Raccoon Eyes Presentation in a Child Diagnosed With Acute Lymphoblastic Leukemia: A Case Report.

Raccoon's eyes (periorbital ecchymosis) may present as the first sign in patients with skull base/base/facial fractures and tumors. In childhood, orbital metastases of neuroblastoma should be considered in the absence of trauma history. Herein, we report a 3-year-old girl diagnosed with acute lymphoblastic leukemia who presented with periorbital ecchymosis. To the best of our knowledge, this is the first pediatric patient with acute lymphoblastic leukemia in the literature who presented with raccoon eyes.

Granulocyte transfusions in life-threatening infections of children with hemato-oncological diseases.

Granulocytes are the most important cells for host defense during infections. Granulocyte suspension transfusions (GTx) may be given as additional treatment in severely neutropenic patients with life-threatening infections when antimicrobial therapy is inadequate. The aim of this study was to evaluate the effectiveness and safety of GTx for the treatment of children with hemato-oncological disease, febrile neutropenia and serious life-threatening infections. Patients who underwent GTx between July 2020 and September 2022 were evaluated retrospectively. Hematologic and clinical response rates, adverse effects, characteristics of infection episodes and survival data of the patients were analyzed. During the study period, 60 patients received a total of 313 GTx for 81 infection episodes with a median number of GTx/infection episode of 3 (range 1-29). The median neutrophil count per bag was 20.8 (range 7.9-68.3) × 109 and the median neutrophil count per kg body weight was 0.82 (range 0.17-9.2) × 109. Clinical response was 85 %. Clinical response decreased significantly as the duration of neutropenia increased (p = 0.002). Hematologic response was calculated in 198 GTx (GTx given with pre-transfusion neutrophil count ≤ 0.5 × 109/L); hematologic response rate was 34 %. The infection-related mortality was 15 % and overall survival rate was 87 % and 70 % on days 30 and 90, respectively. No serious side effects were observed in any patient. Granulocyte transfusions appear to be safe and effective supportive treatment in neutropenic children with hematologic/oncologic diseases and severe infections.

Neonatal portal vein thrombosis: risk factors, diagnosis, treatment recommendations and review of the literature.

BACKGROUND: Neonatal portal vein thrombosis (PVT) is currently more commonly encountered as a result of advances in diagnostic tools and increase in invasive interventions. METHODS: In this study, 11 premature and 12 term infants diagnosed with PVT were retrospectively evaluated for clinical and laboratory characteristics, umbilical catheterization procedure, PVT location, risk factors, treatments, and long-term outcomes. RESULTS: Median age of the patients at diagnosis was 10 days (range 3-90 days), and 69.6% of patients were girls. Of the 23 patients, 87% had left PVT and, 91.3% had at least one thrombosis risk factor, which was sepsis in 73.9% of patients, and presence of umbilical venous catheter in 87%. Totally, 59.1% of PVTs were completely resolved in a median follow-up of 7 months (1 month to 12 months), and 78.3% of these patients had no anticoagulant therapy (ACT). Partial thrombus resolution was achieved in 9 patients (40.9%). Five patients (%21) received ACT. Overall, 34.8% of patients had long-term complications. neonatal PVT is most commonly reported in the left portal vein and there is no evidence for the impact of ACT on reducing the short- or long-term complications. Well designed and larger studies are necessary to clarify this issue, which can facilitate developing appropriate management algorithms. CONCLUSION: Neonatal PVT is most commonly reported in the left portal vein and there is no evidence for the impact of ACT on reducing the short- or long-term complications. Well designed and larger studies are necessary to clarify this issue, which can facilitate developing appropriate management algorithms.

Long-term Results of Splenectomy in Transfusion-dependent Thalassemia.

