Therapeutic approaches in patients with β-thalassemia

Beta-thalassemia (β-thal) is a congenital hemoglobinopathy explained by a decreased level (β+) or absence (βο) of β-globin gene expression. Microcytic hypochromic anemia and various clinical symptoms comprising severe anemia to clinically nonsymptomatic features. Treatment with an ordered blood transfusion and iron chelator agents can decrease transfusion iron overload that causes normal maturation. These patients also are at high risk for secondary iron overload because of erythropheron (GF15–TWSG1) release from erythroblasts resulting in erythroid hyperplasia. Based on the previous studies, chemicals such as hydroxyurea and 5-azacytidine are useful in treating β-hemoglobinopathy, including β-thal and sickle cell disease (SCD). Regarding both side effects and lifelong treatment of these chemical components, researchers have recently regarded gene-based treatments. These techniques, such as micro RNA gene silencing, viral-mediated gene editing, and clustered regulatory interspaced short palindromic repeats (CRISPR)-CAS9 systems, are the most commonly used gene therapy methods. Nowadays, ɣ-globin (fetal globin) gene reactivation is one of the most popular treatments for β-thal. Researches showed that these gene modification methods for γ-globin gene reactivation are also useful in increasing hemoglobin F (HbF) and helping patients with β-thal. In this review study, new therapeutic approaches to manage this disorder are regarded.

Is type 1 diabetes mellitus associated with ABO & Rh blood groups? A cross-sectional study

Background: This study was conducted to determine whether type 1 diabetes mellitus (T1DM) is associated with ABO & Rhesus (Rh) blood groups. Materials and Methods: This analytical cross sectional study was carried out on 77 patients suffering from T1DM and 96 healthy children less than 18 years old referring to Yazd Diabetes Research Center from April 2018 to May 2019. The ABO blood group and Rh factor in both groups were determined. Fasting blood sugar (FBS) and hemoglobin A1C (HbA1c) were measured at baseline, 12 weeks, and 24 weeks in these patients, and the mean of FBS and HbA1C in three-time assessments were considered as the FBS and HbA1C variables. The statistical analysis was performed by SPSS software version 22. Results: About 46.8% in T1DM and 36.5% in the control groups were male. There was a significant difference between groups regarding blood groups (p-value: 0.042). Although the frequency of B+ was 33.8% and 19.8% in the T1DM and controls, respectively, AB+ and O+ were more prevalent in the controls. The mean of FBS was significantly different between groups (p-value: 0.023). Conclusions: The findings revealed that patients with blood group B are more likely to develop T1DM whereas those with blood group O showed a lower tendency towards diabetes.

Therapy-related myeloid leukemia following Pleuropulmonary blastoma: A case report

The development of secondary malignancy (SM) is the most worrisome long-term complication of childhood cancer. Acute myeloid leukemia is the most prevalent neoplasm that occurs after treatment with alkylating agents and topoisomerase II inhibitors. Pleuropulmonary blastoma (PPB) is a rare lung neoplasm in children. Type II and type III of this cancer are markedly aggressive and have a recurrent nature. Chemotherapy, radiation therapy, and hematopoietic stem cell transplant (HSCT) are treatment modalities that make these patients prone to secondary malignancy. Here was presented and discussed a case of myeloid leukemia 3.5 years after treatment of Pleuropulmonary blastoma in a 5.5-year-old boy who was a candidate for high dose chemotherapy and autologous stem cells transplant (auto-SCT) because of frequent recurrence and lack of response to chemotherapy and radiation therapy. It seems this is the first reported case of therapy-related myeloid leukemia (t-AML) after PPB in children. Awareness of the creation of this complication following administration of cytotoxic therapies in the treatment of solid tumors will increase physician attention in the selection of treatment modality as well as the counseling of patients at the time of diagnosis.

