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The significance of tumor cell contamination in marrow and peripheral blood stem cell (PBSC) collections of patients with solid tumors remains controversial. Various methods have been developed to purge tumor cells from autologous stem cell products, including CD34+ selection. PBSC harvests from patients with Ewing family of tumors (EFT) were analyzed for contaminating tumor cells prior and after CD34+ selection using reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry (FC) analyzes. The expression of CD34 was studied by RT-PCR and FC in 14 primary tumors and 13 PBSC harvests, respectively. Tumor cells were identified in the harvests by both methods. In two patients, contaminating tumor cells were evident by RT-PCR only after positive selection. FC analysis confirmed a higher level of tumor cells in the CD34+ fraction. In an attempt to explore this finding, expression of CD34 was detected in 93% of primary tumors and 67% of contaminated harvests. As CD34 is expressed on EFT cells, these cells may be enriched following CD34+ selection of harvests, although the total number of tumor cells is reduced. Other methods of purging, rather than CD34+ selection, should be explored in patients with EFT undergoing autologous stem cell transplantation.Bone Marrow Transplantation (2007) 39, 589–594. doi:10.1038/sj.bmt.1705640; published online 19 March 2007 [ABSTRACT FROM AUTHOR]

Ataxia telangiectasia is an autosomal recessive disease with a striking predisposition of lymphoid malignancies. ATM mutations have been reported in adult sporadic lymphoma and leukaemia. The aim of this study was to investigate the possible involvement of the ATM gene in the carcinogenesis of Hodgkin disease in children. Tumours were obtained from 23 patients and were subjected to mutation screening and loss of heterozygosity analysis. Eight base substitutions were identified in seven patients. Of them, Y54Y, a silent change, was observed in two patients and a known polymorphism, D1853N, in three patients. Of the other two patients, one harboured a combined genotype P604S/F1463C, identified previously in two patients with Hodgkin lymphoma, and the other a novel missense mutation, V595A. The alterations were present in the germ line, and both had a more aggressive disease. In all, 100 matched normal ethnic controls were screened for these mutations and P604S/F1463C was identified in one healthy control. Loss of heterozygosity was identified in four patients and in three of them it was located centromeric to the ATM gene, and, in one, it spanned a large region, indicating the involvement of other tumour-suppressor genes in this disease. Missense variants of the ATM gene are a rare event in childhood Hodgkin disease.British Journal of Cancer (2004) 90, 522-525. doi:10.1038/sj.bjc.6601522 www.bjcancer.com [ABSTRACT FROM AUTHOR]

