% of OS cases. The main etiology of OS is unknown, but various predisposing factors are proposed such as radiation, radiotherapy, some benign bone diseases like Paget's disease or fibrous dysplasia. There is a 5-year survival rate of 68% and it decreases with the increase of age. Positive history of radiotherapy is the main predisposing factor for childhood OS. There is some evidence about the X-ray induced mutation in genomic DNA that leads to osteosarcoma. In the present paper we present a 19-month old girl with a mass located in the inferior margin of the left cheek and orbit. Our case is unique with regard to her young age and sex. Moreover, the tumor was located in an uncommon site and her disease was progressive and resistant.

Correlation between blood lead concentration and iron deficiency in Iranian children.

BACKGROUND: Iron deficiency anaemia is the most common nutritional anaemia among children. Lead toxicity is a serious health threat, especially in developing countries due to environmental pollution. It was thus aimed to investigate correlation between blood lead concentration and iron deficiency in children of Mashhad, Iran. MATERIALS AND METHODS: This cross sectional study was performed on children between 1 year and 10 years, in Imam Reza teaching hospital of Mashhad, Iran, in 2010. Indeed during complete blood count (CBC), we measured iron and total iron binding capacity (TIBC) by colorimetric methods, ferritin by radioimmune assay and blood lead concentration by atomic absorption method. Results were analysed by Statistical Package for Social Sciences (SPSS) (version 11.5), using statistical tests including independent sample t-test, Mann-Whitney U test, Spearman's test and analysis of variance (ANOVA) and Pearson's or Spearman's correlation coefficient. P value ≤ 0.05 was considered as a significant level. RESULTS: We studied 223 cases including 98 control children and 125 patients. All children had lead intoxication. Mean (±SD) blood lead concentration in the control group was 57.1 ± 25.3 (ranged 20-212) µg/dl and in the patient group was 57 ± 20.4 (ranged 10.9-159) µg/dl with no significant difference (P value = 0.713). We also did not find any correlation between blood lead concentration and haemoglobin, ferritin, iron, TIBC, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), white blood cells (WBC) and platelets. CONCLUSION: Based on these results, no correlation was found between blood lead concentration and iron deficiency in the children. Because all children had lead intoxication, further studies in highly polluted and a comparison with a low polluted area are necessary to make a general conclusion.

Pediatric clear cell sarcoma of the kidney with atriocaval thrombus.

Clear cell sarcoma of the kidney (CCSK) is an uncommon neoplasm that accounts for almost 3 % of pediatric renal tumors. Cavoatrial tumor thrombosis is very rare and because of poor response to chemotherapy, invasive surgical interventions such as open heart surgery may be indicated. A 6-year-old girl with CCSK of right kidney was treated with neoadjuvant chemotherapy. According to poor chemosensitivity, surgical intervention was planned. Right atriotomy was done, but intra-atrial part of tumor was very firm and unsuctionable; so the procedure was completed by laparotomy and en bloc resection of tumoral kidney and its cavoatrial extension through a limited venotomy on inferior vena cava. Although radical resection of CCSK with intracaval involvement should be considered as a multidisciplinary approach and intensive care and supports should be provided, atriocaval tumor in growth in CCSK is firm, non friable and non-adherent, and tumor en bloc resection may be possible through a limited venotomy via primary abdominal approach.

Risk factors associated with life-threatening infections in children with febrile neutropenia: a data mining approach.

PURPOSE: To determine risk factors (RFs) and their relationship with life-threatening infection (LTI) in children with febrile neutropenia (FN). METHOD: In this cross-sectional study, from December 2008 to November 2009, all children with FN admitted to Dr Sheikh Pediatric Hospital were enrolled. For each patient, demographic, clinical, and laboratory data were recorded and they were followed up for occurrence of LTI. RESULTS: One hundred and twenty episodes of FN in 68 patients were analyzed. The most common underlying disease was acute lymphoblastic leukemia (53.3%), 9 (7.5%) died from an infection and 35 patients (29.1%) had a LTI. Five variables were identified as RFs for LTI, that is, body temperature ≥39°C (P=0.000), presence of mucositis (P=0.000), abnormal chest x-ray (P=0.001), platelet count <20,000/mm (P=0.000), and absolute neutrophil count <100/mm (P=0.001). Risk of LTI was increasing according to number of RFs presented at the beginning of admission (from 2.8% in patients without RF to 100% in patients with 5 RF). Data mining analysis showed relationship between RFs with platelet count as the most important variable in the high-risk group for LTI. CONCLUSIONS: Evaluation of important RFs and judging the severity of patients' condition by studying the importance and relationship between RF at the time of admission can be a useful method for screening LTI in children with FN.