Dwindled serum IgG levels of Rubella, Diphtheria toxin, Hepatitis B virus and Tetanus Toxoid after chemotherapy; a report from Iranian children with malignancy

Backgrounds: Epigenetic regulation such as DNA methylation plays a major role in chromatin organization Background: Chemotherapy suppresses immunoglobulin production as a result of cell toxicity. Decreased immunoglobulin levels can result in the onset of opportunistic infections. The aim of the current study is to compare the immunoglobulin G (IgG) levels of the selected vaccine-preventable disease (VPD) before and six months after chemotherapy in a group of Iranian children with malignancies. Materials and Methods: In this interventional study, serum levels of Rubella, Diphtheria toxin, Hepatitis B virus (HBV), Tetanus Toxoid, Mumps, and Measles IgG were measured in 30 children with malignancy and previously vaccinated for these diseases. Six months after chemotherapy, serum IgG levels were reassessed and compared with their corresponding pre-chemotherapy levels. Results: In this study, 17 (56.7%) male and 13 (43.3%) female were included. The mean age was 7.69±3.09 years. After chemotherapy, Rubella IgG levels dropped from 73.88±85.11 to 56.59±72.84 IU/mL (P<0.05; r= 0.956; 33.4% become serum negative (SN)). Diphtheria toxin IgG was diminished from 0.683±0.454 to 0.174±0.248 IU/mL (P<0.05; r=0.601; 26.7% SN). Anti-HBV IgG showed a reduction from 46.26±101.56 to 25.56±80.49 IU/mL (p<0.05; r= 0.524; 60% SN) and Anti-Tetanus Toxoid IgG fell down from 1.031±0.582 to 0.321±0.408 IU/mL (p<0.05; r= 0.365; 33.4% SN). Anti-Measles and Anti-Mumps IgGs showed no significant change (p>0.05). Conclusion: Pediatric chemotherapy was associated with dropped serum IgG levels of most VPDs. A good correlation was also observed between serum levels of IgG before and six months after chemotherapy. Revaccination of children with malignancies may be necessary upon declined serum IgG titers.

Evaluation of relationship between biochemical parameters and osteoporosis in patients with β-thalassemia major

Background: Osteoporosis is one of the late complications of β-Thalassemia major. The pathogenesis of osteoporosis depends on different factors. Ineffectiveness of hematopoiesis is the major factor, and the other factors are defected by hormonal functions or biochemical parameters. Osteoclasts hyperactivity in thalassemia increases the serum receptor activator of nuclear factor Kappa B ligand (RANKL), which plays a crucial role in bone development. This study aimed to evaluate the biochemical and hormonal parameters in patients with β-thalassemia major and their association with osteoporosis. Materials and Methods: In this case-control study, 52 patients with β-thalassemia major and 23 with thalassemia minor as controls were enrolled. The patients’ Bone Mineral Density (BMD) was measured using the Dual Energy X-ray absorptiometry (DEXA) method, and 6 mL peripheral blood of the patients and controls was obtained to detect hormonal and biochemical parameters. Data were analyzed using ANOVA, Spearman correlation coefficient, and T-test. Results: The mean of BMD in patients was 0.59±0.01 and 0.69±0.11 in femur and vertebrae, respectively. The biochemical parameters in the (patients/ controls) including calcium and alkaline phosphatase (ALK) were 9.1/ 10.2 mg/dL and 171.1/310 IU, respectively indicating a significant decrease (P< 0.05) compared to the controls. On the contrary, the mean levels of Ferritin and Zinc were 1914.18 µg/L and 113.92 mg/mL, respectively which were significantly increased (P= 0.015 and P=0.045, respectively). There was a negative correlation between the femurs BMD of patients with the RANKL level (r= - 0.8, p = 0.034) and the vertebrae BMD of patients with a Parathormone (PTH) level (r= - 0.8, P = 0.028). Conclusion: The study results indicated that the hyperactivity of RANKL and PTH in thalassemia patients might cause osteoporosis; therefore, detecting biomarkers mentioned above could be useful to diagnose osteoporosis.

