Late side effects of cancer treatment in childhood cancer survivors.

INTRODUCTION: Childhood cancers are usually treated with chemotherapy and radiation. Therefore, understanding the late side effects of such treatments is important to improve the quality of life in childhood cancer survivors. The present study aimed to investigate the late complications of treatments in childhood cancer survivors. METHODS: This study is a retrospective descriptive study. A total number of 93 cases were enrolled in this study. These cases had a history of childhood cancer documented in their medical records at the Shafa Hospital, Ahvaz, Iran. The age range was 5.9-21.3 years and included 62 males and 31 female patients. RESULTS: Many of the patients at this hospital with childhood cancer had experienced chemotherapy side effects as well as late effects of cancer therapy. Hypothyroidism is a late complication of therapy in thoracic cancers and head/neck tumors with relative frequencies of 23.1% and 12.5%, respectively. Scoliosis was observed in the patients undergoing the ABVD + COPP and 8/1 regimens with relative frequencies of 4% and 50%, respectively. Lower growth percentiles were also late side effects of cancer therapy. The highest relative frequency of growth retardation was observed in the <5 age group (46.7%). Restrictive lung changes had an overall relative frequency of 6.5% in male patients with all types of tumors. Sensorineural hearing loss was observed in patients with leukemia and Hodgkin lymphoma with relative frequencies of 8.7% and 24.0, respectively. CONCLUSION: The occurrence of most side effects could be decreased through early diagnosis, dose adjustment of some drugs, and preventative measures.

Long non-coding RNA signatures and related signaling pathway in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a malignancy caused by clonal proliferation of T-cell pre-cursors arising from the thymus. Although the optimized chemotherapy regimen could improve the outcome of such patients, some challenges such as higher risk for induction failure, early relapse and isolated central nervous system (CNS) relapse occurring in T-ALL patients are of great significance, leading to increased mortality rates. Long non-coding RNA (lncRNA) is a key component involved in cell signaling through a variety of mechanisms in regulating gene expression. Oncogenes and tumor suppressors are no exception and their expression can be affected by lncRNAs. In addition, accumulating researches in samples from T-ALL patients as well as pre-clinical studies in mice suggest that the expression profile of lncRNAs in T-ALL could be aberrant, resulting in deregulation of target genes and downstream signaling pathways. In addition, accumulating researches in samples from T-ALL patients as well as pre-clinical studies in mice suggest that the expression profile of lncRNAs in T-ALL could be aberrant, resulting in deregulation of target genes and downstream signaling pathways. These lncRNAs may be determinants of proliferation, apoptosis, and drug resistance observed in T-ALL. Thus, lncRNAs can be a good tool to develop novel strategies against cancer cells in the treatment of relapsed and refractory T-ALL. They can also act as promoting biomarkers in assessing T-ALL and differentiating between patients with poor prognosis and good prognosis.

Clinical and genetic characteristics of hemoglobin H disease in Iran.

Hemoglobin H (Hb H) disease is a subtype of α-thalassemia caused by deletional and/or non-deletional mutations in three alpha-globin genes in which the various genotypes determine the disease severity. This study was aimed to investigate the frequency of alpha gene mutations and genotypes and their correlation with hematological and clinical characteristics in Iran. Among 202 patients diagnosed with Hb H disease through a national study in Iran according to standard methods, we had access to the hematologic and clinical findings and genetic data of 101 patients in whom genetic study was performed. Genomic DNA from peripheral blood was extracted and analyzed for identification of α-globin gene mutations using Multiplex Gap Polymerase Chain Reaction, Reverse Hybridization Assay, and finally Direct DNA Sequencing method. Twenty-one different mutations and thirty genotypes were detected in 101 patients with Hb H disease. In total, 39 patients (38.6%) were deletional and 62 patients (61.4%) were non-deletional type of the disease. The --MED mutation was highly prevalent in almost half of the patients (56.4%). Among various genotypes, -MED/-a3.7 (29.7%) and -α20.5/-α5NT (6.9%) were the most prevalent genotypes found in the studied group. Patients with non-deletional type presented with more severe hematological and clinical findings. Hb H percentage and serum ferritin levels were significantly higher in non-deletional patients in comparison to the deletional group (p < 0.05). 12 (11.9%) and 40 (39.6%) out of 101 patients were on regular and occasional transfusions, respectively. 83% of those with regular transfusion belonged to the non-deletional group. Among transfusion-dependent patients, -MED/αCSα and α20.5/-α5NT were the most common genotypes. In this study, two patients with -α20.5/αCSα and -MED/α-5NT genotypes experienced thrombotic events. This study indicated that although non-deletional genotypes of Hb H disease were responsible for more clinical severity of the disease, due to the presence of severe phenotypes even in deletional types, no definite correlation was found between genotype and phenotype.

