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A single-step impregnation approach is investigated as a synthetic route for photocatalyst synthesis active under visible light. The as-derived photocatalysts exhibited very high degradation rates towards methylene blue (MB) decolorization under visible light despite the high concentration of the initial MB solution concentration. The TiO2-based photocatalysts were prepared using nitrate precursor compounds for copper and silver; thus, Ag/TiO2 and Cu/TiO2 photocatalysts were prepared. The photocatalyst’s physicochemical properties were determined by XRF, BET, and XRD analysis. The metal nature of the titania substrate, the titania matrix effect, and the metal concentration parameters were studied, while the catalyst concentration in the MB initial solution was optimized.

The etiology of childhood neuroblastoma remains largely unknown. In this systematic review and meta-analysis, we summarized and quantitatively synthesized published evidence on the association of maternal modifiable lifestyle factors with neuroblastoma risk in the offspring. We searched MEDLINE up to December 31, 2020 for eligible studies assessing the association of maternal smoking, alcohol consumption and nutritional supplementation during pregnancy with childhood (0–14 years) neuroblastoma risk. Random-effects models were run, and summary odds ratios (OR) and 95% confidence intervals (95% CI) on the relevant associations were calculated, including estimates derived from primary data (n = 103 cases and n = 103 controls) of the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) case control study (2009–2017) in Greece. Twenty-one eligible studies amounting 5163 cases participating in both case-control and cohort/linkage studies were included in the meta-analysis. Maternal smoking and alcohol consumption were not statistically significantly associated with neuroblastoma risk (summary ORsmoking: 1.08, 95% CI: 0.96–1.22, I2 =12.0%, n = 17 studies; summary ORalcohol: 1.01, 95% CI: 0.82–1.18, I2 =0.0%, n = 8 studies). By contrast, maternal vitamin intake during pregnancy was associated with significantly lower neuroblastoma risk (summary OR: 0.57, 95% CI: 0.34–0.95, I2 =58.9%, n = 4 studies). The results of the largest to-date meta-analysis point to an inverse association between vitamin intake during pregnancy and childhood neuroblastoma risk. Future longitudinal studies are needed to confirm and further specify these associations as to guide preventive efforts on modifiable maternal risk factors of childhood neuroblastoma. © 2022

Background: Despite overall striking advances in survival of childhood liver tumors, outcomes remain poor for specific patient segments. We aimed to assess overall survival (OS) of this rare disease and evaluate the generalizability of prognostic variables included in international collaborative systems using, for the first time, harmonized clinical data from two geographically different cohorts (Greece and Moscow). Methods: Data for children (0-14 years) with liver tumors were retrieved from two Southern-Eastern European areas (Greece; 2001-2019 and Moscow; 2012-2019). Kaplan-Meier curves were constructed, and OS values were derived from Cox proportional models controlling for study variables. Results: A total of 171 newly diagnosed cases (54.4% males) were included. The OS5-year exceeded 80% in patients

Aim: Evidence for an association of foetal growth with acute myeloid leukaemia (AML) is inconclusive. AML is a rare childhood cancer, relatively more frequent in girls, with distinct features in infancy. In the context of the Childhood Leukemia International Consortium (CLIC), we examined the hypothesis that the association may vary by age, sex and disease subtype using data from 22 studies and a total of 3564 AML cases. Methods: Pooled estimates by age, sex and overall for harmonised foetal growth markers in association with AML were calculated using the International Fetal and Newborn Growth Consortium for the 21st Century Project for 17 studies contributing individual-level data; meta-analyses were, thereafter, conducted with estimates provided ad hoc by five more studies because of administrative constraints. Subanalyses by AML subtype were also performed. Results: A nearly 50% increased risk was observed among large-for-gestational-age infant boys (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03–2.14), reduced to 34% in boys aged

