The aim of this study was to evaluate children with lymphadenopathy and clinical approach to the suspicion of malignancy. The authors evaluated 457 patients with peripheral lymphadenopathy, less than 19 years of age, and referred to the Pediatric Oncology Department of Gazi University Medical School during the periods March 1996-April 2004. A total of 346 patients had benign disorders and 111 had malignant pathologies. Excisional biopsies were performed to 134 patients. A specific etiology could be found 39% in the benign group. Of the 457 patients, 218 were presented as acute, the rest as chronic lymphadenopathy. In the acute lymphadenopathy group, 98.2% of the patients had benign etiologies. The malignant disorders were mostly represented as chronic lymphadenopathy. Concerning the extension, 193 patients had localized lymphadenopathy and 264 had generalized lymphadenopaties. Cervical region was the most frequent site in both localized and generalized lymphadenopathy groups. Malignancies occurred as generalized lymphadenopathy. Supraclavicular area were involved only in the malignant group. Axillary involvement was predominant in BCG vaccine associated lymphadenitis and mycobacterium tuberculosis. All the lymph nodes less than 1 cm were due to benign causes. The malignant lesions were usually more than 3 cm in diameters. The following findings should alert the pediatrician for the probability of a malignant disorder: lymphadenopathy of more than 3 cm in size, of more than 4 weeks in duration, with supraclavicular involvement, and with abnormal laboratory and radiological findings.

Our study confirms that excellent results are achievable with combined modality therapy in childhood HD. In order to use risk-adapted therapy in children with HD, clinical prognostic factors should be validated with large, multicentered prospective clinical studies.

Side-population (SP) analysis identifies precursor cells in normal and malignant tissues. Cells with this phenotype have increased resistance to many cytotoxic agents, and in malignant disease may represent a primary drug resistant population. To discover whether drug resistant malignant SP cells are nonetheless sensitive to immune-mediated killing, we first established the presence of a malignant CD5+CD19+ SP subset in the blood of 18/21 subjects with B-CLL. We examined the fate of these cells in 6 of these individuals who received autologous hCD40L/IL-2 gene-modified tumor cells as part of a tumor vaccine study. Vaccinated patients showed an increase in B-CLL-reactive T cells followed by a corresponding decline in circulating CD5+CD19+ SP cells. T cell lines and clones generated from vaccinated patients specifically recognized B-CLL SP tumor cells. Elimination of SP cells is likely triggered by their increased expression of target antigens such as RHAMM following stimulation of the malignant cells by hCD40L, since CD8+ RHAMM-specific T cells could be detected in the peripheral blood of immunized patients and were associated with the decline in B-CLL SP cells. Hence malignant B cells with a primary drug resistant phenotype can be targeted by T cell mediated effector activity following immunization of human subjects.

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AimWe aimed to evaluate the coping styles and social support perceived by the children with two different chronic diseases (cancer and bronchiectasis), their mothers’ coping styles and compare them with a control group without any chronic physical or psychiatric disorder.MethodsOur sample consisted of 114 children and adolescents, with an age range from 9 to 15 years. The data were collected by using schedule for affective disorders and schizophrenia for school‐age children‐present and lifetime version, kid‐coping orientation to problems experienced (Kid‐COPE), social support appraisals scale (SSAS), and COPE.ResultsAll three groups were similar with respect to age and sex distribution. Around 50% to 60% of the children in both patient groups had a psychiatric diagnosis. Remarkably, 30% of the children had an internalizing disorder. The most commonly used coping style by the mothers was religious coping in all groups. Kid‐COPE scores did not significantly differ between groups. The scores on Family and Friend subscales of SSAS in the bronchiectasis group were significantly lower when compared with those of participants in hematology‐oncology and control groups.ConclusionChronic medical illnesses may have a similar psychological impact on children regardless of disease‐specific clinical presentations and outcomes. Future studies need to focus on identifying protective and risk factors that potentially mediate psychosocial well‐being.