Evaluating the blood toxicity of functionalized graphene-arginine with anticancer drug ginsenoside Rh2 in balb/c mouse model with breast cancer

Background: Gensenoside Rh2 is an anticancer drug with low toxicity and stability in the body. The aim of this study was to evaluate the blood toxicity of functionalized graphene-arginine with anticancer drug ginsenoside Rh2 in balb/c mouse model with breast cancer. Materials and Methods: Graphene-Arginine (G-Arg) and Graphene-Arginine-ginsenoside Rh2 (G-Arg-Rh2) were synthesized using microwave method. For evaluation of blood toxicity, 32 mice with breast tumors were randomly divided into 4 groups: control (3mg/kg 6 mg / kg PBS sterile), group 1 (6 mg / kg ginsenoside), group 2 (3 mg / kg G-Arg), and group 3 (3 mg / kg G-Arg-Rh2). Treatment was done intravenously once every three days for 32 days. Finally, blood factors were also examined by sampling from the heart. Results: Complete functionalization was proven by FTIR and Raman. Examination of blood factors showed that white blood cells had a very small increase. Anova test showed significant difference among four groups in term of WBC count (p=0.016). Pair sample T test showed that there was significant difference between control and group 1(p=0.036) and control and group 2 (p=0.036). There was no significant difference between control and group 3 (p=0.051). Other blood factors had no significant difference among examined groups (p>0.05). Conclusion: Based on results, after treatment with all designed nanostructures, only white blood cells had a very small increase and inflammatory reactions were statistically similar in all groups. This indicates the high efficiency of designed drug.

A comparative investigation of clients' attitudes toward breaking bad news to patients with cancer

Background: Truth disclosure is one of the major challenges for physicians with cancer patients. The attitude toward breaking news adopted by individuals depends on their cultural background. The present study was conducted at Ardabil University of Medical sciences, Ardabil, Iran, to investigate the attitudes of Turkish-speaking patients with cancer and their families to the disclosure of bad news. Materials and Methods: The present descriptive cross-sectional study used convenience sampling to select 62 patients, 76 family members of young and 58 children. The mean age of the patients was 37.29 years, and their majorities were 32-42 years old. The data were collected using the questionnaire proposed by Managheb et al., which included six dimensions, i.e., suitability of the person, suitability of the time, the place, factors affecting the delivery of bad news, amount of disclosed information, and acceptance. Results: Despite the insignificant differences in the total score of attitude between the groups (P=0.23), significant differences were found in terms of suitability of the time (P=0.017) and affecting factors (P=0.007) between children's families. Also, in parents of children, employment made truth acceptance better (p=0.04). The acuteness of the disease increased the total attitude score in all the participants (P=0.047). Significant relationships were also observed between age and accepting truth (P=0.045), male gender and place of disclosing the truth (P=0.004), male gender and amount of disclosed information (P=0.043), as well as owning a house and accepting truth (P=0.002). Moreover, education was negatively related to the person for truth disclosing (P=0.036) and factors affecting the truth disclosing (P=0.015). Conclusion: There are different circumstances and economic impacts in children's families on their tolerance. Given the difficulty of disclosing the truth to the employee and highly-educated individuals, it is recommended that health workers consider individual conditions in these circumstances.

The Role of Clinical Guidelines for the Management of Chemotherapy-Induced Nausea and Vomiting in Children with Cancer

Background: Nausea and vomiting are among the most important side-effects associated with chemotherapy in children with cancer, affecting the quality of their lives. Clinical guidelines for selecting antiemetics are effective in reducing acute chemotherapy-induced nausea and vomiting (CINV). Materials and Methods: The present quasi-experimental study compared the effectiveness of the Pediatric Oncology Group of Ontario (POGO) CINV guideline with that of conventional arbitrary therapies for CINV in 82 children aged 6 months to 16 years old. Out of 177 cycles of chemotherapy, in 101 cycles patients were treated according to POGO-CINV Guideline; in the other 76 cycles, patients were treated with arbitrary types and doses of antiemetics. Then, vomiting in the first 24 hours after chemotherapy in both groups was measured and compared. Results: In this study, 82 patients hospitalized in the Hematology Department of Dr. Sheikh Children’s Hospital were enrolled, of whom 48 patients (58.7%) were boys and 34 (41.3%) were girls. The mean age of patients was 6.24±4.47 years (6 months to 16 years). The results of the current study showed that using a protocol for the prevention of vomiting based on the patient’s age and the type of chemotherapy is superior to conventional management of CINV. Findings showed that the frequency of nausea and vomiting in the protocol group was significantly reduced in comparison with the control group (p˂0.005). Moreover, a reduction in the frequency of nausea and vomiting was quite significant in the sub-categories of the protocol group who had received high-risk or moderate-risk emetogenic drugs (p˂0.005). Conclusion: The results of the current study showed that using the POGO guideline, which takes into account the patient’s age and the type of chemotherapy, is more effective than arbitrary management of CINV, particularly in children.