Late cardiotoxicity following treatment of malignancy diseases has been long established. Cancer therapeutics-related cardiac dysfunction (CTRCD), acute arrhythmias, pericardial disease, valvopathies and early atherosclerotic Cardiovascular Disease (CVD), are the clinical presentations of cardiotoxicity. Although these clinical modalities can affect adults treated for malignancies, they are more common to present in the pediatric survivors as improvement of prognosis, nowadays exists. Studies have shown that CVD can present earlier than thirty years, post treatment. If adding on this the early and late effect of cardiotoxicity on the developing in childhood cardiovascular system, we are then faced with a new Risk Factor (RF) for CVD. Anthracyclines and its derivatives have served for over fifty years as the road model of studding early, mid and late term cardiotoxicity. Today a vast number of chemical agents are used, many of them with very good results in treating the existing malignancies. Unfortunate, little or even less are known on their potential mechanism of derived cardiotoxicity when used by their own or combined with others and/or radiotherapy (RT). The 2013 existing guidelines by ACC/AHA on surveillance of the cardiovascular health of oncology survivors, are mostly addressing early cardiac adverse effects and CTRCD. Little is mentioned about the development of early CVD, its subclinical diagnosis, prevention and the need of early intervention before clinical events are present. The aim of this paper is to review the exist knowledge and practice on this condition with growing numbers of survivors facing the risk of early atherosclerotic CVD.

Background: Wilms tumour (WT) management represents a success story in pediatric oncology. We aimed to assess, for the first time, the event-free survival (EFS) vs. overall survival (OS) in Southern and Eastern Europe (SEE) using harmonised clinical data collected by childhood cancer registries and to identify respective prognostic factors. Methods: From 1999 to 2017, data for incident WT cases aged 0–14 years from 3 nationwide (Greece, Belarus and Slovenia) and one regional (Greater Poland) SEE registries were collected following common coding. Kaplan–Meier curves were constructed, and EFS vs. OS values were derived from Cox proportional hazard models by study variables. Results: A total of 338 WT cases (45.6% males; median age, 3.19 years; age

Aim: Neuroblastoma outcomes vary with disease characteristics, healthcare delivery and socio-economic indicators. We assessed survival patterns and prognostic factors for patients with neuroblastoma in 11 Southern and Eastern European (SEE) countries versus those in the US, including—for the first time—the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumours (NARECHEM-ST)/Greece. Methods: Overall survival (OS) was calculated in 13 collaborating SEE childhood cancer registries (1829 cases, ∼1990–2016) and Surveillance, Epidemiology, and End Results (SEER), US (3072 cases, 1990–2012); Kaplan–Meier curves were used along with multivariable Cox regression models assessing the effect of age, gender, primary tumour site, histology, Human Development Index (HDI) and place of residence (urban/rural) on survival. Results: The 5-year OS rates varied widely among the SEE countries (Ukraine: 45%, Poland: 81%) with the overall SEE rate (59%) being significantly lower than in SEER (77%; p < 0.001). In the common registration period within SEE (2000–2008), no temporal trend was noted as opposed to a significant increase in SEER. Age >12 months (hazard ratio [HR]: 2.8–4.7 in subsequent age groups), male gender (HR: 1.1), residence in rural areas (HR: 1.3), living in high (HR: 2.2) or medium (HR: 2.4) HDI countries and specific primary tumour location were associated with worse outcome; conversely, ganglioneuroblastoma subtype (HR: 0.28) was associated with higher survival rate. Conclusions: Allowing for the disease profile, children with neuroblastoma in SEE, especially those in rural areas and lower HDI countries, fare worse than patients in the US, mainly during the early years after diagnosis; this may be attributed to presumably modifiable socio-economic and healthcare system performance differentials warranting further research. © 2018 Elsevier Ltd

