[Molecular genetic detection of t(11;22)(q24;12) translocation in Ewing sarcoma and malignant peripheral neuroectodermal tumors].

Ewing's sarcomas and malignant peripheral neuroectodermal tumors (MPNTs) show very little evidence of differentiation and lack characteristic morphological features at the light-microscopic level. These malignancies have always presented a significant differential diagnostic challenge to the pathologist. Electron microscopy, immunohistochemical staining for neural antigens such as neuron-specific enolase (NSE), Leu 7, synaptophysin and, more recently, the detection of Mic-2 gene expression have been included in the routine histopathological diagnostic procedure.

High-dose consolidation with local radiation and bone marrow rescue in patients with advanced neuroblastoma.

Twenty-six children with advanced neuroblastoma were consolidated with cisplatin, BCNU, etoposide, melphalan, 21 Gy of local radiotherapy, and bone marrow rescue in a multicenter study. All patients were over 1 year of age at diagnosis. Twenty-two patients were treated in first complete or partial remission and four in second complete or partial remission.

[Detection of EWS-/FLI-1 gene fusion transcripts by RT-PCR as a tool in the diagnosis of tumors of the Ewing sarcoma group].

Recent cloning of the chromosome breakpoint regions of the reciprocal chromosomal t(11;22) (q24;q12) has revealed that the breakpoints were localized within the EWS gene (Ewings sarcoma gene) on chromosome 22 and the FLI-1 gene on chromosome 11. Thus, molecular genetic techniques were applicable for the detection of this genetic aberration, which occurs as a consistent feature of the Ewings tumor family. By reverse transcription and polymerase chain reaction technique (RT-PCR) in 78% of Ewings sarcoma derived cell lines, and in 91% of primary Ewings tumor tissue t(11;22) specific EWS/FLI-1 fusion transcripts were detected.

Diagnostic value of the molecular genetic detection of the t(11;22) translocation in Ewing's tumours.

One consistent feature of the Ewing's tumour family is the presence of a balanced translocation involving band q12 and band q24 of chromosome 22 and chromosome 11. Recent cloning of the chromosome breakpoint regions of t(11;22)(q24;q12) Ewing's sarcoma translocation has revealed that the breakpoints were localized within the Ewing's sarcoma gene (EWS gene) on chromosome 22 and the Fli-1 gene on chromosome 11. Molecular genetic techniques can thus be applied to the detection of the t(11;22) translocation in Ewing's tumours.

Impact of megatherapy on survival after relapse from stage 4 neuroblastoma in patients over 1 year of age at diagnosis: a report from the European Group for Bone Marrow Transplantation.

Purpose: Relapse from stage 4 neuroblastoma usually carries a poor prognosis. A retrospective study using the European Bone Marrow Transplant (EBMT) Solid Tumor Registry was undertaken to define the role of megatherapy (MGT) in relapsed patients.

Patients And Methods: After relapse, 33 boys and 15 girls with previous stage 4 neuroblastoma received intensification by MGT followed by either autologous (n = 42) or allogeneic (n = 6) bone marrow rescue in 11 European institutions.

Myeloablative radiochemotherapy and hematopoietic stem-cell rescue in poor-prognosis Ewing's sarcoma.

Purpose: The prognosis of patients with multifocal primary and early or multiple relapsed Ewing's sarcoma is poor with conventional chemoradiotherapy and surgery. We evaluated the efficacy and feasibility of a myeloablative regimen administered as consolidation treatment for these patients.

Patients And Methods: The ablative regimens consisted of simultaneous radiochemotherapy: 12 Gy hyperfractionated total-body irradiation (TBI; two doses of 1.

[Results of treatment of primary exclusively pulmonary metastatic Ewing sarcoma. A retrospective analysis of 41 patients].

41 patients presenting with primary metastatic Ewing's sarcoma or malignant peripheral neuroectodermal tumor (PNET) with initial metastases restricted to the lungs and/or pleural space were analysed with respect to clinical manifestation and treatment results retrospectively. All patients were treated according to the protocols CESS 81 and CESS 86 of the German Society of Pediatric Oncology and Hematology (GPOH). The time since diagnosis ranges from 19 to 137 months, with a median of 72 months.

Activity of C1 esterase inhibitor in patients with vascular leak syndrome after bone marrow transplantation.

Vascular-leak syndrome (VLS) is a common complication in the first 3 weeks after bone marrow transplantation (BMT). The patients present with weight gain, generalized edema, ascites, pericardial or pleural effusions, tachycardia, arterial hypotonia, and/or pre-renal failure. The aim of our study was to investigate the role of the complement system in VLS.

[Immune stimulation with interleukin-2 after autologous stem cell transplantation in children and adolescents with solid tumors].

Children with solid tumors of poor prognosis have benefitted from autologous bone marrow transplantation as a treatment modality. Adjuvant interleukin-2 (IL2) therapy has previously been shown to improve prognosis in adults with some solid tumors. In this setting improved survival probability has been attributed to IL2-mediated augmentation of antineoplastic activity of the immune system.