Splenectomy is indicated in transfusion-dependent thalassemia (TDT) only in certain situations. This study aimed to present the effectiveness, complications, and long-term follow-up results of splenectomy in children with TDT. We performed a 30-year single-institution analysis of cases of splenectomy for TDT between 1987 and 2017 and their follow-up until 2021. A total of 39 children (female/male: 24/15) were included. The mean age at splenectomy was 11.2±3.2 years, and their mean follow-up duration after splenectomy was 21.5±6.4 years. Response was defined according to the patient's annual transfusion requirement in the first year postsplenectomy and on the last follow-up year. Complete response was not seen in any of the cases; partial response was observed in 32.3% and no response in 67.6%. Thrombocytosis was seen in 87% of the patients. The platelet counts of 7 (17.9%) patients were >1000 (10 9 /L), and aspirin prophylaxis was given to 22 (56.4%) patients. Complications were thrombosis in 2 (5.1%) patients, infections in 11 (28.2%) patients, and pulmonary hypertension in 4 (10.2%) patients. Our study showed that after splenectomy, the need for transfusion only partially decreased in a small number of TDT patients. We think splenectomy can be delayed with appropriate chelation therapy up to higher annual transfusion requirement values.

Prognostic Factors and Long-term Outcomes in 41 Children With Primary Hemophagocytic Lymphohistiocytosis: Report of a Single-center Experience and Review of the Literature.

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening hyperinflammatory syndrome with diverse clinical manifestations leading to major diagnostic and therapeutic difficulties. This study aimed to evaluate clinical manifestations, prognostic factors, and long-term outcomes in children with primary HLH. Forty-one patients diagnosed with primary HLH were retrospectively evaluated for patient characteristics, HLH gene mutations, clinical and laboratory manifestations, prognostic factors, and long-term outcomes. The median age of the patients at the time of diagnosis was 3 months (minimum to maximum: 1 to 144 mo). There were 23 patients who had HLH mutation analysis performed, 10 patients with PRF1 mutation, 6 with STX11 mutation, and 7 with UNC13D mutation. Thirteen patients (31.7%) had central nervous system involvement. No correlation was found between overall survival and central nervous system involvement. The estimated 5-year overall survival for the patient who had hematopoietic stem cell transplantation was 9.4 times better than the patients who did not receive hematopoietic stem cell transplantation (81.3% vs 16.7%; P = 0.001). Median serum sodium and blood urea nitrogen levels were significantly higher in deceased HLH patients compared with surviving HLH patients ( P = 0.043, and P = 0.017, respectively). Primary HLH has a poor outcome with high mortality, which necessitates well-designed and international clinical trials to improve diagnosis, therapy, and long-term outcomes.

A comparison of hypersensitivity reactions between intravenous and intramuscular applications of native E. coli asparaginase in children with acute lymphoblastic leukemia.

INTRODUCTION: Asparaginase is an indispensable drug in treating childhood acute lymphoblastic leukemia (ALL). Hypersensitivity reactions (HSR) are the most common side effects and interfere with the antineoplastic activity of the drug. This study aims to compare the intramuscular (IM) and intravenous (IV) administration routes of Native Escherichia coli Lasparaginase (L-ASNase) in terms of hypersensitive reactions. METHODS: L-ASNase was randomly administered IV or IM to newly diagnosed ALL patients and HSR was monitored in all patients for 1 h following the end of the IV infusion and for 2 h following the end of the IM administration of L-ASNase. Based on a retrospective review of clinical charts, reactions were identified. In order to determine the severity of each allergic reaction, we used the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 for allergic reactions. RESULTS: A total of 1032 doses of L-ASNase were administered to 85 patients (42 males and 43 females) during the study period. Among 85 patients, 30 reactions were recorded, which means that 35% of the patients reacted. According to the CTCAE, twenty-nine out of 30 reactions (97%) were grade 2, while one (3%) was grade 4. In terms of individual doses, there was a non-significant trend toward increased incidence of reactions with IV administration (3.8% versus 0.9%, p = 0.064). The rate of reactions was higher in patients who received all IV doses (n: 60) as compared to those who received all IM doses (n: 25) (31.7% vs. 3.5%; chi-square= 8.415, p value=0.04). Based on the risk groups and HSR incidence, it was found that high risk group (HRG) patients were significantly more likely to develop HSR compared to the standart risk group (SRG) and intermediate risk group (MRG) patients (chi-square p = 0.003, CI: 95%; odds ratio: 3.12 and 5.91, respectively). CONCLUSIONS: In conclusion, IM administration of L-ASNase causes significantly less HSR to L-ASNase than the IV route. Patients with HRGALL have a higher risk of HSR. Since L-ASNase is still used in many developing countries and there are problems in the supply of Erwinia chrysanthemi ASNase (Erwinia), LASNase can be administered IM to reduce the frequency of HSR.