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

Childhood (0-14 years) lymphomas, nowadays, present a highly curable malignancy compared with other types of cancer. We used readily available cancer registration data to assess mortality and survival disparities among children residing in Southern-Eastern European (SEE) countries and those in the United States. Average age-standardized mortality rates and time trends of Hodgkin (HL) and non-Hodgkin (NHL; including Burkitt [BL]) lymphomas in 14 SEE cancer registries (1990-2014) and the Surveillance, Epidemiology, and End Results Program (SEER, United States; 1990-2012) were calculated. Survival patterns in a total of 8918 cases distinguishing also BL were assessed through Kaplan-Meier curves and multivariate Cox regression models. Variable, rather decreasing, mortality trends were noted among SEE. Rates were overall higher than that in SEER (1.02/106), which presented a sizeable (−4.8%, P =.0001) annual change. Additionally, remarkable survival improvements were manifested in SEER (10 years: 96%, 86%, and 90% for HL, NHL, and BL, respectively), whereas diverse, still lower, rates were noted in SEE. Non-HL was associated with a poorer outcome and an amphi-directional age-specific pattern; specifically, prognosis was inferior in children younger than 5 years than in those who are 10 to 14 years old from SEE (hazard ratio 1.58, 95% confidence interval 1.28-1.96) and superior in children who are 5 to 9 years old from SEER/United States (hazard ratio 0.63, 95% confidence interval 0.46-0.88) than in those who are 10 to 14 years old. In conclusion, higher SEE lymphoma mortality rates than those in SEER, but overall decreasing trends, were found. Despite significant survival gains among developed countries, there are still substantial geographic, disease subtype-specific, and age-specific outcome disparities pointing to persisting gaps in the implementation of new treatment modalities and indicating further research needs. Copyright © 2016 John Wiley & Sons, Ltd.

Background Exploring the effect of maternal and/or childhood diet on offspring leukemogenesis is challenging, given differences in food group categories, their potentially variable impact depending on time window of exposure and the multiple leukemia subtypes. We opted to quantitatively synthesize published data on the association of maternal/child diet with leukemia risk. Methods Medline was searched until June 30th, 2016 for eligible articles on the association of childhood leukemia with consumption of (i) food groups, excluding alcoholic and non-alcoholic beverages, and (ii) specific dietary supplements before/during index pregnancy and childhood. Results Eighteen studies of case-control design (N = 11,720 cases/18,721 controls) were included, of which nine assessed maternal dietary components, five index child's and four both, mainly focusing on acute lymphoblastic leukemia (ALL). Statistically significant inverse estimates for ALL were found (2 studies, 413 cases, 490 controls) for fruit (OR: 0.81, 95% CI: 0.67, 0.99); vegetables (OR: 0.51, 95% CI: 0.28, 0.94); legumes (OR: 0.76, 95% CI: 0.62, 0.94); fish (OR: 0.27, 95% CI: 0.14, 0.53, among the 0–4 year old; 2 studies 215 cases, 215 controls); preconception folic acid supplementation (OR: 0.69, 95%CI: 0.50–0.95; published meta analysis plus 2 studies, 3511 cases, 6816 controls); and use of vitamins during pregnancy (OR: 0.81, 95%CI: 0.74–0.88; published meta analysis plus one study, 5967 cases, 8876 controls). The associations (2 studies) of the remaining food groups and maternal dietary supplements consumption during pregnancy as well as of childhood diet and supplements intake (2–4 studies) were non significant. Conclusions Maternal consumption of specific food groups comprising“healthy” items of the Mediterranean diet, preconception use of folic acid and intake of vitamins during pregnancy were associated with decreased ALL risk. Further research is needed, however preferably with homogeneous dietary information and data on immunophenotypic/cytogenetic subtypes to also explore the interaction of specific macro- and micronutrients intake with gene polymorphisms. © 2017

Purpose: To describe epidemiologic patterns of childhood (0–14 years) lymphomas in the Southern and Eastern European (SEE) region in comparison with the Surveillance, Epidemiology and End Results (SEER), USA, and explore tentative discrepancies. Methods: Childhood lymphomas were retrieved from 14 SEE registries (n = 4,702) and SEER (n = 4,416), diagnosed during 1990–2014; incidence rates were estimated and time trends were evaluated. Results: Overall age-adjusted incidence rate was higher in SEE (16.9/106) compared to SEER (13.6/106), because of a higher incidence of Hodgkin (HL, 7.5/106 vs. 5.1/106) and Burkitt lymphoma (BL, 3.1 vs. 2.3/106), whereas the incidence of non-Hodgkin lymphoma (NHL) was overall identical (5.9/106 vs. 5.8/106), albeit variable among SEE. Incidence increased with age, except for BL which peaked at 4 years; HL in SEE also showed an early male-specific peak at 4 years. The male preponderance was more pronounced for BL and attenuated with increasing age for HL. Increasing trends were noted in SEER for total lymphomas and NHL, and was marginal for HL, as contrasted to the decreasing HL and NHL trends generally observed in SEE registries, with the exception of increasing HL incidence in Portugal; of note, BL incidence trend followed a male-specific increasing trend in SEE. Conclusions: Registry-based data reveal variable patterns and time trends of childhood lymphomas in SEE and SEER during the last decades, possibly reflecting diverse levels of socioeconomic development of the populations in the respective areas; optimization of registration process may allow further exploration of molecular characteristics of disease subtypes. © 2016, Springer International Publishing Switzerland.

