The Comparison of The Efficacy and Safety of Original and Biosimilar Filgrastim in Prevention of Chemotherapy-Induced Neutropenia in Children with Cancer.

OBJECTIVE: In adults and children, the duration of chemotherapy-induced neutropenia and associated complications has decreased because of the prophylactic use of granulocyte colony-stimulating factors (G-CSFs). Biosimilar G-CSFs can play an important role in reducing treatment costs in daily practice. However, some concerns regarding the efficacy and safety of new biosimilar products exist among clinicians. This study compared the efficacy and safety of original and biosimilar filgrastims for the prophylaxis of chemotherapy-induced neutropenia in children. MATERIALS AND METHODS: Thirty children receiving myelosuppressive chemotherapy were enrolled in this study. Filgrastims (5 µg/kg/day) were subcutaneously administered in Group A (biosimilar, Leucostim®; Dem Ilaç) and Group B (original drug, Neupogen®; Roche). Hemoglobin, white blood cell (WBC) count, platelet count, transfusion requirements, duration of hospitalization, and frequency and duration of adverse events including fever, neutropenia, and mucositis were evaluated following 25 treatment cycles in both groups. RESULTS: The hemoglobin value, WBC count, and platelet count on days 1, 5, and 10, and the red blood cell and platelet transfusion requirements, frequency, duration, and severity of mucositis, and durations of fever, febrile neutropenia, and hospitalization were similar in both groups. Although the mean WBC counts on days 1 and 5 were lower in Group A, the difference was statistically insignificant. CONCLUSION: The biosimilar filgrastim, Leucostim, is as effective and safe as the original drug for prophylaxis of chemotherapy-induced neutropenia in children.

Effects of massage therapy on pain and anxiety arising from intrathecal therapy or bone marrow aspiration in children with cancer.

Cancer and its treatment are stressful and reduce the quality of life in children. The aim of this study was to investigate the effect of massage therapy on pain and anxiety arising from intrathecal therapy or bone marrow aspiration in children with cancer. We conducted a controlled pretest/posttest quasi-experimental study at a paediatric oncology unit in Turkey. Twenty-five children were enrolled in this study. Their pain and anxiety were determined using a visual analogue scale. When the pretest and posttest pain and anxiety levels of the groups were compared, no statistically significant difference was found (P > 0.05). It was determined that pain and anxiety levels in the experimental group decreased significantly. This study provides preliminary evidence for the effectiveness in children of massage in reducing pain and anxiety arising from intrathecal therapy or bone marrow aspiration.

Clinical experience with recombinant tissue plasminogen activator in the management of intracardiac and arterial thrombosis in children.

Thrombotic events may complicate the clinical course of many pediatric diseases. Drugs for therapeutic thrombolysis include streptokinase, urokinase and tissue plasminogen activator (t-PA). There is less experience with recombinant t-PA (rt-PA) in children. We aimed to present our experiences with rt-PA in children with intracardiac or peripheral arterial thrombus. We retrospectively reviewed the children who received rt-PA for thrombus. Twenty-two children (13 boys, 9 girls; age range: 1 day-17 years) with intracardiac (n = 5), prosthetic heart valve (n = 2) and peripheral arterial (n = 15) thrombus were evaluated. Twelve (54%) had congenital heart disease, two (9%) had rheumatic heart disease, three (14%) had leukemia and five (23%) had documented sepsis, prematurity or meconium aspiration syndrome. Ten of the 15 peripheral arterial thromboses were observed following cardiac catheterization. Three of the five intracardiac thrombi were detected in children with leukemia. All children received low-molecular-weight heparin. rt-PA (alteplase) infusion (at a dose of 0.01-0.5 mg/kg per h) was administered for different time periods (3-66 h). Ten of 11 patients with peripheral arterial occlusion and three of five patients with intracardiac thrombus showed full recovery. However, there was no response in two patients with intracardiac thrombus and in two patients with heart valve thrombus. Nose bleeding, melena and decreased serum fibrinogen concentration were observed in seven patients during the rt-PA infusion. All bleedings stopped after cessation of rt-PA infusion, and no blood transfusion was required in any patient. We conclude that rt-PA infusion seems effective and well tolerated in children for the treatment of peripheral arterial and intracardiac thrombus.

A case of undifferentiated embryonic liver sarcoma mimicking cystic hydatid disease in an endemic region of the world.

