Can biomarkers predict myocardial iron overload in children with thalassemia major?

AIM: Beta-thalassemia major requires regular blood transfusions throughout life, which in turn leads to iron accumulation in the body. While cardiac T2* MRI is the gold standard in determining cardiac iron accumulation, it is not always feasible, which has led to the search for new biomarkers. Herein, the value of growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide in predicting cardiac iron accumulation is investigated in asymptomatic children with beta-thalassemia major. MATERIALS AND METHOD: Forty-one patients aged 11-21 years and 41 age-, gender-, body mass index-matched healthy controls were included. Serum growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide levels were compared between the patients and controls. Additionally, the relations of these biomarkers with cardiac and liver T2 * MRI were investigated in the patients. RESULTS: In the patients, growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide levels were higher than healthy controls (p < 0.001, p = 0.025, p < 0.001, respectively). There were no significant correlations of growth differentiation factor-15 and N-terminal pro-B-type natriuretic peptide levels with both cardiac and liver T2 * MRI measurements. While there was no significant correlation of serum galectin-3 with cardiac T2 * MRI measurements, a negative correlation was found with liver T2 * MRI measurements (p = 0.040, rho = -0.325). CONCLUSION: All three biomarkers investigated in this study failed to predict myocardial iron accumulation in asymptomatic children with beta-thalassemia major. However, a weak relation between serum galectin-3 level and hepatic iron accumulation was demonstrated.

Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study.

BACKGROUND: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. MATERIALS AND METHODS: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541 ). RESULTS: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus . Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae. CONCLUSION: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.

The time to diagnosis and survival in children with solid tumors and lymphoma: results from a single center in Turkey.

The longer diagnostic intervals in low- and middle-income countries have been proposed among the possible causes of poorer outcomes in children with cancer. In this single-center study from Turkey, the diagnostic intervals and survival status of 138 children with solid tumors and lymphoma (excluding leukemia) were prospectively evaluated. The median total interval (from the beginning of the first cancer-related symptom to the first day of the cancer-specific therapy), the median patient interval (the time interval from the notification of the first cancer-related symptom to the first admission to a healthcare facility), and the median physician interval (the time interval between the first healthcare admission to the first pediatric oncology visit) were 65, 26, and 24 days, respectively. The estimated 5-year overall survival and event-free survival rates were 80.7% and 69.1%, respectively. The longer time intervals were correlated with age, paternal education, localization, and tumor type. Interestingly, none of the time parameters were found to be associated with survival on regression analysis. In conclusion, the diagnostic delay in children with cancer is multifactorial, and the patient- and disease-related factors are as important as the time intervals on survival.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1951903.

Ophthalmologic findings and complications before and after hematopoietic stem cell transplantation: single-center study.

PURPOSE: Different and various system complications and late effects may occur after hematopoietic stem cell transplantation (HSCT). It was aimed to obtain information about the frequency of ophthalmologic complications and their relationship with treatment. METHODS: This retrospective study includes 104 children who underwent HSCT between February 2019 and June 2020 at the Pediatric Bone Marrow Transplant Unit. Patients' ages, genders, diagnosis, transplant types, chemotherapy regimens, transplantation details, conditioning regimens, supportive cares, graft versus host disease (GvHD) prophylaxis, infection episodes, and ophthalmologic findings were evaluated. RESULTS: Of the 104 patients included in the study, 38 (36.5%) were female and 66 (63.5%) were male. Average age ± SD was 8.7 ± 4.91. Considering the diagnoses, the majority of the patients were acute lymphoblastic leukemia (46 patients-44%). Myeloablative regimen was used in 93 (89%) of the patients, and reduced intensity conditioning (RIC) was used in 11 patients (10%). While total body irradiation was applied in 16 (15%) patients, one patient was received cranial radiotherapy. Cyclosporine was used in 96 (92%) patients. CMV reactivation was detected in 54 (51%) of the patients. CMV retinitis was not seen. Ocular pathology was detected in 20 (19%) patients before HSCT and in 12 (11%) patients after HSCT. The most common pathology was dry eye. CONCLUSION: Routine ophthalmologic examinations are important in terms of early diagnosis. In addition, GvHD and CMV prophylaxis is important because of reducing the risk of ocular complications after HSCT.

Deferasirox in children with transfusion-dependent thalassemia or sickle cell anemia: A large cohort real-life experience from Turkey (REACH-THEM).

OBJECTIVES: To evaluate the long-term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion-dependent thalassemia (TDT) and sickle cell anemia (SCA) in Turkey. METHODS: This was a multicenter, prospective cohort study including TDT and SCA patients aged 2-18 years with iron overload (≥100 mL/kg of pRBC or a serum ferritin [SF] level >1000 µg/L) receiving deferasirox. Patients were followed for up to 3 years according to standard practice. RESULTS: A total of 439 patients were evaluated (415 [94.5%] TDT, 143 [32.6%] between 2 and 6 years). Serum ferritin levels consistently and significantly decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5 µg/L (P < 0.001). Serum ferritin decreases were noted in TDT (1804.9 to 1241 µg/L), SCA (1655.5 to 1260 µg/L), and across age groups of 2-6 years (1971.5 to 1499 µg/L), 7-12 years (1688.5 to 1159.8 µg/L), and 13-18 years (1496.5 to 1107 µg/L). Serum ferritin decreases were also noted for all deferasirox dose groups but only significant in patients with doses ≥30 mg/kg/d (n = 120, -579.6 median reduction, P < 0.001). Only 9 (2%) patients had adverse events suspected to be related to deferasirox. Serum creatinine slightly increased but remained within the normal range. CONCLUSIONS: Deferasirox has long-term efficacy and safety in children with TDT and SCA, although higher doses (≥30 mg/kg/d) may be required to achieve iron balance.