Despite the putative intrauterine origins of childhood (0-14 years) leukaemia, it is complex to assess the impact of perinatal factors on disease onset. Results on the association of maternal history of fetal loss (miscarriage/stillbirth) with specific disease subtypes in the subsequent offspring are in conflict. We sought to investigate whether miscarriage and stillbirth may have different impacts on the risk of acute lymphoblastic leukaemia (ALL) and of its main immunophenotypes (B-cell and T-cell ALL), as contrasted to acute myeloid leukaemia (AML).One thousand ninety-nine ALL incidents (957 B-ALL) and 131 AML cases along with 1:1 age and gender-matched controls derived from the Nationwide Registry for Childhood Hematological Malignancies and Brain Tumors (1996-2013) were studied. Multivariable regression models were used to assess the roles of previous miscarriage(s) and stillbirth(s) on ALL (overall, B-, T-ALL) and AML, controlling for potential confounders.Statistically significant exposure and disease subtype-specific associations of previous miscarriage(s) exclusively with AML [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.00, 2.81] and stillbirth(s) with ALL [OR 4.82, 95% CI 1.63, 14.24] and B-ALL particularly, emerged.Differential pathophysiological pathways pertaining to genetic polymorphisms or cytogenetic aberrations are likely to create hostile environments leading either to fetal loss or the development of specific leukaemia subtypes in subsequent offspring, notably distinct associations of maternal miscarriage history confined to AML and stillbirth history confined to ALL (specifically B-ALL). If confirmed and further supported by studies revealing underlying mechanisms, these results may shed light on the divergent leukemogenesis processes.

Background: Despite advancements in the treatment of childhood leukemia, socioeconomic status (SES) may potentially affect disease prognosis. This study aims to evaluate whether SES is associated with survival from childhood leukemia. Methods: The US National Cancer Institute Surveillance, Epidemiology and End Results Program (SEER) 1973-2010 data were analyzed; thereafter, results were meta-analyzed along with those from survival (cohort) studies examining the association between SES indices and survival from childhood leukemia (end-of-search date: 31 March 2014). Randomeffects models were used to calculate pooled effect estimates (relative risks, RRs); meta-regression was also used. Results: We included 29 studies yielding 28 804 acute lymphoblastic leukemia (ALL), 3208 acute myeloblastic leukemia (AML) and 27 650 'any' leukemia (denoting joint reporting of all subtypes) cases. According to individual-level composite SES indices, children from low SES suffered from nearly twofold higher death rates from ALL (pooled RR: 1.83, 95% confidence interval 1.00-3.34, based on four study arms); likewise, death RRs derived from an array of lower area-level SES indices ranged between 1.17 and 1.33 (based on 11 study arms). Importantly, the survival gap between higher and lower SES seemed wider in the United States, with considerably (by 20%-82%) increased RRs for death from ALL in lower SES. Regarding AML, poorer survival was evident only when area-level SES indices were used. Lastly, remoteness indices were not associated with survival from childhood leukemia. Conclusion: Children with lower SES suffering childhood leukemia do not seem to equally enjoy the impressive recent survival gains. Special health policy strategies and increased awareness of health providers might minimize the effects of socioeconomic disparities. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Purpose A balanced chromosomal translocation, t(15;19), resulting in the BRD4-NUT oncogene, has been identified in a lethal carcinoma of young people, a disease described primarily in case reports. We sought to amass a more definitive series of tumors with NUT and/or BRD4 gene rearrangements and to determine distinct clinicopathologic features. Patients and Methods Carcinomas (N = 98) in young individuals (median age, 32.5 years) were screened for NUT and BRD4 rearrangements using dual-color fluorescence in situ hybridization. Four published carcinomas with BRD4 and NUT rearrangements were also evaluated. Immunophenotypic analyses were performed. Results Eleven tumors had NUT gene rearrangements, including eight with BRD4-NUT fusions and three with novel rearrangements, which were designated as NUT variant. All NUT-rearranged carcinomas (NRCs) arose from midline epithelial structures, including the first example arising below the diaphragm. Patients were young (median age, 17.6 years). Squamous differentiation (seen in 82% of NRCs) was particularly striking in NUT-variant cases. In this first description of NUT-variant carcinomas, the average survival (96 weeks, n = 3) was longer than for BRD4-NUT carcinomas (28 weeks, n = 8). Strong CD34 expression was found in six of 11 NRCs but in zero of 45 NUT wild-type carcinomas. Conclusion NRCs arise from midline structures in young people, and NRCs with BRD4-NUT are highly lethal, despite intensive therapies. NUT-variant carcinomas might have a less fulminant clinical course than those with BRD4-NUT fusions. CD34 expression is characteristic in NRCs and, therefore, holds promise as a diagnostic test for this distinctive clinicopathologic entity.

