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Background/Aims: This study presents an analysis of the sonographic and laboratory parameters of solitary kidney in Wilms tumour survivors (TWs) and compares these parameters with those of healthy individuals. Methods: Fifty-three TWs who completed treatment for Wilms tumour and 44 healthy individuals were enrolled. The study protocol consisted of completing a medical history, sonographic examination of the solitary kidney, estimation of glomerular filtration rate (eGFR) by the Schwartz or MDRD formulas, albumin urine excretion and BP measurement. Results: Sonographic signs of kidney damage were observed in 22 (41,5%) TWs. The most frequently detected abnormalities are hyperechoic rings around renal pyramids (28,3% TWs). Hypertrophy of the solitary kidney occurred in 71,7% of cases. The mean volume of the solitary kidney was 77% of the sum of the two kidney volumes in the control group. The median eGFR in the TWs group was 117 with 25Q-105,5, 75Q-130 ml/min/1,73 m2 vs 131,8 with 25Q-124, 75Q-140 ml/min/1,73 m2 in the control group (p=0,000). Six TWs (11,3%) had a value of eGFR below 90 ml/min/1,73 m2. Increased urine albumin excretion (> 30 mg/g) was observed in 7 TWs (13,2%) and in 3 (6,8%) individuals in the control group. Conclusion: Ultrasonographic abnormalities in solitary kidney of TWs are frequent. The most frequently detected abnormalities are hyperechoic rings around renal pyramids. Sonographic examination of TWs ought to be performed not only to detect tumour recurrence but also to assess the signs of kidney damage and their progression.

The rarity of malignant and intermediate vascular tumors in children means that little is known about their clinical course, optimal treatment, and variables predicting survival. A total of 32 children with malignant vascular tumors (14 angiosarcomas [AS], 5 epithelioid hemangioendotheliomas, and 13 intermediate vascular tumors, including other hemangioendotheliomas plus adult-type hemangiopericytomas), registered in the German and Polish Paediatric Soft Tissue Sarcomas Study Groups, were treated following the Cooperative Weichteilsarkom Studiengruppe (CWS)-81, -86, -91, and -96 protocols. Male sex, AS histology, tumor size >5 cm, and T2 invasiveness were independent predictors of inferior 5-year overall survival, while AS histology and T2 invasiveness were predictors of inferior 5-year event-free survival. AS histology was the most important negative prognostic factor for overall survival and event-free survival. Completeness of primary tumor excision was a good prognostic factor for survival in univariate, but not multivariate, analysis. Local therapy (radiotherapy and delayed surgery) were provided to the minority of patients (28% and 38%, respectively) late in the course of disease (after a mean of 9 and 6 months, respectively) and did not prevent local relapses. Response to systemic treatment was poor (44%) and did not prevent local and distant relapses. The clinical course and outcome in childhood epithelioid HE seems to be similar to intravascular tumors and less aggressive than AS. RTX and delayed surgery should be performed more frequently and earlier in the disease course. An urgent need for modification of systemic therapy is needed because of the development of many metastatic and/or combined relapses and poor response to classic chemotherapy. The problem of effective therapy for childhood AS is the most appaling: 13 of 14 patients died of progression despite multimodal treatment.

Analysis of biogenic amines (BAs) in different human samples provides insight into the mechanisms of various biological processes, including pathological conditions, and thus may be very important in diagnosing and monitoring several neurological disorders and cancerous tumors. In this work, we developed a simple and fast procedure using a digitally controlled microextraction in packed syringe (MEPS) coupled to liquid chromatography mass spectrometry (LC-MS) method for simultaneous determination of biogenic amines, their precursors and metabolites in human plasma and urine samples. The separation of 12 low molecular weight and hydrophilic molecules with a wide range of polarities was achieved with hydrophilic interaction chromatography (HILIC) column without derivatization step in 12 min. MEPS was implemented using the APS sorbent in semi-automated analytical syringe (eVol(®)) and small volume of urine and plasma samples, 5 0µL and 100 μL, respectively. We evaluated important parameters influencing MEPS efficiency, including stationary phase selection, sample pH and volume, number of extraction cycles, and washing and elution volumes. In optimized MEPS conditions, the analytes were eluted by 3 × 50 μL of methanol with 0.1% formic acid. The chromatographic separation of analytes was performed on XBridge Amide™ BEH analytical column (3.0mm × 100 mm, 3.5 µm) using gradient elution with mobile phase consisting of phase A: 10mM ammonium formate buffer in water pH 3.0 and phase B: 10mM ammonium formate buffer in acetonitrile pH 3.0. The LC-HILIC-MS method was validated and, in optimum conditions, presented good linearity in concentration range within 10-2000 ng/mL for all the analytes with a determination coefficient (r(2)) higher than 0.999 for plasma and urine samples. Method recovery ranged within 87.6-104.3% for plasma samples and 84.2-98.6% for urine samples. The developed method utilizing polar APS sorbent along with polar HILIC column was applied for simultaneous bioanalysis of trace amounts of polar endogenous biogenic amines in real human urine and plasma samples.

