First-line immunosuppressive treatment in children with aplastic anemia: rabbit antithymocyte globulin.

Immunosuppressive therapy is the treatment of choice in children with acquired severe aplastic anemia (AA) and no HLA-matched family donor. The paper presents results of a multicenter study of 63 children with AA treated with rabbit antithymocyte globulin (r-ATG) and cyclosporine A as the first line treatment in the years 1996-2012. Therapeutic effects were evaluated at Days 112, 180, and 360. At Day 112, remission was achieved in 28 out of the 63 patients (44.4 %), complete remission in 10 patients (15.9 %), and partial remission in 18 (28.5 %). At Day 180, 31 patients (49.2 %) were in remission including 15 cases in complete (23.8 %), and 16 cases in partial remission (25.4 %). One year after therapy onset, 34 patients (64.9 %) were in remission including 24 patients (38.0 %) in complete and 10 (15.9 %) in partial remission. Relapse occurred in 4 patients, from 8 months up to 2 years and 2 months after remission. One child, 5 years after remission, was diagnosed with paroxysmal nocturnal hemoglobinuria. The estimated 10-year overall survival rate and 10-year event-free survival rate were 67 % and 57 %, respectively.

Diagnosis and treatment of renal cell carcinoma in children: a report from the Polish pediatric rare tumor study group.

BACKGROUND: Renal cell carcinoma (RCC) in children is rare, accounting for approximately 1.9-6% of all pediatric renal malignancies. The aim of this study was to transmit our experience in the treatment of RCC in Polish children. METHODS: Clinical data from 21 children (6.3-18 years old) with RCC treated between 1992 and 2009 at Polish pediatric oncological centers were analyzed. RESULTS: In 2 patients, RCC developed as a second malignancy after neuroblastoma or astrocytoma fibrillare, respectively. In 6 patients, initial diagnoses based on imaging studies were unilateral Wilms' tumor, leading to preoperative chemotherapy. The remaining patients underwent surgery at the beginning of treatment. According to the AJCC/TNM staging system, 14 patients had stage I, 5-II, 1-III, and 1-IV. Nephrectomy was performed in 19 patients, heminephrectomy in one, and biopsy in another. Histopathological diagnoses were clear-cell RCC (18 patients), papillary RCC (2 patients), and chromophobe RCC (1 patient). 10 patients were treated with chemotherapy, with or without IL-2, INFα, and antiangiogenic agents. 2 patients died due to disease progression. CONCLUSIONS: RCC in children is mostly operable at diagnosis, resulting in good prognosis. The role of adjuvant chemo- and immunotherapies is unclear. Neoadjuvant chemotherapy proven for children with Wilms' tumors is ineffective, but the delay in adequate therapy did not worsen the outcome if complete nephrectomy is done subsequently.

Serum soluble interleukin-2 receptor, beta2-microglobulin, lactate dehydrogenase and erythrocyte sedimentation rate in children with Hodgkin's lymphoma.

The study was to determine clinical utility of serum soluble interleukin (IL)-2 receptor (sIL-2Ralpha), beta(2)-microglobulin (beta(2)-M), lactate dehydrogenase (LDH) and erythrocyte sedimentation rate (ESR) as markers of diagnosis, prognosis and monitoring of response to therapy in childhood Hodgkin's lymphoma (HL). The markers were measured prospectively before treatment and in complete remission (CR) during and after therapy in 30 children with HL (F/M:19/11; median age: 11.3 years) and once in 50 healthy children (F/M: 24/26; median age: 8.7 years). Median pretreatment levels of all analysed markers were significantly higher than in healthy controls. Increased pretreatment sIL-2Ralpha, LDH and ESR correlated with bulky disease; sIL-2Ralpha, beta(2)-M and ESR with presence of B symptoms and sIL-2Ralpha and LDH with advanced HL stages. There was a correlation between sIL-2Ralpha and LDH and between beta(2)-M and ESR. The levels and rates of elevated markers reflected well the response to chemotherapy, decreasing significantly when patients achieved CR and further on with therapy continuation. Since all patients survived thus the markers' value to predict the outcome was not established. Serum sIL-2Ralpha, beta(2)-M, LDH and ESR may act as markers for diagnostics and used in monitoring of therapy effectiveness in childhood HL. The markers were also increased in subgroups of patients with unfavourable clinical features; however, small sample size of the study did not allow to draw conclusion on their prognostic roles. We were also not able to establish the influence of markers on event free survival and overall survival because all children survived independent of initial clinical characteristics and pretreatment levels of sIL-2Ralpha, beta(2)-M, LDH and ESR.