Pediatric oncology patients are often iron overloaded, due to the multiple blood transfusions necessary during the course of chemotherapy. Our aim is to report the efficacy and safety of deferasirox, an oral iron chelator, in this patient group. Deferasirox was administered to 13 children with malignancies in remission and iron overload. Ferritin, blood urea nitrogen, creatinine, transaminases, and bilirubin were recorded at 4-to 8-week intervals, and hepatic and cardiac iron overload were assessed with magnetic resonance imaging before initiation of treatment. Deferasirox was administered for an average of 6 months (SD=4.5; range, 0.3 to 18.2). Two children presented with skin rash, 1 with gastrointestinal disturbances, and 1 with fully reversible acute renal failure. The mean monthly rate of change in ferritin levels was-10.8 μg/L before initiation of treatment (95% confidence interval [CI],-19.8 to-1.8; P=0.02) and-93.6 μg/L during deferasirox treatment (95% CI,-118.1 to-69.1; P

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. Int J Cancer

Background: Monitoring time trends in the incidence of childhood leukaemias and lymphomas requires efficient and continuous data collecting systems. In countries without official cancer registries, such as Greece, ad hoc nationwide registration of incident childhood leukaemias and lymphomas could help elucidate the underlying aetiology and monitor socioeconomic differentials in health care delivery. Methods: We registered all cases and produced age, gender, type and immunophenotype specific figures and overall crude and age adjusted annual incidence rates and secular trends for 863 leukaemia and 311 lymphoma incident cases diagnosed in children,15 years of age across Greece during 1996-2006, namely the first 11 years of the Nationwide Registry for Childhood Hematological Malignancies. Results: The epidemiological profiles of leukaemias/lymphomas in Greece are similar to those in industrialised countries. No secular trends are observed for either malignancy during the studied period. However, the calculated incidence for leukaemia (46.60 cases per 1 million children annually) is among the highest in the EU-27 (19% higher than average; p < 0.001), whereas that for lymphoma (16.8 cases per 1 million children annually) is around the EU-27 average. Conclusions: Minimal secular changes in childhood leukaemias/lymphomas have been noted recently in the EU-27, which cannot be easily explained in countries with small populations. Therefore, centralised EU databases such as the Automated Childhood Cancer Information System (ACCIS) should be enlarged to generate sufficient statistical power for monitoring time trends. It would be interesting to explore whether different lifestyle patterns across the EU might be responsible for the observed excess leukaemia incidence in countries such as Greece.

Desmoplastic small round cell tumor (DSRCT) is a rare neoplasm with aggressive behavior. Usually it presents as a peritoneal mass, although other cases in various locations have been described. Since less than 10 cases of primary DSRCT in the pleura have been described, it is of interest to report a pediatric case arising from the pleura. The diagnosis was confirmed by molecular detection of the EWS/WT-1 fusion gene product. Multidisciplinary treatment with chemotherapy, radiotherapy, and surgical resection resulted in a progression-free survival time above the median survival, suggesting that this conventional approach could prove effective for this rare and very aggressive malignancy.