The term leucopenia is still a challenge for clinicists in cases of unknown reasons. There are two main groups of leucopenia: 1. Severe, chronic leucopenia (cyclic, inborn, and idiopathic); 2. Acquired or secondary (reasons: some drugs, infections, viral mainly, autoimmune diseases, haematological abnormalities, neoplasms, hiperspleenism and metabolic diseases). The aim of this investigation was an analysis of asymptomatic, lasting over three months leucopenia myelograms of childhood.21 children (6 girls and 15 boys, aged 10-17 years, mean 13.6, median 12 years) were analysed. The children were referred to our clinic by family physicians to investigate the reason of asymptomatic, lasting over three months leucopenia. These children are still under our observation from one till four years. Despite the fact of lasting over three months leucopenia, the general condition of the patients is good. In all the patients the myelogram analysis was performed after May-Grumwald-Giemsa dying, three slides of one hundred cells were counted. Statistical analysis was made using STATISTICA (Stat Soft Polska) programme.Mean number of leucocytes was 3.06x109/ l (median 2.75x109/l, values from 2.46x109/l to 3.53x109/l), mean number of neutrocytes was 1.15x109/l (median 1.07 x 109/l, values from 0.62x109/l to 1470x109/l). Hemoglobin concentration and platelets number were normal. Mean number of marrow cells were within references. However mean number of myelocytes, metamyelocytes, bands and eosynophils were lower than mean number of general population marrow cells (p0.05). Mean values of myeloblasts, neutrophils, and monocytes were statistically higher than in general population (p0.05).1. Hypothesis of obtained differencess in numer of marrow cells would need to be investigated in broad population of patients. 2. Considering that three children presented with positive familial leucopenia history (in one of them grandmother, in two anothers fathers) genetic predisposition can be expected.

Methemoglobinemia is a rare congenital or acquired disease of increased blood methemoglobin concentration. We documented 2 cases of children suffering from neuroblastoma whose postchemotherapy anemia, leucopenia, and stomatitis were complicated by methemoglobinemia after using a formulary oral gel (7.5% benzocaine, doxycycline, nystatin, glycerin). The complication resulted in hospital treatment. Percutaneous oxygen saturation remained at 85% and 87% despite administration of 100% oxygen through a nonrebreather mask. Arterial blood gas analysis showed an oxygen saturation of 98% and 97%, respectively. Spectroscopic measurement showed methemoglobin concentration of 42% and 35.5%, respectively. After red blood cell transfusion and oral ascorbic acid in case 1 and methylene blue in case 2, the patients' condition improved. Although the benzocaine gel is not in use in several medical systems, it should be considered as a possible reason for methemoglobinemia.

Iron is a micronutrient which is essential for the existence of organisms. This element participates in oxygen transport, as well as energetic, metabolic and immunologiocal processes. Disturbances of iron homeostasis lead to multiorgan dysfunction. Iron deficiency anemia is a common disorder in childhood, while iron overload is rarely observed in the developmental age. There are primary and secondary reasons for iron overload. Hereditary hemochromatosis is a metabolic disorder caused by the mutations of genes that control iron metabolism leading to increased intestinal absorption. Secondary hemochromatosis is caused by multiple transfusions, chronic hemolysis, or iron pills and iron-rich food intake. The article reviews the literature devoted to primary iron overload in childhood.

The metabolic differences between normal, healthy cells and neoplastic cells have been exploited by anticancer therapies targeting metabolic pathways. Various studies of malignant processes have demonstrated disturbances in both arginine synthesis and metabolism that enhance or inhibit tumor cell growth. Consequently, there has been an increased interest in the arginine-depleting enzyme arginine deiminase (ADI) as a potential antineoplastic therapy.This review summarizes the literature on the potential anti-cancer therapeutics arginine and ADI, an arginine-catabolizing enzyme. The authors searched the MEDLINE database PubMed using the key words: 'arginine, 'ADI', 'arginine in cancer' and 'ADI and cancer'. The authors evaluate prospective randomized studies on cancer patients between 2004 and 2013 as well as ongoing research found through the US National Institutes of Health trial database.The results of current studies are promising but do not give unequivocal answers and so it is impossible to recommend arginine or its enzyme ADI as a therapeutic. In the opinion of the authors, further identification of arginine-dependent malignant tumors and their metabolism should be investigated. Furthermore, the use of these chemicals, in combination with other chemotherapeutics drugs, should be investigated and indeed may improve the success of arginine-depleting enzymes such as pegylated ADI (ADI-PEG20).

The goal of the work described here was to assess the safety profile of intravenous second-generation ultrasound contrast agents (UCAs) containing sulfur hexafluoride in pediatric contrast-enhanced ultrasound. Between 2010 and 2013, a total of 167 examinations were performed in 137 children referred by the Oncology Department. Approval by an Independent Ethical Review Board on Scientific Research for the intravenous use of an UCA containing sulfur hexafluoride in children with oncologic diseases was obtained. Consent for UCA administration was acquired from the parents or legal guardians. Severe anaphylactic reaction was observed in 0.6% (n = 1). No other adverse events during or after intravenous administration of contrast were observed in the examined group (no changes in heart rate and rhythm, blood pressure, oxygen saturation or respiratory rate). There were no reports of subjective flushing, nausea, transient headaches or altered taste. Although second-generation ultrasound contrast agents are considered potentially safe, all investigators should be prepared for the development of adverse reactions and have provisions in place for all pediatric intravenous contrast-enhanced ultrasound examinations. More multicenter studies are essential to determination of an accurate UCA safety profile.

Acute Myelomonoblastic Leukaemia (ANLL M4) and Aplastic Anemia (AA) are rare childhood diseases. Treatment of ANLL involves chemotherapy and radiotherapy, while immunosuppressive therapy is used in the treatment of AA. In selected cases, both disorders can be treated by performing a Hematopoietic Stem Cell Transplantation (HSCT). In addition, supportive medical care which includes antibiotics, antifungal drugs, packed red cells and platelets, is usually essential due to adverse effects caused by the therapy. Herein, we present a 15- year- old boy with ANLL M4 and a 17- year- old girl suffering from Severe Aplastic Anemia (SAA) for 3 and 4 years respectively, in whom iron overload was noted after they had undergone allogeneic HSCT (allo HSCT). On further diagnosis, co-existence of S65C HFE gene carriage was identified in both of them.

