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Hemophagocytic lymphohistiocytosis (HLH) is a severe systemic syndrome associated with hyperactivation of macrophages and impaired regulation of the immune system. Two forms of HLH are currently recognized: genetically determined or familial (FHLH), and secondarily developed in the course of primary diseases, like autoimmune disorders, rheumatoid disorders, cancers, or infections. In the Polish population, FHLH is rather rare. The aim of the present study was to assess the immune function in a group of children with clinical symptoms suggesting FHLH. Forty five children with suspected HLH of the median age of 4 years and 15 healthy children, taken as a control group, were enrolled into the study. All presented results were obtained with the use of flow cytometry. In the HLH group, there were only three cases identified with the UNC13D gene mutation responsible for the FHLH3 phenotype. Another four children, without known mutation, were classified as FHLH because of frequent recurrence of the disease. In all cases of FHLH, cell cytotoxicity was impaired compared with healthy children (p = 0.003). Perforin expression in FHLH was normal or higher than that observed in controls (p = 0.09). In case of patients with mutation in the Munc13 protein, degranulation was lower than that in healthy children (<5 %). The findings of this study demonstrate that children with known mutations responsible for the FHLH development are immunocompromised. However, it requires further elucidation whether the presence of currently unknown mutations could lead to a similar phenotype.

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We have previously shown in mice that vaccination with three Her-2-peptides representing B-cell epitopes of the extracellular domain of Her-2/neu induces Her-2/neu-specific IgG antibodies with strong anti-tumor activity in vitro and in vivo. We have now finalized a phase I clinical trial with an anti-Her-2/neu vaccine-construct of immunopotentiating reconstituted influenza virosomes with the three peptides in patients with metastatic breast cancer (MBC). Ten MBC patients with low protein overexpression of Her-2/neu of MBC (+ or ++ upon immunohistochemistry, FISH negative) and positive hormone receptor status were enrolled in a single center phase I study. The virosomal formulated vaccine, consisting of 10 microg/peptide, was intramuscularly applied three times on days 1, 28, and 56. The primary endpoint of the study, which lasted 12 weeks, was safety, the secondary endpoint immunogenicity. Local erythema at the injection site was the only vaccine-related side effect occurring in four patients. In 8 of 10 patients an increase in peptide-specific antibody titer measured by ELISA was found. Importantly, the induced antibodies were also directed against the native Her-2/neu protein. Cellular immune responses, as measured by in vitro production of IL-2, IFN-c, and TNF-a of PBMCs showed a marked increase after vaccination in the majority of vaccinees. Notably, the number of CD4+CD25+Foxp3+T regulatory cells, which were significantly increased compared to healthy controls prior to vaccination, was markedly reduced following vaccination. In all, the immunological responses after vaccination indicated that the patients in stage IV of disease were immunocompetent and susceptible to vaccination. The Her-2/neu multipeptide vaccine was safe, well tolerated and effective in overcoming immunological tolerance to Her-2/neu. The induction of anti-Her-2-specific antibodies could result in clinical benefit comparable to passive anti-Her-2 antibody therapy.

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Neuroblastoma is perhaps the most heterogeneous childhood cancer in terms of clinical behavior. Stage of disease, age at diagnosis, levels of urinary catecholamine excretion, N-myc amplification, and DNA ploidy have been found to be significant prognostic factors. The aims of this combined retrospective-prospective study are to verify the prognostic significance of DNA ploidy and to show its correlation with other prognostic signs. Thirty six fresh and thirty three paraffin embedded samples from patients with histologically confirmed neuroblastoma (41 prior to receiving any chemotherapy) were available for flow cytometry DNA analysis. Our results showed that the maturation induced during chemotherapy could give rise to aneuploidy therefore we analyzed the associations between the DNA ploidy and other prognostic markers only in patients examined before chemotherapy. There were no significant correlations between DNA ploidy and urinary catecholamine metabolites levels or tumor localization. DNA aneuploidy was significantly more frequent in patients with lower clinical stage, lower age at diagnosis, and without N-myc gene amplification. Patients with DNA aneuploid neuroblastomas died less frequently than patients with DNA diploid tumors. There were no significant associations among the S-phase or proliferation fraction and other prognostic factors.

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BACKGROUND: DNA contents in cells may be determined by flow cytometry. The relationship between malignant cell aneuploidy and prognosis is known in many types of neoplasms in adults and in children. In some situations, demonstration of an aneuploid clone verifies presence of malignant cells. Aneuploidy is rare in benign diseases. This report summarizes our first experiences with cytometric DNA analysis and shows the method's abilities to other potential users. METHODS AND RESULTS: We investigated DNA contents in blood and bone marrow (BM) specimens of 25 children with leukemia, in 41 unfixed solid tumors after biopsy and in 24 specimens of paraffin embedded neuroblastoma tissue. We also investigated 5 specimens of cerebrospinal fluid (CSF) of patients with medulloblastoma, 18 specimens of CSF from patients with leukemia or lymphoma, 4 pleural exudates suspected from malignancies, and 45 specimens of possibly infiltrated BM from primary solid tumors. As the purpose of this study was to test the method on a relatively small number of specimens, we did not perform statistical analysis of our data. As reported previously, aneuploidy was frequent in CALLA + acute lymphoblastic leukemia and in types of neuroblastoma with favorable prognosis (lower clinical stages and less than 2 years of age). CONCLUSIONS: Our results show that DNA ploidy may be tested by flow cytometry in an easy and fast way. The source of the material may be unfixed tumors, deparaffinized tumors, BM, blood, CSF and pleural exudates.

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Ophthalmoscopic examinations were performed in 96 patients with polyps or another disturbances of the colon, among them 3 cases suffered a histopathologically confirmed familial polyposis of the colon. All 3 cases of the familial polyposis exhibited in the ophthalmological examination pathological changes of the retinal pigment epithelium of both eyes.

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Presented are 4 cases of recurrent pterygium treated by lamellar keratoplasty. The surgical technique and the results of the treatment are described.

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The authors present the surgical technique and the results of treatment of 12 patients with corneal leukoma caused by scalding. In all the cases they performed a perforating keratoplasty. Two years after operation among 7 grafts 5 were transparent. Perforating grafts in leukoma caused by a chemical burn have poor prognosis in contrary to thermic burns.

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