Objectives: To summarize and analyze the experience in CNS involvement (CNSI) in children with sarcomas treated in the above-mentioned institutions. Patients and Methods: From 1990 to 2001, all medical charts were retrospectively reviewed: 19 sarcoma patients (12 boys and 7 girls) were diagnosed with CNSI (4 osteogenic sarcomas, 11 Ewing sarcomas, 2 rhabdomyosarcomas, 1 alveolar soft part sarcoma and 1 mesenchymal chondrosarcoma). Mean age of all patients at the time of initial diagnosis was 14.9 years (range: 4–24 years), mean age at the time when CNSI was diagnosed was 16.9 years (range: 5.5–27 years). Results: The frequency of CNSI among our patients was 6.17%. The following symptoms and signs (sometimes combined) presented: headache (10 patients), nausea and vomiting (6 patients), seizures (11 patients) and focal neurological signs (9 patients). The mean duration of time elapsed since diagnosis of CNSI till death or last follow-up was 5.2 months (SD: ±5.7 months). Four patients received chemotherapy (CT) alone, 8 CT and radiotherapy (RT), 2 RT alone, 3 supportive treatment only, 1 CT and surgery and 1 surgery alone. Sixteen patients died; there was no significant difference in the duration of survival between those who were treated with RT or surgery (mean ± SD: 6.77 ± 6.56 months) and those who received only CT or supportive treatment (mean ± SD: 2.60 ± 2.94 months) (p = 0.07). Brain disease was the main cause of death in all but 1 patient who died 4 days after autologous bone marrow transplantation from uncontrolled sepsis. In 16 patients, CNSI was part of a metastatic disease. Conclusions: Among children with sarcoma, CNSI is encountered in 6.17% of cases. More effective therapy has to be developed in order to improve their outcome.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Fanconi anaemia (FA) is a genetically heterogeneous disease with at least eight complementation groups (A–H). In the present study, we investigated the molecular basis of the disease in 13 unrelated Israeli Jewish (non-Ashkenazi) patients with FA. All 43 exons of the Fanconi anaemia A (FANCA) gene were amplified from genomic DNA and screened for mutations by single-strand conformation polymorphism and DNA sequencing. We identified four ethnic-specific mutations: (1) 2172–2173insG (exon 24), the first ‘Moroccan mutation’; (2) 4275delT (exon 43), the second ‘Moroccan mutation’; (3) 890–893del (exon 10), the ‘Tunisian mutation’; and (4) 2574C > G (S858R), the ‘Indian mutation’. The tetranucleotide CCTG motif, previously identified as a mutation hotspot in FANCA and other human genes, was found in the vicinity of 2172–2173insG and 890–893del. According to our study, the four mutations account for the majority (88%) of the FANCA alleles in the Israeli Jewish (non-Ashkenazi) FA population. A screening of 300 Moroccan Jews identified three carriers of the first ‘Moroccan mutation’, but we did not find any carrier of the second ‘Moroccan mutation’ among 140 Moroccan Jews, nor any carrier of the ‘Tunisian mutation’ among 50 Tunisian Jews. Two ‘Indian mutation’ carriers were identified among 53 Indian Jews. All carriers within each ethnic group had the same haplotype, suggesting a common founder for each mutation. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-I (IGF-I) is a known mitogen for various cell types, including those of the hematopoietic cell system. To study the role of IGF-I in the neoplastic process of leukemia in children, the authors have determined the number of IGF-I binding sites on circulating mononuclear cells of children with acute leukemia as compared to normal children, using binding assays. The IGF-I binding sites per cell on peripheral mononuclear cells of children with leukemia decreased compared to those of the control group (411 +/- 73 and 1334 +/- 227, respectively, p < .001), while their affinity increased (K[sub d] = 0.14 +/- 0.04 and 0.43 +/- 0.16, respectively, p = .05). Furthermore, in the patients, the number of the IGF-I binding sites was significantly lower in the subgroup of the peripheral mononuclear cells, which included lymphocytes and monocytes, as compared to their number in the peripheral blast cells (254 +/- 43.6 and 536 +/- 98.6, respectively, p = .02). A significant reduction was found in serum GHBP levels in the patients as compared to the controls (28.21 +/- 1.93 and 35.83 +/- 2.90, respectively, p = .02), while serum IGF-I and growth hormone levels were similar in patient and control groups. These results suggest a possible involvement of IGF-I in childhood acute leukemia, but further studies are needed to establish whether IGF-I plays a role in this disease. [ABSTRACT FROM AUTHOR]

The aim of the study was to delineate the clinical characteristics of visual pathway tumor in children without neurofibromatosis-I. The authors reviewed the charts of all patients meeting these criteria ( n = 12) who were followed in their center over a 13-year period. In 8 patients the disease was relentlessly progressive, and imaging showed a chiasmatic/hypothalamic, exophytic globular lesion. The remainder had a benign course with long periods of tumor stability; one showed some spontaneous visual improvement. The lesions of the latter subgroup were multilobular, with elongated posterior extension into the optic tract. This differentiation, according to the imaging findings, may have significant therapeutic implications. In the first type, every effort should be made to arrest the disease and decrease the size of the lesion, whereas in the second, despite decreased visual ability, careful observation in the appropriate approach. There are as yet no known biological markers to better delineate these two types of tumor behavior. [ABSTRACT FROM AUTHOR]

Sixty-four adult survivors of childhood cancer, recruited via Israel's pediatric cancer treatment center, participated in a multi-dimensional assessment of long-term adjustment and quality of life in the domains of educational achievement, employment status, military service, family status, health and psychological well-being. Subjects had been diagnosed with cancer prior to age 18, were three years or more off therapy with no evidence of disease, and over 18 years old at the time of the study. Data from structured interviews were compared to responses on similar items from a control group with no history of serious illness during childhood, matched for age, sex, and parental education levels. Results indicated an overall pattern of integration into the social mainstream, with similar objective levels of achievement for survivors and controls for most measures of education, employment, significant relationships, and psychological well-being. Results also indicated certain areas of disadvantage, such as military recruitment difficulties, lower income levels, and higher rates of workplace rejection. Significantly, almost half of the survivor sample reported subjective feelings that their illness experience had impaired their achievement in several domains. Quality of life is considered an important outcome parameter in terms of clinical decision making as well as in guiding preventative and supportive intervention efforts. [ABSTRACT FROM AUTHOR]

