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Abstract 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.

Although isolated central nervous system (CNS) relapses are rare, they may become a serious clinical problem in intensively treated patients with high-risk neuroblastoma (NBL). The aim of this study is the presentation and assessment of the incidence and clinical course of isolated CNS relapses. Retrospective analysis involved 848 NBL patients treated from 2001 to 2019 at 8 centres of the Polish Paediatric Solid Tumours Study Group (PPSTSG). Group characteristics at diagnosis, treatment and patterns of relapse were analysed. Observation was completed in December 2020. We analysed 286 high risk patients, including 16 infants. Isolated CNS relapse, defined as the presence of a tumour in brain parenchyma or leptomeningeal involvement, was found in 13 patients (4.5%; 8.4% of all relapses), all of whom were stage 4 at diagnosis. Isolated CNS relapses seem to be more common in young patients with stage 4 MYCN amplified NBL, and in this group they may occur early during first line therapy. The only or the first symptom may be bleeding into the CNS, especially in younger children, even without a clear relapse picture on imaging, or the relapse may be clinically asymptomatic and found during routine screening. Although the incidence of isolated CNS relapses is not statistically significantly higher in patients after immunotherapy, their occurrence should be carefully monitored, especially in intensively treated infants, with potential disruption of the brain-blood barrier., (© 2022. The Author(s).)

This study presents current recommendations of the Polish Association of Pediatric Surgeons (PTChD) regarding diagnostics and treatment of ovarian lesions in girls. They are based on many years of the authors' clinical experience as well as a review of international literature and include practical clinical guidelines. The recommendations were formulated in cooperation with the Polish Association of Pediatric Oncology and Hematology (PTOHD), Polish Pediatric and Adolescent Gynecology Section of the Polish Society of Gynecologists and Obstetricians (PTG) and Polish Pediatric Section of the Polish Society of Radiology (PLTR). Only better understanding of prepubertal ovarian biology and natural history of its pathology may help to introduce efficient and safe diagnostic and therapeutic strategies for girls. The prepared document has been supplemented with treatment algorithms.

11q23/ MLL rearrangements are frequently detected in pediatric acute myeloid leukemia. The analysis of their clinical significance is difficult because of the multitude of translocation fusion partners and their low frequency. The presence of t(10;11)(p12;q23) translocation was previously identified in pediatric acute myelogenous leukemia (AML). It is considered as the second most common translocation detected in pediatric 11q23/ MLL -rearranged (present KMT2A ) AML, after t(9;11)(p22;q23). The presence of the above translocation was previously identified as an unfavorable prognostic factor. Since June 2015, the Polish Pediatric Leukemia/Lymphoma Study Group has applied the therapeutic protocol requiring extensive diagnostics of genetic changes in pediatric AML. Until November 2019, molecular genetic studies were performed in 195 children with diagnosed AML to identify carriers of fusion gene transcripts for 28 most common chromosomal translocations in acute leukemia. The fusion gene transcript for translocation t(10;11)(p12;q23) involving MLL gene was detected with unexpectedly high frequency (8.9%) in our research. It was the highest frequency of all detected MLL rearrangements, as well as other detected fusion gene transcripts from chromosomal aberrations characteristic for AML. It seems that chromosomal aberration between chromosomes 10 and 11 can be relatively frequent in some populations. Paying attention to this fact and ensuring proper genetic diagnosis seem to be important for appropriate allocation of patients to risk groups of pediatric AML treatment protocols., (Copyright © 2020 Ksiazek, Czogala, Kaczowka, Sadowska, Pawinska-Wasikowska, Bik-Multanowski, Sikorska-Fic, Matysiak, Skalska-Sadowska, Wachowiak, Rodziewicz-Konarska, Chybicka, Muszynska-Rosłan, Krawczuk-Rybak, Grabowski, Kowalczyk, Maciejka-Kemblowska, Adamkiewicz-Drozynska, Mlynarski, Tomaszewska, Szczepanski, Pohorecka, Karolczyk, Mizia-Malarz, Mycko, Badowska, Zielezinska, Urasinski, Karpinska-Derda, Woszczyk, Ciebiera, Lejman, Skoczen and Balwierz.)

