New Insights into Red Blood Cell Microcytosis upon mTOR Inhibitor Administration.

The aim of this study was to evaluate the effect of everolimus, a mammalian target of rapamycin (mTOR) inhibitor, on red blood cell parameters in the context of iron homeostasis in patients with tuberous sclerosis complex (TSC) and evaluate its effect on cell size in vitro. Everolimus has a significant impact on red blood cell parameters in patients with TSC. The most common alteration was microcytosis. The mean MCV value decreased by 9.2%, 12%, and 11.8% after 3, 6, and 12 months of everolimus treatment. The iron level declined during the first 3 months, and human soluble transferrin receptor concentration increased during 6 months of therapy. The size of K562 cells decreased when cultured in the presence of 5 µM everolimus by approximately 8%. The addition of hemin to the cell culture with 5 µM everolimus did not prevent any decrease in cell size. The stage of erythroid maturation did not affect the response to everolimus. Our results showed that the mTOR inhibitor everolimus caused red blood cell microcytosis in vivo and in vitro. This effect is not clearly related to a deficit of iron and erythroid maturation. This observation confirms that mTOR signaling plays a complex role in the control of cell size.

Nodular lymphocyte predominant Hodgkin lymphoma: Experience of Polish Pediatric Leukemia/Lymphoma Study Group.

Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) is a rare clinical entity. To investigate NLPHL clinical course and treatment a survey was performed within Polish Pediatric Leukaemia/Lymphoma Study Group (PPLLSG) participating centers. A questionnaire was sent to all participating centers and analysis of clinical data was performed. From 2010 to 2019, 19 pediatric patients with confirmed NLPHL were registered in Poland. Median age of patients was 12.2 (5.5 - 17.8) years. NLPHL occurred mainly in males (n = 17). Most of the patients (n = 16) had early stage disease - Stage I (n = 6) and stage II (n = 10). Four of the six patients with stage I disease (I A, n = 5; I B, n = 1) underwent complete primary resection. One of these relapsed and was treated with CVP (cyclophosphamide, vinblastine, prednisone) chemotherapy. Two other patients who were not resected completely received CVP chemotherapy and no relapses were observed. Thirteen patients presented with unresectable disease. Of these, eight received three CVP chemotherapy cycles, and five were treated with other chemotherapy regimens. Three relapses were observed and these patients were further treated with chemotherapy and rituximab. One patient underwent autologous stem cell transplantation (auto-SCT). All patients remain alive. Five-year progression-free survival and overall survival for the entire group of patients was 81.6% and 100%, respectively. NLPHL treatment results are consistent with results noted in other countries. Early stage patients have very good outcomes with surgery and observation or low intensity chemotherapy, but this approach may be insufficient in advanced disease.

Evaluation of Changes to the Oral Microbiome Based on 16S rRNA Sequencing among Children Treated for Cancer.

A child's mouth is the gateway to many species of bacteria. Changes in the oral microbiome may affect the health of the entire body. The aim of the study was to evaluate the changes in the oral microbiome of childhood cancer survivors. Saliva samples before and after anti-cancer treatment were collected from 20 patients aged 6-18 years, diagnosed de novo with cancer in 2018-2019 (7 girls and 13 boys, 7.5-19 years old at the second time point). Bacterial DNA was extracted, and the microbial community profiles were assessed by 16S rRNA sequencing. The relative abundances of Cellulosilyticum and Tannerella genera were found to significantly change throughout therapy (p = 0.043 and p = 0.036, respectively). However, no differences in the alpha-diversity were observed (p = 0.817). The unsupervised classification revealed two clusters of patients: the first with significant changes in Campylobacter and Fusobacterium abundance, and the other with change in Neisseria. These two groups of patients differed in median age (10.25 vs. 16.16 years; p = 0.004) and the length of anti-cancer therapy (19 vs. 4 months; p = 0.003), but not cancer type or antibiotic treatment.

Palliative sedation at home for terminally ill children with cancer.