Effect of peppermint-lemon aromatherapy on nausea-vomiting and quality of life in pediatric patients with leukemia: A randomized controlled trial.

BACKGROUND: Nausea and vomiting, frequently induced by chemotherapy, can delay treatment protocols and the healing process. PURPOSE: The aim of this study is to determine how aromatherapy inhalation with peppermint and lemon using a diffuser affects nausea-vomiting management and quality of life in 2-12-year-old children undergoing chemotherapy. DESIGN AND METHODS: The study utilized a pretest-posttest control group experimental design with randomized groups. A total of 90 children who met the inclusion criteria were included in the study. The experimental group received Mentha Piperita and Citrus Lemon essential oils through a diffuser, while the placebo group received water through a diffuser. The control group did not receive any intervention. RESULTS: Pulse and respiratory rates of children treated with aromatherapy were found to be significantly lower than the other groups. After aromatherapy application, quality of life of the children in the experimental group was significantly higher than the other groups. The change in the Index of Nausea, Vomiting, and Retching scores of the experimental group on the 4th chemotherapy cycle compared to the 1st chemotherapy cycle was significantly higher than the change in the other groups. CONCLUSIONS: Consequently, it was determined that inhalation aromatherapy with peppermint-lemon was effective in the management of chemotherapy-induced nausea-vomiting symptoms and quality of life compared to the placebo and control groups. PRACTICE IMPLICATIONS: Inhalation aromatherapy with mint-lemon can be used as an alternative method to improve the quality of life in children with leukemia who suffer from chemotherapy-induced nausea and vomiting.

Diagnosis, Management, and Challenges in Synchronous Bilateral Wilms Tumor in a Horseshoe Kidney: A Case Report.

Horseshoe kidney (HK) refers to a congenital malformation that results from fusion of both the kidneys at one pole, and is the most common renal fusion defect with an incidence of 1 in 400 to 600 individuals. Synchronous bilateral development of Wilms tumor (WT) in an HK is extremely rare. Here, we present a case of synchronous bilateral WT in an HK in an 18-month-old girl. The patient received 12 weeks of preoperative chemotherapy followed by 2-step surgical resection including nephron-sparing surgery (NSS) in both kidneys and left nephrectomy because of positive surgical margin and adjuvant chemotherapy. The patient is still in remission and asymptomatic 6 months after the completion of treatment. In this report, we discuss the treatment modalities of synchronous bilaterally located WT in HK. We conclude that successful outcomes can be obtained with preoperative chemotherapy and NSS in such cases even in the presence of advanced disease and complex anatomic conditions. In addition, the deepest tumor point can be reached during NSS, but total nephrectomy should be considered regarding the possibility of microscopic residue.

Clinical Features and Outcome of Children With Hereditary Spherocytosis.

OBJECTIVE: The aim of this study was to evaluate the demographics, clinical, and laboratory findings and treatment responses of patients with hereditary spherocytosis (HS). MATERIALS AND METHODS: Data of children with HS were examined. Diagnosis was based on clinical history, physical examination, family history, presence of spherocytes on peripheral blood smear, and osmotic fragility test. RESULTS: A total of 101 patients were included. The median (range) age at diagnosis was 38.0 (1 to 188) months. Mild, moderate, and severe forms of HS were present in 29 (28.7%), 15 (14.9%), and 57 (56.4%) patients, respectively. Family history was available in 73 patients and 56 of these (76.7%) had a positive family history for HS. Forty-five (44.5%) patients needed regular transfusions and all of these had severe disease. Although most patients did not require transfusion postsplenectomy, 2 of 45 (4.4%) patients continued to require transfusion. Transfusion dependence was significantly (P<0.001) higher in patients with severe spherocytosis. CONCLUSIONS: In HS, splenomegaly, pallor, and jaundice are the most common clinical features. Splenectomy dramatically reduces hemolysis in most cases and virtually abolishes further requirement for transfusion.