Evaluation of PAX5 gene in the early stages of leukemic B cells in the childhood B cell acute lymphoblastic leukemia.

B-lineage acute lymphoblastic leukemia (B-ALL) is a common subtype of acute leukemia in children. PAX5 plays a central role in B-cell development and differentiation. In this study, we analyzed PAX5 expression levels, transactivation domain mutations/deletions in B-ALL patients (n=115) and healthy controls (n=10). Relative PAX5 mRNA levels were significantly increased in B-ALL patients (p<0.0001). PAX5 expression was also evaluated in three different B-ALL subgroups (pro B, Common B and Pre B ALL) and showed stage specific expression levels. Pro B (p=0.04) and pre B (p=0.04) patients showed significantly high PAX5 mRNA levels compared to stage specific controls. At least one deletion of exons 7-8 or 9 has been identified in the 41% of the patients. CD34 positivity in patients and presence of large deletions (Δ7/8/9) showed a significant correlation (p=0.05). None of our patients showed PAX5 point mutations, but two previously identified SNPs (rs3780135 and rs35469494) were detected. Our results support that PAX5 is a critical factor in B-ALL development and aberrant PAX5 expression especially at early stages may leads to leukemic transformation.

Hereditary spherocytosis with immunoglobulin A nephropathy.

Hereditary spherocytosis is a familial hemolytic anemia. Immunoglobulin A (IgA) nephropathy associated with hereditary spherocytosis has not been reported in children. Here, we report a case of a 17-year-old boy with IgA nephropathy and hereditary spherocytosis. The patient was diagnosed with hereditary spherocytosis at the age of 12 years and splenectomy was done at the age of 15 years. Later, the patient presented with macroscopic hematuria and proteinuria. Kidney biopsy of the boy was consistent with IgA nephropathy. Treatment with angiotensin-converting enzyme inhibitor was started. The patient became free of proteinuria after the 6th month of therapy.

A double-blind, crossover, randomized dose-comparison trial of granisetron for the prevention of acute and delayed nausea and emesis in children receiving moderately emetogenic carboplatin-based chemotherapy.

BACKGROUND: Granisetron is a safe and effective prophylaxis for nausea and vomiting associated with moderate to highly emetogenic chemotherapy. Few trials have been conducted to determine the optimal effective dose of granisetron in children with cancer. The objective of this report was to compare two doses of granisetron in patients with optic pathway tumors receiving moderately emetogenic doses of carboplatin. PATIENTS AND METHODS: In this double-blind, crossover, randomized study, antiemetic efficacy and tolerability of two dose levels (10 and 40 microg/kg) of granisetron in the prevention of acute and delayed nausea/emesis were compared in children and young adults. A total of 18 patients (13 boys) aged 1-23 years (median 7.7 years) treated with a moderately emetogenic dose of carboplatin were randomly assigned to receive either 10 or 40 microg/kg of slow granisetron intravenous (i.v.) infusions at alternating cycles of chemotherapy in a blinded fashion until the end of the study period or until their chemotherapy regimen ended. In this way, the patients acted as their own controls. RESULTS: Patients in the granisetron 10 and 40 microg/kg groups received 104 and 121 cycles of chemotherapy, respectively. There was no significant difference in antiemetic efficacy in terms of nausea and emesis between the dose groups in the first 5 days of chemotherapy. The treatment was well tolerated. CONCLUSION: We conclude that granisetron 10 and 40 microg/kg have comparable efficacy in controlling carboplatin-induced acute and delayed nausea/emesis and is well tolerated in children and young adults.

Helicobacter pylori infection in Turkish children with gastrointestinal symptoms and evaluation of serology.

Helicobacter pylori infection is a common etiopathogenetic factor in children with gastrointestinal symptoms in the developing world. Although serology offers an easy noninvasive method of diagnosis, its sensitivity and specificity are reported to be low among children. In this prospective study, we investigated the frequency and endoscopical and morphological findings of H. pylori infection in 180 Turkish children who underwent upper gastrointestinal endoscopy either for peptic symptoms or on a routine basis and in asymptomatic pediatric patients who underwent endoscopy for other reasons, and then evaluated the diagnostic accuracy of serology in our population. Overall H. pylori infection was diagnosed in 77 of the 180 patients (42.7%) by histology and urease test. The sensitivity of H. pylori specific IgG antibody assay by ELISA was determined to be 100%, while the specificity was 98%, the positive predictive value 97.4%, the negative predictive value 100%. Frequency of H. pylori infection is high in Turkish pediatric patients without gastrointestinal symptoms as well as in children with gastrointestinal complaints. H. pylori specific antibody assay is a noninvasive and sensitive method for the diagnosis of H. pylori infection in the Turkish pediatric population.