CONTEXT: The presence of symptoms that are difficult to control always requires adjustment of treatment, and palliative sedation (PS) should be considered. OBJECTIVES: We analyzed our experience in conducting PS at home for terminally ill children with cancer during a seven-year period. METHODS: We performed a retrospective analysis of medical records of children with cancer treated at home between the years 2005 and 2011. RESULTS: We analyzed the data of 42 cancer patients (18% of all patients); in 21 cases, PS was initiated (solid tumors n = 11, brain tumors [5], bone tumors [4], leukemia [1]). Sedation was introduced because of pain (n = 13), dyspnea (9), anxiety (5), or two of those symptoms (6). The main drug used for sedation was midazolam; all patients received morphine. There were no significant differences in the dose of morphine or midazolam depending on the patient's sex; age was correlated with an increase of midazolam dose (R = 0.68; P = 0.005). Duration of sedation (R = 0.61; P = 0.003) and its later initiation (R = 0.43; P = 0.05) were correlated with an increase of the morphine dose. All patients received adjuvant treatment; in patients who required a morphine dose increase, metoclopramide was used more often (P = 0.0002). Patients did not experience any adverse reactions. Later introduction of sedation was associated with a marginally higher number of intervention visits and a significantly higher number of planned visits (R = 0.53; P = 0.013). CONCLUSION: Sedation may be safely used at home. It requires close monitoring and full cooperation between the family and hospice team. Because of the limited data on home PS in pediatric populations, further studies are needed.

Who receives home-based perinatal palliative care: experience from Poland.

CONTEXT: The current literature suggests that perinatal palliative care (PPC) programs should be comprehensive, initiated early, and integrative. So far there have been very few publications on the subject of home-based PC of newborns and neonates. Most publications focus on hospital-based care, mainly in the neonatal intensive care units. OBJECTIVE: To describe the neonates and infants who received home-based palliative care in Lodz Region between 2005 and 2011. METHODS: A retrospective review of medical records. RESULTS: 53 neonates and infants were admitted to a home hospice in Lodz Region between 2005 and 2011. In general, they are a growing group of patients referred to palliative care. Congenital diseases (41%) were the primary diagnoses; out of 53 patients 16 died, 20 were discharged home, and 17 stayed under hospice care until 2011. The most common cause of death (56%) was cardiac insufficiency. Neurological symptoms (72%) and dysphagia (58%) were the most common clinical problems. The majority of children (45%) had a feeding tube inserted and were oxygen dependent (45%); 39 families received psychological care and 31 social supports. CONCLUSIONS: For terminally ill neonates and infants, perinatal palliative care is an option which improves the quality of their lives and provides the family with an opportunity to say goodbye.

Development of treatment and clinical results in childhood acute myeloid leukemia in Poland.

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 impact of pediatric palliative care education on medical students' knowledge and attitudes.

PURPOSE: Most undergraduate palliative care curricula omit pediatric palliative care (PPC) issues. Aim of the study was to evaluate the pilot education programme. METHODS: All 391 students of Faculty of Medicine (FM) and 59 students of Division of Nursing (DN) were included in anonymous questionnaire study. Respondents were tested on their knowledge and attitude towards PPC issues before and at the end of the programme and were expected to evaluate the programme at the end. RESULTS: For final analysis, authors qualified 375 double forms filled in correctly (320 FM and 55 DN). Before the programme, students' knowledge assessed on 0-100-point scale was low (FM: median: 43.35 points; 25%-75%: (40p-53.3p); DN: 26.7p; 13.3p-46.7p), and, in addition, there were differences (P < 0.001) between both faculties. Upon completion of the programme, significant increase of the level of knowledge in both faculties was noted (FM: 80p; 73.3-100; DN: 80p; 66.7p-80p). Participation in the programme changed declared attitudes towards some aspects of withholding of special procedures, euthanasia, and abortion. Both groups of students positively evaluated the programme. CONCLUSIONS: This study identifies medical students' limited knowledge of PPC. Educational intervention changes students' attitudes to the specific end-of-life issues. There is a need for palliative care curricula evaluation.

Pediatric palliative care education for medical students: development and evaluation of a pilot program.