Accurate detection of the abnormal clone in children with persistent cytopenia (PC) may confirm the diagnosis of myelodysplastic syndrome (MDS) and determine prognosis and evolution of the disease. Bone marrow (BM) samples were obtained from 65 children, 11 of which were finally diagnosed as primary or secondary MDS. Ten to 20 G-banded metaphases were analyzed and FISH was performed using a-satellite probes for chromosomes 7 and 8. Conventional cytogenetic analysis (CCA) was successful in 40/65 samples, revealing clonal aberrations in 3 patients with MDS. FISH was successful in all cases, detecting monosomy 7 and trisomy 8 abnormal clones in 5 patients. Abnormalities were identified in 3/6 children with primary MDS and 3/5 with secondary MDS. None of the patients with PC of etiology other than MDS had a clonal abnormality in the BM. The results confirm the high incidence of chromosome abnormalities in childhood MDS and the sensitivity of FISH in detecting minor abnormal clones.

Hydroxyurea (HU) is an oral drug that ameliorates the clinical course of sickle cell anemia by &#175 increasing the levels of fetal hemoglobin and decreasing the adhesion of red cells to endothelium. Although HU has minimal short-term toxicity, few data are available about the long-term safety and the potential risk for carcinogenesis or leukemogenesis. An 8-year-old child with sickle cell / &#103 0- thalassemia who received HU treatment for painful crises is described. Six months after the initiation of the HU treatment he developed Hodgkin's disease, lymphocyte predominance subtype. Chemotherapy induced a complete remission. After discontinuation of chemotherapy the painful crises recurred and bone marrow transplantation was decided at the age of 12 years. Two years after the bone marrow transplantation, the child is in complete remission without painful crises. Although the authors suggest that the development of Hodgkin's disease is a coexisting event, questions arise about the safety of HU treatment ...

The purpose of this paper is to present the first case of gingival overgrowth, premature root resorption, and alveolar bone loss, which preceded the diagnosis of a stage IVB Hodgkin's lymphoma (HL) in a 9-year-old boy.The child presented complaining of gingival pain which first appeared 3 months prior. Clinical examination revealed inflamed, hyperplastic gingivae, while x-ray showed premature root resorption and alveolar bone loss. Medical work-up was significant for cervical lymphadenopathy. Gingival biopsy, followed by lymph node resection, was performed twice.Histological examination of both gingival biopsies disclosed a mixed inflammatory infiltrate, while classical Hodgkin's lymphoma of the nodular sclerosis type was diagnosed from the second lymph node biopsy. Chemotherapy was instituted with mustard-vincristine-procarbazine-prednizone and adriamycine-bleomycine-vinblastine-dacarbazine. Remission of the lymphoma was observed with concomitant regression of the gingival overgrowth.The inflammatory gingival overgrowth, premature root resorption of deciduous teeth, and alveolar bone loss in this case, in conjunction with the regression of gingival overgrowth which followed the completion of chemotherapy, are strongly indicative of a paraneoplastic manifestation of HL. The postulated mechanism for the development of the manifestation is the constitutive activation of the transcription factor NF-kB. The gingival inflammatory reaction was probably further aggravated by the bacterial-stimulated cytokine secretion released by monocytes.

Non-Hodgkin's lymphomas (NHL) were often erroneously diagnosed as other malignancies and treated accordingly. In this study cisplatin combined with vincristine, cyclophosphamide, and Adriamycin was used incidentally as a front-line treatment in seven children with NHL, because the initial histologic diagnosis was that of a sarcoma. After reevaluation three patients had Ki-1 anaplastic large cell lymphoma of T-cell origin, two abdominal B-cell diffuse high-grade NHL, one mediastinal diffuse large B-cell lymphoma, and one B-cell lymphoma in the stomach. They received at least two courses of cisplatin combined regimen and continued with other protocols for NHL. All patients showed an extremely good response from the first course of therapy and the masses vanished completely. They were followed up for a mean time of 29.5 months and are all in complete remission. The data indicate that cisplatin is active against NHL and might be a promising alternative front-line therapy.