Systemic mastocytosis is a myeloproliferative disorder characterized by growth and accumulation of abnormal mast cells in one or more organs. The symptoms of the disease are due both to the mast cells infiltrating the organs and to the action of its degranulation products. Over 85% of adult patients exhibit point mutations of KIT at position 816 (D816V). Systemic mastocytosis is rare in both adults and children, so treatment is highly individualized; therapy and further treatment is adjusted to each patient's needs. The aim of this study was to present the case of a 14-year old female with systemic mastocytosis and the problems with her treatment. Multidisciplinary management is recommended in systemic mastocytosis.

Background: MYCN oncogene amplification is the most important prognostic factor in neuroblastoma. 25% neuroblastoma tumors have somatic amplifications at this locus but little is known about its constitutional aberrations and their potential role in carcinogenesis. Here, we have performed an array-CGH and qPCR characterization of two patients with constitutional partial 2p trisomy including MYCN genomic region. Results: One of the patients had congenital neuroblastoma and showed presence of minute areas of gains and losses within the common fragile site FRA2C at 2p24 encompassing MYCN. The link between 2p24 germline rearrangements and neuroblastoma development was reassessed by reviewing similar cases in the literature. Conclusions: It appears that constitutional rearrangements involving chromosome 2p24 may play role in NB development.

INTRODUCTION Pre-treatment serum IL-10/IL-12 balance has been recently found deregulated in childhood soft tissue sarcomas (STS). Its role in STS monitoring and assessment of response to therapy is unknown. OBJECTIVE To establish whether serum IL-10 and IL-12 levels and their reciprocal ratios reflect childhood STS course and actual activity and whether G-CSF therapy and central vein catheter (CVC)-related sepsis influence the interleukins levels. MATERIALS AND METHODS ELISA determinations of serum interleukins were performed before treatment, in remission without complications (CR), at relapse and after treatment in 59 STS patients and during G-CSF administration and CVC-related sepsis (in 18) and also in 30 healthy controls. RESULTS In CR IL-10 declined and IL-12 increased as compared to pretreatment levels; in relapse IL-10 rose and IL-12 decreased significantly as compared to levels in CR. Also rates of IL-10, IL-12, and IL-10/IL-12 ratios recently estimated by us as of prognostic significance reflected well the STS course. During G-CSF therapy and CVC-related sepsis, IL-10 increased and IL-12 decreased significantly from levels in CR without complications. IL-10 levels and rates of IL-10 ≥ 11 pg/ml in sepsis could falsely suggest relapse. However, IL-12 levels, rates of IL-12 ≤ 60 pg/ml and/or simultaneous determination of both interleukins differed significantly from levels at relapse. CONCLUSION Serial determinations of serum IL-10 and IL-12 reflected well the course of STS in children and enabled remission and relapse phases to be distinguished. To avoid G-CSF and sepsis influence, IL-12 and IL-10/IL-12 ratio and not IL-10 alone should be analysed.

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a severe drug-induced hypersensitivity syndrome and may be observed after administration of many drugs. Clinical symptoms usually occur 2 to 8 weeks after drug introduction. Because DRESS syndrome is potentially life threatening, it is especially important to diagnose it early. Withdrawal of the drug which induced symptoms is the most important therapeutic option. DRESS syndrome appears mostly in adults. There are relatively few articles on the DRESS syndrome in children. The article presents a case of a 4-year-old girl with a life-threatening clinical course of DRESS syndrome with massive pulmonary involvement. The knowledge of DRESS syndrome clinical symptoms is essential for doctors of various specialties. It is especially important that general practitioners, pediatricians, and pediatric neurologists should be able to take this life-threatening syndrome into consideration for differential diagnosis.

Context: The roles of interleukin 10 (IL-10) and IL-12 in regulation of cancer growth and Th1/Th2 immune responses towards cancer are unclear.Objective: To establish the prognostic significance of serum IL-10 and IL-12 in paediatric soft tissue sarcomas (STS).Materials and methods: ELISA determinations of cytokines were performed as pre-treatment in 59 children with STS and 30 healthy controls.Results: Elevated IL-10 and decreased IL-12 serum levels correlated with advanced disease, poor response to chemotherapy and poor outcome. IL-10 ≥ 9.5 pg/ml, IL-12 ≤ 65 pg/ml and lymph nodes involvement independently predicted poor overall survival (OS) in multivariate Cox analysis.Conclusion: Serum IL-10/IL-12 balance determination may facilitate to assess risk groups and prognosis in childhood STS.

Background Since 1983 four consecutive unified regimens: acute myeloid leukemia-Polish pediatric leukemia/lymphoma study group (AML-PPLLSG) 83, AML-PPLLSG 94, AML-PPLLSG 98 and AML-BFM 2004 Interim, for AML have been conducted by the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG). In this paper, we review four successive studies on the basis of acute myeloid leukemia-Berlin–Frankfurt–Munster (AML-BFM) protocol, in which a stepwise improvement of treatment outcome was observed. Treatment results of the last protocol AML-BFM 2004 Interim are presented in detail. Methods Three hundred and three patients with de novo AML were treated according to the AML-BFM 2004 Interim at 15 Polish centers from January 1, 2005 to June 30, 2011. A confrontation with previous treatment periods was based upon historical, already published data. Results In four consecutive periods, 723 children were eligible for evaluation (208, 83, 195, and 237, respectively). Complete remission rates in consecutive periods were: 71, 68, 81 and 87 %, respectively. The 5-year overall survival rates, event-free survival rates, and relapse-free survival rates were 33, 32, and 45%, respectively for AML-PPLLSG 83 regimen; 38, 36, and 53 % respectively for AML-PPLLSG 94 regimen; 53, 46, and 65 % respectively for AML-PPLLSG 98 regimen, and 63, 52, and 64 % for AML–BFM Interim 2004, respectively. Incidence of early deaths and that due to complications (mainly infections) in the first remission decreased over time from 22 to 4.6 % and from 10 to 5.9 %, respectively. Conclusions Despite continuous improvement in the treatment outcome, the number of failures still remains too high. Further progress seemed to be possible due to continued cooperation of oncology centers within large international study groups.