[Immunoglobulin therapy in patients after autologous and allogeneic bone marrow transplantation].

Following bone marrow transplantation many patients are suffering from an impaired immunoglobulin production. Treatment with intravenous immunoglobulin has significantly reduced the incidence of infections as well as severe graft-versus-host disease during the early posttransplant period. However, no complete protection of the patients has been achieved.

Interferon gamma and tumour necrosis factor alpha induce a synergistic antiproliferative response in human Ewing's sarcoma cells in vitro.

Three human cell lines derived from Ewing's sarcoma (RM-82, VH-64, and WE-68) were investigated to establish the influence of recombinant human interferon gamma (rhIFN gamma) and tumour necrosis factor alpha (rhTNF alpha) on cell proliferation and survival and to characterize IFN gamma and TNF alpha receptor expression. Incorporation of [3H]thymidine into cells was inhibited by rhIFN gamma after 24 h of incubation. Half-maximal inhibition was observed with 10-80 U/ml rhIFN gamma.

Glycogen storage disease type Ib: infectious complications and measures for prevention.

A patient with glycogen storage disease (GSD) type Ib, neutrophenia, chronic inflammatory bowel disease and recurrent abscesses was treated with recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF). GM-CSF (and also granulocyte colony stimulating factor) therapy markedly increased the neutrophil counts and reduced the frequency of infections and inflammation. We conclude that myeloid growth factors are effective for the treatment and prevention of acute infections and chronic inflammatory complications in patients with GSD Ib.

Interleukin 6-induced differentiation of a human B cell line into IgM-secreting plasma cells is mediated by c-fos.

The role of the protooncogene c-fos in interleukin (IL) 6-induced B cell differentiation was assessed. Treatment of SKW 6.4 cells with IL 6 induced a transient and early stimulation of c-fos sense mRNA expression.

Treatment of donor T cell-mediated hematopoietic suppression after haploidentical bone marrow transplantation by T cell modulation in a patient with severe combined immunodeficiency.

An 8-month-old male patient with severe combined immunodeficiency syndrome was transplanted with maternal, haploidentical T cell-depleted bone marrow without prior conditioning therapy. Acute graft-versus-host disease developed 2 weeks post bone marrow transplantation (BMT) and was successfully treated with cortisone. After cortisone withdrawal the patient developed myeloid and B cell depression concomitant with T cell activation.

Biology and pharmacology of hematopoietic growth factors.

Several glycoproteins that control blood formation have recently been characterized. Through their overlapping, synergizing, and antagonistic effects, they regulate hematopoiesis in a highly differentiated network. Large scale production of these colony stimulating factors (CSFs) has been made available by recombinant DNA technology, and a series of clinical studies in a variety of indications has been finished.

Molecular regulation of hematopoietic cytokines: implications and indications for clinical use in pediatric oncology.

Proliferation and differentiation of hematopoietic progenitor cells are regulated by a network of stimulatory and inhibitory cytokines. An understanding of the molecular mechanisms of growth control may provide a physiologic basis for the innovative therapy of bone marrow disorders. Among various accessory cells, bone marrow T lymphocytes are capable of stimulating, as well as inhibiting, hematopoietic progenitor cells.

Granulocyte and granulocyte-macrophage colony-stimulating factors for treatment of neutropenia in glycogen storage disease type Ib.

Two children with glycogen storage disease type Ib associated with numerous recurrent bacterial infections as a result of neutropenia and neutrophil dysfunction were treated with recombinant human granulocyte colony-stimulating factor (G-CSF). One of the two patients was previously treated with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF); therapy had to be discontinued because of severe local side effects. Both colony-stimulating factors at dosages of 3 and 8 micrograms/kg/per day, respectively, increased the average neutrophil counts from less than 300 cells/microliters to more than 1200 cells/microliters.

Defective interferon gamma production in neonatal T cells is independent of interleukin-2 receptor binding.

Newborns are more susceptible to fungal, viral, protozoan, and certain bacterial infections than adults. This susceptibility is due in part to a decreased interferon gamma (IF gamma) production. The present investigation focuses on the role of the IL-2 receptor in the deficient IF gamma production in neonatal T cells.

The granulocyte/macrophage-colony stimulating factor (GM-CSF): basic science and clinical application.

Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF) stimulates the production as well as the function of myeloid cells, i.e. granulocytes and macrophages.

Differential regulation of lymphokine production by distinct subunits of the T cell interleukin 2 receptor.

Most biologic responses to IL-2 have been attributed to interaction of IL-2 with a high affinity receptor which consists of a heterodimer composed of two distinct IL-2-binding proteins (IL-2R alpha/IL-2R beta). However, both low affinity IL-2R alpha (55 kD) and intermediate affinity IL-2R beta (70-75 kD) also appear to be expressed independently on the cell surface. We investigated the receptor-specific regulatory effects of IL-2 on cytokine production in unstimulated and activated T cells.