Considerable clinical variability occurs in adult Gaucher disease type I and three main subtypes may be delineated: a very mild form, a severe form, and a moderate form which itself presents various clinical manifestations. A study based on 25 families from our clinic and a review of published reports showed that when both parents were heterozygous and more than one child was affected with Gaucher disease type I, there was always intrafamilial similarity concerning the three subtypes. In families where one parent and at least one child were affected, variability in the clinical subtype of Gaucher disease type I might occur among the affected members of the family. We propose that the three different clinical subtypes of this disease reflect the genetic heterogeneity of two alleles, G1a and G1b and the three corresponding genotypes represent the three different subtypes of the disease. [ABSTRACT FROM PUBLISHER]

In type I Gaucher's disease, episodes of severe disabling bone pain, the so called bone crises, may be resistant to all analgesics, including narcotics. The demonstration of subperiosteal oedema on magnetic resonance imaging (MRI) led to an attempt to use steroids to relieve the oedema and thereby the pain. On eight occasions, five patients with documented bone crises received conventional dose steroids (20 mg/m2/day) with considerable shortening of the attacks. On six occasions five further patients received high dose methylprednisolone (30 mg/kg intravenously or 1 g/m2 orally daily for two days), which was followed by oral prednisone for three to five days on the last four occasions. In this later group, pain relief was evident within several hours. Three treatments were given on an ambulatory basis. The MRI scan of one of these patients showed no subperiosteal fluid collection five days after high dose steroids had been started, and on subsequent x ray examination, there was no periosteal elevation. This treatment should be considered in cases of Gaucher's disease with bone crises. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH), formerly known as histiocytosis-X, manifests by granulomatous lesions consisting of mixed histiocytic and eosinophilic cells. The hallmark of LCH invasion into the CNS is diabetes insipidus, reflecting local infiltration of Langerhans cells into the posterior pituitary or hypothalumus. In five patients who had early onset LCH with no evidence of direct invasion into the CNS, slowly progressive spinocerebellar degeneration accompanied in some by pseudobulbar palsy and intellectual decline was seen. Neurological impairment started 2.5 to seven years after the detection of LCH. No correlation was found between the clinical syndrome and location of LCH or its mode of treatment. An extensive search for metabolic, toxic, neoplastic, and hereditary aetiologies for progressive cerebellar degeneration was negative. It seems that the clinical entity described here may be considered a new paraneoplastic syndrome related to LCH. It may be induced by the eosinophil derived neurotoxin, which was shown to cause damage to Purkinje cells and pyramidal neurons. [ABSTRACT FROM AUTHOR]

The incidence and severity of osteolytic bone changes in patients with chronic (Type I) Gaucher disease splenectomized in the first decade of life were compared to those in patients of the same age group and similar degree of severity of the disease in whom the spleen remained intact at least until the second half of the second decade. The size of the spleen, measured by palpation, was used as an index of severity. In the splenectomized group osteolytic changes appeared within a few months following splenectomy in six out of eight cases. The changes were severe in five cases and moderate in one. In contrast, in the non-splenectomized group, evidence of bone destruction was found in two out of eight patients and classified as mild in both cases. Furthermore, in three patients in this group, who remained free of bone destruction until splenectomy in the second half of the second decade, osteolytic lesions appeared soon after the operation. Children with chronic Gaucher disease can be spared a great deal of suffering caused by bone disease, if splenectomy is avoided or postponed as far as possible. [ABSTRACT FROM AUTHOR]

The incidence and severity of osteolytic bone changes in patients with chronic (Type I) Gaucher disease splenectomized in the first decade of life were compared to those in patients of the same age group and similar degree of severity of the disease in whom the spleen remained intact at least until the second half of the second decade. The size of the spleen, measured by palpation, was used as an index of severity. In the splenectomized group osteolytic changes appeared within a few months following splenectomy in six out of eight cases. The changes were severe in five cases and moderate in one. In contrast, in the non-splenectomized group, evidence of bone destruction was found in two out of eight patients and classified as mild in both cases. Furthermore, in three patients in this group, who remained free of bone destruction until splenectomy in the second half of the second decade, osteolytic lesions appeared soon after the operation. Children with chronic Gaucher disease can be spared a great deal of suffering caused by bone disease, if splenectomy is avoided or postponed as far as possible. [ABSTRACT FROM AUTHOR]

Analyzes B-lineage childhood acute lymphoblastic leukemia patients for the acute myelocytic leukemia fusion transcript at diagnosis and correlates the findings with duration of remission. Details of patients diagnosed; Event free survival rates of patients; Treatment protocols used in the study.