Editor,—Papanicolaou et al 1 reported their experience of using abdominal ultrasound for the preclinical diagnosis of neuroblastoma in seven infants. The authors suggest that this may be a useful screening technique and urge paediatricians to perform this examination as it is “non-invasive, painless, and safe”. Unfortunately, the authors are clearly unaware of the controversy which surrounds infant screening for neuroblastoma. It has been used throughout Japan since 1985 and has been studied in Europe and North America.2 Screening infants for neuroblastoma greatly increases the observed cumulative incidence of the disease, and up to 75% of all infants detected by biochemical screening have tumours which would otherwise have undergone spontaneous regression and would …

The activity of the enzymes 5-formyl tetrahydrofolate cyclodehydrase and 5,10-methenyl tetrahydrofolate cyclohydrolase has been studied cytochemically in children's primary brain tumors. These enzymes play a significant role in purine biosynthesis. Thirty children, aged 1-12 years, were studied, 12 with medulloblastoma, 14 with glioma grade I-IV, and 4 with ependymoma. The activity of the enzymes was apparent as cytoplasmic granules that sometimes overlie the nucleus of the tumor cells. This coincidence showed that different types of brain tumors exhibit different degrees of enzymic activity, which in some cases correlated positively with the malignant potential of the tumor. Approximately one third of the cases were negative for any activity of these enzymes. The intensity of the staining of 5,10-methenyl tetrahydrofolate cyclohydrolase activity was actually higher than that of 5-formyl tetrahydrofolate cyctodehydrase. The clinical or prognostic significance of these findings remains to be clarified, but we believe that cylochemistry provides a sensitive technique for the detection, localization, and description of these enzymes in brain tumor cells. A clear understanding of the mode of action of these enzymes may contribute to devising novel therapeutic strategies.

In acute lymphoblastic leukemia (ALL) the apoptosis of blast cells in peripheral blood (PB) and bone marrow before and/or during treatment, is of great interest. As the morphological changes during apoptosis provide the most reliable markers, in the present study we utilized a nuclear stain based on ethidium bromide (EtBr) for the rapid qualitative and quantitative measurement of circulating apoptotic cells directly in PB suspensions without fractionation. By using a fluorescent microscope the apoptotic cells appeared clearly visible, making the estimation of their percentage straightforward. We studied apoptosis before and during the onset of chemotherapy in PB from 16 children with ALL at diagnosis, and one upon relapse. In the cases studied at diagnosis the circulating apoptotic cells were found in variable percentages after 24 hours of treatment. Maximal apoptosis was observed after 24 hours of treatment in five cases and after 48 hours in two cases. After 96 hours of treatment the cases studied at diagnosis could be divided into three groups: those with a) negligible apoptotic cells, b) between 8% and 12% apoptotic cells and c) a high percentage of apoptotic cells (more than 20%). The relapsed case was characterized by P-glycoprotein positive blast cells, and circulating apoptotic cells which remained very low at all time points. Thus, it is possible to evaluate the response to treatment by studying apoptosis directly in peripheral blood. Therefore, the maximum apoptotic effect and the percentage of circulating apoptotic cells at the different time intervals must be considered.

Twenty-three children with Langerhans' cell histiocytosis (LCH) have been treated with trimethoprim-sulphamethoxazole (T-S) in a 4-year period. The children are classified in two main groups according to the extent of their disease. Group A includes 16 children with single system disease and group B, seven children with multisystem disease. All patients were treated for 4 weeks to 3 months. The results of treatment are evaluated in terms of response in individual organs involved. All children with single system disease had a good response to the drug. Children with multisystem disease had a good response to some organs but a poorer outcome for the lungs and for the blood. These patients did not respond even to conventional chemotherapy. © 1995 Wiley-Liss, Inc.