Undifferentiated embryonic liver sarcoma (UELS) is a rare highly malignant neoplasm that predominantly occurs in children between 5 and 10 years of age. The typical radiologic appearance on ultrasound and computed tomography of UELS shows a large septated mass having combined cystic and solid components. These radiographic features, however, are not specific to UELS and are shared by other more common and benign diseases of the liver. For example, cystic hydatid disease (CHD), caused by larvae of the Echinococcus tapeworm, is the most common indication for hepatic operations in children residing in endemic regions of the world. Undifferentiated embryonic liver sarcoma and CHD are 2 diseases that share overlapping presenting features of patient age, symptoms, and radiologic appearance. Surgeons who operate in Echinococcal endemic regions must be aware that not all hepatic cystic masses are necessarily CHD and may be other more rare malignant diseases such as UELS.

Resolution of pulmonary hypertension with low-molecular-weight heparin, steroid, and prostacyclin analogue therapy: could it be early-phase pulmonary veno-occlusive disease?

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension. The authors present a case of neuroblastoma with progressive dyspnea, hypoxemia, and pulmonary hypertension. A computed tomography scan of the chest revealed septal thickening and diffuse micronodules. The patient was diagnosed as PVOD and was successfully treated with low-molecular-weight heparin (LMWH) and corticosteroid.

Comparison of safety and effectiveness of two different transfusion rates in children with severe anemia.

We compared the safety and efficacy of 2 transfusion regimens in children with severe anemia (hemoglobin <5 g/dL) and without overt signs of congestive heart failure requiring transfusion of packed red blood cells (PRBCs). Forty-three patients were randomly divided into 2 groups: group A and group B. The transfusion regimens consisted of continuous infusion of PRBC at a rate of 1 mL/kg/h for group A and 3 mL/kg/h for group B. The patients were closely monitored for any clinical signs of heart failure throughout transfusion. Heart and respiratory rate, and arterial blood pressure were measured hourly for 6 hours during transfusion. None of the patients developed any signs of cardiac failure during or after the transfusion. The mean heart rate, respiratory rate, diastolic and systolic blood pressure were similar in both groups throughout transfusion. Group A needed significantly more PRBC units than group B to attain the same hemoglobin increase. Transfusion of PRBC at a rate of 3 mL/kg/h, and at a rate of 1 mL/kg/h, is a safe regimen for children with severe anemia of gradual onset requiring transfusion therapy.

Clinical, electrocardiographic, and laboratory findings in children with amitriptyline intoxication.

BACKGROUND: Amitriptyline is one of the major tricyclic antidepressants, and the data on amitriptyline poisoning in children are limited. OBJECTIVES: To present our experiences with amitriptyline poisoning in children, particularly with regard to its effects on electrocardiogram (ECG) and relation with clinical status. METHODS: Clinical, laboratory, and electrocardiographic findings in 52 children admitted with amitriptyline poisoning were reviewed. Patients were divided into 2 groups according to age, as 6 years or younger (group A) and older than 6 years (group B). RESULTS: Mean age was 4.6 +/- 3.0 years. Thirty-one patients were male, and 41 were 6 years or younger. Ingested amitriptyline dose was known in 23 patients (range, 2.3 mg/kg-27 mg/kg). The most frequent findings were lethargy (76.9%), sinus tachycardia (57.7%), and coma (48.1%). Four patients had a history of convulsion. The most common laboratory abnormalities were hyponatremia (26.9%) and leukocytosis (25%). Elevated transaminase levels were observed in 4 patients. In ECG, 11 (22.4%) patients had QTc prolongation and in 4 (8.2%) of them, it was significant. In 4 patients (8.2%), the QRS duration was 100 ms or longer and in 15 patients, the R wave in aVR was 3 mm or longer. The frequencies of clinical, laboratory, and electrocardiographic findings were similar between the 2 age groups (P > 0.05). No clinically apparent arrhythmias were observed. The positive predictive value of a widened QRS was 100% in terms of coma. None of the patients with an R wave in aVR of less than 3 mm developed convulsion; thus, the negative predictive value of an R wave in aVR of 3 mm or longer was 100% in terms of convulsion. CONCLUSIONS: Amitriptyline poisoning may result in severe toxicity. Frequencies of clinical, laboratory, and ECG findings were similar in the 2 age groups. Amitriptyline overdose results in some ECG changes that can possibly help to predict the results of poisoning. Absence of an R wave in aVR of 3 mm or longer predicts seizures with a high negative predictive value, and a QRS duration of 100 or longer ms predicts coma with a high positive predictive value.

Prevalence of vitamin D deficiency rickets in the eastern part of Turkey.