Background: Children with Down syndrome (DS) have increased risk of myeloid leukemia (ML), but specific treatment protocols ensure excellent outcome. This study was a retrospective analysis of the treatment results and genetic characteristics of ML of DS (ML-DS) in Poland from 2005 to 2019. Methods: All 54 patients with ML-DS registered in the Polish Pediatric Leukemia and Lymphoma Study Group in analyzed period were enrolled to the study. There were 34 children treated with Acute Myeloid Leukemia-Berlin-Frankfurt-Munster 2004 Interim Protocol (group I) and 20 patients treated with ML-DS 2006 Protocol (group II). In the first protocol, there was reduction of the antracyclines doses and intrathecal treatment for ML-DS compared to non-DS patients. In the second protocol, further reduction of the treatment was introduced (omission of etoposide in the last cycle, no maintenance therapy). Results: Probabilities of 5-year overall survival (OS), event-free survival (EFS), and relapse-free survival in the whole analyzed group were 0.85 ± 0.05, 0.83 ± 0.05, and 0.97 ± 0.03, respectively. No significant differences were found between two protocols in the terms of OS and EFS (0.79 ± 0.07 vs. 0.95 ± 0.05, p = 0.14, and 0.76 ± 0.07 vs. 0.95 ± 0.05, p = 0.12, respectively). All deaths were caused by the treatment-related toxicities. Reduction of the treatment-related mortality was noticed (20% in group I and 5% in group II). The only one relapse in the whole cohort occurred in the patient from group I, older than 4 years, without GATA1 gene mutation. He was treated successfully with IdaFLA cycle followed by hematopoietic stem cell transplantation from matched sibling donor. No significant prognostic factor was found in the study group probably due to low number of patients in the subgroups. Conclusions: The study confirms that the reduced intensity protocols are very effective in ML-DS patients. The only cause of deaths was toxicities; however, systematic decrease of the treatment-related mortality was noticed., (Copyright © 2020 Czogala, Pawinska-Wasikowska, Ksiazek, Sikorska-Fic, Matysiak, Skalska-Sadowska, Wachowiak, Rodziewicz-Konarska, Chybicka, Myszynska-Roslan, Krawczuk-Rybak, Grabowski, Kowalczyk, Maciejka-Kemblowska, Adamkiewicz-Drozynska, Bobeff, Mlynarski, Tomaszewska, Szczepanski, Pohorecka, Chodala-Grzywacz, Karolczyk, Mizia-Malarz, Mycko, Badowska, Zielezinska, Urasinski, Nykiel, Woszczyk, Ciebiera, Chaber, Skoczen and Balwierz.)

Objective: The study was to assess whether tumour expressions of hypoxia-inducible factor (HIF)-1α, glucose transporter (GLUT)-1, carbonic anhydrase (CA) IX and vascular endothelial growth factor (VEGF) predict response to neo-adjuvant chemotherapy (naCHT) in children with inoperable rhabdomyosarcoma (RMS). Methods: Immunohistochemical expressions of hypoxia markers were determined semi-quantitatively in tumour tissue microarray of 46 patients with embryonal RMS (RME) and 20 with alveolar (RMA), treated with CWS protocols (1992-2013). Results: In paediatric RME, response to naCHT was influenced significantly by tumour expression of CA IX and GLUT-1. Patients with RMA with low expressions of analysed markers responded well to naCHT, while all poor-responders expressed highly hypoxia markers. Only 5.88% of RMA and 11.11% of RME tumours did not express any of the proteins. In both RME and RMA subgroups, most poor-responders demonstrated simultaneous high expression of ≥3 markers, while most patients expressing ≤2 markers responded well to naCHT. In the whole cohort, co-expression of ≥3 markers, was the only independent factor predicting poor-response to chemotherapy (odds ratio 14.706; 95% CI 1.72-125.75; p  = 0.014). Conclusions: Immunohistochemical expression pattern of four endogenous markers of hypoxia, in tumour tissue at diagnosis, emerges as a promising tool to predict response to naCHT in children with inoperable RMS.