The effect of granulocyte colony-stimulating factors on survival parameters in pediatric patients with acute lymphoblastic leukemia: A retrospective study.

OBJECTIVE: There is a paucity of data concerning the use of granulocyte colony-stimulating factors (G-CSFs) in pediatric patients with acute lymphoblastic leukemia (ALL). The aim of the present study was to evaluate the effect of G-CSF use on relapse-free and overall survival in 358 consecutive, newly diagnosed pediatric ALL patients uniformly treated at the same institution between April 2012 and April 2020. MATERIALS AND METHODS: Patients were evaluated in two separate periods, based on the G-CSF treatment approach. All patients who underwent ALL treatment between April 2012 and December 2016 received G-CSF (G-CSF+ arm; n: 245) in the course of the protocol for reducing the risk of febrile neutropenia and/or inducing neutrophil recovery to prevent any treatment delay. No patients after December 2016 received G-CSF, even if they belonged to the high-risk group, and these were included in the G-CSF- arm (n: 113). RESULTS: Estimated mean relapse-free (106.5 months; 95 % CI 102-110.8 vs 82 months 95 % CI 75.2-88.9; p: 0.794) and overall survival (111.4 months; 95 % CI 108-114.8 vs 85 months 95 % CI 80.4-89.8; p: 0.431) rates were similar between the G-CSF+ and G-CSF- groups. CONCLUSIONS: Our findings indicate that G-CSF use during ALL treatment had no effect on relapse rates or overall survival.

Safety and efficacy of deferasirox in patients with transfusion-dependent thalassemia: A 4-year single-center experience.

This study was organized to determine the efficacy and safety of deferasirox (DFX) in reducing the SF of patients with transfusion-dependent thalassemia (TDT). This is a retrospective, descriptive study of 101 transfusion- dependent patients with thalassemia major who were followed for 48 months. Twenty-nine patients who used an alternative chelator either alone or combined, who were not compliant to the treatment, changed the drug due to adverse reactions, and had multiple transfusions and did not complete 4 years of DFX use were excluded. A total 72 out of 101 patients completed the study. SF decreases were noted for the 6-12 and >18-year age groups, from a median of 1532 ng/mL to 1190 ng/mL, and from 1386 ng/mL to 1165 ng/mL, respectively (p > 0.05). The proportion of patients with SF concentrations >2000 ng/mL is decreased (29% at baseline decreased to 15% at the end of the study) during the 48 months. The median SF of those who used <30 mg/kg/day (n = 38) increased from 767 ng/mL to 1006 ng/mL, whereas the >30 mg/kg/day (n = 34) group's SF concentrations decreased from a median of 1575 ng/mL to 1209 ng/mL (p = 0.029). The decrease of median SF values for Syrian patients was statistically significant (p = 0.043). Most common adverse events were gastric irritation symptoms (19.4%). The total DFX discontinuation ratio was calculated as 9.7%. Although dosages between 25-30 mg/kg/day are adequate to stabilize SF concentrations higher dosages are needed to achieve a statistically significant decrease.

Refugee children with beta-thalassemia in Turkey: Overview of demographic, socioeconomic, and medical characteristics.

AIM: Since the beginning of the Syrian civil war, more than 3.5 million Syrians have been under temporary protection status in Turkey. Because beta-thalassemia (BT) is a prevalent disorder in the Mediterranean countries, we decided to estimate the prevalence of and make an overview of the demographic, socioeconomic, medical characteristics, and healthcare problems of refugee children with BT. PATIENTS: Eighteen Turkish Pediatric Hematology Oncology Centers (PHOC) with 318 refugee children from 235 families participated in the study. The mean age of the patients was 8.1 ± 4.8 years (0.5-21 years). The mean time after immigration to Turkey was 2.5 ± 1.5 years (range, 0.1-7 years). Seventy-two (22.6%) of them were born and diagnosed with BT in Turkey. On physical examination, 82 patients (26%) were underweight and 121 patients (38%) were stunted. The appearance of a thalassemic face was reported for 207 patients (65.1%). Hepatomegaly and splenomegaly were reported in 217 (68.2%) and 168 (52.8%) patients, respectively. The median ferritin level was 2508 ng/mL (range, 17-21 000 ng/mL) at the first admission, and 2841 ng/mL (range, 26-12 981 ng/mL) at the last visit after two years of follow-up in a PHOC (P > 0.05). The most frequently encountered mutation was IVSI-110 (G>A) (31%). Before immigration, only 177 patients (55.6%) reported the use of chelators; after immigration it increased to 268 (84.3%). CONCLUSION: Difficulties in communication, finding a competent translator capable in medical terminology, nonregular use of medications, and insensitivity to prenatal diagnosis were preliminary problems. The current extent of migration poses emerging socioeconomic and humanitarian challenges for refugee patients with BT.