Background aims Several studies have demonstrated that the immunogenicity of chronic lymphocytic leukemia (CLL) cells can be increased by manipulation of the CD40/CD40-ligand (CD40L) pathway. Although immunologic, and perhaps clinical, benefits have been obtained with an autologous CLL tumor vaccine obtained by transgenic expression of CD40L and interleukin (IL)-2, there is little information about the optimal gene transfer strategies. Methods We compared two different CLL vaccines prepared by adenoviral gene transfer and plasmid electroporation, analyzing their phenotype and immunostimulatory activity. Results We found that higher expression of transgenic CD40L was mediated by adenoviral gene transfer than by plasmid transduction, and that adenoviral transfer of CD40L was associated with up-regulation of the co-stimulatory molecules CD80 and CD86 and adhesion molecule CD54. In contrast, transgenic IL-2 secretion was greater following plasmid transduction. These phenotypic differences in the vaccines were associated with different functionality, both ex vivo and following administration to patients. Thus adenoviral vaccines induced greater activation of leukemia-reactive T cells ex vivo than plasmid vaccines. In treated patients, specific T-cell (T helper 1 (Th1) and T helper 2 (Th2) and humoral anti-leukemia responses were detected following administration of the adenoviral vaccine (n = 15), while recipients of the plasmid vaccine (n = 9) manifested only a low-level Th2 response. Progression-free survival at 2 years was 46.7% in the adenoviral vaccine recipients, versus 11.1 % in those receiving plasmid vaccine Conclusions CLL vaccines expressing the same transgenes but produced by distinct methods of gene transfer may differ in the polarity of the immune response they induce in patients.

Background Autosomal recessive osteopetrosis is a genetically and phenotypically heterogeneous disease, caused by defects in osteoclast formation and function. The only available treatment is allogeneic stem cell transplantation that has still high morbidity and mortality. The goal of the present study was to generate iPSCs from bone marrow-derived MSCs of osteopetrosis patients with three most common mutations by using two different integration-free gene transfer methods and compare their efficiencies. The secondary objective was to select the most appropriate integration-free production method for our institutional iPSC bank using this rare disease as a prototype. Methods Two different integration-free gene transfer methods (episomal and Sendai viral vectors) were tested and compared on the same set of patient samples exhibiting three different mutations associated with osteopetrosis. Generated iPSCs were characterized by standard assays, including immunophenotyping, immunocytochemistry, RT-PCR, embryoid body, and teratoma assays. Karyotype analyses were performed to evaluate genetic stability. Results iPSC lines exhibiting typical ESC-like colony morphology were shown to express pluripotency markers by immunofluorescence staining. Over 90% of the cells were found positive for SSEA-4 and OCT3/4 and negative/weak positive for CD29 by flow cytometry. Immunohistochemical staining of teratoma and spontaneously differentiated embryoid body sections confirmed their trilineage differentiation potential. All iPSC lines expressed pluripotency-related genes. Karyotype analyses were found normal. Direct sequencing of PCR-amplified DNA showed that disease-related mutations were retained in the patient-specific iPSCs. Conclusion Generation of iPSC using SeV and episomal DNA vectors have several advantages over other methods like the ease of production, reliability, high efficiency, and safety, which is required for translational research. Furthermore, owing to the pluripotency and self-renewal capacity, patient-specific iPSCs seem to be ideal cell source for the modeling of a rare genetic bone disease like osteopetrosis to identify osteoclast defects, leading to clinical heterogeneity in osteopetrosis patients, especially among those with different mutations in the same gene. Electronic supplementary material The online version of this article (10.1186/s13287-019-1316-8) contains supplementary material, which is available to authorized users.

GS2 is a rare autosomal recessive disease characterized by hypopigmentation, variable immunodeficiency with HLH. HSCT is the only curative treatment for GS2. We analyzed the outcome of 10 children with GS2 who underwent HSCT at our center between October 1997 and September 2013. The median age of the patients at transplant was 13.5 months (range, 6-58 months). All of the patients developed HLH before HSCT and received HLH 94 or HLH 2004 protocols. Donors were HLA-identical relatives in 8 patients, HLA-mismatched relatives in 2 patients. Engraftment was achieved in all except one patient. None of the patients developed acute GVHD. Chronic GVHD occurred in one and veno-occlusive disease occurred in four patients. Eight of the patients are under remission without any neurologic sequelae-median time of disease-free survival is 92.4 months. The present study shows successful transplant outcome without long-term neurologic sequelae in patients with GS2 who underwent HSCT from HLA-related donors.