Iranian Journal of Pediatric Hematology and Oncology
Volume:12 Issue: 4, Autumn 2022

Given that various types of cancer are major causes of death among children and there is no comprehensive study investigating the simultaneous effect of ifosfamide and mesna in the treatment of patients with various types of cancer in our country, this study aimed to assess the effect of ifosfamide and mesna in the treatment of children with various types of cancer.

In the retrospective study, 46 patients with cancer were divided into two groups. In the first group, patients were treated with ifosfamide (800 mg-1g/m2/day) with 500 cc of normal saline and mesna (equivalent to the amount of ifosfamide) in the serum. In the second group, the patient received ifosfamide through serum and mesna at 0, 4, 8, and 16 hours after the ifosfamide injection. This injection continued for three days. Then blood count, hemoglobin, and kidney tests in both groups were examined.

White blood cells in both methods decreased significantly (P<0.01). In the second group, there was a significant difference before and after intervention, regarding hemoglobin level (P<0.01). In addition, more people in the second group showed gastrointestinal complications (P<0.01). There was no significant difference before and after intervention in the the two groups, regarding creatinine and urea levels (P>0.05).

In both groups, a decrease in white blood cells was observed, while kidney toxicity was not observed in any group. The decrease in hemoglobin in the second group was more than in the first group.

Pulmonary arterial hypertension (PAH) may result in cardiomyopathy which is a major cause of death in thalassemia patients. Vitamin D is associated with benefits in cardiovascular disorders. Our purpose was to study effects of vitamin D on pulmonary artery pressure in thalassemia major and intermedia patients.

This randomized trial was performed on 26 patients with thalassemia major (TM) and intermedia (TI) in Amir-Kabir Hospital, Arak, Iran in 2019-2020. Patients were randomized 1:1 to intervention group (vitamin D 50,000 IU/week) and control group (received no supplement) for 20 weeks. Echocardiography was used to measure pulmonary artery pressure and assess cardiovascular function. The levels of 1,25-dihydroxyvitamin D3, ferritin, and cardiac iron content were measured in study groups.

After 20 weeks, pulmonary arterial pressure (PAP), tricuspid regurgitant velocity (TRV), and pulmonary regurgitant velocity (PRV) significantly improved in the intervention group compared to the control group (P= 0.010, P= 0.003, and P= 0.001, respectively). Moreover, ejection fraction (EF) had significant increase in the intervention group compared to the control group (P= 0.008), although vitamin D supplementation had no significant impact on cardiac T2* values (P= 0.827), systolic and diastolic blood pressure (P= 0.388 and P= 0.509, respectively) and serum hemoglobin and ferritin levels (P= 0.557 and P= 0.620) as compared to the control group. However, the levels of 25-OHD3 significantly increased in the intervention group compared to the control group (P= 0.036).

This study showed that vitamin D 50000 IU/week can improve PAP in patients with thalassemia. Sufficient intake of vitamin D may prevent cardiomyopathies related to PAH.

  Deferasirox is an oral iron chelator widely used to treat iron overload in patients with transfusion-dependent β-thalassemia. This study investigated the prevalence of visual and auditory complications caused by deferasirox.

This cross-sectional study included 156 patients aged less than 18 years with transfusion-dependent β-thalassemia and deferasirox iron chelator consumption admitted to the 17 Shahrivar Hospital and the Besat Clinic in Rasht, Iran. All the patients were examined for visual and auditory complications caused by deferasirox in 2019. A checklist of the patients' demographical and clinical data was recorded. Data analysis was done with SPSS and reported by descriptive statistics. Then, Fisher's exact test was performed to examine the association between visual and auditory disorders and the use of deferasirox in terms of disease-related variables including age, sex, age of onset of using chelator, drug use duration, drug dosage, and mean 6-months serum ferritin levels (P <0.05 as the significance level).

  Of a total of 156 patients, 103 (66%) were female and 56 (35.9%) were 20-30 years of age. The prevalence of visual acuity change was 0.6%, and the prevalence of sensorineural hearing loss was 1.3%. There was only one female with the visual disorder decreasing to 9/10 and with a dose of 31-40 mg/kg/day with an average of 1000-2500 ng/ml six-month ferritin. Also, two females with hearing impairment were confirmed with a dose of ≤30 mg/kg/day, and an average of ≤1000 ng/ml six-month ferritin. The Fisher's exact test results showed no significant relationship between visual and auditory disorders with the use of deferasirox in terms of disease-related variables (p>0.05).

The study's findings showed no significant relationship between visual and auditory disorders with deferasirox consumption. The results indicated the safety of deferasirox regarding visual and auditory side effects. More studies are required to confirm the findings.

β-thalassemia is the most common hereditary disease in Iran, and more than 2 million carriers of β-thalassemia live in Iran. On the other hand, our country is located in the thalassemia belt, and no comprehensive study has been conducted regarding the effect of erythropoietin on blood parameters in thalassemia intermedia patients in our region. Therefore this study aimed to investigate the effect of erythropoietin on blood parameters of thalassemia intermedia patients.

This prospective cross-sectional study was conducted on all patients suspected of thalassemia intermedia in Shahid Sadoughi hospital from March 2021 to M 2022.  In the case of diagnosis of microcytic anemia, an electrophoresis test was performed, and people diagnosed with thalassemia intermedia entered the study. Then patients were divided into two groups (the intervention and control groups). The erythropoietin dose was 50-100 units/ kilogram (body weight) three times a week for six months. The measurement of hematocrit and hemoglobin were done using CBC cell counter (Sysmex KX21). Other data were extracted from medical records.