Angiosarcoma in children - still uncontrollable oncological problem. The report of the Polish Paediatric Rare Tumours Study.

Angiosarcoma in children - still uncontrollable oncological problem. The report of the Polish Paediatric Rare Tumours StudyAngiosarcoma is a rare, highly malignant vascular neoplasm with little data available on its clinical course and management in children. Ten children with angiosarcoma (M/F: 6/4; aged 2, 3-16 years) registered in Polish Paediatric Rare Tumours and Soft Tissue Sarcomas Studies between 1992 and 2006. Primary tumour exceeded 5 cm in seven patients and affected mainly deep tissues (heart-2, head/neck, bladder, brain, liver and upper limb - one patient each). Four patients had regional and two metastatic diseases (lungs and bones). Three patients were initially misdiagnosed as haemangioma. Complete primary excision was unfeasible even in local stages. All patients received supplementing chemotherapy with no response in four. Radiotherapy was given to five children, including three after relapse. Three of five secondary tumour resections proved complete. Seven patients experienced relapses (mainly metastatic) and two continuous progression. Relapsed patients received chemotherapy +/- radiotherapy and surgery (three). Nine patients died of disease (overall survival 6-66 months), and one child after mutilating secondary resection is alive. Angiosarcoma in children is highly aggressive with an extremely poor prognosis. Complete primary excision is unfeasible, even in seemingly local stages. The response to chemotherapy is poor and the large number of metastatic recurrences suggests a need for systemic therapy modifications.

Interleukin-12 and tumour necrosis factor-alpha equilibrium is a prerequisite for clinical course free from late complications in children with type 1 diabetes mellitus.

The objective of the study was to analyse levels of IL-12 and TNF-alpha and relate the findings to the occurrence of microangiopathy in children with type 1 diabetes mellitus (DM). We examined a group of 123 children with type 1 DM. Serum levels of IL-12 and TNF-alpha were measured by an immunoenzymatic ELISA technique. TNF-alpha and IL-12 tended to be simultaneously present or absent in the sera of 50% of the children who had not developed complications, thus indicating a state of cytokine's equilibrium. Among the patients with an established retinopathy, two IL-12/TNF-alpha combinations were visible. Either a lack of detectable TNF-alpha was accompanied by measurable IL-12 serum concentrations or TNF-alpha incidence was associated with undetectable IL-12 values. Simultaneous lack of TNF-alpha and presence of IL-12 was associated with a better prognosis as these patients had a significantly lower albumin excretion rate. The state of equilibrium between TNF-alpha and IL-12 is beneficial in patients at early stages of the disease, prior to the occurrence of complications. Shifting the equilibrium towards TNF-alpha seems to promote late complications. It may suggest that a disharmony between pro- and anti-angiogenic function of these cytokines underlie the mechanism by which TNF-alpha and IL-12 shape the disease course.

Serum soluble interleukin 2 receptor alpha in human cancer of adults and children: a review.