The objective of this nation-wide study was to evaluate the epidemiology and profile of bacterial (BI), viral (VI), and invasive fungal disease (IFD) in patients treated for non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) between the years 2013-2015. In the analyzed period of time, within the studied group of 328 children diagnosed and treated for lymphomas, at least one infectious complication (IC) was diagnosed i.e. 39.3% children. In these patients there were 350 episodes of IC, therein 80.6% episodes of BI, 11.1% episodes of VI, and 8.3% episodes of IFD. In both groups, NHL and HL patients, a stable level of bacterial infections, with an increase in resistance rates, and increased levels of viral and fungal infections were observed. Profile of BI does not depend on lymphoma type, with predominance of Gram-negative bacteria and higher prevalence of MDR pathogens. The overall survival of lymphoma patients with IC was comparable for different types of infections.

This study presents a unique series of malignant supratentorial gliomas in children previously cured from non-CNS primary cancer. On neuroimaging these tumors were not specific, so the patients were suspected of cerebral recurrence of their primary neoplasm: leukemia in four children and sarcoma in one child. Histologically, the group contained four glioblastomas and one anaplastic astrocytoma. Three patients underwent neurosurgical resection, while the other two underwent stereotactic diagnostic biopsy only. Despite combined oncological treatment, four children died during 20 months, and only one glioblastoma patient continued to live for another twelve years. Microscopically, the neoplasms consisted of small cells with some morphologic features of astrocytic lineage, having scanty or prominent processes. Microvascular proliferation and focal or diffuse necrosis were encountered in four cases. The GFAP reactivity in neoplastic cells was low or nil, together with the expression of Olig2, vimentin, and nestin. In two cases a subpopulation of synaptophysin-positive cells was present. Molecular immunohistochemical profiling revealed the expression of phosphorylated forms of PI3Kp110 and AKT, in parallel to a strong PTEN and p53 positivity. The tumors were of IDH1R132H-wild type and immunoreactive for ATRX, HER3, and EGFR. Secondary malignant gliomas in pediatric cancer survivors pose a diagnostic challenge. The present study shows that these tumors are of IDH wild type, PI3K/AKT-activated, having no PTEN and EGFR mutations. Therefore, the biopsy of brain tumors in such patients is crucial both for accurate diagnosis and material preservation for molecular typing.

Introduction: The authors aimed to answer the following questions: 1) What level of knowledge of type 1 diabetes do the parents of children and young adults with this disease have? 2) Will this level of knowledge increase after 1 year of observation? 3) Does improving the knowledge of young adults and their parents result in better metabolic control of the patients?, Material and Methods: This study included 227 patients between the ages of 5 and 20 years with type 1 diabetes. The research was conducted from March 2009 to June 2011. The following two time points were examined: the beginning of the study (test 1a) and one year later (test 1b). The knowledge levels of the patients and parents were obtained using a survey and a knowledge test., Results: Comparison of the results from the two study time points showed that the respondents had a significantly higher level of knowledge after 1 year ( p = 0.001). The comparison of glycated hemoglobin levels between the two time points in patients with type 1 diabetes revealed that the levels were significantly higher at test 1b compared to test 1a ( p = 0.0005)., Conclusions: The parents of children and young adults with type 1 diabetes demonstrate a satisfactory level of theoretical knowledge of therapeutic conduct and self-monitoring principles. The test 1b results demonstrated a higher level of theoretical knowledge in all respondents and poorer metabolic control. Poorer metabolic control in some patients suggests that metabolic control in type 1 diabetes depends on factors other than education. Further research is necessary to determine these additional factors.