Radiographic Features of the Maxillofacial Anomalies in Beta-Thalassemia Major: With New View.

BACKGROUND: Beta- thalassemia major causes the basic skeletal changes due to ineffective erythropoiesis in suffering patients. The aim of the study was to determine the frequency of maxillo-facial anomalies and the hemoglobin and ferritin levels in patients with beta-thalassemia major compared to the healthy control group. METHODS: The present study was performed on 72 beta- thalassemia major patients and 70 healthy control group in Ahvaz, Southwest Iran, from Jan 2014 to Mar 2015. Panoramic radiographs were taken using a standard procedure. The frequency of abnormalities including enlargement of bone marrow spaces, small maxillary sinuses, thickness of inferior mandibular cortex, prominent antegonial notch, absence of inferior alveolar canal and thin lamina dura, were determined by two Oral and Maxillofacial Radiologist. We also paid to identification of the relationship between abnormalities frequency and hemoglobin and ferritin levels during previous 6 months in thalassemia patients. RESULTS: The mean age of case and control groups was 18.6±7.25 and 17 ± 6. 55 yr, respectively. The frequency of abnormalities in the case and control groups was as follows, enlargement of bone marrow spaces [69 (95.8%) vs 3 (4.3%)], small maxillary sinuses [45 (62.5%) vs 1(1.4%)], reduced thickness of inferior mandibular cortex [21(29.2%) vs 6 (8.6%)], prominent antegonial notch [10 (13.9%) vs 2 (2.9%)], absence of inferior alveolar canal [68(94.4%) vs 41(58.6%)] and thin lamina dura [40 (55.6%) vs 5 (7.1%)]. CONCLUSION: The all above mentioned abnormalities in patients with beta-thalassemia major was higher than the control group. Moreover, the frequency of maxillo-facial abnormalities decreased by increasing hemoglobin and decreasing ferritin.

Occult Hepatitis B Virus Infection among ß-Thalassemia Major Patients in Ahvaz City, Iran.

Occult Hepatitis B Infection (OBI) is a critical risk factor for triggering post-transfusion hepatitis (PTH), cirrhosis, hepatocellular carcinoma, and hepatitis B virus (HBV) reactivation, which ß-thalassemia major (BTM) patients are at risk of it due to multiple blood transfusions. This study was aimed at determining the prevalence of OBI among BTM patients from Khuzestan Province, Iran. In this cross-sectional study, 90 thalassemia patients, who have received blood 36 to 552 times, participated referred to the Shafa hospital of Ahvaz city from January 2018 to April 2019. ELISA for determining serological markers (HBsAg, anti-HBc, anti-HBs, and anti-HCV) and real-time PCR for detecting HBV-DNA were performed; Nested PCR was conducted for DNA sequencing and determining the genotype of OBI case. Phylogenetic and statistical analyses were done by R package. Of 90 subjects enrolled in this study; 95.5% (86/90) were HBsAg negative, and the frequency of OBI among them was 1.16% (1/86). The anti-HBs, anti-HBc, and anti-HCV were detected in 80.00%, 7.78%, and 12.2% of patients, respectively. HBV-DNA was assessed at four HBsAg-positive subjects as well, and all of them were negative. The phylogenetic analysis showed that the detected HBV DNA in the OBI case belongs to the genotype D. This research, for the first time, demonstrated that OBI is present among ß-thalassemia patients in Iran. Also, further studies are necessary to determine the actual prevalence of OBI among BTM patients in Iran to decisions concerning OBI screening, especially in transfusion centers.