Cancer growth and development is associated with the stimulation of the innate immune system, including enhanced interleukin 2 receptor (IL-2R) expression in immune cells and its shedding into the circulation in a soluble form of sIL-2Ralpha. In most haematological malignancies, including different types of leukaemias and lymphomas, sIL-2Ralpha has been found to be released directly from the surface of neoplastic cells thus reflecting the tumour bulk, turnover and activity. Several studies have proved that not only lymphoid cancer cells, but also some non-lymphoid cancer cells, express IL-2R on their surface. They include malignant melanoma and carcinomas of the kidney, head and neck, oesophagus and lung. It is suggested that in most malignant solid tumours, elevated levels of sIL-2Ralpha are likely to be the product of normal peripheral mononuclear cells activated in response to the neoplasm's growth or that they are released from activated lymphoid cells infiltrating neoplastic tissues. This latter hypothesis has been proved by discovering the high expression of CD25 on the cell surface of most of these cells. Although the precise source and biological role of sIL-2Ralpha has not been clarified definitively, pretreatment serum levels of sIL-2Ralpha have been shown to reflect the activity, advancement and biological aggressiveness of many types of cancer in adults and children as well as to correlate with prognosis and overall survival. The possibility of enriching the diagnostic tools of oncologists with a new biochemical marker of activity of neoplasms resulted in numerous studies and reports concerning the clinical usefulness of sIL-2Ralpha measurements in adult and, less frequently, in paediatric malignancies. This article presents the actual knowledge concerning the structure, source and biological function of sIL-2Ralpha in patients with haematological and non-haematological malignancies. The authors review the published data on clinical applicability of soluble IL-2Ralpha determination in terms of diagnostics, prognosis and treatment monitoring of particular types of malignant disorders both in adults and in children. They also provide an insight into the clinical usefulness of sLL-2Ralpha-blocking antibodies in patients with cancer, and in those who reject organ transplants, develop graft-versus-host disease after allogeneic bone marrow transplantation and are affected with autoimmune disorders.

Serum level of soluble interleukin-2 receptor alpha correlates with the clinical course and activity of Wilms' tumour and soft tissue sarcomas in children.

Wilms' tumour (WT) and soft tissue sarcomas (SA) in children lack reliable biochemical markers. This study was carried out to determine the clinical significance of serum soluble interleukin-2 receptor alpha (sIL-2Ralpha) in the diagnostics and treatment monitoring of children with WT and SA. The study included 48 children: ten with WT, eight with SA and 30 healthy controls. The sIL-2Ralpha levels (ELISA) and rates of elevated sIL-2Ralpha values were estimated prospectively at diagnosis and in complete remission during treatment and after therapy. As the dependence on age was determined, the levels of sIL-2Ralpha were expressed as multiplications of the upper value of the normal range for a particular age ( xN). Median pretreatment levels of sIL-2Ralpha in patients exceeded those of healthy controls (1.79 xN for WT and 1.53 for SA vs. 0.61 for controls; p < 0.001) as did the rates of elevated sIL-2Ralpha values (80% of WTand 87.5% of SA patients vs. 0% of controls). Good response to therapy was paralleled by a significant decline of pretreatment sIL-2Ralpha levels and its elevated rates. Thus, sIL-2Ralpha determination may be of some value in the diagnostics and treatment monitoring of childhood WT and SA.

A correlation of microvascular density and proliferative activity to clinical and histological characteristics in neuroblastoma.

Seventy-four neuroblastoma patients were analyzed according to the clinical data including age, stage, bone metastases, primary tumor localization, tumor diameter, LDH, and serum ferritin. Histological examination of tumor specimens comprised calculation of proliferative index (PI) on slides stained with anti Ki-67 antibody and assessment of microvascular density (MVD) on anti-CD34 stained sections. Wide range of PI (1.5-79; median 37.8%) and MVD (41-385; median 172/mm2) values was observed. Significant relationship between higher PI and tumor diameter more than 5 cm (40.3 vs 37.2%) was found. Lower PI was found more frequently in stroma-rich tumors. Significantly higher median MVD was found in infant tumors and in smaller tumors <5 cm. Tendency to inverse relationship between PI and MVD was observed. The high values of both PI and MVD were found in some aggressive tumors in patients >1-year old. We evaluated the new parameter: proliferative-vascular index (PVI) as PVI=PIxMVD which ranged from 213-18333. Among eleven patients >1 year old, with PVI >7000, seven (64%) had a poor outcome within the mean period of 22 months. Our results suggest that the simultaneous estimation of proliferative activity and vascularity of neuroblastomas could be studied as a prognostic indicator. Further investigations are needed to confirm this finding.

Twenty years of Polish experience with three consecutive protocols for treatment of childhood acute myelogenous leukemia.