Thiol Disulfide Homeostasis and Ischemia-modified Albumin Level in Children With Beta-Thalassemia.

OBJECTIVE: It is well known that increased oxidative stress leads to tissue damage in beta-thalassemia (ß-thal) patients. Thiols are one of the most important antioxidant agents, and thiol/disulfide (SH/SS) homeostasis is a novel oxidative stress marker. This study aimed to investigate the relationship of thiol levels, SH/SS homeostasis, and ischemia-modified albumin (IMA) in patients with ß-thal. MATERIALS AND METHODS: A hundred transfusion-dependent ß-thal patients and 41 healthy controls were included in the study. RESULTS: Native thiol, total thiol, disulfide, catalase, and IMA levels were significantly higher in the ß-thal group compared with the control group (P<0.02). There were no correlation between serum ferritin level and SH/SS homeostasis, and weak positive correlations were found between serum ferritin and IMA (r=0.242, P=0.022). CONCLUSIONS: Our study results suggest that antioxidant systems try to compensate for peroxidative damage in the patients' group and serum IMA level was found increased because of increased oxidative status. To the best of our knowledge, there has been no report evaluating plasma dynamic SH/SS homeostasis in ß-thal patients.

Hemophagocytic Lymphohistiocytosis Associated With Visceral Leishmaniasis.

This is the report of a 2-year-old boy who presented with fever, cytopenia, and splenomegaly. The patient was diagnosed with hemophagocytic lymphohistiocytosis (HLH) and treated with HLH-2004 protocol. Repeated bone marrow aspiration showed amastigotes on follow-up. In endemic countries, visceral leishmaniasis should be considered in the differential diagnosis to avoid chemotherapy toxicity.

Ferrous sulfate (Fe2+) had a faster effect than did ferric polymaltose (Fe3+) on increased oxidant status in children with iron-deficiency anemia.

OBJECTIVE: The purpose of this study was to compare the total oxidant and antioxidant effect of different oral iron preparations in children with iron-deficiency anemia (IDA). METHODS: A total of 65 children with IDA were randomized to receive 5 mg Fe/kg/d iron (II) sulfate (Fe(2+) group, n=33) or iron (III)-hydroxide polymaltose complex (Fe(3+) group, n=32); healthy controls (n=28) were also included in the study. Serum total thiol (-SH), total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), and hematological profile were evaluated at the baseline and on day 8 and day 30 of the therapy. RESULTS: Serum TOS and OSI levels were significantly higher and total -SH and total antioxidant capacity levels were significantly lower in the study groups at the beginning of therapy than in the controls (P>0.001). In multivariate analysis, after controlling for multiple confounding factors, on days 8 and 30, serum TOS and OSI levels were not different in the Fe(3+) group, whereas they were significantly reduced in the Fe(2+) group (P≤0.033). CONCLUSIONS: Serum total oxidant status was significantly increased in children with IDA, and Fe(2+) was highly effective in correcting elevated oxidative status.

Efficacy of deferasirox in children with ß-thalassemia: single-center 3 year experience.

