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PurposeWe conducted an open-label, single-arm Phase I/II clinical trial in metastatic CRPC (mCRPC) patients eligible for docetaxel combined with treatment with autologous mature dendritic cells (DCs) pulsed with killed LNCaP prostate cancer cells (DCVAC/PCa). The primary and secondary endpoints were safety and immune responses, respectively. Overall survival (OS), followed as a part of the safety evaluation, was compared to the predicted OS according to the Halabi and MSKCC nomograms.Experimental designTwenty-five patients with progressive mCRPC were enrolled. Treatment comprised of initial 7 days administration of metronomic cyclophosphamide 50 mg p.o. DCVAC/PCa treatment consisted of a median twelve doses of 1 × 107 dendritic cells per dose injected s.c. (Aldara creme was applied at the site of injection) during a one-year period. The initial 2 doses of DCVAC/PCa were administered at a 2-week interval, followed by the administration of docetaxel (75 mg/m2) and prednisone (5 mg twice daily) given every 3 weeks until toxicity or intolerance was observed. The DCVAC/PCa was then injected every 6 weeks up to the maximum number of doses manufactured from one leukapheresis.ResultsNo serious DCVAC/PCa-related adverse events have been reported. The median OS was 19 months, whereas the predicted median OS was 11.8 months with the Halabi nomogram and 13 months with the MSKCC nomogram. Kaplan-Meier analyses showed that patients had a lower risk of death compared with both MSKCC (Hazard Ratio 0.26, 95% CI: 0.13–0.51) and Halabi (Hazard Ratio 0.33, 95% CI: 0.17–0.63) predictions. We observed a significant decrease in Tregs in the peripheral blood. The long-term administration of DCVAC/PCa led to the induction and maintenance of PSA specific T cells. We did not identify any immunological parameter that significantly correlated with better OS.ConclusionsIn patients with mCRPC, the combined chemoimmunotherapy with DCVAC/PCa and docetaxel was safe and resulted in longer than expected survival. Concomitant chemotherapy did not preclude the induction of specific anti-tumor cytotoxic T cells.

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The aim of this study was to assess the accuracy of serological tests in combination with clinical symptoms for diagnosing celiac disease (CD) according to the new proposed European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria. We retrospectively assessed children and adolescents aged 16 months -19 years who were examined for suspicion of CD (n = 345). Evaluation of clinical symptoms and the presence of tissue transglutaminase (anti-TG-IgA) and endomysial antibodies (EMA-IgA) as well as intestinal biopsies was performed in all patients. Human leukocyte antigens (HLAs) were not included. Among 345 biopsied children, 213 (62 %) children had anti-TG titers >10 times the upper limit of normal (ULN) and positive EMA antibodies. Ninety-nine (29 %) children also had symptoms suggestive of CD in addition to EMA positivity and elevated titers of anti-TG >10 times the ULN. In patients who were asymptomatic, but positive for EMA, and had anti-TG antibodies >10 times the ULN, the specificity of tests for Marsh 2-3 was only 85 %, while in symptomatic patients with the same antibodies levels, the specificity was 99 %. Conclusion: Our results reveal that intestinal biopsies could be omitted in 28 % of patients when the new ESPGHAN guidelines are applied. Due to high accuracy of serological tests in combination with clinical symptoms for diagnosis of CD, the new guideline seems to be applicable even without the use of HLA testing.