Turkey, especially its eastern part, has been accepted as endemic for vitamin D deficiency rickets (VDDR). In a study performed by our team in the region in 1998, the incidence of VDDR was 6.09% in children aged between 0-3 years. In 2005, the Ministry of Health initiated a free vitamin D supplementation campaign nationwide for every infant to eradicate VDDR. In this study, we aimed to investigate the prevalence of VDDR in children aged between 0-3 years in order to evaluate the effectiveness of this campaign. Between March 2007 and February 2008, 39,133 children aged between 0-3 years who were brought to different pediatric outpatient clinics in Erzurum, Turkey, were examined for VDDR. VDDR diagnosis was made by radiological and biochemical findings in the cases who were initially suspected of having clinical VDDR. During a one-year period, 39 (0.099%) of the 39,133 patients were diagnosed with VDDR. None of the cases with rickets was taking vitamin D supplementation. The most frequent physical findings were rachitic rosary, enlargement of the wrists, and craniotabes. The laboratory findings of the cases were compatible with VDDR; serum calcium (Ca) 7.5 +/- 1.9 mg/dL, PO4 4.4 +/- 1.3 mg/dL, alkaline phosphatase (ALP) 1,341 +/- 823, 25-hydroxyvitamin D (25 (OH) D) 5.8 +/- 2.9 ng/mL, intact parathyroid hormone (iPTH) 240 +/- 106 pg/mL. It was concluded that, although VDDR has been a continuing childhood health problem, a nationwide free vitamin D supplementation campaign initiated by the government appeared to be effective in eliminating VDDR.

Late side effects of high-dose steroid therapy on skeletal system in children with idiopathic thrombocytopenic purpura.

Corticosteroids have been widely used in the treatment of idiopathic thrombocytopenic purpura (ITP). We evaluated the late side effects of high-dose methylprednisolone (HDMP) therapy on bone metabolism in children with ITP. Twenty-eight children with acute ITP treated with HDMP (30 mg/kg/d for 3 d then 20 mg/kg/d for 4 d) and 28 controls were enrolled in the study. Bone mineral density (BMD), urinary calcium creatinine ratio, urinary levels of deoxypyridinoline, serum levels of calcium, phosphate, parathyroid hormone, total alkaline phosphatase, and bone-specific alkaline phosphatase were measured in both groups. Magnetic resonance imaging of the femoral head was performed only in study group. The mean levels of serum phosphate, parathyroid hormone, urinary deoxypyridinoline, and calcium creatinine ratio were significantly increased in the study group. There was no significant difference between the 2 groups in terms of serum calcium, total alkaline phosphatase, bone-specific alkaline phosphatase, and BMD values. There was a statistically significant negative correlation between cumulative steroid dose and BMD values in study group (r = -0.379). Osteonecrosis was observed in 3 of 25 patients by magnetic resonance imaging. In conclusion, HDMP therapy, especially in high cumulative doses, increases the bone resorption and may cause osteonecrosis in children with ITP.

Vacuolated cells in bone marrow aspirate of children with neuroblastoma.

Cytoplasmic vacuoles that have been seen in FAB L3-type lymphoblasts are not usual in neuroblastoma. The authors report three children with neuroblastoma having vacuolated cells mimicking L3-type lymphoblasts on bone marrow aspiration smears.

Isolated left ventricular noncompaction in children: two cases with different manifestations.

Isolated noncompaction of the ventricular myocardium is an uncommon disorder characterized by an excessively prominent trabecular meshwork seen in the early period of embryogenesis. The clinical presentation of noncompaction includes a high prevalence of heart failure, thromboembolic events and arrhythmias. Echocardiography is the procedure of choice for the diagnosis of noncompaction. We report two demonstrative patients with isolated noncompaction of the left ventricular myocardium and review the available related literature.

Ovarian volume and uterine length in neonatal girls.

This study was undertaken to establish reference values for the size of the uterus and ovaries in newborns. We also studied the frequency and follow-up of functional ovarian cysts in healthy neonatal girls. Pelvic ultrasonography was performed on 55 normal newborns. Right and left ovarian volumes positively correlated with birth weight and length, but there was no correlation between uterine length and any of the parameters studied. In a total of 55 newborns, 16 ovarian cysts were detected by transabdominal ultrasound: six neonates (10.9%) had cysts on the left side, ten (18.2%) on the right side, and two (3.6%) had bilateral cysts. All were uncomplicated homogeneous cysts and resolved spontaneously. A higher percentage of cysts was found in the 26 infants weighing 2,500-2,999 g, ten (38.4%) of whom had cysts, than in the 29 infants weighing 3,000 g or more, four (13.7%) of whom had cysts (p < 0.05). Newborns with cysts were followed up, and the cysts resolved spontaneously within 3 months in all but three patients in whom resolution took almost 6 months. Right and left ovarian volumes were positively correlated with birth weight and length, but no significant correlation was found between uterine length and any parameter. In conclusion, ovarian volume was found to be reduced in newborns with relatively low birth weight as well as intra-uterine growth retardation. Functional cysts were more prevalent among low birth weight girls. We suggest that small ovaries and ovarian dysfunction may have a prenatal origin, and further studies on normal and growth-retarded newborns are needed.