The aim of the study was to assess the carbohydrate and lipid metabolism disturbances as well as weight in children after brain tumors treatment. The study included 33 boys (53.2%) and 29 girls (46.8%) aged 11.6 ± 3.9. 22 patients underwent treatment for tumors of hypothalamic-pituitary(h-p) area: IA–surgery(19/22); IB–surgery and radiotherapy(3/22). 40 patients were treated for tumors outside the h-p area: IIA– with surgery, chemo-and radiotherapy(22/40); IIB–only with surgery(15/40); IIC–patients treated for optic nerve glioma with chemotherapy(3/40). BMI was assessed before and after the treatment. OGTT, HbA1c, lipid profile and WHtR after treatment were assessed. Indices of insulin resistance: HOMA-IR, Quickie, Matsuda and de Fronzo were calculated. 63% overweight/obese patients of IA-group and 27% of IIA-group were observed. Hyperinsulinemia was noted in 44% of IA-group, 20% of IIA-group, and insulin resistance in 38% of IA and 15% of IIA. DM2 was diagnosed in 1 patient of IA-group, IFG in 1 patient of IIB, IGT in 1 patient of IA and 1 patient of IIC. Dyslipidemia was noted in 47% of IA-group, elevated level of LDL-cholesterol in 30% of IIA-group. The excessive weight gain, hyperinsulinemia and dyslipidemia were observed primarily in children treated for hypothalamic-pituitary tumors.

Background. ALL is the most common indication for allogeneic hematopoietic stem cell transplantation (allo- HSCT) in children. Objective. The analysis of results of therapy in children and adolescents treated for ALL with allo-HSCT. Patients and methods. A total number of 41 patients undergoing allo-HSCT due to ALL between 2003 and 2012. In 17 patients HSCT was performed from related donor and in 24 from unrelated donor. A source of hematopoietic stem cells was peripheral blood in 21 patients, bone marrow in 18 patients and cord blood in 2 patients. Results. At present, 27 (65.8%) patients stay alive. Among 14 deaths, 8 were regarded as transplant-related mortality, and 6 as a relapse of disease. Transplant-related mortality was 8/41 (19.5%), including 7 (17%) in early posttransplant period (before day +100). Probability of survival for all patients was: pDFS=0.652±0.091 (mean disease-freesurvival was 3.8 years, 95%CI=2.7-4.8), pOS=0.630±0.080 (mean survival 3.9 years, 95%CI=3.0-4.8). The only factor predicting overall survival was time of pre-transplant relapse: for very early relapses pOS=0.333±0.157, for early relapses pOS=0.666±0.272 and for late relapses pOS=0.833±0.152 (p=0.010). Conclusions. Allo-HSCT from well-matched unrelated donors or genoidentical sibling donors is an effective treatment with acceptable toxicity in pediatric ALL. Precise HLA typing and matching resulted in a low incidence of acute and extensive chronic GVHD which is an important achievement for the quality of life in children and adolescents. The results from this study demonstrate the feasibility of a harmonized HSCT approach in pediatric ALL. Wstęp. Ostra białaczka limfoblastyczna (ALL) jest najczęstszym wskazaniem do przeszczepiania allogenicznych hematopoetycznych komórek macierzystych (allo-HSCT) u dzieci. Celem pracy była analiza wyników leczenia ALL u dzieci poddawanych allo-HSCT w ośrodku bydgoskim. Pacjenci i metodyka. Badaniami objęto 41 pacjentów leczonych w latach 2003-2012. W 17 przypadkach wykonano transplantację od dawcy rodzinnego, a w 24 od dawcy niespokrewnionego. Źródłem komórek hematopoetycznych była krew obwodowa u 21 pacjentów, szpik kostny u 18 pacjentów oraz krew pępowinowa u 2 pacjentów. Wyniki. W momencie zakończenia analizy żyło 27 (65,8%) pacjentów. Spośród 14 zgonów, 8 było zależnych od procedur transplantacyjnych, a 6 od wznowy choroby podstawowej. Śmiertelność zależna od powikłań transplantacyjnych wyniosła 8/41 (19,5%), w tym 7 (17%) we wczesnym okresie poprzeszczepowym (do dnia +100). Prawdopodobieństwo przeżycia dla całej badanej grupy wyniosło: pDFS=0,652±0,091 (średnie przeżycie bez wznowy 3,8 lat, 95%CI=2,7-4,8 lat), pOS=0,630±0,080 (średnie przeżycie 3,9 lat, 95%CI=3,0-4,8 lat). Jedynym czynnikiem prognostycznym terapii był czas wystąpienia wznowy kwalifikującej do transplantacji: dla wznów bardzo wczesnych pOS=0,333±0,157, dla wznów wczesnych pOS=0,666±0,272 i dla późnych pOS=0,833±0,152 (p=0,010). Wnioski. Allo-HSCT od zgodnych dawców rodzinnych lub niespokrewnionych jest efektywną terapią o akceptowalnej toksyczności w ALL. Precyzyjny dobór dawcy skutkuje niskim odsetkiem ostrej i przewlekłej GVHD, co może wpływać na jakość życia. Wyniki przeprowadzonej analizy pokazują kierunki terapii z zastosowaniem HSCT w ALL u dzieci i młodzieży.