Polymorphisms in genes involved in breast cancer among Iranian patients.

This review gives a summary of the important genetic polymorphisms in breast cancer with a focus on people in Iran. Several single nucleotide polymorphisms were considered as breast cancer susceptibility polymorphisms within genes (STK15, ERRs, ESR1, p53, SEP15, AURKA, SHBG, SRC, FAS, VEGF, XRCC1, GST, NFκB1, XPC, XRCC3, sirtuin-3, NKG2D). Cytosine-adenine repeat (IGF-I), rs3877899, G-2548A, GGC (eRF3a/GSPT1), IVS2nt-124A/G have shown an increased risk of breast cancers and a decreased risk has been observed in 4G/5G (PAI-1), rs6505162, tri-nucleotide (GCG TGFBR1). We observed that the signaling pathways and antioxidant related genes are the main molecular processes associated with breast cancer progression. Further studies on types of polymorphisms in breast cancer could validate the prognostic value of biomarkers.

Identification of Three Novel Mutations in the FANCA, FANCC, and ITGA2B Genes by Whole Exome Sequencing.

BACKGROUND: Various blood diseases are caused by mutations in the FANCA, FANCC, and ITGA2B genes. Exome sequencing is a suitable method for identifying single-gene disease and genetic heterogeneity complaints. METHODS: Among families who were referred to Narges Genetic and PND Laboratory in 2015-2017, five families with a history of blood diseases were analyzed using the whole exome sequencing (WES) method. RESULTS: We detected two novel mutations (c.190-2A>G and c.2840C>G) in the FANCA gene, c. 1429dupA mutation in the FANCC gene, and c.1392A>G mutation in the ITGA2B gene. The prediction of variant pathogenicity has been done using bioinformatics tools such as Mutation taster PhD-SNP and polyphen2 and were confirmed by Sanger sequencing. CONCLUSIONS: WES could be as a precise tool for identifying the pathologic variants in affected patient and heterozygous carriers among families. This highly successful technique will remain at the forefront of platelet and blood genomic research.

Prevalence of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae Causing Bloodstream Infections in Cancer Patients from Southwest of Iran.

INTRODUCTION: This study aimed to evaluate the frequency rate of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) causing bloodstream infections (BSIs) in cancer patients referred to one of the major referral hospitals in Ahvaz city, southwest Iran. MATERIALS AND METHODS: In this study, 1700 blood cultures were collected from 610 cancer patients suspected to have BSI from October 2016 to August 2017 referred to the Shafa cancer hospital, Ahvaz, southwest of Iran. The blood culture bottles were incubated aerobically at 35-37ºC for 24 hours and then sub-cultured on routine microbiology culture media. The bacterial colonies were identified using standard tests. The antibiotic susceptibility testing was achieved by the disc-diffusion method. The phenotypic detection of ESBLs was carried out by the combination disc-diffusion test (CDDT). Finally, the polymerase chain reaction (PCR) was performed to investigate the presence of bla TEM, bla CTX, bla SHV, and bla PER genes. RESULTS: The prevalence of BSI in cancer patients was 16.4% (100/610). Gram-negative rods with rate of 74% (74/100) were the most prevalent bacteria. The frequency of Enterobacteriaceae family was 21% including Escherichia coli (n: 8), Klebsiella pneumoniae (n: 6), Enterobacter spp. (n: 5), Citrobacter freundii (n: 1), and Serratia marcescens (n: 1). All isolates were multidrug-resistant (resistance to three or more antibiotics). The results of CDDT showed that 42.8% (9/21) of Enterobacteriaceae isolates had a positive ESBL test of which 100% (9/9) indicated positive band for at least one of the ESBL genes by PCR method. The bla CTX-M and bla TEM genes were detected in 38% (8/21) and 23.8% (5/21) of isolates, respectively, while the bla SHV and bla PER were not detected in any isolates. CONCLUSION: Based on the results, surveillance, and antibiotic stewardship programs should be implemented for cancer patients to prevent the spread of more ESBL-PE that have limited therapeutically choices.