Iron participates in oxygen transport, energetic, metabolic, and immunologic processes. There are 2 main causes of iron overload: hereditary hemochromatosis which is a primary cause, is a metabolic disorder caused by mutations of genes that control iron metabolism and secondary hemochromatosis caused by multitransfusions, chronic hemolysis, and intake of iron rich food. The most common type of hereditary hemochromatosis is caused by HFE gene mutation. In this study, we analyzed iron metabolism in 100 healthy Polish children in relation to their HFE gene status. The wild-type HFE gene was predominant being observed in 60 children (60%). Twenty-five children (25%), presented with heterozygotic H63D mutation, and 15 children (15%), presented with other mutations (heterozygotic C282Y and S65C mutation, compound heterozygotes C282Y/S65C, C282Y/H63D, H63D homozygote). The mean concentration of iron, the level of ferritin, and transferrin saturation were statistically higher in the group of HFE variants compared with the wild-type group. H63D carriers presented with higher mean concentration of iron, ferritin levels, and transferrin saturation compared with the wild-type group. Male HFE carriers presented with higher iron concentration, transferrin saturation, and ferritin levels than females. This preliminary investigation demonstrates allelic impact on potential disease progression from childhood.

Iron overload resulting from the mutation of genes involved in iron metabolism or excess dietary intake has been reported to negatively influence human physical performance. The aim of this study was to test the hypothesis that adolescents bearing a hemochromatosis gene (HFE) mutation in contrast to adults with the same mutation will not experience iron accumulation and their aerobic capacity will be similar to that of age-matched controls. Thirteen boys participated in the study. Seven of them are carriers of H63D mutation in the HFE gene and six were wild type. Fitness levels were assessed using the cardiopulmonary exercise test. In addition, iron status and inflammatory markers were determined. We observed that cardiovascular fitness was significantly lower in the group bearing the HFE mutation compared to the control group. Moreover, the HFE mutation group achieved lower maximal power output compared to the control group. There were no differences in blood ferritin concentrations between the two groups which indicates similar amounts of stored iron. Obtained data do not confirm our hypothesis. On the contrary, it was demonstrated that HFE mutation is associated with a lower level of aerobic capacity, even in the absence of iron accumulation.

Introduction: 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., Areas Covered: 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., Expert Opinion: 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).

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.

A total number of 817 children with acute lymphoblastic leukemia (ALL) and 181 with acute myeloblastic leukemia (AML) were assessed for individualized tumor response testing (ITRT) profile as a prognostic factor in long-term follow-up. For each patient, ITRT, initial response to therapy and long-term outcome were assessed. In initial ALL, an impact on long-term response was shown in ITRT for 13 drugs, while in initial AML only for cytarabine. For patients with ALL, a combined five-drug ITRT profile for prednisolone, l-asparaginase, vincristine, cytarabine and daunorubicin or doxorubicin had predictive value for probability of disease-free survival (pDFS) in univariate analysis, whereas in multivariate analysis, bone marrow response by day 33 was the only prognostic factor. For patients with AML, no factor had prognostic value for pDFS in univariate analysis, while ITRT to cytarabine almost reached significance. In conclusion, ITRT can possibly be regarded as a risk factor in childhood acute leukemias.

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.

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.

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.

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.

Introduction: The majority of hyperglycaemic incidents in oncohaematological patients treated with glucocorticosteroids remain undiagnosed. The aim of our study was to work out a detailed protocol for the control of carbohydrate metabolism and to evaluate whether such a protocol can help in diagnosis of carbohydrate metabolism disturbances in oncohaematological paediatric patients., Material and Methods: A one hundred and twenty-eight children treated for proliferative diseases of the haematopoietic system and severe aplastic anaemia with therapeutic protocols including glucocorticosteroids were divided into two groups. Group I consisted of 70 children, whose blood glucose was evaluated on random occasions (retrospective analysis). Group II consisted of 58 children included in the programme of intensive carbohydrate metabolism control (prospective analysis). We compared the incidence of hyperglycaemia in both groups as well as the number of hyperglycaemic incidents per individual therapeutic protocol., Results: A significantly higher incidence of transient hyperglycaemia was noted in oncohaematological patients in the programme of early carbohydrate metabolism disturbances diagnosis than in the other group (22.4% vs. 5.7% respectively; p = 0.008), especially in patients treated with the ALL IC-BFM 2002 protocol for the high risk group (arm A and B), the ALL-REZ BFM 2002 protocol, and in a heterogenous group of children (protocols ALCL 99, Euro-LB02, Interfant-06, WPSAA) (p = 0.042, 0.021 and 0.002, respectively)., Conclusions: The improvement of transient hyperglycaemia detection may constitute the first step towards the reduction of unfavourable consequences of hyperglycaemia. Prospective studies are required to demonstrate the influence of normal carbohydrate metabolism on the frequency of infectious complications in this group.