Until 1983, results of treatment of acute myelogenous leukemia (AML) in Poland with different regimens were very poor. In 1983, the Polish Pediatric Leukemia/Lymphoma Study Group introduced a unified treatment protocol--a modified version of BFM-83 protocol. This led to an increase in the curability of AML from 15% to approximately 32%. In 1994, a modification was made: the high-risk patients (>5% blasts in bone marrow on day 15 of therapy and all M5 cases) received two additional cycles with intermediate-dose cytarabine (ID-ARAC). This led to a nonsignificant improvement in the 5-year event-free survival (EFS) rate from 32 to 36%. A new treatment protocol employing idarubicin in place of daunorubicin was introduced in 1998 and produced better initial responses, increase in the number of patients attaining remission after induction therapy and proportional increase of standard-risk patients. The probability of 5-year EFS (pEFS) for the whole group of patients increased from 36 to 47%. In standard- and high-risk groups, the 5-year pEFS was 62 and 33%, respectively. The probability of 5-year disease-free survival was 58% in the whole group, and there were no differences between risk groups. Unsatisfactory treatment results in children classified into the high-risk group are principally due to the low remission rate.

In vitro sensitivity of leukemic cells to nucleoside derivatives in childhood acute leukemias: good activity in leukemic relapses.

Nucleoside analogues such as fludarabine and cladribine are used in therapy of indolent lymphomas and leukemias in adults, while cytarabine is used mainly in protocols for acute leukemias. Mechanisms of their activity is based on inhibition of enzymes involved in DNA, RNA and protein synthesis. The objective of the study was the analysis of in vitro cellular drug sensitivity in childhood acute lymphoblastic (ALL) and myeloid (AML) leukemia. Isolated leukemic cells obtained from 264 patients, including 152 initial ALL, 45 relapsed ALL, 54 initial AML and 13 relapsed AML were tested for cytotoxicity for fludarabine, cladribine, and cytarabine by the MTT assay. Drug concentration lethal to 50% of tested cells was regarded as a value of drug resistance. Three tested nucleoside analogues showed highest cytotoxicity against initial ALL samples. Samples of relapsed ALL and initial AML were more resistant than ALL de novo ones. Unexpectedly, no differences were observed between initial and relapsed AML samples for all tested drugs, what suggests that nucleoside analogues are active drugs in relapsed AML, which is commonly regarded as a resistant disease. All tested drugs presented significant cross-resistance in each of analyzed subgroups. In summary, tested nucleoside analogues presented relatively good activity against childhood leukemias at relapse stage.

Remaining problems and controversies in the management of childhood head and neck soft tissue sarcomas: Retrospective (national) Multicenter Study of the Polish Pediatric Solid Tumors Group.

Soft tissue sarcomas in children are a heterogeneous group of malignant diseases. Among these, tumors localized in the head and neck region are especially difficult to treat. While multidisciplinary care has dramatically improved the prognosis of sarcoma patients, their treatment remains uncertain because of demand on radical surgical resection of the tumor. Achieving cure without deforming or mutilating the child remains the primary goal of treatment. This study is the multicenter (nationwide, 11 Polish centers) retrospective analysis of the treatment results in children having soft tissue sarcoma in the head and neck region during the previous decade (from 1991 to 2001). Late effects of the treatment are documented in long-term survivals. Eighty-five children from 1 to 212 months of age were included. Different multimodal treatment protocols were utilized (CWS-91, SIOP-MMT-91, and CWS-96). The median observation time was 25 months. Data on long-term effects were collected in 34 long-term survivals. Complete remission was achieved in 68 (80%) patients. Primary treatment failure occurred in 13 (15.3%) patients, all of whom succumbed in disease progression. Relapse occurred in 21 (30.9%) patients primarily achieving complete remission. Second primary neoplasm occurred in 3 children. The estimated 5-year event-free survival and the 5-year total survival rates for the whole group are 0.38 and 0.55, respectively. The main late effect documented in long-term survivals were cosmetic defects in 12 (35.3%) and visual field deficit or blindness in 8 (26.5%). Despite substantial improvement of the prognosis of pediatric soft tissue sarcomas, the multimodal treatment of head and neck region tumors remains controversial. Improved long-term outcome and focusing on psychosocial difficulties raise the important and difficult problem of functional results and cosmesis. Tumors localized in the orbit carry an excellent prognosis. However, the main late sequela is vision impairment and cosmetic defect due to the therapy given many years earlier. Two other tumor localizations--the parameningeal and nonparameningeal ones--still have bad prognosis. The observations made in this study confirm that main prognostic factors are the size of the primary tumor and the tumor stage. The worst prognosis remains invasive tumor (T2-stage) with a size over 5 cm. Individually adjusted multimodal therapy, which imperatively needs to be radical, though not mutilating, might minimize the late effects. Psychosocial problems in long-term survivors need to be focused on at the national level and better support must be provided in the future, involving a team of different medical and paramedical profiles.