UNLABELLED: In Poland, medical curricula cover palliative care for adults, not for children. This paper evaluates feedback of students who participated in a pilot pediatric palliative care education program. METHOD: An anonymous questionnaire was designed for the students; they were asked to assess each aspect of the program on a scale of 0 to 6 (0 denoted complete dissatisfaction; 6, complete satisfaction). RESULTS: 207 students participated in the program, 197 evaluated it, and 160 formed the research data group. More than 50 percent gave the program 5 points (mean +/- SD; 4.91 +/- 0.9). A total of 79 students (44 percent) assessed the material as 51 to 75 percent new, and 56 students (31 percent) placed it between 76 and 100 percent. A majority indicated that the material would be most useful to them in their future clinical work. Most respondents (78 percent) stated that pediatric palliative care should be included in the pediatrics curriculum. The contribution of the program instructors was given a high score (on average, 5.26 +/- 0.52). CONCLUSION: The pediatric palliative care education program was feasible, and it was well received by the students who undertook it.

Nijmegen breakage syndrome (NBS) as a risk factor for CNS involvement in childhood acute lymphoblastic leukemia.

Central nervous system (CNS) involvement is an independent risk factor for poor event-free survival and relapse confined to the CNS. Knock-out mice deprived of RAG2, the protein involved in DNA repair, developed leukemic infiltration within leptomeninges. Therefore, we hypothesized that DNA repair deficiencies in humans, such as Nijmegen breakage syndrome (NBS), may constitute a risk factor for CNS dissemination of acute lymphoblastic leukemia (ALL). Having analyzed the incidence of CNS2/CNS3 status at diagnosis of ALL in two independent cohorts from the Polish Pediatric Leukemia/Lymphoma Study Group, we noticed that among children with NBS CNS involvement was significantly frequent.

[Genotyping and minimal residual disease study in children with acute myeloid leukemia: preliminary results]. / Genotypowanie i oznaczania choroby resztkowej u dzieci z ostra bialaczka mieloblastycznq: wstepne wyniki.

The aim of the paper is to present the initial results of molecular examination which was started in 2006 for children with acute myeloid leukemia. Better knowledge of biology of this disease, can result in establishing of new risk factors what allows more precise patient stratification to different therapeutic groups. Study was obtained patients until to 18 years of age treated according to AML-BFM 2004 INTERIM protocol in 14 centers of the Polish Pediatric Leukemia/Lymphoma Study Group. Mononuclear cells were collected from bone marrow on time points established according to the AML-BFM 2004 INTERIM protocol. Collected cells were isolated on Ficoll gradient, and RNA and DNA were isolated using TRIZOL reagent. To synthesize cDNA an amount of 1 mg of total RNA was used. To perform quantitative RT-PCR and RQ-PCR reactions 4 fusion gene transcripts (AML1-ETO, CBFb-MYH11, PML-RARA /subtype bcrl and bcr3/) were used according to the protocol established by Europe Against Cancer Program. An expression of WT1 gene was tested additionally. An analysis of ABL control gene was used to normalize of achieved results. Determination of duplication of FLT3 gene in DNA sample was performed with starters complementary to JM region. Genotyping was performed in 75 patients with acute myeloid leukemia so far. AML1-ETO fusion gene transcript was found in 14 patients (19%). PML-RARA (subtype bcr3) and CBFB-MYH11 gene transcripts were detected in 3 (4%) and 3 (4%) patients, respectively. Duplication of FLT3 gene was found in 4 (5.3%) cases. Between 67 tested children over expression of WT1 was present in 51 patients (76%). Analysis of MRD level in subsequent time points showed systematic decrease of number of fusion gene transcript copies and gene WT1 expression. To establish the rate of molecular marker presence in AML in children and the influence of the presence of MRD on the treatment results as well, the study has to be conducted on a larger group of patients with longer follow-up.

[Can children with Hodgkin's disease be treated with chemotherapy only?]. / Czy dzieci z choroba Hodgkina moga byc leczone wylacznie chemioterapia?

