Sophia Polychronopoulou

In vitro fertilization and risk of childhood leukemia in Greece and Sweden.

Cancer risk in children born after in vitro fertilization (IVF) remains largely unknown. We aimed to investigate risk of leukemia and lymphoma following IVF using two nationwide datasets.

Parental Occupational Pesticide Exposure and the Risk of Childhood Leukemia in the Offspring: Findings From the Childhood Leukemia International Consortium

Maternal occupational pesticide exposure during pregnancy and/or paternal occupational pesticide exposure around conception have been suggested to increase risk of leukemia in the offspring. With a view to providing insight in this area we pooled individual level data from 13 case‐control studies participating in the Childhood Leukemia International Consortium (CLIC). Occupational data were harmonized to a compatible format. Pooled individual analyses were undertaken using unconditional logistic regression. Using exposure data from mothers of 8,236 cases, and 14,850 controls, and from fathers of 8,169 cases and 14,201 controls the odds ratio (OR) for maternal exposure during pregnancy and the risk of acute lymphoblastic leukemia (ALL) was 1.01 [95% confidence interval (CI) 0.78, 1.30] and for paternal exposure around conception 1.20 (95% 1.06, 1.38). For acute myeloid leukemia (AML), the OR for maternal exposure during pregnancy was 1.94 (CI 1.19, 3.18) and for paternal exposure around conception 0.91 (CI 0.66, 1.24.) based on data from 1,329 case and 12,141 control mothers, and 1,231 case and 11,383 control fathers. Our finding of a significantly increased risk of AML in the offspring with maternal exposure to pesticides during pregnancy is consistent with previous reports. We also found a slight increase in risk of ALL with paternal exposure around conception which appeared to be more evident in children diagnosed at the age of 5 years or more and those with T cell ALL which raises interesting questions on possible mechanisms.

Burnout, staff support, and coping in Pediatric Oncology.

Goals of workThe goals of the study were the following: (1) to study the rate of burnout of the staff in Pediatric Oncology and compare it with that of a group of staff in other pediatric specialties, (2) to find out if job satisfaction, role clarity, staff support, and ways of coping are related to the burnout of these two groups, and (3) as a secondary aim, to identify other parameters, i.e., profession, experience, having children, etc., which might affect burnout, staff support, and ways of coping.Materials and methodsThe study group (n = 58) consisted of the staff of two Pediatric Oncology units and a Bone Marrow Transplantation unit, and the control group (n = 55) consisted of the staff of two Pediatric departments and one Pediatric Orthopedics department. The Maslach Burnout Inventory, the Staff Support Questionnaire, the Shortened Ways of Coping Questionnaire—Revised, and the Social Readjustment Scale were used.Main resultsNo differences were found in burnout between Pediatric Oncology staff and that of other specialties, the existing staff support, and the ways of coping. Decreased role clarity and wishful thinking, as a way of coping, were positively correlated to emotional exhaustion, whereas a negative correlation of the lack of role clarity existed with personal accomplishment. Not having children and less experience increased burnout in both groups studied.ConclusionsThe hospital management and the heads of departments should be knowledgeable of ways to prevent burnout in their staff. Strategies targeting role clarity and wishful thinking are useful toward this goal.

Maternal smoking during pregnancy and childhood lymphoma: a meta-analysis.

Results from epidemiological studies exploring the association between childhood lymphoma and maternal smoking during pregnancy have been contradictory. This meta‐analysis included all published cohort (n = 2) and case–control (n = 10) articles; among the latter, the data of the Greek Nationwide Registry for Childhood Hematological Malignancies study were updated to include all recently available cases (‐2008). Odds ratios (ORs), relative risks and hazard ratios were appropriately pooled in three separate analyses concerning non‐Hodgkin lymphoma (NHL, n = 1,072 cases), Hodgkin lymphoma (HL, n = 538 cases) and any lymphoma (n = 1,591 cases), according to data availability in the included studies. An additional metaregression analysis was conducted to explore dose–response relationships. A statistically significant association between maternal smoking (any vs. no) during pregnancy and risk for childhood NHL was observed (OR = 1.22, 95% confidence interval, CI: 1.03–1.45, fixed effects model), whereas the risk for childhood HL was not statistically significant (OR = 0.90, 95% CI: 0.66–1.21, fixed effects model). The analysis on any lymphoma did not reach statistical significance (OR = 1.10, 95% CI = 0.96–1.27, fixed effects model), possibly because of the case‐mix of NHL to HL. No dose–response association was revealed in the metaregression analysis. In conclusion, this meta‐analysis points to a modest increase in the risk for childhood NHL, but not HL, among children born by mothers smoking during pregnancy. Further investigation of dose–response phenomena in the NHL association, however, warrants accumulation of additional data.