In vitro comparative antileukemic activity of various glucocorticoids in childhood acute leukemia.

Resistance to glucocorticoids is nowadays one of the strongest adverse risk factors in the treatment of childhood acute lymphoblastic leukemia (ALL). Differential in vitro antileukemic activity of various glucocorticoids and their cross-resistance pattern in childhood acute lymphoblastic and myeloblastic leukemia was determined by means of the MTT assay in 49 successfully tested samples of childhood acute leukemia. The equivalent antileukemic concentrations of respective drugs against lymphoblasts in de novo ALL samples were: 35 microM of hydrocortisone; 8 microM of prednisolone; 1.6 microM of methylprednisolone; 0.47 microM of dexamethasone and 0.23 microM of betamethasone. In comparison to initial ALL samples, the group of relapsed ALL was more resistant to: prednisolone (38-fold, p=0.004), dexamethasone (>32-fold, p=0.004), methylprednisolone (37-fold, p=0.039), betamethasone (38-fold, p=0.018) and hydrocortisone (33-fold, p=0.030). The group of acute myeloid leukemia (AML) samples were resistant to: prednisolone (>83-fold, p<0.001), dexamethasone (>32-fold, p<0.004), methylprednisolone (>65-fold, p=0.003), betamethasone (>66-fold, p=0.004) and hydrocortisone (61-fold, p=0.007), when compared to ALL at presentation. A significant cross-resistance between all used glucocorticoids as well as between glucocorticoids and other tested anti-leukemic drugs was found. In some individual cases in vitro glucocorticoid cross-resistance was less pronounced and relatively good antileukemic activity of betamethasone was observed.

Clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18.

We report the results of detailed clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18. Classical cytogenetics and fluorescence in situ hybridization (FISH) analysis with the chromosome 18 painting probe identified five non-mosaic and two complex mosaic 46,XX,dup(18)(p11.2)/47,XX,dup(18)(p11.2),+r(18) and 46,XX,dup(18)(p11.32)/47,XX,dup(18)(p11.32),+r(18) cases. FISH analysis was performed for precise characterization of the chromosome 18 breakpoints using chromosome 18-specific short-arm paint, centromeric, subtelomeric, and a panel of fifteen Alu- and DOP-PCR YAC probes. The breakpoints were assessed with an average resolution of approximately 2.2 Mb. In all r(18) chromosomes, the 18q terminal deletions ranging from 18q21.2 to 18q22.3 ( approximately 35 and 9 Mb, respectively) were found, whereas only in four cases could the loss of 18p material be demonstrated. In two cases the dup(18) chromosomes were identified as inv dup(18)(qter-->p11.32::q21.3-->qter) and inv dup(18)(qter-->p11.32::p11.32-->p11.1: :q21.3-->qter)pat, with no evidence of an 18p deletion. A novel inter-intrachromatid mechanism of formation of duplications and ring chromosomes is proposed. Although the effect of "ring instability syndrome" cannot be excluded, the phenotypes of our patients with characteristic features of 18q- and 18p- syndromes are compared and correlated with the analyzed genotypes. It has been observed that a short neck with absence of cardiac anomalies may be related to the deletion of the 18p material from the r(18) chromosome.

[Application of Ethyol during chemotherapy in patients with impaired kidney function. Description of three cases]. / Zastosowanie ethyolu u pacjentów z uposledzona funkcja nerek poddawanych chemioterapii. Opis 3 przypadków.

Nephrotoxicity is observed in 30% of patient's treated with chemotherapy schedules based on cisplatin analogues. Ethyol (amiphostin) was used as a protectant of kidney in 3 paediatric patients with neoplastic disease. Two patients suffered from Wilms tumour. One of them, a 5 month old boy presented with agenesis of the right kidney and stage II tumour in the left kidney. Bilateral Wilms tumour was recognised in a 6 year old girl. In both cases glomerular filtration was diminished. The third patient was a girl aged 5 who had isolated relapse of neuroblastoma in the central nervous system. Primary treatment caused nephrotoxic complications such as Fanconi syndrome and diminished glomerular filtration (66 ml/min). In these 3 cases Ethyol was used every lime before analogues of cisplatin were given. Tolerance and the effect of this protectant were good.