Individualization of the topotecan dosing can reduce inter-patient variability, toxicity, and at the same time increases chemotherapy efficacy. Topotecan dosing based on simultaneous drug monitoring and pharmacokinetic analysis can yield more accurate and precise estimation of the topotecan systemic exposure than that attainable with the fixed dosing approach. Therefore, a combined approach could provide a tool assisting the clinicians in individualization of the topotecan dosing. The aim of the study was to estimate the topotecan exposure in pediatric patients with acute myeloid leukemia (AML) based on the plasma concentration-time data and using the pharmacokinetic analysis. The primary goal was achieve the correct estimation of the target plasma area against the topotecan concentration-time curve (AUC) in a 5 day course of cladribine followed by monitored topotecan in pediatric patients with recurrent/refractory AML. A sensitive and selective reversed-phase liquid chromatographic-mass spectrometry (LC-MS) assay was developed to quantify total topotecan in the human plasma samples. This method, with its lower quantification limit of 1 ng/ml, was validated over a linear range of 1-150 ng/ml. Under the proposed approach, the topotecan dosing was selected so as to achieve the final AUC value of 140±20 ng/ml h. The presented analytical and pharmacokinetic data demonstrate that the proposed approach can be a practical, useful, efficient, and accurate tool for individualizing the topotecan dosing in children with AML.

In contrast to the occurrence of brain metastases advanced malignant tumours in adult cancer patients, the dissemination of solid tumours to the brains of paediatric cancer patients is very uncommon. We present a neuro-pathological and clinical study of a group of children and adolescents with brain metastases (BM) from extracranial solid malignancies. The analysed patients were diagnosed with soft tissue sarcomas (three), germ cell tumours (three), or osteosarcoma, neuroblastoma, clear cell sarcoma of the kidney, or pleuropulmonary blastoma (one each). In our series, BM frequently coexisted with pulmonary metastases. Three different metastatic patterns were discernible: a solitary tumour, multiple lesions and diffuse parenchymal dissemination. Two cases showed haemorrhagic presentation. Most of the children died due to BM progression, while children with germ cell tumours showed the best prognosis. The histopathological pictures of BM can be different from the primary tumour, showing dedifferentiation or a diverse neoplastic component. The autopsy examination can still be helpful in the final diagnosis of certain cases with atypical clinical presentations.

Aims: To test the hypothesis that Wilms tumour survivors (WTs) experience increased disturbance in renal function, even after prompt treatment, compared to patients with unilateral renal agenesis (URA). Methods: To assess the renal function of 30 WTs and 17 individuals with URA, the estimated glomerular filtration rate (eGFR) was calculated using the Schwartz and Filler formulas as well as the new Schwartz equation for chronic kidney disease. To measure kidney damage, serum levels and urine excretion of β2-microglobulin (B2M), cystatin C (Cys C), neutrophil gelatinase-associated lipocalin (NGAL) were tested, N-acetyl-β-glucosaminidase (NAG), and albumin urine excretion and urine sediment were examined. Blood pressure was measured. Results: No differences were found between the groups in terms of eGFR, serum Cys C, B2M and NGAL concentrations. The urine excretion of Cys C, NGAL and NAG was similar in both groups. URA patients had higher B2M excretion than WTs. Arterial hypertension was present in 7/30 (23%) WTs and 1/17 (6%) patients with URA. Conclusions: WTs have similar eGFR to individuals with URA and are more likely to have arterial hypertension. The patients with URA have signs of tubular damage. This study demonstrates the need for nephrological monitoring of individuals with a single kidney.

Objectives Deregulated serum IL-10, IL-12 and their reciprocal balance have been stated in malignancies of adults. In children with cancer the issue has not been investigated so far. Design and methods To determine the diagnostic and prognostic roles of pre-treatment serum levels of IL-10 (Th2 cytokine), IL-12 (Th1) and their ratios (measured by the IL-10 and IL-12p70 ELISA kits; Endogen) in 91 children with soft tissue sarcomas (STS), Hodgkin's lymphomas (HL) and acute lymphoblastic leukemias (ALL). Results Median IL-10 and IL-12 levels were significantly higher in cancer patients than in healthy controls. Increased IL-10 indicated presence of general symptoms in HL and high risk group in ALL. Elevated IL-10 and IL-10/IL-12 ratios and decreased IL-12 correlated with poor-risk histology in STS, poor response to therapy, relapse and death from cancer. Multivariate analysis identified IL-10/IL-12 ratio > 0.14 and IL-12 Conclusion Pre-treatment serum levels of IL-10, IL-12 and IL-10/IL-12 balance in children with STS, HL and ALL may be of value as additional prognostic tools to predict the response to therapy and probability of EFS and OS.

Malignant high-grade gliomas are the most common secondary neoplasms in children cured of acute lymphoblastic leukaemia (ALL). Although many predisposing factors exist (including systemic or intrathecal chemotherapy, young age, brain infiltration and genetic predispositions), cranial irradiation appears to be the strongest one. Three cases of secondary high-grade gliomas (two multiform glioblastomas, grade IV; one anaplastic astrocytoma, grade III) developed in ALL survivors (F–M, 1:2) 3 to 6.3 years after stopping ALL therapy according to BFM-90 trial. All tumours were supratentorial, contrast-enhancing, space-occupying, highly advanced and aggressive. Possible risk factors and current therapeutic options for paediatric ALL and malignant gliomas are reviewed and discussed. Prognosis in secondary malignant gliomas in children is poor (overall survival of 5, 10 and 19 months) despite intense therapy. Thus, protocols for paediatric ALL reduce prophylactic cranial irradiation in favour of intrathecal and intravenous high-dose MTX. Nevertheless, ALL survivors must undergo systematic, long-term surveillance for early detection of intracranial neoplasms.

Patients with neurofibromatosis type 1 (NF1) are predisposed to developing soft tissue sarcomas (STS). We report on four cases of STS diagnosed in locally advanced, unresectable stages in children with NF1 (three girls, one boy; age = 8 months–14 years). All patients received protocols for STS: Cooperative Weichteilsarkomstudie 91, 96 and 2002. One patient with limb rhabdomyosarcoma entered complete remission but developed late metastatic relapse and died of progression despite complete excision and autologous bone marrow transplantation. The other patient with bladder rhabdomyosarcoma died of neutropenia-related sepsis without remission. Patients with malignant peripheral nerve sheet tumour and malignant triton tumour located in the pelvis did not respond to therapy. One of them died of disease progression, while the other is disease-free 6 years post-therapy after mutilating tumour resection. STS in NF1 seem to display poor prognosis in spite of combined therapy; thus, children with NF1 should remain under detailed control of the oncologist.