Genetic variants in immunoregulatory genes and risk for childhood lymphomas

To investigate whether single nucleotide polymorphisms (SNPs) in key cytokine and innate immunity genes influence risk for childhood lymphomas, we genotyped 37 children with Hodgkin’s (HL) and 48 with non‐Hodgkin’s lymphoma (NHL), aged (1 month–14 yr), along with their 85 age‐ and gender‐matched controls suffering from mild medical conditions. Genotypic analysis was performed for 10 SNPs from nine genes with important role in immunoregulatory pathways (IL4, IL4R, IL6, IL10, IL12, IL18, TNFα, IFNγ, CD14). Analysis of SNPs genotypes revealed that the CD14 −159 C>T polymorphism was associated with significantly increased risk for HL regarding both the CC and CT genotypes (ORCC: 5.36; 95% CI, 1.30–22.14; P = 0.02, ORCT: 3.76; 95% CI, 1.00–14.16; P = 0.05). An indicative association between IL18−137 G>C polymorphism with the CC genotype and NHL did not reach, however, statistical significance (ORCC, 3.78; 95% CI, 0.87–16.38; P = 0.08). In conclusion, our findings suggest that genetic variation in the CD14–159 loci may be associated with childhood HL risk; these preliminary findings need to be further confirmed in sizeable multi‐centre studies along with determination of cytokines, which could provide an insight on the biologic basis underlying these findings.

Transient and chronic neutropenias detected in children with different viral and bacterial infections

AIM The aim of the study was to identify the relationship of acquired neutropenias with infections in childhood and to assess their course, complications, short and long-term outcome. METHOD During a two-year period, all children admitted to the pediatric ward with neutropenia were investigated for underlying infections with indices of infection, cultures of body fluids and serological tests. RESULTS Sixty-seven previously healthy children, aged (median, 25-75%) 0.7 years (0.2-1.5), were identified with neutropenia (frequency: 2.0%). An infectious agent was identified in 34/67 cases (50.7%) (viral infection: n=24, bacterial: n=10). In 50/67 (74.6%) children, neutropenia recovered within 2 months (transient neutropenia, TN), while in 17/67 (25.4%) of them it persisted for more than two months. Two years after diagnosis 50/67 children (74.6%) accepted to be reassessed. Of these children, 8/50 (16%) remained neutropenic (neutropenic children, NC), while 42/50 had recovered completely. CONCLUSION Neutropenia during childhood is usually transient, often following viral and common bacterial infections, does not present serious complications and in the majority, it resolves spontaneously. However, in a significant percentage of patients, neutropenia is discovered during the course of an infection, on a ground of a preceding chronic neutropenic status.

An integrated evaluation of socioeconomic and clinical factors in the survival from childhood acute lymphoblastic leukaemia: a study in Greece.

An evaluation of the role of socioeconomic factors in the survival of children with leukaemia, controlling for major clinical prognostic indicators, has been attempted in very few studies and the role of these factors may be different in various cultural settings. Our investigation aims to study the independent role of socioeconomic factors on the prognosis of childhood acute lymphoblastic leukaemia (ALL) in Greece. During a 7-year period (1996–2002) 293 cases of incident ALL were diagnosed and followed up in four Childhood Haematology-Oncology Units, which covered over half of all childhood ALL cases nationwide. At the time of diagnosis, information concerning age, gender, maternal schooling, maternal marital status, sibship size, distance of residence from the treating centre, attendance of day care centre and clinical information was recorded. The influence of these factors on survival was studied by modelling the data through Coxs proportional-hazards regression. After adjustment for clinical prognostic factors, children of mothers who were not currently married, were of low educational level or were living far from the treating centre tended to have lower survival (P-values 0.02, 0.14 and 0.08, respectively). There was also evidence that two factors that are predictive of disease occurrence, that is sibship size and attendance of day care centre, may also predict survival (P-values 0.04 and 0.26, respectively). In conclusion, socioeconomic factors are likely to influence survival from ALL at least in some sociocultural contexts. Moreover, there is evidence that factors that could affect incidence of ALL through modulation of herd immunity may also have prognostic implications for this disease.