Currently over 90% of children and adolescents with Hodgkin's disease (HD) can be cured thanks to use of multidrug chemotherapy (CT) combined with involved-field radiotherapy (IF-RT). However, the intensive treatment may increase the risk of late complications which may impair the patients' quality of life. In order to decrease the incidence of late complications the protocol with limited use of IF-RT was introduced in centers of Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG). This study presents the treatment results of patients treated with CT only in comparison with the therapy results of children treated with CT and IF-RT. From 1997 to 2006, 634 children (age: 2-22,5 years) with HD were treated in 14 oncological centers of PPLLSG. Majority of patients received CT (3-8 cycles of MVPP/B-DOPA) combined with IF-RT. In 45 patients with IA-IIA stages presenting favorable risk factors (small mediastinal tumor, peripheral nodular mass of a maximum diameter < 6 cm, involvement of less than three nodular regions, ESR < 50 mm after 1 h, histologic type other than lymphocyte depletion and very good treatment response assessed after 3 CT cycles) IF-RT was omitted. Among 634 children first complete remission (RC) was not achieved in 2.4% of patients. Relapses occurred in 24 children (3.9%). The rates of 5-year overall survival (OS), relapse-free survival (RFS) and event-free survival (EFS) were 97%, 96% i 92%, respectively. All patients treated with CT only remain in first CR. All serious late complications (including 7 second neoplasms) occurred in patients treated with CT combined with RT. Seven children died because of severe complications, among them two in first CR (aplastic anemia, sepsis). Our results show that the use of CT only in precisely selected group of patients with HD do not impair the treatment results and may decrease the risk of late life threatening complications. Treatment response assessment with the use of PET may in future increase the number of patients treated without RT and limit the need of the use of invasive diagnostic methods in patients with residual mass.

[Treatment results of children with neuroblastoma: report of Polish Pediatric Solid Tumor Group]. / Wyniki leczenia dzieci ze zwojakiem zarodkowym wspólczulnym: wstepny raport Polskiej Pediatrycznej Grupy Guzów Litych.

Approximately 60 children aged 0-18 years are diagnosed of NBL each year in Poland. About 60% of all patients suffering from NBL have a chance for durable cure. Unfortunately the prognosis for patients within the high-risk group accounting for more than 50% of all NBL patients remains poor despite the introduction of more intensive chemotherapy regimens with radical surgery procedures and megachemotherapy with subsequent stem cell transplantation. Only one third of patients in this group can be cured. To improve the treatment results of the high-risk patient group and to decrease the rate of therapy related side effects current European treatment protocols have been introduced systematically in Poland. In February 2009 information about 389 patients (age 0.1-16.5 years) diagnosed between 2001 and 2008 were obtained. Results of therapy of 319 patients who started treatment from 2001 to 2007 were analyzed. Between 104 infants and 215 children over 1 year of age, stage 4 of disease was found in 25% and 54.5%, respectively. In this period additionally to European treatment protocols, two another protocols were used. Satisfactory treatment results were obtained in 104 infants (5-year event free survival /EFS/=82.6%), irrespective of the type of treatment protocol. Over 5-year EFS for children over 1 year of age in 1, 2 and 3 stage of disease was: 100%, 86.3% and 64.5%, respectively. On the contrary, 107 patients with 4 stage of disease achieved the 5-year EFS of 27% only. Treatment results obtained in patients treated according to the European HR-NBL-1/ESIOP protocol were better than for patients treated according to other treatment protocols (5-year EFS: 31.1% and 16.4%, respectively), but difference between these groups was not significant. Between 2001 and 2007 data reporting increased to 81% from 19% noted earlier. Unfortunately, results of treatment for children over 1 year of age remain still unsatisfactory. That is why there is a need of improvement of modern, unified treatment realization as well as better data reporting. For realization of these aims adequate financial support is essential.

[Acute respiratory failure in a 16-yr-old girl with alveolar soft part sarcoma]. / Problemy diagnostyczne i terapeutyczne ostrej niewydolnosci oddechowej u 16-letniej dziewczynki z miesakiem tkanek miqkkich.

BACKGROUND: Intensive treatment in oncology often leads to severe complications, including infection and coagulation disturbances. Among the most serious are fungal infections which are often life-threatening, and difficult to recognize and treat. We present a patient with severe pneumonia and pleural effusion, that developed during treatment of a soft tissue sarcoma with pulmonary metastases. CASE REPORT: A 16-year-old girl was admitted to the ITU because of marked dyspnoea, bilateral pneumonia and pleural effusion. She was intubated and placed on a ventilator, and bilateral pleural drains were inserted. She also required vigorous inotropic support (dopamine + noradrenaline). CRP was 12.5-19.8 mg dL(-1) and procalcitonin was below 1 ng mL(-1)). Lung metastases and tuberculosis were excluded and fungal infection suspected. Aspergillus DNA was detected in bronchoalveolar lavage, and in blood serum (PCR). Amphotericin B and voriconazole were instituted, but without evident success, The girl was severely distressed, required mechanical ventilation with an F1O2 of 0.6, while her CRP increased to 28.4 mg dL(-1). The amphotericin was stopped and replaced with caspofungin, resulting in rapid improvement in her clinical status. The girl was extubated after 21 days of ventilation, however due to a very severe opioid withdrawal syndrome with extreme agitation, she was re-intubated. After a further two weeks on methadone and sedatives, she was extubated again, this time successfully, One month later she was discharged from the hospital, still on oral voriconazole. CONCLUSION: Fungal infection should always be considered in immunocompromised patients with clinical signs of systemic infection. Recognition and treatment of pulmonary aspergillosis is difficult and may require multi drug therapy.

