Neuroblastoma among children in Southern and Eastern European cancer registries: Variations in incidence and temporal trends compared to US.

Neuroblastoma comprises the most common neoplasm during infancy (first year of life). Our study describes incidence of neuroblastoma in Southern-Eastern Europe (SEE), including - for the first time - the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST)/Greece, compared to the US population, while controlling for human development index (HDI). Age-adjusted incidence rates (AIR) were calculated for 1,859 childhood (0-14 years) neuroblastoma cases, retrieved from 13 collaborating SEE registries (1990-2016), and were compared to those of SEER/US (N = 3,166; 1990-2012); temporal trends were assessed using Poisson regression and Joinpoint analyses. The overall AIR was significantly lower in SEE (10.1/million) compared to SEER (11.7 per million); the difference was maximum during infancy (43.7 vs. 53.3 per million, respectively), when approximately one-third of cases were diagnosed. Incidence rates of neuroblastoma at ages <1 and 1-4 years were positively associated with HDI, whereas lower median age at diagnosis was correlated with higher overall AIR. Distribution of primary site and histology was similar in SEE and SEER. Neuroblastoma was slightly more common among males compared to females (male-to-female ratio: 1.1), mainly among SEE infants. Incidence trends decreased in infants in Slovenia, Cyprus and SEER and increased in Ukraine and Belarus. The lower incidence in SEE compared to SEER, especially in infants living in low HDI countries possibly indicates a lower level of overdiagnosis in SEE. Hence, increases in incidence rates in infancy noted in some subpopulations should be carefully monitored to avoid the unnecessary costs health impacts of tumors that could potentially spontaneously regress.

Role of vaccinations and prophylaxis in rheumatic diseases.

Targeted strategies for reducing the increased risk of infection in patients with autoimmune rheumatic diseases include vaccinations as well as antibiotic prophylaxis in selected patients. However, there are still issues under debate: Is vaccination in patients with rheumatic diseases immunogenic? Is it safe? What is the impact of immunosuppressive drugs on vaccine immunogenicity and safety? Does vaccination cause disease flares? In which cases is prophylaxis against Pneumocystis jirovecii required? This review addresses these important questions to which clinicians and researchers still do not have definite answers. The first part includes immunization recommendations and reviews current data on vaccine efficacy and safety in patients with rheumatic diseases. The second part discusses prophylaxis for Pneumocystis pneumonia.

Mannose binding lectin and ficolin-2 polymorphisms are associated with increased risk for bacterial infections in children with B acute lymphoblastic leukemia.

BACKGROUND: We aimed to investigate whether the presence of mannose binding lectin (MBL2), ficolin 2 (FCN2) polymorphisms or the combined deficiency significantly influence the risk and subsequently the frequency of chemotherapy-induced bacterial infections in children with B acute lymphoblastic leukemia (B-ALL). PROCEDURE: MBL2 polymorphisms for exon 1 and FCN2 polymorphisms for promoter regions -986, -602, -557, -64, -4 and exon 8 regions +6,359, +6,424 were determined in children with B-ALL. FCN2 haplotype was determined by gene sequencing. Number and duration of FN episodes as well as number of bacterial infections were recorded during induction chemotherapy. RESULTS: Forty-four children with B-ALL (median age 4.3 years, 65.9% males) suffered from 142 FN episodes and 92 bacterial infections (40.2% Gram positive and 59.8% Gram negative). MBL2 low-risk genotype was found in 59.1%, medium-risk in 31.8% and high-risk in 9%. FCN2 low-risk haplotypes were detected in 38.2%, medium-risk in 44.1% and high-risk in 17.6%. MBL2 genotype and FCN2 haplotype were not associated with increased frequency of FN episodes. MBL2 medium/high-risk genotype and FCN2 medium/high-risk haplotype were associated with prolonged duration of FN (P = 0.007 and P = 0.001, respectively) and increased number of bacterial infections (P = 0.001 and P = 0.002, respectively). The combined MBL2/FCN2 medium/high-risk genotype was associated with an increased number of bacterial infections (P = 0.001). CONCLUSIONS: MBL2 and FCN2 single or combined deficiencies are associated with increased duration of FN episodes as well as increased number of bacterial infections in children with B-ALL suggesting a prognostic role of these genes.