Dear Editor, We present a case of a 6-year-old boy of Polish origin who was diagnosed with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to Seoul mutation. The patient was born prematurely in the 36th week of gestation. There was no history of any hematological disorders in parental families. At birth, it was noted that the patient presented severe hyperbilirubinemia (19 mg/dl). Infection and serological conflict were ruled out as possible causes of jaundice. At the age of 6 weeks, anemia of prematurity was diagnosed, and due to a Hb concentration of 7.2 g/dl, packed red cells were transfused. During infancy, his hemoglobin concentration approximately ranged between 9.5 and 10.5 g/dl. At the age of 2 years, the boy presented with hemolytic crisis during a rotaviral infection. His full blood count values were as follows: Hb 6.9 g/dl, RBC 2.3 × 1012/l, MCV 92 fl, reticulocytes 4 %, PLT 436 × 109/l, WBC 8,464 × 106/l, and bilirubin 2.0 mg/dl. Both direct and indirect antiglobulin tests were negative. There was no hepato- or splenomegaly. Hereditary spherocytosis was excluded using the eosin-5-maleimide flow cytometry test. After receiving a packed red cell transfusion and symptomatic treatment, his condition improved. The observation period after treatment was uneventful with hemoglobin concentration, reticulocyte count, and bilirubin concentration all normal. At 6 years, he presented with a succeeding severe hemolytic crisis during an upper respiratory tract infection. A Hb concentration of 3.0 g/dl led to a broader diagnostic criteria—G6PD activity was found reduced—1.65 IU/g Hb (norm 13.55 ± 2.45 IU/g Hb). Genomic DNA was then isolated using the MagNA Pure Compact Nucleic Acid Isolation Kit I (Roche, Germany). PCR was used to amplify the coding sequence of exons from 9 to 12 of the glucose-6-phosphate dehydrogenase (G6PD) gene. The DNA fragments generated by PCR amplification were purified using the QIAquick PCR Purification (Qiagen, Germany) and directly sequenced with BigDye Terminators and the appropriate primers using an ABI Prism 377 sequencer (Applied Biosystems, CA, USA). The obtained mutation was then confirmed by restriction endonuclease digestion by DdeI (Fermentas, Lithuania). DNA sequencing revealed a 306 Gly⟶Ser (G6PD Seoul, class 2) mutation (Fig. 1). Moreover, the mother gene mutation carriage was proven. Currently, the patient is in stable condition presenting with temporary mild hemolysis during sporadic infections. His parents were informed to avoid certain medicines and ingestion of fava bean products. Although G6PD deficiency is the most common enzyme disorder worldwide, it has rarely been reported among Poles [1–4]. Clinical and numerous other studies of G6PD deficiency demonstrate that the disorder is most prevalent in the Mediterranean area, in Asia, and in Africa [5]. As a result of global population movements, hemoglobin disorders are now increasingly common in the formerly nonindigenous countries of Northern and Western Europe [6]. As far as Poland is concerned, we have not experienced any immigration boom; hence, the incidence of G6PD deficiency is still low. However, Mediterranean mutations predominate herein, and some autochthonic mutations were also reported [3, 4]. Our patient presented with neonatal hyperbilirubinemia and anemia that were interpreted as symptoms of prematurity. After his first hemolytic crisis, hereditary spherocytosis, being a more common cause of hemolysis in Central Europe, was excluded [7]. The ultimate and unexpected diagnosis of glucose-6-phosphate deficiency was made after a succeeding hemolytic crisis. Considering the rarity of this disorder in our country, we performed a molecular analysis which revealed a 306Gly->Ser mutation known in literature as the Seoul mutation [8]. Structures of human Δ G6PD (lack of 25 N-terminal residues) in complex with NADP+ and glucose-6-phosphate (G6P) have been described by Kotaka et al. [9], PDB entries 2BH9 and 2BHL, respectively. Models of wt and G306S mutated enzymes were built in complex with NADP+ and G6P. To check the influence of this mutation on the protein structure, both structures were subjected to energy minimization using AmberFF99 force field as implemented in SYBYLx2.0, Tripos Inc., USA. Residues of the strand βH, to which belongs G306, interact with helix αo and the loop between αo and βO, so main structural changes are observed in those regions. It is significant as the previously described mutations located there, for example P489L and P489S, belong to class 1 [10, 11]. The G306S mutation induces changes in structural NADP+ as well as G6P sites because a fragment neighboring both regions is affected. We observed changes in orientation of K360, involved in the interaction with G6P, as well as orientations of residues in F237–E239, described as bridging from G6P site to the structural NADP+ site [9]. We speculate that the appearance of G6PD mutations, previously found in different parts of the world in the Polish population, corroborates that these mutations may have arisen due to separate events, rather than being descendants of individual ancient mutations.

Background Selective eating behaviours have been reported mainly in children with mental retardation and adolescents on strict vegan diets. Aims To draw attention that prolonged food selectivity, along with parental indifference can lead to life-threatening complications from malnutrition. Methods Analysis of food selective behaviours in two adolescents referred to Dept. of Paediatrics, Haematology and Oncology, Medical University of Gdansk, Poland in 2007 and 2013 respectively, suspected of aplastic anaemia. Results Both adolescents presented with pallor, weakness and fatigue. A 17-year-old male with autism, encephalopathy and psychomotor retardation exhibited cachexia, contractures of joints, peripheral oedemas, massive bruising and bleedings, and trophic skin changes. A 13-year-old female suffered from dizziness and infections. CBC in both patients showed severe anaemia, leukopenia and thrombocytopenia. In myelograms, megaloblastic dysplasia was found, confirmed by serum vit. B12 deficiency. The boy had also deficiency of ferrum, folate, hypoproteinemia, dyslipidemia and electrolyte disturbances. Upon interview, both patients demonstrated selective eating behaviours, and extremely restricted diets for over 10 (male) and 2 (female) years. The boy ate only chocolates, bread, milk, french fries and tea. The girl didn’t eat meat or animal-based products. Both children required blood cell transfusions followed by vit. B12 supplementation and nutritional support. Conclusion Severe prolonged food selectivity in children, along with parents’ indifference and/or unawareness, can lead to life-threatening hematologic complications. Physicians should consider food selectivity among the causes of nutritional and hematologic deficits in children. Parents need to be taught how to avoid nutritional deficiencies in children with selective eating patterns.