Result

In the current study, the mean age of patients in the intervention and control groups was 9.15±1.53 and 8.35± 6.90 years old, respectively (p=0.9). The mean hematocrit level in the intervention and control groups was 28.05± 4.06 and 23.45± 3.22 %, respectively (P<0.001). The mean hemoglobin level in the two groups was 9.15± 1.53 and 7.65± 1.23 g/dL respectively (p=0.002). The mean hematocrit level before and after the intervention was 25±3.71 and 28.05±4.06 %, respectively. The mean hemoglobin levels before and after therapy were 7.9±1.52 and 9.15±1.53 g/dL, respectively.

According to the findings, hemoglobin and hematocrit increased in thalassemia intermedia patients taking erythropoietin. Therefore it seems that recombinant erythropoietin can be helpful in these patients.

About 10-20% of children suffering from acute lymphoblastic leukemia (ALL), experience a relapse, which is a major cause of their death. Purine nucleotide analogs are frequently prescribed to maintain the treatment of ALL. Cytosolic 5´-nucleotidase (NT5C2) catalyzes the 5´ dephosphorylation of purine analogs. Gain-of-function mutations in the NT5C2 gene result in resistance to the treatment with purine analogs and subsequently in the relapse of the disease.

In this descriptive study, bioinformatics tools were used to assess the effect of single nucleotide polymorphisms (SNPs) in the NT5C2 gene on the function and structure of the protein. So, 352 missense variants were retrieved from the NCBI database and analyzed by SIFT, PROVEAN, PMut, PANTHER, PolyPhen2, SNPs & Go, and PhD-SNP servers. Then, structural evaluations were performed using HOPE, NetSurp-2.0, and PyMOL. Moreover, stability and evolutionary preservation were assessed by I-Mutant2.0 and ConSurf, respectively.

As many as 31 nsSNPs were predicted to be affecting the protein function and stability. Also, the native residues were found to be evolutionarily preserved. The structural evaluation demonstrated that a change of hydrophobicity, flexibility, size, charge, or surface accessibility due to 24 nsSNPs would lead to the change of noncovalent interactions and then the conformation of the protein.

Identification of biomarkers is significant in the prediction of relapses in ALL children. In this study, bioinformatics tools served to identify 24 high-risk deleterious nsSNPs in the NT5C2 gene. These mutations can be used to predict resistance to chemotherapy and relapse in ALL patients.

A low level of L-glutamine, a precursor of nicotinamide adenine dinucleotide (NAD) in red blood cells (RBCs), is identified as an underlying mechanism for the potential decrement of the NAD redox and the incidence of pain crisis in sickle cell anemia (SCA). The aim of this study is to assess the impact of oral L-glutamine therapy on pain crisis reduction in patients with SCA and sickle β°-thalassemia.

In this pilot clinical trial, 15 patients with SCA and sickle β°-thalassemia with the mean age of 17.2 ± 6.07 were examined to evaluate the efficacy of L-glutamine therapy in pain crises. All the subjects received oral L-glutamine (0.3 gr /kg of body weight) every day for 8 weeks. With respect to the effects of L-glutamine on pain crisis, the subjects were in contact with the physicians at least once or more per week. Blood samples were taken at different follow-up times to evaluate the laboratory characteristics of the patients.

Pain crises occurred for 1-3 times (mean: 1.29 ± 1.05) during 12 months before the L-glutamine therapy. With no significant change, the patients had lower numbers of painful crises (mean: 0.80 ± 0.58) at the end of a 4-week period compared to the period before the L-glutamine therapy (P = 0.466). Fewer pain crises with a mean of 0.33 ± 0.51 occurred during 8 weeks of L-glutamine therapy than in the pre-treatment period (P = 0.038).

The results of the present study showed that oral L-glutamine can mitigate a pain crisis and improve the sickle RBCs and reticulocyte count in SCA. This suggests that L-glutamine therapy can increase the antioxidant potential of sickle RBCs.

Sickle cell anemia (SCA) is an inherited monogenic disorder. The clinical symptoms of SCA are protean, including vaso-occlusion, hemolysis, early stroke, leg ulcers, multi-organ failure, and increased risk of premature death. Hematopoietic stem cell transplantation is the only treatment identified to reduce SCA-related organ damage. Unfortunately, graft rejection is a significant impediment to these strategies.

The current standard of treatment for the past two decades is limited to myeloablative-matched sibling donors, which is likely to be only for minor patients and is feasible for non-malignant giant disease. Cumulative studies showed that HSCT increases overall survival and quality of life in patients with SCA.

Hematopoietic stem cell transplantation (HSCT) is significantly associated with a higher risk of graft versus host disease and moderate mortality risk. New strategy lacking standard donors includes cord blood, matched unrelated donors/ Haploidentical donors.

This review summarized evidence from HSCT clinical trials from different transplantation methods, specific HSCT and HSCT-related health problems that need to be addressed in medical contexts with patients and family members, and other areas that enhance the quality of life in SCA.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of excessive immune activation, which is characterized by fever, hepatosplenomegaly, cytopenias, hyperferritinemia, hypertriglyceridemia, and/or hypofibrinogenemia, and evidence of hemophagocytosis. Secondary HLH is often seen in adults and categorized based on autoimmune, infections-related, and malignancy-associated etiologies such as A-HLH, I-HLH, and M-HLH, respectively. This study presented a rare case of HLH developing concurrently at the time of diagnosis of T-cell Acute Lymphoblastic Leukemia (T- ALL) with a unique presentation of membranous tonsillitis in a 10-year-old boy. In all of the cases of T-ALL reported in the pediatric age group, HLH develops post-therapy or at the relapse. The first presentation of leukemia as membranous tonsillitis and concurrent clinic laboratory findings of HLH is rare and can mislead the diagnosis. Therefore, prompt diagnosis is the mainstay of therapy and can considerably improve the prognosis.