[Changes in the lipid profile in children with acute lymphoblastic leukaemia - the influence of the disease and its treatment]. / Zmiany w profilu lipidowym u dzieci z ostra bialaczka limfoblastyczna- wplyw choroby i jej leczenia.

UNLABELLED: The aim of the study was a prospective evaluation of the lipid profile in children with acute lymphoblastic leukaemia, before and during the treatment with L-asparaginase. PATIENTS AND METHODS: Twenty-four children treated according to the ALLIC 2002 protocol entered the study. Blood samples were collected during the induction phase of treatment, on the 1st, 21st and 30(33)th day. The concentration of the total cholesterol, HDL and LDL cholesterol and triglycerides was determined. The results were analyzed in relation to the Body Mass Index, the WBC count and L-asparaginase activity. At the moment of diagnosis significantly low concentration of total cholesterol (124 mg/dl (103-153) vs 161 mg/dl (143-185), p=0,011) and HDL cholesterol (23 mg/dl (17-27) vs 56 mg/dl (44-64), p=0,00001) were observed, as well as high concentration of triglycerides (112 mg/dl (83-162) vs 73 mg/dl (62-99), p=0,009). The concentration of LDL cholesterol was similar to that observed in the control group. During further treatment the increase of the total cholesterol concentration was observed, but it was still significantly lower, when compared with the control. The values of triglycerides were significantly higher then those observed in healthy children (day 21: 88 mg/dl (67-170), p=0.08, day 33: 111 mg/dl (96-104) p=0.0004). The concentration of HDL cholesterol has increased during the treatment, but it was still lower than the HDL concentration in the control group (day 38: mg/dl (29-53), day 33: 30 mg/dl (16-50), p=0.009). No association between lipid concentration and BMI, WBC and L-asparaginase activity were found. CONCLUSIONS: At the moment of diagnosis of ALL the potentially atherogenic lipid profile could be established. This tendency subsists during the induction phase, regardless of slight differences in particular lipid fractions.

[Does the residual mediastinal mass have prognostic significance in children with Hodgkin's disease (HD)?]. / Czy obecnosc przetrwalej zmiany w sródpiersiu ma znaczenie prognostyczne w chorobie Hodgkina (HD) u dzieci?

Prognostic significance of residual mediastinal tumor mass in children treated for HD as well as the choice of the optimal management of these cases still remains unknown. In years 1994-2001 in 10 PPLLSG participating centers 480 children (age 2-19.7 years) were treated for HD (stages I-IV). In 338 cases initial mediastinal/lung hilus involvement was present. All patients with initial mediastinal/lung hilus involvement were treated with multidrug chemotherapy combined with involved field radiotherapy. In five cases remission was not achieved. Complete remission (CR) was achieved in 226 patients and uncertain complete remission (UCR) in 107 patients, in whom after completion of planned treatment residual changes in mediastinum/lung hilus were identified in radiological examinations. Twenty four children with persistent mediastinal tumor underwent thoracoscopy or thoracotomy. In only one case histopathological examination revealed the presence of neoplastic cells in mediastinal mass tissue, in 2 another cases cystic changes in mediastinum were present, in one case thymic tissue was identified, necrotic tissue was present in 20 cases. Among 107 children with residual mediastinal tumor and 226 patients with CR achieved, relapses occurred in 6 and 18 patients respectively. Over 5-year relapse-free survival was 92.4% and 91.3% respectively. Patients with the presence of mediastinal/lung hilus tumor after the completion of the treatment do not have an increased risk of relapse, but before the completion of therapy they require careful, clear-sighted and repeated examinations including computed tomography (CT), magnetic resonance imaging (MRI) and especially positron emission tomography (PET) to evaluate the nature of persistent lesions. Only in clinically and radiologically doubtful cases tumor biopsy with subsequent histopatological examination should be performed.