Rare non-Wilms' tumors in children.

We report our institutional experience of the management of 2 cases of rare non-Wilms' tumors; a rhabdoid tumor in a 17-month old boy and a clear cell sarcoma in a 5-year old girl. The two patients were treated with ifosfamide/carboplatin/etoposide (ICE) alternating with vincristine/doxorubicin/cyclophosphamide (VDC) and cyclophosphamide/etoposide (CE) alternating with vincristine/doxorubicin/cyclophosphamide (VDC) and radiotherapy, respectively. Both patients showed full response with no significant adverse events. At 2-year follow up, they are disease and relapse free. Although contemporary treatment regimens are very promising, multicenter collaborative studies are needed in order to define a standard treatment for non-Wilms' tumors.

Candida hellenica var. hellenica as a possible cause of respiratory infection in a child with acute myeloid leukemia.

Candida hellenica var. hellenica (teleomorph Zygoascus meyerae) is a member of the genus Zygoascus that comprises species isolated from environmental sources such as damaged grapes. A case of a possible pneumonia due to this uncommon yeast in a pediatric oncology patient suffering from acute myeloid leukemia is described. To our knowledge, this is the first report concerning the isolation of the species from a pediatric patient and the second in humans.

Enterococcus faecalis: an unusual cause of meningitis in a child with non-Hodgkin lymphoma.

Enterococcal meningitis is an uncommon disease in children, most frequently reported in infants or in children with central nervous system pathology. We report a rare case of Enterococcus faecalis meningitis in an 11-year-old child with non-Hodgkin lymphoma. The patient during the course of chemotherapy became neutropenic, febrile, agitated, and disoriented with clinical signs of meningeal irritation. Culture of cerebrospinal fluid yielded Enterococcus faecalis. The patient was successfully treated with ampicillin without any neurological defects.

Fungal brain abscesses in leukemia.

Invasive fungal infections remain a life threatening complication in children with hematological malignancies. The brain represents a common site of hematogenously disseminated infections from an extracranial focus. We report our experience in the diagnosis, radiological aspects and therapeutic approach of fungal brain abscesses in 2 children receiving chemotherapy for acute lymphoblastic leukemia (ALL).

Bone mineral density in survivors of childhood acute lymphoblastic leukemia.

The aim of our study was to evaluate bone metabolism with measurement of bone mineral density (BMD) after management (chemo-, radiotherapy) for childhood acute lymphoblastic leukemia (ALL). Bone mineral density (g/cm2) of lumbar spine was measured by dual energy X-ray absorptiometry (Norland bone densitometer) in 18 children with ALL and a median of 34 months' post-diagnosis with no history of relapse, secondary malignancy, or transplantation. In addition, patients' BMDs were correlated with particular attention to age, sex and time (years) from completion of chemotherapy. The results were compared with healthy age- and sex-matched controls of the same population and expressed as standard deviation scores (SDS). Mean age of children was 9.8 +/- 3.7 years. Of 18 children (10 boys and 8 girls), 13 were grouped as standard and 5 as high-risk, respectively. Based on z-score values, 9 were classified as normal (z-score <1 SD), 7 as osteopenic (z-score 1-2.5 SD) and 2 as osteoporotic (z-score >2.5 SD). Children with ALL had reduced lumbar BMDs (z score -0.99) in comparison to healthy controls (z score -0.14) (p=0.011), which is indicative of relative osteopenia. Moreover, the reduced BMD was associated with patient age (z score -0.14 and -1.52 for ages <10 and >10 years, respectively, p=0.016). Reduced BMD was not correlated with time from completion of chemotherapy (p=0.33), risk group (p=0.9) and sex (p=0.3). We conclude that children's BMDs are reduced after completion of chemotherapy for ALL. The causes are multifactorial and mainly related to antineoplastic treatments, such as corticosteroids and methotrexate, physical inactivity and cranial irradiation. We suggest that further studies are needed to evaluate the long-term effect on BMD in these children and to prevent pathological fractures later in life.