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.

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.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

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<40 pg/mL as significant predictors for shorter EFS and OS, respectively., 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.

Purpose: 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., Methods: 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., Results: 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., Conclusions: 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.

Objects: Patients with neurofibromatosis type 1 (NF1) are predisposed to developing soft tissue sarcomas (STS)., Materials and Methods: 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., Conclusion: 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.

Unlabelled: THE AIM of the study was to evaluate the incidence of pulmonary complications in children cured from Hodgkin's disease (HD)., Material and Methods: 42 children with HD were treated in the Department of Paediatrics, Haematology, Oncology and Endocrinology, Medical University of Gdansk, between 1994 and 2004. Stages of HD: II--26 children, III--10, IV--6; general symptoms (group B) were present in 50% of patients. Mediastinal involvement was found in 33 children, lung parenchyma infiltration in seven and bronchi involvement in one. In 1/3 of these patients the localization of HD within the chest was massive and symptomatic with signs of the superior caval vein symptoms, cough, dyspnea and cardiac tamponade. The treatment was conducted according to the schemes of the Polish Paediatric Leukaemia /Lymphoma Study Group. Eleven patients required therapy modification including six, in whom the intense line II chemotherapy Salvage 95 was introduced. 29 patients received chest irradiation with doses between J 75 and 36.5 Gy. Pulmonary function was evaluated from the results of clinical examination, 1 chest radiography (CXR), computed tomography, spirometry and lung scintigraphy., Results: Pulmonary complications occurring as fatigue and diminished physical effort tolerance was observed in only two children. Some of the remaining 40 patients demonstrated asymptomatic abnormalities in the analysed tests. Abnormalities in CXR (upper mediastinal fibrosis, postoperational changes within the diaphragm and pneumonitis) were found in six children, minor ventilation problems in spirometry--in 12 and decreased lung perfusion in five. The scintigraphic signs of lung embolisation were not observed in our material. Most of the pulmonary complications occurred in children with enlarged lymph notes located within the chest, especially these with bulky disease presenting with cardio-pulmonary symptoms. In this group of patients the chest irradiation was performed in all except four children, three patients were also administered aggressive salvage chemotherapy., Conclusion: The pulmonary complications in children after completed therapy of HD are not common and mainly asymptomatic and occur predominantly in patients with massive mediastinal and/or lung involvement at diagnosis. The issue needs further evaluation of a more numerous group of HD survivors and a longer follow-up.

Between 1997 to 1999 in 9 centres of the Polish Paediatlic Leukemia/Lymphoma Study Group, 167 children and adolescents (aged 2-19 years) with stage 1 to IV Hodgkin's disease (HD) were treated according to a regimen with a limited use of radiotherapy (RT). All patients received B-DOPA and MVPP chemotherapy. The number of cycles of chemotherapy was adjusted in respective risk groups. In 13 children with stage IA and IIA disease with favourable prognostic factors chemotherapy alone was used. In other patients the dose of RT applied to lymphatic regions was 15-46,4 Gy. In case of a small tumour at presentation and good response to initial chemotherapy the RT dose was 15-16 Gy. In other cases doses of 25-30 Gy were planned. The use of higher doses, particularly exceeding 35 Gy, in eleven patients, was not justified. Among all the 167 patients, three oftliem (1.2%) with advanced disease (Stage III-1V) did not achieve first remission. The 4-year overall survival (OS), relapse free survival (RFS) and event free survival (EPS) were 99%. 93% and 90%, respectively. Relapses occurred in 8 children (first remission lasted for 4-29 (median = 9 months). All 13 children in whom chemotherapy alone was used remain in first remission. In the group of children who received RT in the dose of 15-16 Gy relapse occurred in one child. Our preliminary analysis indicates that limited use of RT in selected cases of HD in children and adolescents did not show worse results of treatment. However, the assessment of possible influence of this regimen on the decreased rate of late complications requires longer follow-up.