Cytoprotective effect of amifostine in the treatment of childhood neoplastic diseases--a clinical study including the pharmacoeconomic analysis.

Amifostine is an active aminothiol, which has unique properties as a radio- and chemoprotective agent. It has been reported to prevent myelosuppression and reduce the toxic effects of intensive cancer treatment. In the study, 57 courses of chemotherapy in 18 children treated because of neoplastic disease were analyzed to assess the early side effects induced by cytotoxic anticancer therapy. In 18 of them amifostine was used as the cytoprotective agent. The estimation of adverse effects was made in accordance to WHO scale of toxicity, and the pharmacoeconomic analysis was based on the costs of intravenous antibiotics, G-CSF, GM-CSF, blood preparations, immunoglobulins and days of hospitalization. The amifostine use in supportive therapy of neoplastic diseases in children decreases the number of infections thanks to the diminishing of myelotoxic effect. This not only improves the comfort of the patient but also shortens the time of hospitalization. The amifostine therapy limits the costs of treatment, but high price of the drug itself, makes however, the chemotherapy with cytoprotection comparable in pharmacoeconomic analysis to the standard treatment.

Carrier frequency of mutation 657del5 in the NBS1 gene in a population of Polish pediatric patients with sporadic lymphoid malignancies.

Nijmegen breakage syndrome (NBS) is a human autosomal recessive disease characterized by genomic instability and enhanced cancer predisposition, in particular to lymphoma and leukemia. Recently, significantly higher frequencies of heterozygous carriers of the Slavic founder NBS1 mutation, 657del5, were found in Russian children with sporadic lymphoid malignancies, and in Polish adults with non-Hodgkin lymphoma (NHL). In addition, the substitution 643C>T (R215W) has also been found in excess among children with acute lymphoblastic leukemia (ALL). In an attempt to asses the contribution of both mutations to the development of sporadic lymphoid malignancies, we analyzed DNA samples from a large group of Polish pediatric patients. The NBS1 mutation 657del5 on one allele was found in 3 of 270 patients with ALL and 2 of 212 children and adolescents with NHL; no carrier was found among 63 patients with Hodgkin lymphoma (HL). No carriers of the variant R215W were detected in any studied group. The relative frequency of the 657del5 mutation was calculated from a total of 6,984 controls matched by place of patient residence, of whom 42 were found to be carriers (frequency = 0.006). In the analyzed population with malignancies, an increased odds ratio for the occurrence of mutation 657del5 was found in comparison with the control Polish population (OR range 1.48-1.85, 95% confidence interval 1.18-2.65). This finding indicates that the frequency of the mutation carriers was indeed increased in patients with ALL and NHL (p < 0.05). Nonetheless, NBS1 gene heterozygosity is not a major risk factor for lymphoid malignancies in childhood and adolescence.

[Analysis of microvascular density and the expression of vascular-endothelial growth factor (VEGF) and its membrane receptor Flk-1 in neuroblastoma]. / Analiza gestosci naczyniowej oraz ekspresji sródblonowo-naczyniowego czynnika wzrostu (VEFG) i jego receptora blonowego (FLK-1) w neuroblastoma.

AIM: To assess selected angiogenic markers; microvascular density and the expression of VEGF and Flk-1 in relation to clinical features and morphologic types of neuroblastoma. PATIENTS AND METHODS: Eighty-two children with neuroblastoma were studied. Morphological assessment was performed in paraffin embedded tissues of the primary tumours. Microvessels within tumour tissue were counted on immunohistochemically stained sections using anti CD34 antibody. The expression of VEGF and Flk-1 was estimated semiquantitively in immunohistochemically stained sections with adequate antibodies. The results of angiogenic studies were referred to the clinical data: age, clinical stage, localization and site of the primary tumour, serum LDH and ferritin at diagnosis. The correlation between angiogenic markers and morphological type of neuroblastoma was also evaluated. RESULTS: Microvascular density varies in a wide range (32-325/mm(2)). There was no significant statistical difference between previously untreated and tumours assessed after chemotherapy. Analyzing the correlations between the angiogenic markers and clinical features we found a converse relation between the age and microvascular density. The highest expression of VEGF was found in adrenal tumours in comparison to other localizations. Undifferentiated and poorly differentiated tumours presented a higher expression of VEGF and higher vascular density. Non significant higher expression of VEGF and higher vascular density was noticed in smaller <5 cm tumours. CONCLUSIONS: Correlations were found between the microvascular density and the age, diameter and the localisation of the primary tumour. Expression of VEGF depends on the localisation of the tumour. Neuroblastoma tumours arising in small children and poorly differentiated types of neuroblastoma indicate higher angiogenic activity.