Spinal epidural extraskeletal Ewing sarcoma in an adolescent boy: a case report.

Extraskeletal Ewing sarcoma (EES) represents a rare soft tissue malignant neoplasm histologically similar to skeletal Ewing sarcoma. It occurs mainly in adolescents and young adults and commonly affects the paravertebral regions. The differential diagnosis includes other small, blue round cells tumors. The authors report a case of an EES involving the spinal epidural and paravertebral spaces in an adolescent boy. EES diagnosis was confirmed by features of histologic analysis and immunohistochemistry and by the presence of the t(11;22)(q24;q12) chromosomal translocation by reverse transcriptase-polymerase chain reaction.

Metabolic syndrome in children and adolescents with acute lymphoblastic leukemia after the completion of chemotherapy.

The metabolic syndrome is a cluster of potent risk factors for cardiovascular diseases. To provide information on the late complications of chemotherapy for acute lymphoblastic leukemia (ALL), the authors prospectively studied the frequency of overweight, obesity, and metabolic syndrome in survivors of ALL in the initial years after the completion of therapy. Children and adolescents were classified as having the metabolic syndrome if they met three or more of the following criteria: hypertriglyceridemia, low levels of high-density lipoprotein (HDL), high fasting glucose, obesity, and hypertension. Obesity was defined on the basis of Body Mass Index (BMI) (kg/m2) standard deviation scores or z-scores. Cutoff points for triglycerides and HDL were taken from equivalent pediatric percentiles with the cutoff points proposed by the Adult Treatment Panel III (ATPIII). Hyperglycemia was defined using the ATPIII cutoff points. Elevated systolic or diastolic blood pressure was defined as a value greater than the 95th percentile for age, gender, and height. Fifty-two subjects (29 male and 23 female) with a median age of 15.2 years (range 6.1-22.6 years) were evaluated. Median interval since completion of therapy was 37 months (range 13-121 months). All of them had been treated according to the ALL-BFM 90 chemotherapy protocol and none had received cranial radiotherapy. Of the 52 subjects, 25 (48%) were overweight (BMI z-score >1.5) and 3 (5.76%) were obese (BMI z-score >2); among them, 1 was severely obese (BMI z-score >2.5). Three criteria for the metabolic syndrome (high triglyceride levels, glucose intolerance, and obesity) were fulfilled by three subjects (5.76%). Twenty-nine subjects (55.7%) had at least one risk factor for metabolic syndrome. Hyperglycemia and hypertension were infrequent. Prompt recognition of the risk factors for metabolic syndrome and intervention seem mandatory to ensure early prevention of cardiovascular disease in survivors of ALL.

Evaluation of bone metabolism in children with acute lymphoblastic leukemia after induction chemotherapy treatment.

Osteopenia and osteoporosis are currently receiving particular attention as late effects of therapy in survivors of childhood acute lymphoblastic leukemia (ALL). The aim of this study was to evaluate abnormalities in bone mass and mineral homeostasis in children with ALL after induction therapy (during consolidation treatment). Lumbar spine (L2-L4) bone mineral density (BMD, g/cm(2)) was measured by dual energy X-ray absorptiometry in 20 children with ALL, a median of 25.9 months postdiagnosis and results were expressed as z-scores relative to healthy Caucasian children (controls). Serum levels of intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), calcium, phosphate, and magnesium were also analyzed. In addition, the body mass indexes (kg/cm(2)) of patients and controls were calculated. Results were compared with those of 40 healthy controls. Among the 20 children with ALL (12 boys and 8 girls), 12 presented z-scores < 1 SD (normal) and 8 were osteopenic (z-score between 1 and 2.5 SD). In addition, children with ALL had reduced lumbar BMDs (z-score -0.817) in comparison to healthy controls (z-score -0.353) (p = .04). Moreover, alkaline phosphatase and intact parathyroid hormone values were significantly increased compared to controls values. The data demonstrate that bone metabolism in children with ALL during consolidation therapy is disturbed, resulting in a reduced BMD and z-score with respect to healthy controls. Since a reduced BMD predisposes to osteopenia and osteoporosis, specific attention and therapeutic interventions should be considered.