Background Little is known about how children adapt to life after cancer and what factors influence this process. Aim To investigate psychological and social aspects of life of paediatric cancer survivors (PCS). Material and methods Questionnaire survey included 69 PCS (F/M 35/34; mean age 14 years), 2–6 years after oncologic treatment in Department of Paediatrics, Haematology and Oncology, Medical University of Gdansk, Poland. Data was categorised by gender and cancer type (leukaemia and lymphomas, LL-44 and solid tumours, ST-25). Results 40% of PCS found adjusting to new life difficult. 67% of girls with ST admitted to depression and constant thinking and learning about disease. 40% of patients felt afraid of recurrence (mainly boys with ST) and avoided thinking and talking about it. Half of patients complained of unsatisfactory health. Patients with ST (24%) and after surgery (58%) reported the worst self-estimation, which was associated with visible sequelae of disease/therapy. Cosmetic evidences concerned mostly ST patients while functional-LL. Losing hair was problematic mainly for girls; 30% of PCS felt uglier/worse than peers. 40% of girls and of ST patients felt bullied and reported problems with meeting new people. Instead, PCS kept close contacts with other patients met in clinic. 70% of respondents planned to have children, but 65% of them feared they may also develop cancer. Conclusions Adaptation to life after cancer is influenced by type of malignancy and gender and is particularly problematic in children with visible sequelae of disease/therapy. Psychological and social support of PCS is essential.

Glomerular filtration rate (GFR) was evaluated in 32 Wilms' tumour survivors (WTs) in a cross-sectional study using 99 Tc-diethylene triamine pentaacetic acid (99 Tc-DTPA) clearance, the Schwartz formula, the new Schwartz equation for chronic kidney disease (CKD), cystatin C serum concentration and the Filler formula. Kidney damage was established by beta-2-microglobulin (B-2-M) and albumin urine excretion, urine sediment and ultrasound examination. Blood pressure was measured. No differences were found between the mean GFR in 99 Tc-DTPA and the new Schwartz equation for CKD (91.8 ± 11.3 vs. 94.3 ± 10.2 ml/min/1.73 m(2) [p = 0.55] respectively). No differences were observed between estimated glomerular filtration rate (eGFR) using the Schwartz formula and the Filler formula either (122.3 ± 19.9 vs. 129.8 ± 23.9 ml/min/1.73 m(2) [p = 0.28] respectively). Increased urine albumin and B-2-M excretion, which are signs of kidney damage, were found in 7 (22%) and 3 (9.4%) WTs respectively. Ultrasound signs of kidney damage were found in 14 patients (43%). Five patients (15.6%) had more than one sign of kidney damage. Eighteen individuals (56.25%) had CKD stage I (10 with signs of kidney damage; 8 without). Fourteen individuals (43.75%) had CKD stage II (6 with signs of kidney damage; 8 without). The new Schwartz equation for CKD better estimated GFR in comparison to the Schwartz formula and the Filler formula. Furthermore, the WT survivors had signs of kidney damage despite the fact that GFR was not decreased below 90 ml/min/1.73 m(2) with 99 Tc- DTPA.

Introduction Neurofibromatosis type 2 (NF2) is an inherited, rare autosomal dominant syndrome characterised by the development of multiple benign cranial and spinal tumours, peripheral neuropathy, ophthalmological and cutaneous lesions. Herein, we report one case of NF2 treated with multivariate chemotherapy. Material and methods A 13-year-old female presented with multiple cranio-spinal tumours in MRI. First symptoms were progressive changes in vision, left-sided paresis, unilateral sensorineural hearing loss, and left hypoglossal nerve paresis. The patient underwent palliative, partial surgical resection of the tumour which was located in a posterior fossa. Histopathological examination showed a psammomatous meningioma located near the great foramen and schwannomas of VIII nerve in the cerebello-pontine angle. Clinical and radiological examination revealed a rapid progression of the disease. As such, multivariate chemotherapy was used. The patient died 4 years after diagnosis. Conclusion NF2 patients with multiple tumours at diagnosis may not be treatable with surgery alone and, as a result, presentation with such a disease in childhood results in poor prognosis. The unification of management strategies in NF2 patients is highly desirable.

Simple and sensitive liquid chromatography (LC) methods with fluorescence (FL) detection for the determination of bendamustine (BM) in human plasma and urine were developed and validated. The procedure of BM extraction from a plasma sample involved solid-phase extraction with a C18 SPE column, while liquid–liquid extraction with dichloromethane was applied for a urine sample. In both methods, cinoxacin was used as the internal standard. Chromatographic separations were performed on a Synergi Max-RP column, while FL detector was set at the excitation wavelength of 328 nm and the emission wavelength of 420 nm. The LC-FL methods were validated for accuracy, precision, selectivity, linearity, recovery, and stability. The detection limits for BM were 0.5 and 2.5 ng mL−1 in plasma and urine, respectively. The intra-day and inter-day precisions were less than 9.86 %, while the accuracies were higher than 92.63 and 94.29 % for BM in plasma and urine, respectively. The proposed LC-FL methods were sensitive, robust, and specific, allowing reliable drug quantification in plasma and urine samples. The methodologies were successfully applied to monitoring of BM in a child with cancer treated with BM. Electronic supplementary material The online version of this article (doi:10.1007/s10337-016-3103-3) contains supplementary material, which is available to authorized users.