[Treatment regimen for children and adolescents with Hodgkin's disease designed to decrease late complications of radiotherapy]. / Program leczenia choroby hodgkina u dzieci i mlodziezy zmierzajacy do ograniczenia powiklan po radioterapii.

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.

[A severe adverse event after vaccine for diphtheria, tetanus, pertussis and poliomyelitis (DTP + polio) in a 4.5 month old infant]. / Powiklanie o ciezkim przebiegu po szczepieniu przeciw Blonicy, Tezcowi, Krztuscowi oraz Poliomyelitis (DTP + Polio) u 4,5 miesiecznego niemowlecia.

Neurological complications of immunisation are rare. We report the case of neuroallergic reaction 5 days after receiving the second course of DTP + Polio vaccine in a 4.5 month old girl. The pathological signs developed 48 hours after the vaccination. On admission the infant demonstrated a persistent fever (39 degrees C), resistant to Paracetamol, unusual crying, irritability, consciousness disorder, and opistotonus. Physical examination showed generalised mild, macular rash and redness and swelling at the injection site. The neurological assessment revealed weakness of upper and lower limbs, meningeal signs such as stiff neck, Kernigs and Brudzinski signs. There were no pathological changes in the CSF. The diagnosis was established as the neuro-allergic Adverse Event Following DPT + Polio Immunisation. After 10 day treatment with Dexamethasone and Phenobarbital the infant was discharged with no neurological changes. A psychomotorical development is good.

[Enormous tumour in the right atrium of a Wilms' tumour patient]. / Olbrzymi guz prawego przedsionka u dziecka z nerczakiem zarodkowym (guzem wilmsa).

Formation of neoplastic thrombus in vena cava inferior (VCI) is well known in Wilms' tumour. We demonstrate a case of large neoplastic mass in the right atrium as prolongation from vena cava inferior in a 2 years and 2 months old girl with Wilms' tumour. The long preoperative chemotherapy (7 months) reduced the tumour and the thrombus. The surgical removal of the tumour and the thrombus was followed by further chemotherapy. During postoperative chemotherapy the control USG examinations showed the presence of a stable mass in a caval wall (a neoplastic mass or a scar?). The extension of the thrombus into the right atrium remains a therapeutic problem which has not been yet resolved.

A case with 47,XXY,del(11)(q23) karotype-coexistence of Jacobsen and Klinefelter syndromes.

A case with 47,XXY, del(11)(q23) karyotype-coexistence of Jacobsen and Klinefelter syndromes: A two-year-old dysmorphic male child was found to have 47,XXY,del(11)(q23) karyotype. Domination of the clinical features of Jacobsen syndrome was observed: mild mental retardation, trigonocephaly, ptosis, downward slanting palpebral fissures, low set ears, carp-shape mouth and micrognathia. Transient thrombocytopenia and leukopenia were also present. Over the following five years gynecomastia and eunuchoid body proportions became evident as clinical features of Klinefelter syndrome. This is the first description of the coexistence of both syndromes.

[Dynamics of the course of neoplastic disease and status of antioxidant system]. / Dynamika przebiegu choroby nowotworowej a stan bariery antyoksydacyjnej ustroju.

The decreased ability to remove free radicals from organism is one of the factors which furthers the development of neoplastic process. Enzymes and substrates which can remove free radicals from organism from antioxidant barrier. The appreciation of some elements of antioxidant organism barrier in children with neoplastic disease was the study's purpose. We examined 100 children in the age from 6 months to 16 years (60 patients with malignant solid tumors and 40 healthy children as a control group). We investigated glutathione peroxidase, catalase and superoxide dismutase activities in erythrocytes. In these children we studied also catalase activity, ceruloplasmin concentration and antioxidant barrier level in plasma. We estimated antioxidant elements in patients with cancer before, during and after treatment and during remission and progression of the disease. The decrease of total antioxidant barrier was typical in introductory period of neoplastic disease. We observed the increase of superoxide dismutase and glutathione peroxidase in erythrocytes and catalase activity in plasma in children with clinical remission but we found the gradual decrease of ceruloplasmin level in plasma.