Melatonin and Immunomodulation: Connections and Potential Clinical Applications

Melatonin is the main hormone secreted by the pineal gland in the human brain. It has a strong impact on the sleep-wake cycle and is considered a general modulator of the human circadian rhythm. Apart from these well-established properties, melatonin possesses immunomodulatory, antioxidative and antiinflammatory properties. The potential ability of this hormone to act synergistically with several cytokines by enhancing their antitumoral activity and dramatically decreasing their adverse effects has placed melatonin among the new and promising agents in cancer immunotherapy. The use of the neurohormone alone or in combination with cytokines and traditional chemotherapeutic drugs is currently under vigorous investigation. Experimental and clinical trials have already depicted some of the immunomodulatory and antitumor effects of melatonin, delineating the need for further research in this field.

Fulminant Aeromonas hydrophila infection during acute lymphoblastic leukemia treatment

Aeromonas hydrophila septicemia has a fulminant course and it has been usually reported in immunocompromised hosts and rarely among children with leukemia. High morbidity and mortality is associated with A hydrophila infections. We describe the case of a child with acute lymphoblastic leukemia who presented with septicemia due to A hydrophila. The patient presented with fever and skin discoloration during a febrile neutropenia episode, which rapidly evolved into bacteremia and extensive thigh suppuration, fasciitis, and myonecrosis. Apart from antibiotic treatment, surgical debridement to relieve compartment pressure and prevent further lower extremity compromise was promptly performed. Despite long delays in chemotherapy and an extensive tissue gap, primary closure of the involved area was possible with full cosmetic and functional limb recovery, and the patient has remained in clinical remission for more than 7 years.

Clinical and morphological features of paediatric myelodysplastic syndromes: a review of 34 cases

Background: The clinical and morphological spectrum of myelodysplastic syndromes (MDS) during childhood has not yet been completely documented. We herein present the clinical features and morphological data from peripheral blood (PB), bone marrow aspirates (BMA) and bone marrow biopsies (BMB) of a series of paediatric MDS patients, with particular emphasis on their specific morphological characteristics and their diverse underlying genetic background. Patients and methods: Thirty‐four patients with MDS (median age 8.45 y) were consecutively diagnosed and treated during a period of 15 y (1988–2002). Diagnosis was based on clinical manifestations, morphology of PB, BMA and BMB, and cytogenetic analysis of BM cells. Clonogenic methyl‐cellulose cell cultures were performed in 23/34 patients. Patients were categorized into group A [26 primary/de novo MDS, i.e. refractory anaemia (RA) 18, RA with excess of blasts (RAEB) 2, RAEB in transformation (RAEB‐t) 6] and group B (8 secondary MDS, i.e. RA 4, RAEB 1, RAEB‐t 3). Treatment options varied according to protocols active during the period of the study and the availability of a suitable BM donor. Survival probabilities were estimated using the Kaplan‐Meier method. Results: Dysplastic features of the erythroid, myeloid and megakaryocytic lineage were detected at BMA in 85%, 50% and 90% of the patients, respectively, while decreased cellularity was found at BMB in 21/34 patients (60%). RA patients of group A presented at BMB significant hypocellularity (14/18) as a prominent finding due to decrease of the myeloid (13/18 patients) and/or the megakaryocytic (14/18 patients) lineage. Hypocellularity in RA was accompanied by dysplasia of the erythroid (17/18 patients) and megakaryocytic (16/18 patients) lineage, the presence of abnormal localization of immature precursors (ALIP, 8/18 patients), fibrosis (5/18) and stromal changes (11/18). Chromosomal aberrations were revealed in 17/34 patients, of which monosomy 7 was present in seven. Cell cultures demonstrated abnormal myeloid and/or erythroid in vitro clonal growth pattern in all the examined patients. An associated disorder or inherited disease, was identified in 14/26 patients (54%) with primary MDS. Cumulative survival of group A patients was 44.2% (RA 66.6%, RAEB/RAEBt 14.6%; p= 0.001), and of the whole group 42.4%, at 14 y.