Summary Subject To present the analisis of initial clinical symptoms and difficulties in establishing proper diagnosis. Material and methods Data on 32 patients with the diagnosis of parameningeal malignant neoplasms were subjected to a retrospective analysis. The study group consisted of 9 girls and 23 boys, at the age of 2–17. The analysis involved clinical symptoms prior to diagnosis, the response to treatment, possible necessary modifications of therapeutic schemes and treatment outcome in particular histological types of parameningeal malignant neoplasms. Results The length of history taking in the whole group ranged from 2 weeks to 24 months. The dominant symptoms were directly associated with the local growth of the tumour and its spread to the regional lymph nodes. The extent of spread of the neoplasm in children with STS was found to be: III°in 14 and IV° in 3 patients. All the children with NHL-B were originally assigned to group Baccording to LMBand the patients with lymphoepithelioma to III° (2 children) and IVA° (4 children) according to TNM and AJCC. Among the patients with parameningeal malignant neoplasms, 21/32 children demonstrated CR after the complete treatment, including 8/17 with STS and all patients with NHL-B,4/6 with lymphoepithelioma. Seven patients died: 5 with STS and 2 with lymphoepithelioma. The prognosis of four patients undergoing treatment for STS recurrences is uncertain. Conclusions Non-characteristic initial clinical symptoms and signs of parameningeal tumours, often suggestive of an inflammatory process, results in diagnostic difficulties. Since radical resection of parameningeal neoplasms in children is impossible, the prognosis depends on the neoplasm's sensitivity to chemo- and radiotherapy.

Introduction Valproic acid is a commonly used anti-epileptic drug. Hematological toxicities are among the occasionally observed adverse effects of this medication. Case presentation We present the case of a 13-year-old Caucasian boy who demonstrated mild anemia 12 months after the introduction of valproic acid therapy. A bone marrow biopsy revealed maturation arrest of proerythroblasts. Conclusion Prompt diagnosis and valproic acid discontinuation resulted in the patient’s recovery.

Introduction: In vitro drug resistance profile has so far provided information on chemosensitivity of leukemic cells in acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML). Previous studies have shown that for most tested drugs, patients with relapse had higher IRTR than those with de novo ALL or AML. The objective of this study was the analysis and comparison of the individualized tumor response testing (ITRT) between first and second relapse in children with ALL or AML. Patients: A total of 186 pediatric leukemic samples (154 ALL and 32 AML) were tested for ex vivo chemosensitivity for up to 22 drugs. ALL samples included 113 samples obtained at first relapse, and 41 obtained at second relapse. AML samples included 22 samples obtained at first relapse, and 10 obtained at second leukemic relapse. The distribution of patients between first and second relapse groups was comparable. Methods: In vitro drug resistance was tested by the MTT assay. The drug concentration that was inhibitory to 50% of the cells (IC50) was calculated from the dose-response curve and was used as a measure of ex vivo drug resistance for each sample. The relative resistance (RR) between groups analyzed for each drug was calculated as the ratio of the mean values of the IC50 of the respective groups for this drug. Only patients who had a successful MTT assay at diagnosis were included in the study. The following drugs were used: prednisolone, dexamethasone, vincristine, idarubicin, daunorubicin, doxorubicin, mitoxantrone, L-asparaginase, cytarabine, fludarabine, cladribine, clofarabine, treosulfan, thiotepa, melphalan, 4-HOO-cyclophosphamide, 4-HOO-ifosfamide, bortezomib, busulfan, 6-mercaptopurine, and 6-thioguanine. For patients with ALL, combined drug resistance profile to prednisolone, vincristine and L-asparaginase (PVA score) was also analyzed. Results: ALL: In comparison to first relapse, second relapsed childhood ALL were more resistant to most of tested drugs. Median PVA score in multiple relapsed patients was 8 vs 6 for patients at first relapse (p=0.004). The median relative resistance value between patients with multiple relapse and those with first relapse for all tested drugs was 2.0, indicating higher drug resistance on second relapse. Multiple relapsed ALL samples were more drug resistant to: prednisolone (>1.9-fold), dexamethasone (>1.5-fold), vincristine (3.1-fold), L-asparaginase (5-fold), mitoxantrone (2.4-fold), cytarabine (4.3-fold), mercaptopurine (2.2-fold), thioguanine (4.8-fold), etoposide (2.6-fold) and melphalan (2.7-fold). On the other hand, lymphoblasts at second relapse were comparably resistant to: daunorubicin, doxorubicin, 4-HOO-cyclophosphamide, 4-HOO-ifosfamide, busulfan, treosulfan, fludarabine, clofarabine and bortezomib. No drug showed a trend towards better cellular sensitivity at first versus second relapse. AML: No significant differences between ITRT at first and second relapse of childhood AML were found. Of the all drugs analyzed, no drug was found for which significantly higher resistance of myeloblasts was observed at second relapse when compared to first relapse of AML. The median RR value between second and first relapse of all tested drugs was 1.0; for 10 drugs the RR was less than 1 (i.e. assumed better sensitivity on subsequent relapse) and for another 11 drugs, the RR value was greater than 1 (i.e. higher drug resistance on subsequent relapse). No drug showed a trend towards better cellular sensitivity at first versus subsequent relapse, as the differences were not significant for each tested drug. Conclusion: In comparison to first relapse, leukemic blasts of children at second relapse of ALL are more in vitro resistant to most of tested drugs. Contrary, myeloblasts of children at second relapse of AML show drug resistance comparable to first relapse. (This study was supported by NCN Grant DEC-2011/03/D/NZ5/05749.) Disclosures No relevant conflicts of interest to declare.