[Results of immunosuppressive therapy in children with severe aplastic anaemia. Report by the Polish Paediatric Leukaemia and Lymphoma Study Group]. / Efekty leczenia immunosupresyjnego ciezkiej postaci anemii aplastycznej u dzieci. Raport polskiej pediatrycznej grupy ds. leczenia bialaczek i chloniaków.

INTRODUCTION: Bone marrow transplantation from HLA identical family donors is the treatment of choice for children with severe aplastic anaemia (SAA). When no donor is available, combined immunosuppressive therapy is given. AIM: Evaluation of results of immunosuppressive therapy in children with severe aplastic anaemia. MATERIAL AND METHODS: SAA was diagnosed in 85 children (31 girls, 54 boys) aged 2-17.5 years in the eleven centres of the Polish Paediatric Leukaemia and Lymphoma Study Group (PPLLSG) in Poland between 1993-2003 years. All patients received protocol of the Severe Aplastic Anaemia Working Party of the Europe Bone Marrow Transplant (EBMT): antilymphocyte globulin or antithymocyte globulin, cyclosporin A, prednisolone and granulocyto- or granulocyto-macrophagic-cell stimulation factor was additionally administered during deep neutropenia. Haematological response was evaluated on day 84, 112 or 180 of the therapy. RESULTS: complete remission occurred in 43 patients (50.5%), partial remission in 22 (25.4%), no response was obtained in 20 children (23.7%) in 180 day of the therapy. Period of observation was from 12 months to 10.5 years. During this time relapse occurred in 6 patients (7%). We observed 16 deaths: 7 early during the first 3 months of immunosuppressive therapy (IS) and 9 after the first 3 months of IS. CONCLUSION: the actual survival at 10-years, after immunosuppressive therapy is 81.2% in our group. Transformation to leukaemia or myelodysplastic syndrome (MDS) was not observed in any of our patients. We observed one case with paroxysmal nocturnal haemoglobinuria (PNH).

Skin involvement in highly malignant non-Hodgkin lymphomas of childhood and adolescence.

OBJECTIVE: The aim of this study was to demonstrate the clinical spectrum of highly malignant cutaneous non-Hodgkin lymphoma (NHL) in children and to define the outcome among these patients. MATERIAL AND METHODS: A retrospective analysis of children with NHL treated at Polish oncology centers was carried out in order to determine patients with skin involvement. Thirteen subjects with primary and 4 with secondary cutaneous NHL were studied. The diagnosis of NHL was based on histological and immunohistochemical examination of skin biopsy. RESULTS: Nine of 13 cases of primary cutaneous NHL presented as a tumors. Other manifestations were as follows: hard infiltration, edema of subcutaneous tissue, maculopapular lesions, and generalized erythroderma. The mean time between the first cutaneous symptoms and diagnosis of NHL was 5.6 +/- 3.3 months. Secondary cutaneous lesions during the course of NHL were described as maculopapular or nodular eruption. In addition, 2 subjects had generalized ichthyosis. Among patients with primary cutaneous NHL, 11 (84.6%) subjects are still alive without any signs of the disease. Two children (15.4%) died. In patients with secondary skin involvement during the course of NHL only one child is still alive with a residual tumor mass in the mediastinum. The estimated 5-year overall survival for primary cutaneous NHL was significantly better than for individuals with secondary cutaneous NHL (p = 0.02). CONCLUSIONS: Primary cutaneous NHL has a relatively favorable prognosis. On the other hand, cutaneous metastases of extracutaneous NHL seem to be a poor prognostic factor.