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Item does not contain fulltext, Despite advances in transplant medicine, prevalence of complications after hematopoietic stem cell transplantation (HSCT) remains high. The impact of pre-HSCT oral health factors on the incidence and severity of complications post-HSCT is poorly understood. The aim of this prospective, observational study was to analyze oral health in patients planned for HSCT. Patients ≥18 years requiring HSCT were included from five sites between 2011-2018. General health, oral findings and patient-reported symptoms were registered in 272 patients. Oral symptoms around disease onset were reported by 43 patients (15.9%) and 153 patients (58.8%) reported oral complications during previous chemotherapy. One third of patients experienced oral symptoms at the oral examination before conditioning regimen and HSCT. In total, 124 (46.1%) patients had dental caries, 63 (29.0%) had ≥one tooth with deep periodontal pockets, 147 (75.0%) had ≥one tooth with bleeding on probing. Apical periodontitis was observed in almost 1/4 and partially impacted teeth in 17 (6.3%) patients. Oral mucosal lesions were observed in 84 patients (30.9%). A total of 45 (17.4%) of 259 patients had at least one acute issue to be managed prior to HSCT. In conclusion, oral symptoms and manifestations of oral disease were prevalent in patients planned for HSCT. The extent of oral and acute dental diseases calls for general oral screening of patients pre-HSCT.

Item does not contain fulltext, Hemophagocytic lymphohistiocytosis (HLH; hemophagocytic syndrome) is a rare syndrome of potentially fatal, uncontrolled hyperinflammation. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is indicated in primary, recurrent or progressive HLH, but information about its outcomes in the adult population is limited. We obtained data about 87 adult (≥18 years of age) patients retrospectively reported to the EBMT. The median survival time was 13.9 months. The three and five-year overall survival (OS) was 44% (95% CI 33-54%). Among 39 patients with a follow-up longer than 15 months, only three died. Relapse rate was 21% (95% CI 13-30%), while NRM reached 36% (95% CI 25-46%). Younger patients (<30 years of age) had better prognosis, with an OS of 59% (95% CI 45-73%) at three and five years vs 23% (95% CI 8-37%) for older ones. No difference in survival between reduced and myeloablative conditioning was found. To our knowledge, this is the largest report of adult HLH patients who underwent allo-HSCT. Patients who survive the first period after this procedure can expect a long disease-free survival. Both reduced intensity and myeloablative conditioning have therapeutic potential in adult HLH.

Contains fulltext : 175137.pdf (publisher's version ) (Closed access), Atypical chronic myeloid leukaemia (aCML) is an aggressive malignancy for which allogeneic haematopoietic stem cell transplantation (allo-HSCT) represents the only curative option. We describe transplant outcomes in 42 patients reported to the European Society for Blood and Marrow Transplantation (EBMT) registry who underwent allo-HSCT for aCML between 1997 and 2006. Median age was 46 years. Median time from diagnosis to transplant was 7 months. Disease status was first chronic phase in 69%. Donors were human leucocyte antigen (HLA)-identical siblings in 64% and matched unrelated (MUD) in 36%. A reduced intensity conditioning was employed in 24% of patients. T-cell depletion was applied in 87% and 26% of transplants from MUD and HLA-identical siblings, respectively. According to the EBMT risk-score, 45% of patients were 'low-risk', 31% 'intermediate-risk' and 24% 'high-risk'. Following allo-HSCT, 87% of patients achieved complete remission. At 5 years, relapse-free survival was 36% and non-relapse mortality (NRM) was 24%, while relapse occurred in 40%. Patient age and the EBMT score had an impact on overall survival. Relapse-free survival was higher in MUD than in HLA-identical sibling HSCT, with no difference in NRM. In conclusion, this study confirmed that allo-HSCT represents a valid strategy to achieve cure in a reasonable proportion of patients with aCML, with young patients with low EBMT risk score being the best candidates.