Abstract 4112 New treatment protocols have improved significantly the survival of patients with acute lymphocytic leukemia (ALL). However, there is a risk of relapse, which depends on disease classification and the protocol of chemotherapy administered. In case of relapse, new remission has to be achieved to proceed to bone marrow transplantation (BMT). For this reason, new therapies for remission induction, except standard chemotherapy, are under investigation. Clofarabine, a new class agent, is a nucleoside analogue of purine which inhibits DNA synthesis and repair by blocking ribonucleoside reductase and DNA polymerase. It also disrupts mitochondrial membrane, driving to cell apoptosis. We describe two children with B-cell ALL, in whom clofarabine was administered because of disease resistance. Case 1: Girl, 12 years old, with ALL, presented a second bone marrow (BM) relapse. The first relapse was also in BM and was presented 30 months after the end of primary chemotherapy. Remission was achieved with chemotherapy based on protocol ALL-REZ-BFM 96. In the second relapse, that occurred one year after the end of ALL-REZ-BFM 96, conventional cytogenetics analysis showed an apparently normal female karyotype 46,XX, while molecular cytogenetics analysis (FISH) showed 3 and 4 copies of AML1 gene in 10.7% and 82.4%, of analyzed nuclei respectively. Clofarabine was administered in 52mg/m2/24h for 5 days, every 4-6 weeks. It was well tolerated. Moderate myelotoxicity presented, early after the end of regimen that was uncomplicated. Mild and transient elevation of transaminases was detected in the peripheral blood. Reevaluation after 3 cycles of clofarabine, revealed morphologic and cytogenetic remission. The patient underwent successful heterologous BMT. Case 2: Boy 18 years old with ALL presented a first BM relapse 22 months after the end of initial chemotherapy. Conventional cytogenetics analysis showed an apparently normal male karyotype 46,XY, while molecular cytogenetics analysis (FISH) was negative for clonal rearrangement involving the MLL gene and TEL/AML1, or BCR/ABL hybrid genes. Chemotherapy was administered based on protocol ALL-REZ BFM 96, but remission was not achieved. Clofarabine in 52mg/m2/24h for 5 days was administered. The patient presented mild uncomplicated myelotoxicity. Remission was achieved after the first cycle of clofarabine and the patient underwent successful heterologous BMT. Conclusion Clofarabine administration in children with refractory ALL seems to achieve disease remission and is well tolerated. More studies are needed to establish clorafabine as first line therapy in patients with relapsed ALL, prior to bone marrow transplantation. Disclosures: No relevant conflicts of interest to declare.

Disturbances in the production of adipocyte-derived hormones may represent a new link explaining the well-known relationship between obesity and increased prevalence of malignancies. Very few studies have evaluated adipokines concentration at diagnosis and during remission of a cancer. Purpose of our study was to investigate adipocytokines secretion, at diagnosis and during chemotherapy in children with acute lymphoblastic leukemia (ALL). Patients and Methods: Measurements were performed at diagnosis, after the induction-consolidation phase and at standard time points before each cycle in nine consecutive patients with ALL aged 2–7 years (median 4.3 yrs). All patients suffered from ≥5% BMI reduction in the 6 months before recruitment. BMI and leukemic burden were estimated at the same time points and correlated with adipocytokines levels. Nine healthy children matched for age and sex were used as controls. Results: At diagnosis, mean adiponectin levels were low (12.6±2.3 μg/ml vs. 18.2±2.4 μg/ml in controls, p0.05) and the negative association of leptin and resistin with BMI do not persist (−0.098, p>0.05 and −0.094, p>0.05 respectively). Delta mean adiponectin was negatively correlated with leukemic burden (−0.439, p=0.019), while delta mean leptin and resistin was positively correlated with it (0.581, p=0.011 and 0.375, p=0.031, respectively). Delta mean adiponectin was negatively correlated with delta mean LDH (−0.315, p=0.041), delta mean triglycerides (−0.412, p=0.025) and positively correlated with delta mean HDL-C (0.306, p=0.042), while delta mean leptin and resistin was positively correlated with delta mean LDH (0.423, p=0.028, and 0.387, p=0.032, respectively), delta mean triglycerides (0.372, p=0.035, and 0.523, p=0.022, respectively) and negatively correlated with delta mean HDL-C (−0.467, p=0.020, and −0.356, p=0.034, respectively). Finally, delta mean BMI-SD was positively correlated with delta mean HDL-C (0.502, p=0.018) and negatively with delta triglycerides (−0.420, p=0.023) and delta LDH (−0.605, p Conclusion: Our results suggest that low serum adiponectin level and high leptin and resistin level are present in almost all patients with ALL at diagnosis. This is probably due to neuroendocrine imbalance and inflammation. The abnormalities are restored during remission. More studies are needed to substantiate associations between leukemia development and these hormones in the population of ALL children.

STUDY OF MINIMAL RESIDUAL DISEASE (MRD) IN B-CELL LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA OF CHILDHOOD WITH THE USE OF THE SPECIFIC IMMUNOGLOBULIN VARIABLE HEAVY CHAIN FAMILY (VH) OLIGONUCLEOTIDES 87