Association of Body mass index and serum ferritin level in pediatrics with Beta-thalassemia major disease

Background: Beta-thalassemia major is a type of inherited blood disease that results in variable outcomes such as severe anemia due to haemoglobin chains. Recurrent and lifelong blood transfusions as a treatment in beta-thalassemia major disease lead to iron deposition in various organs and cause the failure of multiple organs. Failure of affected organs leads to Body mass index (BMI) abnormality. This study aimed to evaluate the association between BMI and serum ferritin level as a marker for iron overload. Materials and Methods: A cross-sectional study designed and conducted with total number of 740 paediatrics, with mean age about 14.2±8.7 years old and with beta-thalassemia major requiring recurrent blood transfusion. Patient information, including demographics, serum ferritin level and percentage of BMI, was recorded and analysed by SPSS 25.0 and the statistical significant level, considered as 0.05. Results: A total number of 740 paediatrics with beta-thalassemia major disease (mean age about 14.2±8.7 years) were included to study to examine the association between serum ferritin level and their BMI. The total mean serum level of ferritin calculated about 3326 ± 3859 Nanogram/mililitter (ng/ml). Totally, 447 (60.4%) case of them had BMI percentile less than 5%, 274 (37.02%), 16 (2.16%) and 3 (0.4%) had BMI percentile 5%-85%, 85%-95% and more than 95%. There was no relation between gender and serum ferritin levels. The relationship between age and BMI has been positive (P=0.002). Finally, it resulted that there was a negative relationship between the BMI percentile and mean serum ferritin levels in paediatrics with beta-thalassemia major (P=0.031). Conclusion: Frequent Blood transfusion is associated with elevated serum ferritin level in paediatrics with beta-thalassemia major disease and experiencing lower percentiles of BMI in these patients.

The Effect of the Transfusion Protocol on Transfusion Rates and Short-term Outcomes of Preterm Infants in a Tertiary Neonatal Intensive Care Unit

Background: The aim of this study was to compare the epochs before and after the revision of the transfusion guideline, and determine their effects on transfusion rates and short-term outcomes in preterm infants. Materials and Methods: This retrospective study was conducted to investigate the effect of the new transfusion guideline. Infants who were born <32 weeks of gestation and received red blood cell (RBC) transfusion in their first 6-weeks of life were divided into two epochs according to adopting the new transfusion guideline. The demographic and clinical data of the patients were compared between these two periods. Results: Fifty-six infants were included (Period 1, n=22; Period, n=34). The number of transfusions, total and cumulative volume of the transfusions were similar in the two periods. There was an inverse relationship between the gestational age and the number of transfusions in both periods (r=-0.575, p=0.005, and r=-0.494, p=0.003), and there was an inverse relationship between the birth weight and the number of transfusions in period 2 (r=-0.423, p=0.013). The ratio of total phlebotomy volume to estimated total blood volume was higher in period 2 (p=0.029). There was a direct relationship between the phlebotomy loss and volume of RBC transfused in period 2 (r=0.487, p=0.003). The incidence of morbidities was similar in the two periods. Conclusion: Changing only the transfusion protocol did not decrease the transfusion number. Although transfusion guidelines were adopted rigorously, it seems to be impossible to reduce RBC transfusion rates unless anemia prevention strategies were also in place.