BACKGROUND: Iron chelation therapy is an important component in the management of patients with ß-thalassemia. METHODS: The study included 87 children with transfusion-dependent ß-thalassemia aged 2-17 years (mean, 8.2 ± 4.1 years), 49 (56%) of whom were male. The patients received deferasirox 9-40 mg/kg per day as a single dose for 36 months. They were clinically and laboratory monitored. RESULTS: The treatment was generally well tolerated. Drug-related adverse events, including abdominal pain (14.9%) and nausea (5.8%), high alanine aminotransferase more than double the upper limit of normal (5.8%), and non-progressive rise in serum creatinine (2.3%), were generally mild to moderate, transient, and reduced in frequency over time. Two patients discontinued treatment due to severe abdominal pain and nausea. Mean deferasirox dose was calculated as 21.2 ± 8.6, 23.7 ± 8.1, 30.7 ± 8.2 and 32.4 ± 7.6 mg/kg per day at 0, 12, 24 and 36 months, respectively. Mean (median) serum ferritin level was found to increase progressively during the first 22 months of treatment, from 3.161 ± 1.683 ng/mL (2.760 ng/mL) to 3.679 ± 1.997 ng/mL (3.071 ng/mL; P < 0.001) and then decreased gradually to 2.907 ± 1.436 ng/mL (2.670 ng/mL; P = 0.023) at 36 months. CONCLUSION: Deferasirox is safe and well tolerated; doses 21-24 mg/kg per day were not able to maintain stable iron balance, but ≥ 30 mg/kg per day was able to reduce iron in regularly transfused pediatric patients.

N-Acetylcysteine supplementation reduces oxidative stress and DNA damage in children with ß-thalassemia.

There are several reports that increased oxidative stress and DNA damage were found in ß-thalassemia major (ß-TM) patients. In this study, we aimed to evaluate the effects of N-acetylcysteine (NAC) and vitamin E on total oxidative stress and DNA damage in children with ß-TM. Seventy-five children with transfusion-dependent ß-thalassemia (ß-thal) were randomly chosen to receive 10 mg/kg/day of NAC or 10 IU/kg/day of vitamin E or no supplementation; 28 healthy controls were also included in the study. Serum total oxidant status (TOS) and total antioxidant capacity (TAC) were measured, oxidative stress index (OSI) was calculated, and mononuclear DNA damage was assessed by alkaline comet assay; they were determined before treatment and after 3 months of treatment. Total oxydent status, OSI, and DNA damage levels were significantly higher and TAC levels were significantly lower in the thalassemic children than in the healthy controls (p < 0.001). In both supplemented groups, mean TOS and OSI levels were decreased; TAC and pre transfusion hemoglobin (Hb) levels were significantly increased after 3 months (p ≤ 0.002). In the NAC group, DNA damage score decreased (p = 0.001). N-Acetylcysteine and vitamin E may be effective in reducing serum oxidative stress and increase pre transfusion Hb levels in children with ß-thal. N-Acetylcysteine also can reduce DNA damage.

Switching from Deferasirox Dispersible Tablets to Deferasirox Film-Coated Tablets: Is There an Effect on Ferritin Levels in Children and Adolescents with Transfusion-Dependent Anemia?

OBJECTIVE: To investigate the effect of switching from deferasirox dispersible tablet (DT) to deferasirox film-coated tablet (FCT) on serum ferritin (SF) levels in transfusion-dependent patients. MATERIALS AND METHODS: Patients who received regular erythrocyte transfusion and whose treatment was switched from DT to FCT were included in the study. FCT start date was taken as the index date. Patients were followed over 2 equal and long periods, both before and after index date. RESULTS: Thirty-two patients were included, and the comparison periods ranged from 4 to 12 months. The SF values increased from a median of 1723 ng/mL (range 717-5369 ng/mL) to 1.853 ng/mL (range 924-5478 ng/mL) after switching from DT to FCT (P = .036). While there was a significant increase in median SF after switching in Turkish patients (1467 ng/mL to 1778 ng/ mL, P = .010) and patients ≥12 years (1598-1848 ng/mL, P = .009), there was an insignificant (P = .859) decrease in SF in immigrant children. Considering only the post-switch period, there was a non-significant increase in median SF in the entire cohort, while SF decreased significantly in immigrant children (P = .026). No serious side effects were observed in any patient that would cause discontinuation of treatment. CONCLUSION: Overall, higher SF value was observed with FCT compared to DT in short term. There were different results between patient groups. Our results suggest that FCT is more effective than DT in patients with high basal ferritin and who are actually incompatible with treatment and should be preferred first in these patients.