Bleeding symptoms in patients diagnosed as type 3 von Willebrand disease: Results from 3WINTERS-IPS, an international and collaborative cross-sectional study.

BACKGROUND: Type 3 von Willebrand's disease (VWD) patients present markedly reduced levels of von Willebrand factor and factor VIII. Because of its rarity, the bleeding phenotype of type 3 VWD is poorly described, as compared to type 1 VWD. AIMS: To evaluate the frequency and the severity of bleeding symptoms across age and sex groups in type 3 patients and to compare these with those observed in type 1 VWD patients to investigate any possible clustering of bleeding symptoms within type 3 patients. METHODS: We compared the bleeding phenotype and computed the bleeding score (BS) using the MCMDM-1VWD bleeding questionnaire in patients enrolled in the 3WINTERS-IPS and MCMDM-1VWD studies. RESULTS: In 223 unrelated type 3 VWD patients, both the BS and the number of clinically relevant bleeding symptoms were increased in type 3 as compared to type 1 VWD patients (15 versus 6 and 5 versus 3). Intracranial bleeding, oral cavity, hemarthroses, and deep hematomas were at least five-fold over-represented in type 3 VWD. A more severe bleeding phenotype was evident in patients having von Willebrand factor antigen levels < 20 IU/dL at diagnosis in the two merged cohorts. In type 3 patients, there was an apparent clustering of hemarthrosis with gastrointestinal bleeding and epistaxis, whereas bleeding after surgery or tooth extraction clusters with oral bleeding and menorrhagia. CONCLUSIONS: In the largest cohort of type 3 VWD patients, we were able to describe a distinct clinical phenotype that is associated with the presence of a more severe hemostatic defect.

Association between HLA-DRB1*01 and HLA-DRB1*15 with alloimmunisation in transfusion-dependent patients with thalassaemia.

BACKGROUND: Alloantibody production is one of the most challenging complications in transfusion-dependent thalassaemia patients. Haemolytic anaemia, an increase in blood consumption, difficulty in haematopoietic stem cell transplantation and reduced quality of life are consequences of alloimmunisation. The most predisposed antigens (Ags) for alloantibody development are Rh and Kell blood group Ags. OBJECTIVE: The aim of the present study is to evaluate any correlation between HLA-DRB1 alleles and Rh and Kell alloantibodies. MATERIALS AND METHODS: Fifty-two non-responders (control) and 54 responders (case) were enrolled in this study. Alloantibody detection was performed using the tube method. Genotyping of HLA-DRB1*01 and HLA-DRB1*15 was conducted by single-specific primer-polymerase chain reaction. RESULTS: In the responder group, 77.8% were hyper-responders (more than one alloantibody), and only 22.2% were mono-responders. Most detected alloantibodies were Anti-K (94.4%), followed by Anti-E (64.8%), Anti-C (29.6%) and Anti-D (25.9%). There was a significant difference in HLA-DRB1*15 between responder and non-responder groups, 73.7% vs 26.3%, respectively. (P = .029, OR = 3.290; 95%CI). Our results showed that HLA-DRB1*15 was more frequent in hyper-responders than mono-responders (92.9% vs 7.1%) (P = .007). The greatest HLA-DRB1*15 was seen in Anti-K (P = .014, odds ratio [OR = 3.784]; 95% confidence interval [CI]) and Anti-E (P = .011, OR = 3.609; 95%CI) alloantibodies. There is no association between HLA-DRB1*01 and alloimmunisation. CONCLUSION: Our findings showed that there is a significant correlation between HLA-DRB1*15 and Anti-K and Anti-E alloantibodies. These findings can be useful in detecting susceptible thalassaemic patients and improving transfusion management.

A review of molecular mechanisms involved in anticancer and antiangiogenic effects of natural polyphenolic compounds.