Item does not contain fulltext, BACKGROUND: Cystic fibrosis (CF) is a common genetic disease caused by mutations of the CF transmembrane conductance regulator (CFTR) gene. Persistent lung inflammation, characterized by increasing polymorphonuclear leukocyte recruitment, is a major cause of the decline in respiratory function in CF patients, and is a leading cause of morbidity and mortality. CFTR is expressed in various cell types, including leukocytes, but its involvement in the regulation of leukocyte recruitment is unknown. METHODS: Ex vivo adhesion and chemotaxis, flow cytometry, immunofluorescence, GTPases activity assays. RESULTS: We found that chemoattractant-induced activation of beta1 and beta2 integrins and of chemotaxis is defective in mononuclear cells isolated from CF patients. In contrast, polymorphonuclear leukocyte adhesion and chemotaxis were normal. The functionality of beta1 and beta2 integrins was restored by treatment of CF monocytes with the CFTR correcting drugs VX325 and VX809. Moreover, treatment of healthy monocytes with the CFTR inhibitor CFTR inh-172 blocked integrin activation by chemoattractants. In a murine model of lung inflammation, we found that integrin-independent migration of CF monocytes into the lung parenchyma was normal, whereas, in contrast, integrin-dependent transmigration into the alveolar space was impaired. Finally, signal transduction analysis showed that in CF monocytes chemoattractant-triggered activation of RhoA and CDC42 rho small GTPases, controlling integrin activation and chemotaxis respectively, was strongly deficient. CONCLUSION: Altogether, these data highlight the critical regulatory role of CFTR in integrin activation by chemoattractants in monocytes and identify CF as a new, cell-type selective, leukocyte adhesion deficiency disease providing new insights on CF pathogenesis.

The development of prostate cancer is dependent on heredity, androgenic influences, and exposure to environmental agents. A high intake of dietary fat is associated with an increased risk of prostate cancer, either through influence on steroid hormone profiles or through production of carcinogenic compounds that require biotransformation by enzymes. The polymorphic glutathione S-transferase (GST), N-acetyltransferase (NAT), and cytochrome P450 (CYP) enzymes are of particular interest in prostate cancer susceptibility because of their ability to metabolize both endogenous and exogenous compounds, including dietary constituents. Association between different NAT2, CYP2D6, CYP2C19 and GSTP1 genotypes and prostate cancer was studied in a Swedish and Danish case-control study comprising 850 individuals. The combined Swedish and Danish study population was analysed by polymerase chain reaction for the NAT2 alleles *4, *5A, *5B, *5C, *6 and *7, and for the CYP2D6 alleles *l, *3 and *4. The Swedish subjects were also analysed for the CYP2C19 alleles *1 and *2, and the GSTP1 alleles *A, *B and *C. No association was found between prostate cancer and polymorphisms in NAT2, CYP2D6, CYP2C19 or GSTP1. An association between CYP2D6 poor metabolism and prostate cancer was seen among smoking Danes; odds ratio 3.10 (95% confidence interval 1.07; 8.93), P = 0.03, but not among smoking Swedes; odds ratio 1.19 (95% confidence interval 0.41; 3.42), P = 0.75. Smoking is not a known risk factor for prostate cancer, and the association between CYP2D6 poor metabolism and prostate cancer in Danish smokers may have arisen by chance.

Androgens play an important role in the development of prostate cancer. Androgen regulating genes that show allelic variation may be susceptibility factors for the disease. One of these genes, CYP17, encodes the cytochrome P450c17alpha enzyme. It catalyses steroid 17alpha-hydroxylase/17,20 lyase activities at key points in testosterone biosynthesis. We investigated the association between a polymorphism in the CYP17 gene and prostate cancer in a population-based case-control study. All individuals studied were Caucasians born in Sweden, 178 were consecutive clinical prostate cancer patients, and 160 were age-matched control individuals randomly selected from the same catchment area. DNA was extracted from blood samples. A CYP17 gene fragment was amplified by polymerase chain reaction. The MspA1I restriction enzyme, which recognizes the base pair substitution, was used to identify the allelic variants CYP17A1 and CYP17A2. Significantly more men homozygous for the CYP17A1 allele were found among prostate cancer patients compared with control individuals; odds ratio 1.61 (95% confidence interval 1.02; 2.53), P = 0.04. According to a preliminary report, the CYP17A1/A1 genotype leads to higher circulating androgen levels, possibly by encoding for a more active androgen synthesizing CYP17 enzyme. Consequently, the CYP17A1/A1 genotype, which was found in a higher frequency among prostate cancer patients, may prove to be one of the important susceptibility factors for prostate cancer. If verified, this genotype is likely to convey a larger risk on a population basis, than the rare hereditary prostate cancer genes do.