The aim of this review is to obtain a further understanding of the reported inhibitory effects of polyphenols on cancer cell proliferation and angiogenesis process and the probable mechanisms by which these natural compounds inhibit proliferation of cancer cells and angiogenesis. Growing evidence indicates that polyphenols are beneficial against human fatal diseases such as cancer. Because angiogenesis has a critical role in tumor growth and metastasis, therefore, we decided to review the potential anticancer and antiangiogenic activities and molecular mechanisms of different groups of known polyphenolic compounds. As knowledge and data on anticancer and antiangiogenic effects of plant-derived phenols are on the rise, it may be possible in the near future to develop and discover specific polyphenolic compounds with potent anticancer and antiangiogenic activity for treatment of malignant tumors.

The Effect of a Training Program Based on the PRECEDE-PROCEED Model on Lifestyle of Adolescents with Beta-Thalassemia: A Randomized Controlled Clinical Trial.

Background: Lifestyle is a key issue in the concept of health promotion. Lifestyle includes all activities that encourage optimum physical, spiritual, and mental functions. The aim of this study was to determine the effect of a training program based on PRECEDE-PROCEED Model on lifestyle of adolescents with beta thalassemia. Materials and Methods: In this clinical trial study, 64 adolescents (age 16-20) who referred to the Thalassemia Center of Ahvaz (2015) were selected and randomly divided into two groups: experimental and control group. The components of the PRECEDE-PROCEED Model were used for planning, implementation and evaluation of the program. Changes in predisposing, reinforcing, enabling factors and lifestyle were immediately and a month after the intervention were assessed by a questionnaire based on PRECEDE-PROCEED Model and the Health-Promoting Lifestyle Profile. Results: The intervention had significantly positive effect on predisposing, enabling and reinforcing factors immediately and a month after the intervention (P < 0.05). Repeated measures analysis of variance showed a significant positive increase in the six dimensions of lifestyle score in the experimental group from baseline to one-month follow-up (P < 0.05). Conclusion: This study showed that the theory-based training program in adolescents suffered from beta thalassemia disease could improve the adolescent's awareness and attitude of healthy lifestyle.

The Frequency, Antifungal Susceptibility and Enzymatic Profiles of Candida Species Isolated from Neutropenic Patients.

BACKGROUND: Neutropenia, as a predisposing factor for invasive candidiasis, is defined as a reduction in neutrophil count to less than 1500/mm3. It is a common condition in patients with hematological malignancy and cytostatic chemotherapy. Extensive chemotherapy and prophylaxis with antifungals have increased the resistance of Candida isolates to antifungal drugs. Although, Candida albicans is the most common causative agent among neutropenic patients, there is an increasing rate of non-albicans species. Extracellular enzymes activity pattern and antifungal agent sensitivity profiles are two important factors for spreading resistant strains. OBJECTIVES: The aim of the present study was to identify the Candida strains isolated from hospitalized neutropenic patients. The patterns of antifungal susceptibility of the causative agents to antifungals and the extracellular enzymes activity of the isolates were also evaluated. PATIENTS AND METHODS: In the present study, 243 urine and 243 oral swab samples were collected from neutropenic patients and inoculated on CHROMagar Candida. In addition, 100 blood samples were also inoculated in biphasic Brain Heart Infusion medium. Several yeast isolates were isolated from samples and identified by classical and molecular techniques. The profiles of extracellular enzymes and the susceptibility of recovered agents to amphotericin B, fluconazole and caspofungin were also evaluated. RESULTS: A total of 110 yeast strains isolated from urine and oral cavities were identified as C. albicans (51.8%), C. krusei (25.5%), C. glabrata (6.4%) and other yeasts (16.3%). No yeast species was isolated from blood samples. Our result showed that in 90% of the isolates, the range of secretion of extracellular enzymes was medium (2+) and high (3+), however only a few isolates were negative for this characteristic. All isolates were sensitive to caspofungin and fluconazole, whereas 54.7% of isolates were resistant to amphotericin B. CONCLUSIONS: We found a marked increase in the incidence of non-albicans species (48.2%) among neutropenic patients. Only a few strains failed to produce extracellular enzymes. Finally, in addition to fluconazole, caspofungin can be considered as the first line treatment against Candida species among neutropenic patients.

Adrenal extramedullary hematopoiesis associated with ß-thalassemia major.

The presence of apparently normal hematopoietic tissue outside of bone marrow cavity is defined as extramedullary hematopoiesis (EMH). EMH is a rare complication in thalassemia major (TM) and adrenal gland as well. This report describes a case of adrenal EMH in a 26-year-old man with ß-TM. He has been transfused with regular blood transfusion since 9 months. During the routine physical examination he was incidentally found to have a hypoechoic mass at his abdominal ultrasonography. Abdominal computed tomography scan revealed a right well-defined suprarenal mass 7.7×7.3×5.8 cm in size. The diagnosis of EMH was confirmed with ultrasonographic-guided fine needle biopsy. Treatment options which include intensified regular blood transfusion and hydroxyurea have been started.

Better differential diagnosis of iron deficiencyanemia from beta-thalassemia trait.

OBJECTIVE: Iron deficiency anemia (IDA) and ß- Thalassemia Trait (ß-TT) are the most common forms of microcytic anemia. This study was conducted to compare the validity of these discrimination indices in differentiating ß- Thalassemia Trait (ß-TT) from IDA by calculating their sensitivity, specificity and Youden's index. METHODS: Totally 323 subjects (173 children and 150 adult) with microcytic anemia were involved in this study. We calculated 10 discrimination indices in all patients with IDA and ß-TT. We divided the patients into two different groups as younger and older than 10 years. RESULTS: None of indices showed sensitivity and specificity of 100% in the patients older than 11 years, but only Shine and Lal Index showed sensitivity close to 90% and specificity of 100% in the patients younger than 10 years. The most accurate discriminative index for patients younger than 10 years was Shine & Lal and in case of patients older than 11 years it was RDWI. Youden's index for Shine & Lal & RBC Count and for RDWI & RBC Count indices has most diagnostic value for younger and older than 10 years, respectively. CONCLUSION: None of the indices was completely sensitive and specific in differentiation between ß-TT and IDA. MCHD mean and median were very close to normal values for both IDA and ß-TT patients, but in case of MHDL we have found mean and median were significantly higher than normal values in ß-TT and lower than those in IDA patients. In our study, Youden's index of RBC and S & L were the highest and the most reliable discrimination indices in differentiating ß-TT from IDA in the patients younger than 10 years and for patients older than 11 years, the most reliable discrimination indices were RBC and RDWI.

Existence of cord compression in extramedullary hematopoiesis due to beta thalassemia intermedia.

Extramedullary hematopoiesis (EMH) is a rare disorder, characterized by the appearance of hematopoietic elements outside of the bone marrow, which occurs in patients with chronic myeloproliferative disorders or congenital hemolytic anemias. We report a case with thalassemia intermedia, EMH in spinal cord and a paravertebral mass. We report the case of a 20 year old female who initially presented with back pain and leg weakness was found to have paravertebral mass in the spinal cord.

Iron-deficiency anemia among children in southwest Iran.

BACKGROUND: Iron deficiency is a major health problem worldwide and especially in developing countries. Iron-deficiency anemia has adverse effects on the development of children. OBJECTIVE: The purpose of this study was to determine the prevalence of iron-deficiency anemia in children under 5 years of age in southwest Iran. The study also sought to investigate the association between socioeconomic, demographic, cultural, and nutritional factors and iron-deficiency anemia in the selected area. METHODS: A randomized, cross-sectional study was performed of children 6 to 59 months of age living in urban and rural areas of Ahwaz District in Khuzestan Province. At eight randomly selected health centers, the children's height (or length) and weight were measured, and information on length and weight at birth was obtained from growth charts. Blood samples were taken from 337 randomly selected children. RESULTS: The results showed that 43.9% of the children had anemia and 29.1% iron-deficiency anemia. The highest prevalence of iron-deficiency anemia was in the 12- to 24-month age group. In the urban areas, infants 6 to 11 months of age had the highest prevalence of iron-deficiency anemia. CONCLUSIONS: The high prevalence of iron-deficiency anemia among children in southwest Iran indicates a major nutrition and health problem.